Search

Fusion will be and needs to be achieved. But when? Its primary fuel, deuterium, exists in sufficient quantity to satisfy any conceivable energy demands for thousands of millions of years. The cost of obtaining it from water is less than one per cent the present cost of coal. Is fusion power a distant dream or a near-term possibility? The first applications could come in the 1980s. Richard F. Post, a physicist, is head of the magnetic mirror program in controlled thermonuclear research at the Lawrence Radiation Laboratory, Livermore, California. This report on progress in fusion research was adapted from his presentation on April 26, 1971 to the National Academy of Sciences Symposium on "Energy for the Future." [ABSTRACT FROM AUTHOR]

This paper extends fundamental theorems of summability theory to double sequences using stretching by blocks technique. We prove Steinhaus- and Buck-type theorems for double sequences, characterizing sequences that resist summability by RH-regular matrices and providing conditions for P-convergence. The preservation of P-divergence under block stretching is demonstrated, and a characterization of P-limit points via this method is established. We also show the impossibility of summing all block stretchings with a single RH-regular matrix. These results provide a more comprehensive framework for analyzing double sequences under matrix transformations. [ABSTRACT FROM AUTHOR]

Background: The application of normo- and hyperbaric O2 is a common therapy option in various disease patterns. Thereby, the applied O2 affects the whole body, including the blood and its components. This study investigates influences of pressure and oxygen fraction on human blood plasma, nutrient media, and the functions of neutrophil granulocytes (PMNs). Methods: Neutrophil migration, reactive oxygen species (ROS) production, and NETosis were examined by live cell imaging. The treatment of various matrices (Roswell Park Memorial Institute 1640 medium, Dulbecco's Modified Eagle's Medium, H2O, human plasma, and isolated PMNs) with hyperbaric oxygen (HBO) was performed. In addition, the expression of different neutrophil surface epitopes (CD11b, CD62L, CD66b) and the oxidative burst were investigated by flow cytometry (FACS). The application of cold atmospheric plasma (CAP) to normoxic and normobaric culture media served as a positive control. Soluble reaction products such as H2O2, reactive nitrogen species (RNS: NO2− and NO3−), and ROS-dependent dihydrorhodamine oxidation were quantified by fluoro- and colorimetric assay kits. Results: Under normobaric normoxia, PMNs migrate slower and shorter in comparison with normobaric hyper- or hypoxic conditions and hyperbaric hyperoxia. The pressure component has less effect on the migration behavior of PMNs than the O2 concentration. Individual PMN cells produce prolonged ROS at normoxic conditions. PMNs showed increased expression of CD11b in normobaric normoxia, lower expression of CD62L in normobaric normoxia, and lower expression of CD66b after HBO and CAP treatment. Treatment with CAP increased the amount of ROS and RNS in common culture media. Conclusions: Hyperbaric and normobaric O2 influences neutrophil functionality and surface epitopes in a measurable way, which may have an impact on disorders with neutrophil involvement. In the context of hyperbaric experiments, especially high amounts of H2O2 in RPMI after hyperbaric oxygen should be taken into account. Therefore, our data support a critical indication for the use of normobaric and hyperbaric oxygen and conscientious and careful handling of oxygen in everyday clinical practice. [ABSTRACT FROM AUTHOR]

We generalize a theorem of Ding relating the generalized Loewy length g ℓ ℓ (R) and index of a one-dimensional Cohen-Macaulay local ring (R , m , k). Ding proved that if R is Gorenstein, the associated graded ring is Cohen-Macaulay, and k is infinite, then the generalized Loewy length and index of R are equal. However, if k is finite, equality may not hold. We prove that if the index of a one-dimensional Cohen-Macaulay local ring is finite and the associated graded ring has a homogeneous nonzerodivisor of degree t , then g ℓ ℓ (R) ≤ index (R) + t − 1. Next we prove that if R is a one-dimensional hypersurface ring with a witness to the generalized Loewy length that induces a regular initial form on the associated graded ring, then the generalized Loewy length achieves this upper bound. We then compute the generalized Loewy lengths of several families of examples of one-dimensional hypersurface rings over finite fields. Finally, we study a graded version of the generalized Loewy length and determine its value for numerical semigroup rings. [ABSTRACT FROM AUTHOR]

A signature event in the history of psychology occurred in 1919 when Jean Piaget was asked to standardize Cyril Burt's tests of intelligence on Parisian children. Impressed by the errors students made, Piaget studied the underlying reasoning process of these children. This led to Piaget 's new méthode clinique for studying the intelligence of children and its development. But why was there a need for such standardization? How did Burt's intelligence test differ from Binet's version? How did Burt's version pave the way for Piaget's very different kind of intelligence test – from IQ tests to tests of operatory intelligence? I examine the history of this series of events pointing out the difference between Binet's version and Burt's version, how they differed from Piaget's similar questions and how the standardization of Burt's intelligence tests paved the way for Piaget's different type of intelligence test, a test of operatory intelligence. [ABSTRACT FROM AUTHOR]

