Early Points Research Articles

Potential Health Disparities in the Early Detection and Prevention of Pancreatic Cancer.

Pancreatic cancer remains one of the deadliest cancers in the United States. Some types of pancreatic cysts, which are being detected more frequently and often incidentally on imaging, have the potential to develop into pancreatic cancer and thus provide a valuable window of opportunity for cancer interception. Although racial disparity in pancreatic cancer has been described, little is known regarding health disparities in pancreatic cancer prevention. In the present study, we investigate potential health disparities along the continuum of care for pancreatic cancer. The racial and ethnic composition of pancreatic patients at high-volume centers in Indiana were evaluated, representing patients undergoing surgery for pancreatic cancer (n=390), participating in biobanking (972 pancreatic cancer patients and 1984 patients with pancreatic disease), or being monitored for pancreatic cysts at an early detection center (n=1514). To assess racial disparities and potential differences in decision-making related to pancreatic cancer prevention and early detection, an exploratory online survey was administered through a volunteer registry (n=708). Results: We show that despite comprising close to 10% or 30% of the Indiana or Indianapolis population, respectively, African Americans make up only about 4-5% of our study cohorts consisting of patients undergoing pancreatic surgery or participating in biobanking and early detection. Analysis of online survey results revealed that given the hypothetical situation of being diagnosed with a pancreatic cyst or pancreatic cancer, the vast majority of respondents (>90%) would agree to undergo surveillance or surgery, respectively, regardless of race.Only a minority (3-12%) acknowledged any significant transportation, financial, or emotional barriers that would impact a decision to undergo surveillance or surgery. This suggests that the observed racial disparities may be due in part to the existence of other barriers that lie upstream of this decision point. Racial disparities exist not only for pancreatic cancer but also at earlier points along the continuum of care such as prevention and early detection. To our knowledge, this is the first study to document racial disparity in the management of patients with pancreatic cysts who are at risk of developing pancreatic cancer. Our results suggest that improving access to information and care for such at-risk individuals may lead to more equitable outcomes.

Immature Dendritic Cell therapy in early life promotes peripheral tolerance of autoreactive T cells delaying onset and incidence of T1D.

Abstract Type 1 Diabetes (T1D) is a complex autoimmune disease characterized by T cells mediating the destruction of insulin-secreting ß-cells in the pancreatic islets of Langerhans. Evidence suggests both central and peripheral T cell tolerance mechanisms fail in the development of T1D. The non-obese diabetic (NOD) mouse model is a spontaneous model of T1D that shares many characteristics to human disease. Studies in adult pre-diabetic NOD mice using immature dendritic cells (iDCs) as therapy result in delaying disease onset and, in some cases, lowering disease incidence. The mechanism by which DCs confer protection to diabetes is largely unknown, but is thought to occur in an antigen-independent manner; driven by tolerogenic cytokines. Broadly, DCs are also known to induce peripheral tolerance by activation induced cell death, anergy and inducing the development of regulatory T cells (iTregs). In the past twenty years, the existence of a neonatal window of tolerance has highlighted the importance of tolerogenic mechanisms to prevent autoimmunity. Therefore, we hypothesized DC therapy administered at a neonatal stage in NOD mice will result in protection to the development of T1D. Our studies treating NOD mice with iDCs from an early point in life demonstrate that donor iDCs migrate to the pancreatic draining lymph nodes, modulate the microenvironment diminishing islet T cell infiltration and T cell activation, culminating in a significant delay in the onset and incidence of T1D.

