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The novel traits that drive cancer often arise by nonheritable cellular variability that is subsequently stabilized by heritable genetic and epigenetic changes – phenotypes come first and genetic changes come second.Classic cancer genes such as KRASand TP53increase cellular plasticity, providing the nonheritable phenotypic variability that drives cancer.Evolutionary theory predicts that recombination of different developmental plasticity programs often creates the novelty that generates new traits.Lung cancer studies show exactly the type of developmental plasticity and recombination predicted by evolutionary theory, creating the new cellular phenotypes that drive tumor progression.Pancreatic cancer studies show how KRAS-driven cellular plasticity triggers the novel cellular interactions that create the tumor microenvironment.

All-inorganic cesium lead halide perovskites possess excellent thermal stability, a feature that renders them highly favorable for optoelectronic applications with an elevated thermal budget. Employing a coevaporation approach for their deposition holds promise for manufacturing at an industrial level, owing to improvements in device scalability and reproducibility. For unlocking the full potential of vacuum-evaporated perovskite thin films, it is crucial to delve deeper into their crystallization process, which, as a solid-state reaction, has been less investigated compared to the crystallization process of, most commonly used, solution-based methods. In this work, we employ spectroscopic ellipsometry, a nondestructive, high speed, and high accuracy characterization method, to study the real time annealing effect on thermally coevaporated CsPbI2Br thin films in a temperature range between 25 and 300 °C. We achieve this by developing a singular dynamic model that can be fitted in real time as a function of temperature, providing insights into how thermal annealing influences the perovskite film’s morphology and optical constants. Based on the latter, we derive the temperature dependence of the thermo-optic coefficient and Urbach energy as well as analyze the interband transition energies via critical point analysis. We demonstrate that the γ- to β-phase transition can be identified through a pronounced shift in the bandgap energy, whereas the β- to α-phase transition can be discerned by a sharp increase in the film’s roughness. We corroborate the obtained fit results with additional in- and ex situ measurements, such as in situ grazing incidence wide-angle X-ray scattering, atomic force microscopy, reflectance/transmittance, and profilometry.

Three standards for photovoltaic (PV) performance and capacity testing are evaluated for bifacial PV system reporting: performance ratio, ASTM E2848, and a new draft of IEC 61724-2. In this context, challenges and recommendations for rear irradiance instrumentation are described for three types of bifacial irradiance sensors—horizontal albedometer, backward-facing reference cells (or pyranometer), and bifacial reference module. A year of operating field data for single-axis tracked bifacial and monofacial systems was collected, including periods of high surface albedo due to snow ground cover. If snowy conditions are included, we found that all three methods performed comparably to the monofacial baseline case, but only if rear-measured irradiance is incorporated into the expected energy calculation. The lowest RMS error was obtained by following the draft IEC 61724-2 standard and using a calibrated bifacial reference module for bifacial irradiance resource. If measured rear irradiance is unavailable, field conditions either need to be filtered to avoid variable (snowy) albedo or an albedometer measurement can be used in conjunction with modeled rear irradiance along with the draft IEC procedure. Additional practical factors are described, including the proper placement of rear irradiance sensors and the proper interpretation of IEC 61724-1 bifacial performance ratio calculations.

Abstract:In 2022, annual global military expenditure reached a record high of $2,240 billion. Much of the recent increase in spending is directly linked to the Russian invasion of Ukraine, which itself represents a failure of the global institutions that are meant to prevent and manage such conflicts. Adedeji Ebo, Director and Deputy to the United Nations High Representative for Disarmament Affairs, spoke to GJIA about the challenges facing multilateralism and how international arms control can adapt in response.

Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance1. In addition to genetic mutations2, recent research has identified a role for non-genetic plasticity in transient drug tolerance3and the acquisition of stable resistance4,5. However, the dynamics of cell-state transitions that occur in the adaptation to cancer therapies remain unknown and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell-state transitions accompanied by a progressive increase in cell fitness, which we denote as the ‘resistance continuum’. This cellular adaptation involves a stepwise assembly of gene expression programmes and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that epithelial-to-mesenchymal transition or stemness programmes—often considered a proxy for phenotypic plasticity—enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify the acquisition of metabolic dependencies, exposing vulnerabilities that can potentially be exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell-state transitions.