This study provides the first report of a quantitative trail locus (QTL) in maize (Zea mays) for resistance to the southern root-knot nematode (SRKN) (Meloidogyne incognita). The SRKN can feed on the roots of maize in the U.S. Southern Coastal Plain region and can cause yield losses of 30% or more in heavily infested fields. Increases in SRKN density in the soil may reduce the yield for subsequently planted susceptible crops. The use of maize hybrids with resistance to SRKN could prevent an increase in SRKN density, yet no genetic regions have been identified that confer host resistance. In this study, a B73 (susceptible) x Ky21 (resistant) S5 recombinant inbred line (R1L) population was phenotyped for total number of eggs (TE) and root weight. This population had been genotyped using single-nucleotide polymorphisms (SNPs). By utilizing the SNP data with the phenotype data, a single QTL was identified on chromosome 5 that explained 15% of the phenotypic variation (PV) for the number of eggs and 11 % of the P V for the number of eggs per gram of root (EGR). Plants that were homozygous for the Ky2l allele for the most associated marker PZA03172.3 had fewer eggs and fewer EGR than the plants that were homozygous or heterozygous for the B73 allele. Thus, the first QTL for SRKN resistance in maize has been identified and could be incorporated into maize hybrids. [ABSTRACT FROM AUTHOR]

The modeling field is rapidly evolving and expanding to address new research topics and to connect with new disciplines. As such, what constituted a good modeling research contribution ten years ago may not be the same today. We try to distill some insights of what we (and the community we aim to represent) consider today as key elements of a good research paper in the field of software and systems modeling. Such insights—which will need to evolve and adapt with time—will be useful not just for authors of new papers, but also for reviewers and editors. [ABSTRACT FROM AUTHOR]

Currently 30-day mortality is commonly used as a quality indicator for cardiac surgery; however, prediction models have not included the role of cardiopulmonary bypass (CPB). We hypothesized that reproducing currently utilised prediction model methods of 30-day mortality using the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR) would identify relevant CPB predictors. Nine centers in Australia and New Zealand collected data using the ANZCPR between 2011–2020. CPB parameter selection was determined by evaluating association with 30-day mortality. Data were divided into model creation (n = 15,073) and validation sets (n = 15,072). Bootstrap sampling and automated variable selection methods were used to develop candidate models. The final model was selected using prediction mean square error and Bayesian Information Criteria. The average receiver operating characteristic (ROC), p -value for Hosmer—Lemeshow chi-squared test and MSE were obtained from multifold validation. In total, 30,145 patients were included, of which 735 (2.4%) died within 30 day of surgery. The area under the ROC curve for the model including CPB parameters was significantly greater than preoperative risk factors only (0.829 vs 0.783, p < 0.001). CPB parameters included in the predictive model were CPB time, red blood cell transfusion, mean arterial pressure <50 mmHg, minimum oxygen delivery, cardiac index <1.6 L/min/m2. CPB parameters improve the prediction of 30-day mortality. Randomised trials designed to evaluate modifiable CPB parameters will determine their impact on mortality. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984–1988; era 2, 1989–1993; era 3, 1994–1998; era 4, 1999–2003; era 5, 2004–2008; era 6, 2009–2014; era 7, 2015–2018 and era 8, 2019–2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey–Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure. [ABSTRACT FROM AUTHOR]

The article presents the discussion on exploring senescence as a therapeutic target for osteoarthritis, emphasizing the importance of understanding the mechanisms underlying cellular senescence in joint tissues. Topics include complexity of the senescence phenotype, the role of DNA damage in senescence initiation, and the therapeutic implications of targeting IRF1 in osteoarthritis.

Subsurface sandstone reservoirs sealed by overlying, low-permeability layers provide capacity for long-term sequestration of anthropogenic waste. Leakage can occur if reservoir pressures rise sufficiently to fracture the seal. Such pressures can be generated within the reservoir by vigorous injection of waste or, over thousands of years, by natural processes. In either case, the precise role of intercalated mudstones in the long-term evolution of reservoir pressure remains unclear; these layers have variously been viewed as seals, as pressure sinks, or as pressure sources. Here, we use the geological record of episodic fluid venting in the Levant Basin to provide striking evidence for the pressuresource hypothesis. We use a Bayesian framework to combine recently published venting data, which record critical subsurface pressures since ~2 Ma, with a stochastic model of pressure evolution to infer a pressure-recharge rate of ~30 MPa/Myr. To explain this large rate, we quantify and compare a range of candidate mechanisms. We find that poroelastic pressure diffusion from mudstones provides the most plausible explanation for these observations, amplifying the ~3 MPa/Myr recharge caused primarily by tectonic compression. Since pressurized mudstones are ubiquitous in sedimentary basins, pressure diffusion from mudstones is likely to promote seal failure globally. [ABSTRACT FROM AUTHOR]

This study addressed the formation of co‐crystals from Quercetin and Curcumin by mechanochemical treatment employing ball mill grinding. The binary system was initially studied using molecular complementarity and hydrogen bond propensity analysis structural tools available in Mercury software. This study was performed from CCDC reported structural data for Curcumin and Quercetin dihydrate used as starting reagents. Reaction conditions, such as Quercetin: Curcumin molar ratio, grinding time, and solvent‐assisted variables, were optimised to synthesise a new solid phase from the binary system. The synthesised product was characterised by differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and powder X‐ray diffraction techniques. Finally, to compare the anti‐oxidant capacities from the pure components, eutectic mixtures previously reported and the new crystalline phase was evaluated in vitro using the 1,1‐diphenyl‐2‐pycril‐hydrazylhydrate radical inhibition method. The co‐crystal phase and eutectic mixtures present higher anti‐oxidant activity with values around 5.0 mg/L compared to pure Quercetin (3,444 mg/L) and Curcumin (9,141 mg/L), using only half of the molecules. These results indicate Quercetin molecule is synergically active with the Curcumin molecule in the binary mixtures. [ABSTRACT FROM AUTHOR]