Fasting Metabolic Profiles are Cell-Autonomous in Elephant Seal Primary Muscle Cells

Northern elephant seals ( Mirounga angustirostris) undergo prolonged terrestrial fasts during energetically intensive life stages including breeding, molting, and postnatal development. Fasting-tolerant vertebrates generally extend the second phase of fasting, during which body mass declines but homeostasis is preserved through reliance on lipid fuel sources and sparing of body protein stores. In elephant seals, the postnatal fast coincides with development of the extensive body oxygen stores required to support extended breath-hold diving, as well as an increased capacity for apnea-related metabolic suppression. Studies in grizzly bears, another large-bodied fasting-tolerant mammal, have identified both serum-derived and intrinsic cellular regulation of the adipocyte metabolic phenotype. However, it is unknown whether these mechanisms extend across species, tissue, or fasting type (active vs inactive). Thus, we derived proliferative primary skeletal muscle cells (myoblasts) from weaned elephant seal pups; biopsies that yielded cells were collected at both early (~1 week) and late (~8 weeks) points in the postnatal fast. We found that total ATP production rate was greater in myoblasts collected from animals late in the fast (27% increase over early, p=0.08). Throughout the fast, myoblasts relied predominantly on glycolytic rather than oxidative ATP production (p<0.001), and this reliance increased as the fast progressed (p<0.014). Together, these data suggest that metabolic reliance is at least partially cell-autonomous in elephant seal myoblasts. KNA is supported by an NSF Graduate Research Fellowship (DGE 1752814 & 2146752) and a UC Berkeley Fellowship. JPV-M is supported by a NIH/NIGMS grant (R35GM146951). Research was funded by UC Berkeley startup funds and the Winkler Family Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Some Early Studies of Isotropic Turbulence: A Review

A re-examination of some early classic turbulence literature, mainly of isotropic turbulence, is given in this selective review. Some early studies, including original concepts and points, are reviewed or highlighted. Two earliest studies and six major original concepts are found: (i) Lord Kelvin’s pioneering elementary studies of homogeneous, isotropic turbulence; (ii) Kelvin’s early introduction of Fourier Principles into turbulence studies; (iii) the Kelvin elementary concept of the direct energy cascade; (iv) the Kelvin early concept of the symmetry of turbulence; (v) the Taylor concept of the coefficient of eddy viscosity; (vi) the Taylor concept of the ‘age’ of the eddy; (vii) the Taylor–Fage–Townend concept of small eddies or microturbulence or small scale turbulence; and (viii) the Obukhov concept of a function of the inner Reynolds number (i.e., Re dependent coefficient) in both the balance equation and the energy distribution equation (the two-thirds law). Both Kelvin and Taylor should be regarded as the co-founders of the statistical theory of homogeneous, isotropic turbulence. The notion, ‘the Maxwell–Reynolds decomposition of turbulent flow velocity’, should be used. The Kolmogorov–Obukhov scaling laws are reviewed in detail. Heisenberg’s inverse seventh power spectrum is briefly reviewed. The implications or significances of these early studies, original concepts and points are briefly discussed, with special reference to their possible links with modern approaches and theories.

Age-related changes in muscle coordination patterns of stepping responses to recover from loss of balance

IntroductionReactive stepping capacity to recover from a loss of balance declines with aging, which increases the risk of falling. To gain insight into the underlying mechanisms, we investigated whether muscle coordination patterns of reactive stepping differed between healthy young and older individuals. MethodsWe performed a cross-sectional study between 15 healthy young and 14 healthy older adults. They recovered from 200 multidirectional platform translations that evoked reactive stepping responses. We determined spatiotemporal step variables and used muscle synergy analysis to characterize stance- and swing-leg muscle coordination patterns from the start of perturbation until foot landing. ResultsWe observed delayed step onsets in older individuals, without further spatiotemporal differences. Muscle synergy structure was not different between young and older individuals, but age-related differences were observed in the time-varying synergy activation patterns. In anterior-posterior directions, the older individuals demonstrated significantly enhanced early swing-leg synergy activation consistent with non-stepping behavior. In addition, around step onset they demonstrated increased levels of synergy coactivation (mainly around the ankle) in lateral and anterior directions, which did not appear to hamper foot clearance. ConclusionAlthough synergy structure was not affected by age, the delayed step onsets and the enhanced early synergy recruitment point at a relative bias towards non-stepping behavior in older adults. They may need more time for accumulating information on the direction of perturbation and making the corresponding sensorimotor transformations before initiating the step. Future work may investigate whether perturbation-based training improves these age-related deficits.