The evidence for acute effects of air pollution on mortality in India is scarce, despite the extreme concentrations of air pollution observed. This is the first multi-city study in India that examines the association between short-term exposure to PM2·5and daily mortality using causal methods that highlight the importance of locally generated air pollution.

Objective: Traditionally, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, requiring the routine use of a formal operating room. Pediatric bedside tracheostomy in an intensive care unit (ICU) setting has not been widely reported, in contrast to the widespread adult bedside ICU tracheostomy. Transport of these critically ill, multiple life support systems dependent patients can be technically difficult, labor intensive, and potentially risky for these patients. Our study aimed to demonstrate the safety and efficacy of bedside tracheostomy in the pediatric ICU.Materials and Methods: A retrospective analysis of all pediatric patients undergoing tracheostomy at a tertiary care center, between 1st of January 2013 and 31st of December 2019.Results: During the study period, 117 pediatric patients underwent tracheostomy, 57 (48.7%) were performed bedside while 60 (51.3%) were performed in the operating room. Patients’ ages ranged from 2 weeks to 17 years of age, with a median age of 16 months. No case of bedside tracheostomy necessitated a shift to the operating room. There was no difference in 30-day morbidity and mortality between the 2 groups.Conclusions: Our results suggest that pediatric open bedside tracheostomy in an ICU setting is a safe procedure, with similar complications and outcomes compared to tracheostomy performed in the operating room.

Pregnancy air pollution exposure (PAPE) has been linked to a wide range of adverse birth and childhood outcomes, but there is a paucity of data on its influence on the placental epigenome, which can regulate the programming of physiological functions and affect child development. This study aimed to investigate the association between prenatal air pollutant exposure concentrations and changes in placental DNA methylation patterns, and to explore the potential windows of susceptibility and sex-specific alterations.

Most people complain about having too much to do and too little time in which to do it. And most have heard advice along the lines of, 'Work smarter, not [...]

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the ‘anthropomorphous apes’1–3, with a proposed role in contributing to human bipedalism4–6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element—inserted into an intron of the TBXTgene7–9—pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxtisoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxtisoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxtisoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription–replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics.

SLC5A6encodes the sodium-dependent multivitamin transporter, a transmembrane protein that uptakes biotin, pantothenic acid, and lipoic acid. Biallelic SLC5A6variants cause sodium-dependent multivitamin transporter deficiency (SMVTD) and childhood-onset biotin-responsive peripheral motor neuropathy (COMNB), which both respond well to replacement therapy with the above three nutrients. SMVTD usually presents with various symptoms in multiple organs, such as gastrointestinal hemorrhage, brain atrophy, and global developmental delay, at birth or in infancy. Without nutrient replacement therapy, SMVTD can be lethal in early childhood. COMNB is clinically milder and has a later onset than SMVTD, at approximately 10 years of age. COMNB symptoms are mostly limited to peripheral motor neuropathy. Here we report three patients from one Japanese family harboring novel compound heterozygous missense variants in SLC5A6, namely NM_021095.4:c.[221C>T];[642G>C] p.[(Ser74Phe)];[(Gln214His)]. Both variants were predicted to be deleterious through multiple lines of evidence, including amino acid conservation, in silico predictions of pathogenicity, and protein structure considerations. Drosophilaanalysis also showed c.221C>T to be pathogenic. All three patients had congenital brain cysts on neonatal cranial imaging, but no other morphological abnormalities. They also had a mild motor developmental delay that almost completely resolved despite no treatment. In terms of severity, their phenotypes were intermediate between SMVTD and COMNB. From these findings we propose a new SLC5A6-related disorder, spontaneously remitting developmental delay with brain cysts (SRDDBC) whose phenotypic severity is between that of SMVTD and COMNB. Further clinical and genetic evidence is needed to support our suggestion.