This article is an editorial from the International Journal of Public Leadership, reflecting on the changes and challenges in public leadership research. The author discusses the profound societal and global changes, such as the COVID-19 pandemic, and the impact of politics on public leadership. They also highlight the importance of networks and collaborations in advancing research in this field. The article concludes by emphasizing the need for research to address enduring challenges, such as rebuilding credibility in public leadership and supporting democracy. The author expresses confidence in the new editor-in-chief, Professor Tim Mau, to continue advancing the impact of public leadership research. [Extracted from the article]

The purpose of this study was to establish the technical merit, feasibility, and generalizability of a new measure of understanding of informed consent for use with clinical research participants. A total of 109 teens/young adults at a large, pediatric medical center completed the consenting process of a hypothetical biobanking study. Data were analyzed using a combination of classical and modern theory analytic methods to produce a final set of 19 items referred to as the uConsent scale. A requirement of the scale was that each item mapped directly onto one or more of the Basic Elements of Informed Consent from the 2018 Final Rule. Descriptive statistics were computed for each item as well as the scale as a whole. Partial credit (Rasch) logistic modeling was then used to generate difficulty/endorsability estimates for each item. The final, 19‐item uConsent scale was derived using inferential methods to yield a set of items that ranged across difficulty levels (−3.02 to 3.10 logits) with a range of point‐measure correlations (0.12 to 0.50), within‐range item‐ and model‐fit statistics, varying item types mapped to both Bloom's Taxonomy of Learning and required regulatory components of the 2018 Final Rule. Median coverage rate for the uConsent scale was 95% for the 25 randomly selected studies from ClinicalTrials.gov. The uConsent scale may be used as an effective measure of informed consent when measuring and documenting participant understanding in clinical research studies today. [ABSTRACT FROM AUTHOR]

We present a study of the effects of strain on the magnetocrystalline anisotropy energy and magnetic moments of Y 2 Fe 14 B bulk alloy. The study has been performed within the framework of density functional theory in its fully relativistic form under the generalized gradient approximation. We have studied seven different in-plane a lattice constant values ranging from 8.48 up to 9.08 Å with an increment of δ a = 0.1 Å. For each a value, we carried out an out-of-plane c parameter optimization, achieving the corresponding optimized lattice pair (a , c). We find a large variation in the site resolved magnetic moments for inequivalent Fe, Y, and B atoms for different lattice expansions and a negative contribution to the total moment from the Y sites. We find a strong variation in the magnetocrystalline anisotropy with the c / a ratio. However, the calculated variation when coupled with thermodynamic spin fluctuations is unable to explain the experimentally observed increase in the total magnetic anisotropy, suggesting that a different physical mechanism is likely to be responsible in contrast with previous interpretations. We show that opposing single- and two-ion anisotropy terms in the Hamiltonian gives good agreement with the experiment and is the probable origin of the non-monotonic temperature dependence of the net anisotropy of Y 2 Fe 14 B bulk alloy. [ABSTRACT FROM AUTHOR]

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose‐positron emission tomography, the role of interval compressed chemotherapy in patients aged 18 years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high‐dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole‐lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. Plain Language Summary: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults.For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma.Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma. Debates remain in defining the standard of care for treating Ewing sarcoma. This set of consensus statements from the National Ewing Sarcoma Tumor Board is intended to provide clarity and recommendations for the upfront management of these patients. [ABSTRACT FROM AUTHOR]

This mini-review describes the role of the solute carrier (SLC)15 family of proton-coupled oligopeptide transporters (POTs) and particularly Pept2 (Slc15A2) and PhT1 (Slc15A4) in the brain. That family transports endogenous di- and tripeptides and peptidomimetics but also a number of drugs. The review focuses on the pioneering work of David E. Smith in the field in identifying the impact of PepT2 at the choroid plexus (the blood-CSF barrier) as well as PepT2 and PhT1 in brain parenchymal cells. It also discusses recent findings and future directions in relation to brain POTs including cellular and subcellular localization, regulatory pathways, transporter structure, species differences and disease states. [ABSTRACT FROM AUTHOR]