Early identification of golimumab-treated patients with higher likelihood of long-term retention.

The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Retrospective non-interventional database analysis. Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.

Monitoring for liver cancer post-gene therapy-How much and how often?

Hepatocellular carcinoma (HCC) has long been recognized as a complication in people with chronic liver disease, particularly those with cirrhosis. Two gene therapies for haemophilia A and B recently approved in Europe and the US utilize adeno-associated virus (AAV) vectors designed to target hepatocytes. A number of other AAV gene therapies are undergoing clinical investigation for both liver and extrahepatic diseases, many of which likely transduce hepatocytes as well. Although AAV vectors predominantly persist in episomal forms, concerns about insertional mutagenesis have arisen due to findings in pre-clinical models and in a small subset of human HCC cases featuring wild-type AAV integrations in proximity to potential oncogenes. Despite the absence of any causative link between AAV vector therapy and HCC in approved extrahepatic gene therapies or haemophilia gene therapy trials, the package inserts for the recently approved haemophilia gene therapies advise HCC screening in subsets of individuals with additional risk factors. In this review, we discuss HCC risk factors, compare various screening modalities, discuss optimal screening intervals, and consider when to initiate and possibly discontinue screening. At this early point in the evolution of gene therapy, we lack sufficient data to make evidence-based recommendations on HCC screening. While AAV vectors may eventually be shown to be unassociated with risk of HCC, we presently favour a cautious approach that entails regular surveillance until such time as it is hopefully proven to be unnecessary.

Risk and protective factors associated with child welfare involvement among maternal-infant dyads affected by prenatal substance use

A 5-year retrospective cohort study (n = 4,178) was conducted to identify trends and outcomes associated with child welfare-involved maternal-infant dyads affected by perinatal substance use in Colorado. Two linked data sources were used: (1) vital records birth and death certificate data on live births between 2013 and 2019 and (2) child welfare data from the Statewide Automated Child Welfare Information System. Data integration and de-identification work was accomplished by the Linked Information Network of Colorado and authorized by state legislation. Two tools were available for identity resolution: (1) the Senzing identity resolution application and (2) SQL queries. Binary logistic regression was used to explore how a birthing person’s demographic characteristics, use of prenatal care, Special Nutrition Program for Woman, Infants, and Children (WIC) enrollment during pregnancy, health of birthing person during pregnancy and delivery, and the newborn’s health at the time of birth related to child welfare removal within the first 60 days. Factors associated with an increased risk of infant removal includeless than adequate prenatal care, lower household income, low participation in WIC, andgreater medical fragility of the newborn. For infants removed from the home, the rate of placement with relatives while in foster care decreased by 15 % (2016–2019). This is a concern as placing children with relatives is shown to promote healthy child development. Findings bring into focus opportunities for prevention, treatment, and support of maternal-infant dyads affected by substance use during the perinatal period and offers insight into early entry points for preventing the need for family separation by child welfare.

Revealing early pest source points and spreading laws of Pantana phyllostachysae Chao in Moso bamboo (Phyllostachys pubescens) forests from Sentinel-2A/B images

Pantana phyllostachysae Chao is a leaf-eating pest that poses a significant threat to bamboo forest health. Current research mainly focuses on statically identifying damage using remote sensing images. However, the mechanism behind the damage's traceability remains unclear, making it difficult to pinpoint early infestation sources accurately. Additionally, our understanding of the pest's spreading laws is limited. This study leverages Sentinel-2A/B images from February to November 2021 to investigate P. phyllostachysae infestation traceability through the dynamic age algorithm and indicator analysis method. The results shed light on the distribution of early pest sources over the study period. By analyzing both the overall pest infestation “cluster” and its center of gravity, we dissect P. phyllostachysae infestation characteristics and paths monthly throughout the study period. Our findings reveal three zones with strong spreading momentum, three with slow spreading momentum, and two transitional zones during the February-November period, aligning with P. phyllostachysae occurrence patterns. However, the direction of P. phyllostachysae spreading varies, likely due to a combination of meteorological, topographical, vegetative biochemical, and human activity factors. This study introduces innovative approaches for identifying early pest source points and understand their spreading laws, contributing to more effective pest prevention and control in forest ecosystems.