The 'taxation of the digital economy' is currently at the top of the global international tax policymaking agenda. A core claim some European governments are advancing is that user data or user participation in the digital economy justifies a gross tax on digital receipts, new profit attribution criteria, or a special formulary apportionment factor in a future formulary regime targeted specifically at the 'digital economy. ' Just a couple years ago the OECD undertook an evaluation of whether the digital economy can (or should) be 'ring-fenced' as part of the BEPS project, and concluded that it neither can be nor should be. Importantly, concluding that there should be no special rules for the digital economy does not resolve the broader question of whether the international tax system requires reform. The practical reality appears to be that all the largest economies have come to agree either that a) there is something wrong with the taxation of the 'digital economy, ' or b) there is something more fundamentally wrong with the structure of the current international tax system given globalization and technological trends. This paper is intended as a limited exploration of the second (or third, or fourth) best. It analyzes three policy options that have been discussed in general terms in the current global debate. First, I consider whether 'user participation' justifies changing profit allocation results in the digital economy alone. I conclude that applying the user participation concept in a manner that is limited to the digital economy is intellectually indefensible; at most it amounts to mercantilist ring-fencing. Moreover, at the technical level user participation faces all the same challenges as more comprehensive and principled proposals for reallocating excess returns among jurisdictions. Second, I consider one such comprehensive international tax reform idea, loosely referred to by the moniker 'marketing intangibles. ' This idea represents a compromise between the present transfer pricing system and sales or destination-based reforms to the transfer pricing regime. I conclude that splitting taxing rights over 'excess' returns between the present transfer pricing system and a destination-based approach is complex, creates new sources of potential conflict, and requires relatively extensive tax harmonization. This conclusion applies equally to user participation and marketing intangibles. If such a mechanism were nevertheless pursued, I suggest that a formulary system for splitting the excess return is the most manageable approach. Third, I consider 'minimum effective taxation' ideas. I conclude that, as compared to the other two policy options discussed herein, minimum effective taxation provides a preferable path for multilateral cooperation., Table of Contents Introduction I. Background A. The Decline of the Arm's-Length Standard B. The Relationship Between the Arm's-Length Standard, Jurisdiction to Tax, and the Attribution of Profits to PEs [...]

Shape morphing is vital to locomotion in microscopic organisms but has been challenging to achieve in sub-millimetre robots. By overcoming obstacles associated with miniaturization, we demonstrate microscopic electronically configurable morphing metasheet robots. These metabots expand locally using a kirigami structure spanning five decades in length, from 10 nm electrochemically actuated hinges to 100 μm splaying panels making up the ~1 mm robot. The panels are organized into unit cells that can expand and contract by 40% within 100 ms. These units are tiled to create metasheets with over 200 hinges and independent electronically actuating regions that enable the robot to switch between multiple target geometries with distinct curvature distributions. By electronically actuating independent regions with prescribed phase delays, we generate locomotory gaits. These results advance a metamaterial paradigm for microscopic, continuum, compliant, programmable robots and pave the way to a broad spectrum of applications, including reconfigurable micromachines, tunable optical metasurfaces and miniaturized biomedical devices.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5?µm or less (PM2.5) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM2.5was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m3increase in PM2.5.We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM2.5exposure 1 day (OR?=?1.07, 95% CI?=?1.03–1.11) and 4 days (OR?=?1.04, 95% CI?=?0.99–1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR?=?1.17, 95% CI?=?1.08–1.28) and otitis media 4 and 7 days prior to clinical encounter (OR?=?1.09, 95% CI?=?1.02–1.16 and OR?=?1.08, 95% CI?=?1.02–1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM2.5exposures.

Background: This study investigated the association between involutional ectropion and chronic inflammatory diseases of the eyelid and ocular surface, and other systemic diseases. Methods: This case-control study was conducted using electronic medical records from Clalit Health Services in Israel, 2001–2022. Patients diagnosed with involutional ectropion were compared to two control groups: one with senile cataracts and another with other ophthalmic diseases. The groups were matched 1:3 by birth year, sex, and ethnicity. Mixed models were used to assess differences in demographics, periocular, ocular, and systemic diseases between the groups. Conditional logistic regression was used to estimate the odds ratios (OR) and adjust for confounders. Results: A total of 1786 patients with involutional ectropion and 5358 matched individuals in each control group were included. The average age of the patients with involutional ectropion was 77 ± 10 years, and 60% were men. Significant associations were found between involutional ectropion and several inflammatory diseases: blepharitis (OR 4.25, 95% confidence interval [CI]: 3.68–4.91), chalazion (OR 3.01, 95% CI: 2.3–3.94), hordeolum (OR 2.27, 95% CI: 1.8–2.86), dermatitis of the eyelid (OR 1.69, 95% CI: 1.16–2.47), chronic conjunctivitis (OR 3.49, 95% CI: 2.86–4.26), pterygium (OR 2.21, 95% CI: 1.71–2.86), hypertension (OR 1.5, 95% CI: 1.31–1.72), dyslipidaemia (OR 1.46, 95% CI: 1.3–1.64), and rheumatic disease (OR 1.9, 95% CI: 1.5–2.4). Conclusions: Periocular, ocular surface, and systemic inflammatory diseases are independent risk factors for involutional ectropion. Further research is necessary to fully understand these associations.