Mushrooms containing amatoxin are found worldwide and represent a challenging poisoning for the clinician and consulting poison center. This study evaluates the experience of a large poison system with possible amatoxin-containing mushroom ingestion calls. A 10-year retrospective review of the California Poison Control System database was performed for amatoxin mushroom ingestion calls resulting in hospitalization. Cases found were abstracted and data statistically analyzed for association with a composite endpoint of death, liver transplant, and/or the need for dialysis. Amatoxin-containing mushroom calls are infrequent with the vast majority (98.4 percent) coming from Northern California during the rainier first and fourth quarters (October through March) of the year. Elevated initial aminotransferase activities and international normalized ratios were predictive of the composite negative outcome. The mortality plus liver transplant and hemodialysis composite rate was 8.2 percent, consistent with current literature. The California Poison Control System has relatively few amatoxin-containing mushroom ingestion calls that result in hospitalization but those that are reported mostly occur in Northern California. Treatment bias towards the sickest patients may explain the association of intravenous fluid use or treatment with acetylcysteine or silibinin with meeting the composite outcome. The initial presence of elevated hepatic aminotransferase activity and international normalized ratios are poor prognostic indicators and are likely reflective of late presentation, an advanced toxic phase of amatoxin poisoning, and/or delays in time to obtain poison center consultation. [ABSTRACT FROM AUTHOR]

New higher-order models of brain networks can provide new insights into brain organization and function while helping to address outstanding questions in network neuroscience. Edge-centric models shift the focus away from neural elements (nodes) onto edges. Edge time-series are an exact decomposition of correlation-based functional networks and facilitate the detection of overlapping communities while offering estimates of time-varying connectivity at framewise temporal resolution. Network neuroscience has emphasized the connectional properties of neural elements – cells, populations, and regions. This has come at the expense of the anatomical and functional connections that link these elements to one another. A new perspective – namely one that emphasizes 'edges' – may prove fruitful in addressing outstanding questions in network neuroscience. We highlight one recently proposed 'edge-centric' method and review its current applications, merits, and limitations. We also seek to establish conceptual and mathematical links between this method and previously proposed approaches in the network science and neuroimaging literature. We conclude by presenting several avenues for future work to extend and refine existing edge-centric analysis. [ABSTRACT FROM AUTHOR]

In application-oriented mathematics, particularly in the context of nonlinear system analysis, phase plane analysis through SageMath offers a visual display of the qualitative behaviour of solutions to differential equations without inundating students with cumbersome calculations of the plane-phase. A variety of examples is usually given to illustrate phase-plane behaviour. We approach these problems by considering a problem containing a single real parameter that exemplifies the various situations clearly and simply. We developed two computer programs in SageMath: one program calculates aspects of the Jacobian matrix and displays the phase plane portraits, the other determines the centre manifold. Computations and images generated with computer codes are useful in understanding dynamic models in biology, physics and engineering that involve planar non-linear autonomous differential equations. This paper covers analytical and computational skills that are helpful for students and teachers. [ABSTRACT FROM AUTHOR]

Systematic error from selection bias, uncontrolled confounding, and misclassification is ubiquitous in epidemiologic research but is rarely quantified using quantitative bias analysis (QBA). This gap may in part be due to the lack of readily modifiable software to implement these methods. Our objective is to provide computing code that can be tailored to an analyst's dataset. We briefly describe the methods for implementing QBA for misclassification and uncontrolled confounding and present the reader with example code for how such bias analyses, using both summary-level data and individual record-level data, can be implemented in both SAS and R. Our examples show how adjustment for uncontrolled confounding and misclassification can be implemented. Resulting bias-adjusted point estimates can then be compared to conventional results to see the impact of this bias in terms of its direction and magnitude. Further, we show how 95% simulation intervals can be generated that can be compared to conventional 95% confidence intervals to see the impact of the bias on uncertainty. Having easy to implement code that users can apply to their own datasets will hopefully help spur more frequent use of these methods and prevent poor inferences drawn from studies that do not quantify the impact of systematic error on their results. [ABSTRACT FROM AUTHOR]

Background and aims: With an external additional working channel (AWC) endoscopic mucosal resection (EMR) as well as endoscopic submucosal dissection (ESD) can be extended to techniques termed "EMR+" and "ESD+." These novel techniques are systematically compared to EMR and ESD under the use of a double-channel endoscope (DC). Methods: Our trial was conducted prospectively in a pre-clinical porcine animal model (EASIE-R simulator) with standardized gastric lesions measuring 3 or 4 cm. Results: EMR+ and EMR DC showed both good results for 3 cm lesions with no adverse events and an en bloc resection rate of 73.33% (EMR+) and 60.00% (EMR DC, p = 0.70). They came to their limits in 4 cm lesions with muscularis damages of 20.00% (EMR+), 13.33% (EMR DC, p ≥ 0.99) and decreasing en bloc resection rates of 60.00% (EMR+) and 46.67% (EMR DC, p = 0.72). ESD+ and ESD DC were both reliable concerning en bloc resection rates (100% in all groups) and adverse events (0.00% in 3 cm lesions, 12.50% muscularis damages in both ESD+ and ESD DC in 4 cm lesions). Resection time was slightly shorter in all groups with the AWC compared to DC although only reaching significance in 3 cm ESD lesions (p < 0.05*). Conclusions: With the AWC, a standard endoscope can easily be transformed to double-channel functionality. We could show that EMR+ and ESD+ are non-inferior to EMR and ESD under the use of a double-channel endoscope. Consequently, the AWC presents an affordable alternative to a double-channel endoscope for both EMR and ESD. [ABSTRACT FROM AUTHOR]