A KEY PARTNER ONLY NOW? THE PRESENT-CENTREDNESS IN KOREA’S VIEWS OF ITS ECONOMIC RELATIONS WITH SOUTHEAST ASIA

Common public narratives in South Korea note that “Southeast Asia has recently emerged as its key economic partner.” Yet, these accounts are typically presented only with recent economic statistics and are largely devoid of context or nuance. In particular, they lack consideration of historical references, creating the impression that Korea-Southeast Asia ties are only a “recent” development. This “presentist” tendency is not only ahistorical in itself, but it may also produce a misleading appreciation of South Korea’s relations with Southeast Asia. By reviewing statistical information relevant to Southeast Asia’s economic importance to South Korea, particularly in trade and foreign direct investment, this article shows that SE Asia became Korea’s top economic partner at a much early point in time. It also discusses the factors that may have contributed to the popularity of such a presentist view in the public conscience.

Milk consumption and behavior of calves in automated calf feeders as early indicators of weaning liveweight

Modern intensive dairy farming relies on data to aid and prioritize management decisions made on farm. Decisions made early in an animal's life can have lasting effects on welfare, productivity, longevity, and profitability. Precision technology such as automated calf feeders (ACF) allow the customization of feeding programs, but despite this, weaning weights (WWT) vary substantially between calves. This observational study used a 3-yr dataset comprising 1,440 female Holstein Friesian calves at a single intensive commercial dairy farm (Dairy Australia feeding system 5; indoor, total mixed ration) using ACF to (1) determine the variability in WWT (as a proxy of animal performance) of calves within this system; (2) identify the contributing factors responsible for the variation in WWT; and (3) identify potential early management intervention points that could be indicative of the performance of calves at weaning within the system. Calves entered the ACF at 10 d of age with 12 calves per ACF; calves were weighed at birth and weaning using weigh scales. We discovered a large range of calf WWT (41–118 kg/head) at ~60 d of age despite the application of strict uniform management protocols. Our results from modeling showed that WWT was significantly and positively associated with birth weight (BWT), with low BWT calves (<36 kg) achieving an average of 70 kg weight at weaning. In contrast, heavier BWT (>36 kg) calves achieved an average of 82 kg at weaning. Based on calf feeder data, cumulative milk consumption and cumulative unrewarded visits to the feeder, as well as BWT, were identified as indicators of greater WWT as all these were highly significant terms in the model for WWT. Results suggest that quantifying consumption and number of visitations to the ACF at d 5 may allow farmers to identify, with time to intervene, calves underperforming within the feeder or system, therefore increasing their potential for growth. Additionally, this demonstrated that greater milk consumption (>30 kg) and interaction with the feeder up to d 5 in the feeder is more likely to yield a WWT >75 kg, identifying a potential point for management intervention for calves below consumption and interaction thresholds (e.g., by developing alarm systems based on consumption or visitation number).