We consider the problem of learning uncertainty regions for parameter estimation problems. The regions are ellipsoids that minimize the average volumes subject to a prescribed coverage probability. As expected, under the assumption of jointly Gaussian data, we prove that the optimal ellipsoid is centered around the conditional mean and shaped as the conditional covariance matrix. In more practical cases, we propose a differentiable optimization approach for approximately computing the optimal ellipsoids using a neural network with proper calibration. Compared to existing methods, our network requires less storage and less computations in inference time, leading to accurate yet smaller ellipsoids. We demonstrate these advantages on four real-world localization datasets.

Indirect calorimetry (IC)-guided nutrition might positively affect the clinical outcome of critically ill patients. In this systematic review and meta-analysis, our objective was to assess the benefit of isocaloric nutrition guided by IC, compared to hypocaloric nutrition, for critically ill patients admitted to the intensive care unit (ICU). We performed a systematic review of all randomized controlled trials published through January 2021, assessing the benefit of isocaloric nutrition guided by IC. The primary outcome was 28-day all-cause mortality. Secondary outcomes were ICU and 90-day all-cause mortality, rate of nosocomial infections, and adverse events. Four trials evaluating 1052 patients were included. Patients treated with isocaloric nutrition had a lower 28-day mortality rate (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.63–0.99, P= 0.04). No between-group difference was found in ICU and 90-day mortality (RR 0.92, 95% CI 0.68–1.23, P= 0.56 and RR 0.88, 95% CI 0.72–1.07; P= 0.2, respectively) and in the rate of nosocomial infections (RR 1.15, 95% CI 0.77–1.72, P= 0.51). A pooled analysis of studies that evaluated the benefit of isocaloric nutrition guided by IC, for critically ill patients in the ICU, has shown reduced 28-day mortality. However, there was no difference in 90-day mortality and nosocomial infection rate.

Abstract: The oxidation of chromium in dry O2 and in O2 + 10%H2O at 600 and 700 °C is studied. Scale morphology is investigated by several methods, including scanning electron microscopy (SEM) of cross sections prepared by focussed ion beam milling (FIB). In O2 + H2O at 600 and 700 °C, chromium forms a duplex scale consisting of an inner barrier oxide and a discontinuous outer oxide made up of blade-shaped crystals. Thermogravimetric (TG) measurements show that water vapour influences chromium oxidation by causing vaporization of the protective oxide, resulting in paralinear oxidation kinetics. An extension of the original treatment by Tedmon is deduced, which allows for the determination of the evaporation rate constant k s and the parabolic oxidation rate constant k d from TG data acquired during short exposures. The results show that k d is the same in dry O2 and in O2 + 10%H2O. Equivalently, the transport properties of chromia are the same in the two environments. The equilibrium constant of CrO2(OH)2 formation from chromia is reported. The activation enthalpy of the vaporization reaction is determined.

Pulse shape discrimination (PSD) is required for many radioactive particle monitoring applications. Classical PSD methods commonly struggle at high event rates in the presence of pile up, and are therefore utilized for low event rates. We present a PSD algorithm that combines classic approaches with deep learning techniques. The algorithm provides both detection and classification of the pulses at high event rates. While PSD algorithms for high event rates are often limited to two piled-up pulses, our algorithm is designed and tested for detection and classification under severe pile-up conditions, where three or more pulses are piled up. The algorithm was tested on both experimental data from a $\text {Cs}_{{2}}\text {LiYCl6:Ce}$ (CLYC) detector and on synthetic data. The algorithm’s detection and discrimination performance is compared to current state-of-the-art methods. The algorithm’s performance is characterized under varying event rates, signal-to-noise ratio (SNR) conditions, and neutron-to-gamma event rate ratios.