The median of a standard gamma distribution, as a function of its shape parameter k, has no known representation in terms of elementary functions. In this work we prove the tightest upper and lower bounds of the form 2−1/k(A + k): an upper bound with A = e−γ (with γ being the Euler–Mascheroni constant) and a lower bound with A=log(2)-13. These bounds are valid over the entire domain of k > 0, staying between 48 and 55 percentile. We derive and prove several other new tight bounds in support of the proofs. [ABSTRACT FROM AUTHOR]

There is a perception today that is broadly held but rarely voiced: That our political, economic, social, and academic institutions are increasingly unfit for public purpose. How students experience and prepare for a world of deep social change and unrelenting technological advances is something that educators can influence profoundly. There are four mindset capabilities that serve as an illuminating lens for viewing one's teaching with fresh eyes and a reassuring sense of clarity regarding how to prepare learners to adapt and embrace a world of continuous societal and workplace disruption: Psychological Safety, Empathic Concern, Step Up-Step Back Leadership, and Community Problem Solving. [ABSTRACT FROM AUTHOR]

Aim: To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children. Method: Children diagnosed with FND at a regional children's hospital were prospectively recruited by weekly active surveillance for 36 months. Demographic, clinical, and follow‐up data were retrospectively extracted by review of electronic records. Descriptive statistical analyses were used. Results: Ninety‐seven children (age range 5–15 years) met the case definition of FND (annual incidence 18.3 per 100 000 children). Children with FND were likely to be female (n = 68 [70%]) and older (median 13 years) with no difference in the Scottish Index of Multiple Deprivation (marker of socioeconomic status) compared with the general childhood population. Functional motor (41%) and sensory (41%) symptoms were most common; other somatic symptoms such as headache (31%) and pain (27%) were frequent. Self‐reported psychiatric symptoms and infection/inflammation were the most common predisposing and precipitating factors respectively. At a median of 15 months follow‐up, 49% of 75 children reported improvement or resolution of FND symptoms with no prognostic factors found. Interpretation: At this regional centre, FND in children had a higher incidence than previously reported and a less optimistic outcome than in some other studies. [ABSTRACT FROM AUTHOR]

Introduction: Collection of peripheral blood stem cells (PBSCs) from healthy donors is a well-established process. We aimed to identify factors predictive of successful CD34+ PBSC collection and established a formula capable of predicting CD34+ cell yield. Methods: We retrospectively evaluated 588 healthy adult donors (median age 29 years, range 18–69 years) at our institution from 2017 to 2022. The predicted minimal number of CD34+ cells was calculated as follows: (peripheral CD34+ cells/µL × adjusted collection efficiency of 30%) × total liters processed. This formula was further modified according to donor and recipient body weight (BW). Results: Median total collection was 8.0 × 106 CD34+ cells/kg BW (range 1.0–47.1 × 106 cells/kg BW) with 522 donors (89%) collecting ≥5.0 × 106 cells/kg of recipient BW. A second leukapheresis (LP) was performed in 49 donors. Need for two LPs was more common in female donors (OR 6.68, 95% CI, 2.62–17.05; p < 0.001), donors with higher age (OR for 10 years difference 1.53, 95% CI, 1.15–2.03, p = 0.003), donors with WBC count <30 × 109/L after 5 days of granulocyte-colony stimulating factor (G-CSF) stimulation (OR, 4.33; 95% CI, 1.59–11.83; p = 0.004), and a donor/recipient weight ratio <1 (OR 6.21, 95% CI, 2.69–14.34; p < 0.001). Predictive factors for optimal LP (i.e., ≥5.0 × 106 CD34+ cells/kg of recipient BW) were peripheral blood (PB) CD34+ cell count >50/µL (OR 12.82, range 6.34–25.92, p < 0.001), male donor (OR 2.77, range 1.06–7.23, p = 0.04), and a donor/recipient weight ratio >1 (OR 3.12, range 1.57–6.24, p = 0.001). WBC, platelets, hemoglobin, and age had no significant predictive value. Predicted versus observed number of CD34+ cells/kg BW collected demonstrated a very strong linear correlation (r = 0.925, 95% CI, 0.912–0.936, p < 0.0001). Conclusions: Of the routinely monitored indicators in PBSC donors, CD34+ cell count in PB is the most important factor in predicting G-CSF-induced PBSC yields. Higher age, female sex, WBC <30 × 109/L, and a donor/recipient weight ratio <1 are useful indicators for identifying suboptimal mobilizers. The modified formula has shown successful and consistent performance in the prediction of key outcome measures including the minimum CD34+ cell collection, determination of the required length of apheresis, and whether a second day of PBSC collection was necessary to achieve the respective collection goal. [ABSTRACT FROM AUTHOR]