Longitudinal Mediating Effect of Self-esteem in the Bidirectional Relationship between School Life Adaptation and Life Satisfaction of Multicultural Children

Objectives: This study sought to verify bidirectionality by examining a bidirectional relationship of school life adaptation and life satisfaction with self-esteem as a mediating variable over time.Methods: Based on data from 2,245 elementary school students extracted from Year 1 (2019), Year 2 (2020), and Year 3 (2021) of the Multicultural Youth Panel Survey (MAPS 2nd), this adopted structural equation modeling method using the autoregressive cross-lagged modeling.Results: The study derived the following results. First, adaptation to school life at a previous point affected self-esteem at a later point, self-esteem at a previous point affected life satisfaction at a later point. In other words, school life adaptation in 4th grade had a positive effect on life satisfaction in 6th grade through selfesteem at 5th grade. Second, life satisfaction at a previous point affected self-esteem at a later point. Selfesteem at an earlier point had an effect on school life adaptation at a later point. That is, life satisfaction in 4th grade had a positive effect on school life adaptation in 6th grade through self-esteem at 5th grade.Conclusion: This study found a bidirectional relationship of school life adaptation and life satisfaction with self-esteem as a mediating variable over time.

Pilot Study Assessing Student Interest in Combined Residency Training Pathways With Radiation Oncology

Most medical students have limited exposure to radiation oncology (RO) before deciding which specialty to choose for residency. This may limit the number and diversity of RO applicants. The purpose of this study was to determine students' views on a combined pathway program of RO with internal medicine (IM), as well as other related medical specialties, as a potential means of overcoming barriers to interest in RO and the early decision point to solo training in a highly specialized field. In July to August 2022, all 299 United States student and postgraduate year 1 members of the American Society for Radiation Oncology were sent an electronic survey assessing their views on advantages and disadvantages of a combined IM/RO training pathway, and interest in several options of combined pathway programs. Eighty participants completed the survey (response rate 27%). Thirty-four (43%) were very or extremely interested in IM/RO residency (median Likert-type rating 3, IQR 2-4). The most important potential advantages of an IM/RO pathway included greater flexibility in employment options (n = 51, 64%), enhanced general medical knowledge to facilitate ambitions in other career pathways (n = 46, 58%), improved patient care (n = 43, 54%), and having a pathway for combined hematologic/oncology and RO board certification (n = 46, 58%). In comparison to IM/RO, participants were significantly more interested in a combined RO and hematology/oncology program (median Likert-type rating 5, IQR 5-5, P = .005). Among the subgroup of 26 survey participants who believed it less likely they would apply for RO residency, 18 (69%) thought an IM/RO pathway would increase their interest in RO (median Likert-type rating 4, IQR 3-5). Interest in IM/RO did not differ by gender, race, or ethnicity. Combined training pathways involving RO were viewed positively by survey respondents, and may be particularly appealing to those less committed to a career in RO. Further research will help guide recommendations for the creation of these programs.

Abstract B068: Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer

Abstract The traditional cancer paradigm, in which radiographic scan precedes biopsy which precedes diagnosis, has several limitations, but lack of patient identification prior to biopsy lies at the crux. Here we describe the results of our retrospective pilot study, in which we characterize the output of a natural language processing (NLP) model we utilized to review and flag radiology reports suspicious for pancreas cancer and demonstrate its potential for identification of patients with pancreas cancer at earlier points in the diagnostic framework. A RadBERT based NLP model was utilized to identify radiology reports suspicious for pancreas cancer that were generated within the Northwell Health system in January 2023. These outputs were then manually reviewed retrospectively and labelled as non-suspicious non-cystic, non-suspicious cystic, or suspicious non-cystic. For patients with suspicious non-cystic lesions, chart review was performed to determine whether these findings were indicative of a new pancreatic malignancy, and if so, whether the patient had received further care. Our NLP reviewed 17,339 radiology reports in January 2023 and identified 917 of these reports as suspicious for pancreas cancer, representing imaging from 852 patients across our health system. 38% of patients had normal or atypical but non-suspicious non-cystic lesions (322). 46% of patients had non-suspicious cystic lesions (389) and 17% of patients had suspicious non-cystic lesions suspicious for a primary pancreatic neoplasm (149); 10 of these reports observed simultaneous cystic and neoplastic pancreas lesions. Of the patients with suspected neoplastic lesions, 55% had been previously diagnosed with pancreas cancer. 45% were new diagnoses and upon chart review, of these, only 36% underwent biopsy in our health system with an average of 22 days between radiology report and biopsy while 30% were seen by an outpatient oncologist within our health system with an average of 32 days between radiology report and visit. 64% did not proceed to further workup in our health system with 35% for whom further workup was not recommended, 19% who elected against further workup, 23% who were scheduled for internal follow-up that did not occur, and 23% who were scheduled for external follow-up. Notably, when compared to the January outputs of other cohort building tools, NLP identified 67 new patients with pancreas cancer, while pathology report identified 15, ICD10 problem list identified 17, and cancer registry identified 13. Our NLP approach identified the greatest proportion of patients with newly diagnosed pancreas cancer compared to traditional identification measures and of these patients identified by our model, in the context of the traditional cancer care paradigm, only 1/3 proceeded to further workup within our health system before facing a striking nearly month of lead-time between radiology report and biopsy/outpatient oncology visit. We are now working to leverage this model to prospectively identify and navigate patients identified by NLP to address this gap in real-time. Citation Format: Kristen M. John, Anthony Carvino, Shama Khan, Ellen Chen, Deepak Saluja, Matthew Barish, Daniel A. King. Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B068.