•Aspacytarabine enables delivery of high-dose cytarabine to unfit patients without the prohibitive cerebellar and gastrointestinal toxicities.•Aspacytarabine treatment resulted in a CR rate of 36.9% with no prolonged neutropenia or thrombocytopenia during postremission therapy.

Clinical simulators are an important resource for medical students seeking to improve their fundamental surgical skills. Three-dimensional (3-D) printing offers an innovative method to create simulators due to its low production costs and reliable printing fidelity. We aimed to validate a 3-D printed knot-tying simulator named Nodo-Tie.

AbstractThe classic herding model examines the asymptotic behavior of agents who observe their predecessors’ actions as well as a private signal from an exogenous information structure. In this paper, we introduce a self-interested sender into the model and study her problem of designing this information structure. If agents cannot observe each other, the model reduces to Bayesian persuasion. However, when agents observe predecessors’ actions, they may learn from them, potentially harming the sender. We identify necessary and sufficient conditions under which the sender can nevertheless obtain the same utility as when the agents are unable to observe each other. (JEL D82, D83, D91)

ABSTRACTPurposeTo evaluate risk factors for pterygium and prevalence of periocular and systemic diseases among patients with pterygium.MethodsA retrospective case-control study was conducted among members of Clalit Health Services (CHS) in Israel, from 2001 to 2022. A total of 13,944 patients diagnosed with pterygium were included. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Mixed models were used to assess differences in demographic characteristics, ocular and systemic diseases between the groups. Generalized estimating equation (GEE) logistic regression was used to estimate the odds ratios (OR) and adjust for confounders.ResultsThe average age of pterygium patients was 49 ± 17 years; 51% were male. The results showed significant associations between pterygium and risk factors of vernal kerato-conjunctivitis (OR 2.52, 95% confidence interval [CI]: [1.96–3.24]), chronic allergic conjunctivitis (OR 1.98, 95% CI: [1.65–2.39]), blepharitis (OR 1.91, 95% CI: [1.78–2.04]), chalazion (OR 1.47, 95% CI: [1.30–1.67]) and unspecified systemic allergy (OR 1.21, 95% CI [1.09–1.34]), after adjusting for rural residency status. Glaucoma (OR 0.74, 95% CI [0.64–0.85]) and smoking (OR 0.70, 95% CI [0.66–0.75]) were protective factors against pterygium.ConclusionSystemic and periocular inflammatory and allergic diseases are risk factors for pterygium.

Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of Candida albicansimmunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal Candidaovergrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with C. albicanspatient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in C. albicansIgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.

Leiomyoma is a benign tumor that develops from smooth muscle. The distribution of smooth muscle is limited, especially in the bone, and intraosseous leiomyoma in the mandible is extremely rare. Herein, we present a case of asymptomatic intraosseous leiomyoma in the right mandible of a 56-year-old woman and a literature review. The patient had no clinical symptoms, but a radiograph of the teeth and an orthopantomogram revealed a well-circumscribed radiolucent lesion in the right mandible. Computed tomography revealed bone resorption and thinning of the lingual and buccal cortical bones. In contrast, magnetic resonance imaging revealed signal intensity similar to muscle in T1-weighted images and high signal intensity with internal heterogeneity in fat-suppressed T2-weighted images. Histopathological examination revealed an abundance of spindle-shaped cells, S100 protein and cytokeratin-negative cells, and smooth muscle actin and CD31 positive cells. As a result, the lesion was suspected to be a leiomyoma, and the tumor was excised under general anesthesia. A pathological examination after the surgery confirmed the diagnosis of leiomyoma. More than a year after the surgery, there was no evidence of recurrence. To the best of our knowledge, 25 cases of intraosseous leiomyomas have been reported. Intraosseous leiomyoma in the head and neck region is uncommon and difficult to detect, although it can occur in the mandible.

Confinement of rock bolts by the surrounding rock formation has long been recognized as a positive contributor to the pull-out behavior, yet only a few experimental works and analytical models have been reported, most of which are based on the global rock bolt response evaluated in pull-out tests. This paper presents a laboratory experimental setup aiming to capture the rock formation effect, while using distributed fiber optic sensing to quantify the effect of the confinement and the reinforcement pull-out behavior on a more local level. It is shown that the behavior along the sample itself varies, with certain points exhibiting stress drops with crack formation. Some edge effects related to the kinematic freedom of the grout to dilate are also observed. Regardless, it was found that the mid-level response is quite similar to the average response along the sample. The ability to characterize the variation of the response along the sample is one of the many advantages high-resolution fiber optic sensing allows in such investigations. The paper also offers a plasticity-based hardening load transfer function, representing a "slice" of the anchor. The paper describes in detail the development of the model and the calibration/determination of its parameters. The suggested model captures well the coupled behavior in which the pull-out process leads to an increase in the confining stress due to dilative behavior.