Background: About half of AML patients achieving complete remission (CR) display measurable residual disease (MRD) and eventually relapse. FLYSYN is an Fc-optimized antibody for eradication of MRD directed to FLT3/CD135, which is abundantly expressed on AML cells. Methods: This first-in-human, open-label, single-arm, multicenter trial included AML patients in CR with persisting or increasing MRD and evaluated safety/tolerability, pharmacokinetics and preliminary efficacy of FLYSYN at different dose levels administered intravenously (cohort 1–5: single dose of 0.5 mg/m2, 1.5 mg/m2, 5 mg/m2, 15 mg/m2, 45 mg/m2; cohort 6: 15 mg/m2 on day 1, 15 and 29). Three patients were treated per cohort except for cohorts 4 and 6, which were expanded to nine and ten patients, respectively. Primary objective was safety, and secondary efficacy objective was ≥ 1 log MRD reduction or negativity in bone marrow. Results: Overall, 31 patients were treated, of whom seven patients (22.6%) experienced a transient decrease in neutrophil count (two grade 3, others ≤ grade 2). No infusion-related reaction or dose-limiting toxicity was observed. Adverse events (AEs) were mostly mild to moderate, with the most frequent AEs being hematologic events and laboratory abnormalities. Response per predefined criteria was documented in 35% of patients, and two patients maintained MRD negativity until end of study. Application of 45 mg/m2 FLYSYN as single or cumulative dose achieved objective responses in 46% of patients, whereas 28% responded at lower doses. Conclusions: FLYSYN monotherapy is safe and well-tolerated in AML patients with MRD. Early efficacy data are promising and warrant further evaluation in an up-coming phase II trial. Trial registration This clinical is registered on clinicaltrials.gov (NCT02789254). [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is an etiologically and clinically heterogeneous condition. Accumulating evidence suggests that persons with lifetime histories of comorbid AUD and non-alcohol substance use disorder (DRUG) constitute an important subgroup of AUD. This study evaluated the distinctiveness of the comorbid AUD/DRUG behavioral phenotype in a community sample with respect to risk factors, AUD course features, and outcome variables assessed at age 30. Contrast groups included persons with histories of AUD only, DRUG only, and neither AUD nor DRUG. Methods: This research utilized a prospective study design with an age-based cohort (n = 732). Participants completed four comprehensive diagnostic evaluations during the high-risk periods of adolescence, emerging adulthood, and young adulthood. Results: The comorbid AUD/DRUG group was distinguished from the AUD only group by risk factors, AUD course features, and outcomes. Group differences in outcomes were also explained by overall substance use disorder (SUD) severity. Persons with AUD/DRUG comorbidity were indistinguishable from those with DRUG only histories with respect to risk factors and outcomes but demonstrated greater overall SUD severity. Persons with AUD only were indistinguishable from those with neither AUD nor DRUG histories in risk factor endorsements and were mostly similar in outcomes. Conclusions: Findings collectively suggest that young adults with histories of AUD only and those with comorbid AUD/DRUG are drawn from dissimilar populations. Similarities between the AUD only group with those absent AUD or DRUG histories are likely related to the former group's developmentally limited AUD course accompanied by relatively few or short-lived alcohol-related problems. [ABSTRACT FROM AUTHOR]

The purpose of this article is to propose and provide a blueprint for a graduate‐level curriculum in clinical data science, devoted to the measurement, acquisition, care, treatment, and inferencing of clinical research data. The curriculum presented here contains a series of five required core courses, five required research courses, and a list of potential electives. The coursework draws from but does not duplicate content from the foundational areas of biostatistics, clinical medicine, biomedical informatics, and regulatory affairs, and may be reproduced by any institution interested in and capable of offering such a program. This new curriculum in "clinical" data science will prepare students for work in academic, industry, and government research settings as well as offer a unifying knowledge base for the profession. [ABSTRACT FROM AUTHOR]

The purpose of this study was to construct the life history of Dana "Pokey" Chatman, a successful African American, female basketball coach. The study was guided by elements from critical race feminism. Data were collected through formal semistructured interviews, informal interviews, and documents and artifacts. They were analyzed through analytic induction and constant comparison. Key findings were that Pokey faced a considerable amount of marginalization and experienced a steady flow of microaggressions with the exception of the time she worked in Eastern Europe. Pokey's mother, sister, childhood community, love of sport, university teammates, and head coach all played a role in helping her overcome the racism she faced. Pokey's life history is inspiring and should encourage other women of color who have similar ambitions to persist in their efforts to become sports coaches. It can also be employed in efforts to transform the working environments of African American, female coaches. [ABSTRACT FROM AUTHOR]

The article argues for the necessity of school choice in preserving religious liberty and freedom of belief. It discusses how the current education system can impede these freedoms and proposes equal funding for students to attend public, private secular, or private religious schools of their choice. It highlights the importance of parental autonomy in education and the constitutional implications of K-12 educational funding equity.

U.S. presidential primary debates are influential but under-researched. Before 2015, all of these debates, both Democratic and Republican, had 10 candidates or fewer. The first Republican debate in 2015, however, abided 17 candidates. They were split into two segments, with the 10 best-polling candidates in the main (prime-time) segment and the others in an 'undercard' session. A comparable pattern applied for the next six Republican debates. Concern arose not only because many candidates were crowded into a session but also because the undercard candidates were seen as receiving inferior exposure. The Democratic presidential primary debates that started four years later encountered similar difficulty. An authorized policy caused their candidates in each of the first two debates to be limited to 20, randomly divided into two groups of 10 appearing on successive nights. For remedy, this paper examines innovative debate plans, for different numbers of candidates, that feature symmetry among all candidates and entail many short segments with relatively few candidates in each. We apply combinatorial designs—balanced incomplete block designs and regular pairwise balanced designs, which are analogous to the games Spot It Jr.! Animals and (full-fledged) Spot It!, respectively. [ABSTRACT FROM AUTHOR]