Teachers' Challenges in Preparing Grade R Learners for School-readiness and Strategies Used to Activate Learner-readiness

The purpose of this study was to investigate the challenges that affect Grade R (kindergarten) learners’ readiness for learning, and the strategies used to ensure learner-readiness when entering Grade 1. Learning readiness is an ongoing process from the beginning to the end of an individual’s life. Learners at this early point in their lives (Foundation Phase) begin with their formal learning based on play, arithmetic, cultural activities, and reading and writing practice. The study engaged four teacher-participants: two Grade R teachers, and two Early Learnerhood Development practitioners from Grade 1. The case study research design was selected to elicit data through semi-structured open-ended interviews in natural settings to gain in-depth information which was analysed via the thematic analysis approach. The study findings revealed that teachers experienced challenges due to poor infrastructure, overcrowded classrooms, lack of resources, policy of passing all Grade R learners, admission of non-documented learners, and learners who skipped pre-school. To address these challenges which impacted Grade R learners’ readiness to enter Grade 1, teachers were resourceful and planned innovative and interesting play-based lessons. This ensured that Grade R learners’ readiness is largely play-based to develop them holistically by involving them in creative indoor and outdoor activities.

AMIDR: A Complete Pulse Method for Measuring Cathode Solid-State Diffusivity

Lithium transport within cathode material is driven by diffusion. While fast cathode diffusion is desired, solid-state diffusivity is one of the most difficult cell material properties to measure. However, it is an important property to understand as cathode capacity is often limited by poor diffusivity. GITT (Galvanostatic Intermittent Titration Technique) is a common diffusivity measurement method. This technique is accomplished by applying a series of constant current pulses to a cell and analyzing the voltage response. While easy to use, this method only measures near the surface of the active material by assuming that it takes the geometry of a semi-infinite plane. This approximation means that GITT is only accurate when measuring the very initial voltage response. However, the voltage response cannot be analyzed too early as this may amplify error produced by CDL (double layer capacitance) and RI (interface resistance) found at the cathode-electrolyte interface which GITT does not account for. EIS (Electrochemical Impedance Spectroscopy), an AC method, is better suited for distinguishing CDL/RI from diffusivity but also struggles to evaluate diffusivity beyond the surface of active material within a reasonable time frame1. In addition, instruments capable of quality EIS are often cost prohibitive compared to DC cell testers.The voltage responses after the first few moments of a pulse are relevant when evaluating cell behaviour in real-world applications and should be considered to produce comprehensive measurements of diffusivity and its performance impact. AMID (Atlung Method for Intercalant Diffusion) is a multi-rate pulse method produced by this lab which uses a series of pulses, both short/fast and long/slow, and an approximation-free analytical model (developed by Sven Atlung) for diffusion in a spherical particle, not a semi-infinite plane2. However, AMID cannot differentiate diffusion impedance from resistance and therefore requires that resistance be considered negligible. In addition, while AMID mathematics are free of approximations, the typical multi-rate pulse protocol does require that series of pulses be approximated as singular pulses3. Lastly, the multi-rate pulse protocol limits the state-of-charge resolution of diffusivity measurements.AMIDR (Atlung Method for Intercalant Diffusion and Resistance) incorporates a GITT-style single pulse protocol with AMID-style mathematics