Central-limit (Brownian) approximations are widely used for the performance analysis and optimization of queueing networks because of their tractability relative to the original queueing models. The stationary distributions of the approximations are used as proxies for those of the queues. The convergence of suitably scaled and centered processes provides mathematical support for the use of these Brownian models. As with the central limit theorem, to establish convergence, one must impose assumptions directly on the primitives or indirectly on the parameters of a related optimization problem. These assumptions reflect an interpretation of the underlying parameters--a classification into so-called heavy-traffic regimes that specify a scaling relationship between the utilization and the arrival rate. Here, it matters whether a utilization of 90% in a queue with an arrival rate of [lambda] = 100 is read as [rho]([lambda]) = 0.9 = 1 - 1/[square root of ([lambda])] or as p([lambda]) = 0.9, because different interpretations lead to different limits and, in turn, to different approximations. However, from a heuristic point of view, there is an immediate Brownian (i.e., normal) analogue of the queueing model that is derived directly from the primitives and requires no scaling interpretation of the parameters. In this model, the drift is that of the original queue, and the noise term is replaced by a Brownian motion with the same variance. This is intuitive and appealing as a tool, but it lacks mathematical justification. In this paper, we prove that for the fundamental M/GI/1 + GI queue, this direct intuitive approach works: the Brownian model is accurate uniformly over a family of patience distributions and universally in the heavy-traffic regime. The validity of this approach extends to dynamic control in that the solution of the directly derived diffusion control problem is universally accurate. To build mathematical support for the accuracy of this model, we introduce a framework built around 'queue families' that allows us to treat various patience distributions simultaneously, and it uncovers the role of a concentration property of the queue. Funding: This research was supported in part by the National Science Foundation [NSF Grant CMMI-1662294] and the Hong Kong Research Grants Council [Projects 24500314 and 14502815]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/opre.2017.1715. Keywords: M/GI/1+ GI * universal approximation * stationary distribution * Stein's method, 1. Introduction The Basic Building Block (the M/M/1 Queue). The fundamental building block of queueing theory is the M/M/1 queue in which Poisson arrivals with Exponential service requirements are processed [...]

We study dynamic matching policies in a stochastic marketplace for barter, with agents arriving over time. Each agent is endowed with an item and is interested in an item possessed by another agent homogeneously with probability p, independently for all pairs of agents. Three settings are considered with respect to the types of allowed exchanges: (a) only two-way cycles, in which two agents swap items, (b) two-way or three-way cycles, (c) (unbounded) chains initiated by an agent who provides an item but expects nothing in return. We consider the average waiting time as a measure of efficiency and find that the cost outweighs the benefit from waiting to thicken the market. In particular, in each of the above settings, a policy that conducts exchanges in a greedy fashion is near optimal. Further, for small p, we find that allowing three-way cycles greatly reduces the waiting time over just two-way cycles, and conducting exchanges through a chain further reduces the waiting time significantly. Thus, a centralized planner can achieve the smallest waiting times by using a greedy policy, and by facilitating three-way cycles and chains, if possible. Funding: The second author acknowledges the research support of the National Science Foundation [Grant SES-1254768]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/opre.2017.1644. Keywords: barter * matching * market design * random graphs * dynamics * kidney exchange * platform * control policy, 1. Introduction Thousands of incompatible patient-donor pairs enroll at kidney exchange clearinghouses every year around the world in order to swap donors. Kidney exchange is just one example of a [...]