This aim of this editorial is to highlight progress made in brain barrier and brain fluid research in 2022. It covers studies on the blood-brain, blood-retina and blood-CSF barriers (choroid plexus and meninges), signaling within the neurovascular unit and elements of the brain fluid systems. It further discusses how brain barriers and brain fluid systems are impacted in CNS diseases, their role in disease progression and progress being made in treating such diseases. [ABSTRACT FROM AUTHOR]

While genetic disorders may directly impact the BBB/NVU, they may also make the BBB/NVU susceptible to other injuries. For example, while enzyme replacement therapies can alleviate the peripheral symptoms of some lysosomal storage disorders, current protein-based therapies do not sufficiently penetrate the BBB to improve CNS pathologies. In addition, gene deletion and overexpression studies in animals and cells are extremely important in dissecting protein- and cell-specific effects on normal BBB/BCSFB function and pathology. The past decade has seen major advances in our understanding of how genetic disorders alter blood-brain barrier (BBB), blood-retinal barrier (BRB) and blood-CSF barrier (BCSFB) function. [Extracted from the article]

Objectives: The Joint tissueActivity and Damage Exam (JADE) is a point-of-care (POC) musculoskeletal ultrasound (MSKUS) protocol for non-radiologists to evaluate hemophilic arthopathy. Our aim was to determine the consistency of cross-sectional analyses of direct tissue measurements (JADE protocol) and clinical Hemophilia Joint Health Score [HJHS] and functional joint assessments (arc) at three clinic visits. Methods: We prospectively studied adults (n = 44) with hemophilia (A or B) of any severity and arthropathy at 3 North American sites. We assessed HJHS, total arc, and JADE parameters (bilateral elbows, ankles, and knees) at study entry, at ≈12–18 months, and at ≈24–36 months, and used MSKUS to evaluate painful episodes between study visits. JADE measurements included osteochondral alterations, cartilage thickness, and soft tissue expansion at sentinel positions. Associations between joint HJHS and total arc with each JADE variable were examined with random intercept models. Results: At each visit increasing HJHS and decreasing total arc were associated in the expected direction with increasing length of OAs and soft tissue expansion in all joints, and decreasing cartilage thickness in the knee. However, HJHS associations with cartilage thickness were U-shaped for elbow and ankle (i.e. cartilage thinning and thickening). Associations between total arc and cartilage thickness followed a similar curve. (Near) normal levels of both joint parameters (HJHS and total arc) were associated with normal ranges of cartilage thickness. JADE views were also helpful to detect hemarthrosis in association with joint pains. Conclusions: POC MSKUS applying direct tissue measurements using the JADE protocol provided reproducible cross-sectional associations with joint health outcomes on three visits. These findings advance protocol validation and enable iterative adaptations resulting in JADE protocol version 2. [ABSTRACT FROM AUTHOR]

Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Drosophila Genetic Reference Panel inbred lines with whole genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome. Validation of candidate genes by RNAi knockdown confirmed the role of the dopamine 2-like receptor (Dop2R) in promoting egg laying. We replicated the Dop2R effect in an independently collected productivity dataset and showed that the effect of the Dop2R variant was mediated in part by regulatory gene expression variation. This study demonstrates the strong potential of genome-wide association analysis in this diverse panel of inbred strains and subsequent functional analyses for understanding the genetic architecture of fitness traits. [ABSTRACT FROM AUTHOR]

The first aim of these studies was to compare growth patterns of healthy kittens neutered during growth with growth standards created for sexually-intact kittens. A second aim was to clarify the impact of neutering in kittens on body composition and body shape. Study 1 was a retrospective observational study comparing median growth trajectories of healthy, client-owned domestic shorthair (DSH) kittens in optimal body condition and neutered at different ages, with previously-created growth standards from a similar, sexually-intact, population. The neuter groups contained between 3.0k and 9.3k cats. For all neuter groups in both sexes, the median growth trajectory inclined upwards after the procedure, with this being more marked in female than in male kittens. This upwards inclination was less marked for kittens neutered later during growth in both sexes, with the effect being least in kittens neutered after 28–29 weeks. Study 2 was an analysis of new body composition and zoometric data from a previously-published randomised study, comparing growth-related measures between 11 pairs of sexually-intact and neutered (at 19 weeks age) female DSH cats in a research population. Before neutering, the growth pattern in neutered kittens and sexually-intact kittens was similar, but neutered kittens were heavier by 52 weeks (mean difference in fold change vs. 10 weeks 1.34, 95-CI: 1.07–1.72), had a greater fat mass (mean difference in fold change vs. 10 weeks 1.91, 95-CI 1.09–3.21) and greater lean mass (mean difference in fold change vs. 10 weeks 1.23, 95-CI: 1.03–1.48). Abdominal girth (mean difference in fold change vs. 10 weeks 1.20, 95-CI: 1.04–1.39) and rib cage length (mean difference in fold change vs. 10 weeks 1.18, 95-CI: 1.02–1.36) were also greater, but there were no differences in other zoometric measurements. Veterinarians should consider the potential impact that neutering has on gain of adipose tissue, especially early neutering in female kittens. Bodyweight should be monitored closely during growth and especially after neutering to prevent inappropriate weight gain. [ABSTRACT FROM AUTHOR]