modified to account for resistance as shown in Figure 1b). AMIDR collects pulse data with a pseudo-logarithmic time distribution. This means that the same number of data points is collected in 0.1-1.0 seconds, 1.0-10 seconds, 10-100 seconds and so on. Unlike GITT which measures diffusivity at an early arbitrary point in a pulse, AMIDR considers the entire length of a pulse comprehensively. Fractional capacity is calculated for each datapoint by dividing the actual capacity with the ideal “impedance-free” capacity expected at that voltage as shown in Fig 1c). These fractional capacity values, normalized from 0-1, are fitted to the modified Atlung model. This modified Atlung model is nearly the same as the original Atlung model except an additional term is added for capacity limited by resistance. Unlike AMID, AMIDR measures both diffusivity and resistance simultaneously by using both as fitting parameters. Lastly, while CDL is usually small enough for RI to behave simply like ohmic resistance on relatively short time scales (>0.1 seconds), AMIDR has the option to account for CDL/RI when relevant such as near the bottom of a complete discharge.AMIDR is a new diffusivity measurement method tailored for cathode material in Li-ion batteries. By combining the advantages of various previous diffusivity methods, AMIDR eliminates many of their concerns and sources of error such as sampling of only the material surface, alternate confounding sources of impedance, and expensive equipment as seen in Figure 1a). When paired with proper cell design (i.e. ultra-low single layer cathode loading to remove pore impedance and reference electrodes to remove anode impedance), AMIDR can produce high resolution diffusivity measurements with improved accuracy and applicability to real-world cell performance.References C. Deng and W. Lu, Journal of Power Sources, 473, 228613 (2020).A. Liu et al., J. Electrochem. Soc., 168, 070503 (2021).M. Doyle, J. Newman, and J. Reimers, Journal of Power Sources, 52, 211–216 (1994). Figure 1. (a) Comparison of various Diffusivity measurements. (b) The modified Atlung model for diffusion in a spherical particle. (c) How pulse data is converted to the unitless Atlung model. Figure 1

Explaining neurological factors of hearing loss through digital technologies

The study investigated how inclusion of the considerable amount of knowledge generated through basic research in multisensory experiences can be brought into clinical paediatric audiology with a specific focus to enhance understanding of the neurological implications of childhood hearing loss. ObjectivesThe overall aim of the project was to investigate how to use emerging technologies to enhance the understanding of the neurological impact of paediatric hearing loss. The specific objectives were to develop an app and to evaluate its ease of use and the understanding of neurology by all types of stakeholders and end-users. MethodsA collaborative participatory and human centred research design was used. This methodological approach brought stakeholders into the design process at an early point of time and workshops mapped the content and interaction of the iterative development of the app. Nine clinicians from Copenhagen Hearing and Balance Centre and 4 media technologists from Multisensory Experience Lab participated in the development of the app-prototype. Evaluations were made by use of questionnaires completed by stakeholders and end-users and focus group interviews. Eight parents with children with hearing loss, 13 internal stakeholders and 14 external stakeholders participated in the evaluation of the app. ResultsThe app was overall positively evaluated. End users/parents with children with hearing loss were slightly more positive than stakeholders/professionals in audiology. ConclusionsApps are a future media for providing health care information and it proved both relevant and applicable to start using apps also to provide complex information such as neurological implications of childhood hearing loss.