ABSTRACTThere is increasing pressure on local authorities to restructure themselves to meet current expectations from the public. Multilevel governance has emerged as one method for such restructuring. Using the results of a survey conducted among 1733 residents of local authorities in Israel, we explore the effects of three specific multilevel governance reforms – the merging, disaggregation and clustering of local government authorities – on residents’ assessments about local governance and democracy. Our findings underscore the importance of public support for the structural reform. Those who become involved in soft reforms involving bottom-up groups and voluntary coalitions that cluster together are more likely to trust their local authority, feel it responds to their needs satisfactorily and listens to them. However, the more support they express, the more their perceptions are attenuated. In contrast, residents of local authorities that amalgamated with other communities that then went through hard reforms, such as merging and disaggregation involving up-scaling and top-down reforms, had fewer positive opinions about these issues. Only residents who strongly favoured the merger had positive perceptions about local governability and participation in decision-making and were satisfied with local services and trusted the local government. We discuss these findings and draw conclusions about their implications for local structural reforms in an era of local and regional governance.

Online awareness is essential to learning from one’s experiences, enabling adaptive self-management, often challenged among adolescents with attention-deficit hyperactivity disorder (ADHD). This study used an online awareness tool, the Occupational Performance Experience Analysis (OPEA), to examine (a) the online awareness of occupational performance of adolescents with ADHD and controls and (b) the potential modifiability of online awareness after a brief mediation redirecting attention to task demands and contextual factors. Seventy adolescents with and without ADHD were administered the OPEA after completing cognitive assessments. The OPEA comprises a verbal description of experiences, scored for representation of main actions, temporal context, and coherence, completed again after mediation. Results point to significantly less coherent descriptions of occupational performance among adolescents with ADHD compared with adolescents without ADHD; modifiability was only examined in the ADHD group and demonstrated significantly more coherent descriptions after mediation. Findings may elucidate online awareness of occupational performance as an occupational therapy intervention target for adolescents with ADHD.

We compared the effectiveness of physician-directed clinical decision support (CDS) administered via electronic health record versus patient-directed education to promote the appropriate use of opioids by conducting a cluster-randomized trial involving 82 primary care physicians and 951 of their patients with chronic pain. Primary outcomes were satisfaction with patient-physician communication consumer assessment of health care providers and system clinician and group survey (CG-CAHPS) and pain interference patient-reported outcomes measurement information system. Secondary outcomes included physical function (patient-reported outcomes measurement information system), depression (PHQ-9), high-risk opioid prescribing (>90 morphine milligram equivalents per day [≥90 mg morphine equivalent/day]), and co-prescription of opioids and benzodiazepines. We used multi-level regression to compare longitudinal difference-in-difference scores between arms. The odds of achieving the maximum CG-CAHPS score were 2.65 times higher in the patient education versus the CDS arm (P = .044; 95% confidence interval [CI] 1.03–6.80). However, baseline CG-CAHPS scores were dissimilar between arms, making these results challenging to interpret definitively. No difference in pain interference was found between groups (Coef = −0.64, 95% CI −2.66 to 1.38). The patient education arm experienced higher odds of Rx ≥ 90 milligrams morphine equivalent/day (odds ratio = 1.63; P = .010; 95% CI 1.13, 2.36). There were no differences between groups in physical function, depression, or co-prescription of opioids and benzodiazepines. These results suggest that patient-directed education may have the potential to improve satisfaction with patient-physician communication, whereas physician-directed CDS via electronic health records may have greater potential to reduce high-risk opioid dosing. More evidence is needed to ascertain the relative cost-effectiveness between strategies.

Objective: To better understand health experiences among Two Spirit and lesbian, gay, bisexual, transgender, and queer and questioning (LGBTQ+) American Indian/Alaska Native (AI/AN) people, we examined experiences with access to health care of 223 AI/AN Two Spirit and LGBTQ+ people.Methods: Participants of the Pride and Connectedness 2020 survey, conducted through the Northwest Portland Area Indian Health Board, were asked about barriers to seeking and accessing care through a 10-question scale. We compared cisgender and gender-diverse participant demographic and scale responses to explore potential differences based on gender identity using the Pearson χ2test of independence and ordinal logistic regression, respectively.Results: Both cisgender and gender-diverse participants experienced at least some difficulties accessing health care. Finances, lack of psychologists/other mental health support, and lack of psychological support groups for Two Spirit and LGBTQ+ communities were the top 3 barriers to care experienced by all participants (84%, 82%, and 80%, respectively). Compared with cisgender participants, gender-diverse participants were more likely to report difficulties accessing care for nearly all questions on the 10-question scale and nearly 3 times more likely to report fear of being mistreated within the health care system based on their gender identity (adjusted odds ratio = 2.9; 95% CI, 1.8-4.9; P< .001).Conclusions: Increased access to mental health services and improved health care provider training that focuses on culturally relevant and gender-affirming practices would benefit the health and well-being of AI/AN people who identify as Two Spirit and LGBTQ+.