Excavations at the Orange Valley hospital for the enslaved in Trelawny Parish, Jamaica, have revealed rich deposits of early nineteenth-century artifacts. These artifacts, when analyzed in conjunction with the building itself, surviving documents, and the broader landscape in which it stands, speak to the lives of enslaved people of African descent during the period of amelioration. Archaeology is beginning to reveal how plantation hospitals were employed to perpetuate the institution of slavery; while also illuminating how the enslaved patients and workers in the hospital were able to create meaningful lives and identities, that reflected their own traditions, despite the brutal drudgery of sugar production. [ABSTRACT FROM AUTHOR]

The article discusses osteoarthritis (OA), a common form of arthritis in humans and various animal species. It highlights the challenges in translating findings from rodent models of OA to effective human treatments due to differences in risk factors, genetic diversity, disease progression, and pain assessment.

In applications critical to the geological, materials, and engineering sciences, deformation occurs at strain rates too small to be accessible experimentally. Instead, extrapolations of empirical relationships are used, leading to epistemic uncertainties in predictions. To address these problems, we construct a theory of the fundamental processes affecting dislocations: storage and recovery. We then validate our theory for olivine deformation. This model explains the empirical relationships among strain rate, applied stress, and dislocation density in disparate laboratory regimes. It predicts the previously unexplained dependence of dislocation density on applied stress in olivine. The predictions of our model for Earth conditions differ from extrapolated empirical relationships. For example, it predicts rapid, transient deformation in the upper mantle, consistent with recent measurements of postseismic creep. [ABSTRACT FROM AUTHOR]

The purpose of the study was to construct the life history of Mateo, an American Latino/Hispanic college basketball coach. The study was guided by elements from Latino/a/x critical race (LatCrit) theory. Data were collected through formal semi-structured interviews, informal interviews, and documents and artifacts. They were analyzed by employing analytic induction and constant comparison. Key findings were that Mateo faced considerable marginalization and was frequently subjected to microaggressions. He was able to overcome this racism due to his determination and support from his family and mentors. Mateo's experiences of racism and the political and cultural context led him to develop an activist element in his coaching pedagogy. His life history may inspire other Latinos/as/x and Hispanics to consider coaching as a career or help those who are struggling to realize this goal. It may also play a part in improving the coaching culture for Latinos/as/x and Hispanics. [ABSTRACT FROM AUTHOR]

Plan E for Education is my proposal that a proportion of the educational resources generated in publicly funded universities be made freely available for sharing and use by others. Thus, high quality education, produced through public funding, could be made available to other universities and individual autodidacts and for the development of innovative educational delivery methods. This would be the educational equivalent of initiatives that require publicly funded research to be published in open access journals or platforms. Available educational resources would involve whole or sections of courses including assessments, not just isolated resources. Plan E would require the establishment and curation of open repositories and might consider a peer review system for educational materials to mirror that already used for research publications. Academic credit could then flow to those who publish and review educational resources and extend to other academic input such as updating the work and creating instructional materials. There is considerable expertise and enthusiasm for, as well as successful examples of, open access education globally, but this is unevenly spread, and its adoption is hindered by factors at institutional and individual educator levels. Most university-generated educational material is still kept behind institutional paywalls. If we accept the need for change so that, as for research outputs, educational resources become open to access, Plan E might provide the global impetus for such change and make a contribution to reducing inequality in access to higher education. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA copy number (mtDNAcn) in tissues and blood can be altered in conditions like diabetes and major depression and may play a role in aging and longevity. However, little is known about the association between mtDNAcn and personality traits linked to emotional states, metabolic health, and longevity. This study tests the hypothesis that blood mtDNAcn is related to personality traits and mediates the association between personality and mortality. Methods: We assessed the big five personality domains and facets using the Revised NEO Personality Inventory (NEO-PI-R), assessed depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), estimated mtDNAcn levels from whole-genome sequencing, and tracked mortality in participants from the Baltimore Longitudinal Study of Aging. Results were replicated in the SardiNIA Project. Results: We found that mtDNAcn was negatively associated with the Neuroticism domain and its facets and positively associated with facets from the other four domains. The direction and size of the effects were replicated in the SardiNIA cohort and were robust to adjustment for potential confounders in both samples. Consistent with the Neuroticism finding, higher depressive symptoms were associated with lower mtDNAcn. Finally, mtDNAcn mediated the association between personality and mortality risk. Conclusions: To our knowledge, this is the first study to show a replicable association between mtDNAcn and personality. Furthermore, the results support our hypothesis that mtDNAcn is a biomarker of the biological process that explains part of the association between personality and mortality. Funding: Support for this work was provided by the Intramural Research Program of the National Institute on Aging (Z01-AG000693, Z01-AG000970, and Z01-AG000949) and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. AT was also supported by the National Institute on Aging of the National Institutes of Health Grant R01AG068093. [ABSTRACT FROM AUTHOR]

In 1971, Chow and Teicher presented a probability approximation Theorem via summability methods. The goal of this article is to extend Chow and Teicher results to higher dimension. To achieve this we consider multidimensional totally monotonic and independent identically random variables. Using these notions we present a series of approximation type theorems. [ABSTRACT FROM AUTHOR]