Don't throw the associative baby out with the Bayesian bathwater: Children are more associative when reasoning retrospectively under information processing demands.

Causal reasoning is a fundamental cognitive ability that enables individualsto learn about the complex interactions in the world around them. However, the mechanisms that underpin causal reasoning are not well understood. For example, it remains unresolved whether children's causal inferences are best explained by Bayesian inference or associative learning. The two experiments and computational models reported here were designed to examine whether 5- and 6-year-olds will retrospectively reevaluate objects-that is, adjust their beliefs about the causal status of some objects presented at an earlier point in time based on the observed causal status of other objects presented at a later point in time-when asked to reason about 3 and 4 objects and under varying degrees of information processing demands. Additionally, the experiments and models were designed to determine whether children's retrospective reevaluations were best explained by associative learning, Bayesian inference, or some combination of both. The results indicated that participants retrospectively reevaluated causal inferences under minimal information-processing demands (Experiment 1) but failed to do so under greater information processing demands (Experiment 2) and that their performance was better captured by an associative learning mechanism, with less support for descriptions that rely on Bayesian inference. RESEARCH HIGHLIGHTS: Five- and 6-year-old children engage in retrospective reevaluation under minimal information-processing demands (Experiment 1). Five- and 6-year-old children do not engage in retrospective reevaluation under more extensive information-processing demands (Experiment 2). Across both experiments, children's retrospective reevaluations were better explained by a simple associative learning model, with only minimal support for a simple Bayesian model. These data contribute to our understanding of the cognitive mechanisms by which children make causal judgements.

Artificial Intelligence–Powered Assessment of Pathologic Response to Neoadjuvant Atezolizumab in Patients With NSCLC: Results From the LCMC3 Study

IntroductionPathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate. MethodsWe determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = 151) performed by one of the 47 local pathologists and three central pathologists. ResultsFor concordance among visual determination of percent viable tumor, the interclass correlation coefficient was 0.87 (95% confidence interval [CI]: 0.84–0.90). Agreement for visually assessed 10% or less viable tumor (major PathR [MPR]) in the primary tumor was 92.1% (Fleiss kappa = 0.83). Digitally assessed percent viable tumor (n = 136) correlated with visual assessment (Pearson r = 0.73; digital/visual slope = 0.28). Digitally assessed MPR predicted visually assessed MPR with outstanding discrimination (area under receiver operating characteristic curve, 0.98) and was associated with longer disease-free survival (hazard ratio [HR] = 0.30; 95% CI: 0.09–0.97, p = 0.033) and overall survival (HR = 0.14, 95% CI: 0.02–1.06, p = 0.027) versus no MPR. Digitally assessed PathR strongly correlated with visual measurements. ConclusionsArtificial intelligence–powered digital pathology exhibits promise in assisting pathologic assessments in neoadjuvant NSCLC clinical trials. The development of artificial intelligence–powered approaches in clinical settings may aid pathologists in clinical operations, including routine PathR assessments, and subsequently support improved patient care and long-term outcomes.

Сказка «О козе и козлятах» на рушанском и хуфском языках

This article presents the texts of “The Goat and her kids”, a folk tale in the Rushani and Khufi languages. The Rushani version of the story was recorded by A. K. Pisarchik in 1943; the Khufi text was recor‑ ded in 1951 by V. S. Sokolova. Both texts are transcribed on the basis of the phonological principle using international Iranian transcrip‑ tion, with Russian translation; in the Rushani version the phonetic features of speech are also noted. In the present publication these texts are provided with morpheme-by-morpheme glossing. Both texts are valuable written documents that record an unwrit‑ ten language at a relatively early point in time. Despite the significant similarity of the cultural traditions and folklore of the Western Pamir peoples, the example of this folk tale highlights discrepancies in plot, theme and cast of characters. Differing from the more common story, widespread in Central Asia, about a fight between a goat and a wolf, the Rushani and Khufi tales presented here notably replace the antagonist with a bear.