ABSTRACTWomen in urban neighborhoods often face disproportionately higher levels of environmental and social stressors; however, the health effects from urban stressors remain poorly understood. We evaluated the association between urban stress and depression, fatigue, and sleep disruption in a cohort of 460 women in Mexico City. To assess urban stress, women were administered the Urban Annoyances scale. Six constructs were summarized to create an overall index. Depressive symptoms were assessed using the Edinburgh Depression Scale; the Patient-Reported Outcomes Information System scales were used to assess sleep disruption and fatigue. Linear regression models were used to estimate the association with continuous symptoms comparing women with high stress to those with lower levels. Models were adjusted for socioeconomic status, education, age, social support, and previous depressive symptoms. High urban stress was associated with greater depressive symptoms (β: 1.77; 95% CI: 0.83, 2.71), fatigue (β: 2.47; 95% CI: 0.87, 4.07), and sleep disruption (β: 2.14; 95% CI: 0.54, 3.73). Urban stress plays an important role in women’s psychological and physical health, highlighting the importance of including these measures in environmental health studies. Urban interventions, such as promoting alternative transport options, should additionally be addressed to improve health of urban populations.

Peroxisome proliferator-activated receptor δ (PPARδ) is considered to be a pharmaceutical target to treat metabolic diseases including atherosclerosis, but there is no PPARδ agonist available for clinical use. We have previously reported the discovery of piperidinyl/piperazinyl benzothiazole derivatives as a new series of PPARδ agonists using docking-based virtual screening methods. In the present study, we found that introduction of a pyrrolidine group into the 4-position of their central piperidine rings enhances hPPARδ activity and subtype selectivity. This led to the discovery of 21having strong PPARδ agonist activity (EC50= 3.6 nM) with excellent ADME properties. Furthermore, 21significantly suppressed atherosclerosis progression by 50–60% with reduction of the serum level of MCP-1 in LDLr-KO mice.

N,N-Dimethylformamide (DMF) is an essential solvent in industries and pharmaceutics. Its market size range was estimated to be 2 billion U.S. dollars in 2022. Monitoring DMF in solution environments in real time is significant because of its toxicity. However, DMF is not a redox-active molecule; therefore, selective monitoring of DMF in solutions, especially in polar aqueous solutions, in real time is extremely difficult. In this paper, we propose a selective DMF sensor using a molybdenum disulfide (MoS2) field-effect transistor (FET). The sensor responds to DMF molecules but not to similar molecules of formamide, N,N-diethylformamide, and N,N-dimethylacetamide. The plausible atomic mechanism is the oxygen substitution sites on MoS2, on which the DMF molecule shows an exceptional orientation. The thin structure of MoS2–FET can be incorporated into a microfluidic chamber, which leads to DMF monitoring in real time by exchanging solutions subsequently. The designed device shows DMF monitoring in NaCl ionic solutions from 1 to 200 μL/mL. This work proposes the concept of selectively monitoring redox-inactive molecules based on the nonideal atomic affinity site on the surface of two-dimensional semiconductors.

Abstract. Call centers attribute different values to different customer segments. These values are reflected in quality-of-service targets. The prevalent target service factor (TSF) formulation requires, for example, that 80% of [...]

Point of Care Ultrasound (POCUS) is used to evaluate the injured pediatric elbow. Standard of care, however, remains radiography. POCUS performed in the setting of normal radiographs have been obtained may demonstrate radiologic occult lipohemarthrosis indicative of occult fracture. We reviewed our pediatric emergency department (PED) POCUS archive for lipohemarthrosis, and then isolated those cases with normal elbow radiography. Radiography was deemed to be normal per the interpretation of the treating PED physician, and was reviewed for this series by an experienced ABR board certified pediatric radiologist. Fracture on POCUS was defined as fracture line or lipohemarthrosis in a posterior sagittal or transverse view of the distal humerus. Fracture was confirmed by signs of cortical healing on follow‐up radiography, or clinical course consistent with fracture as documented by an orthopedist. We identified four children with elbow fractures who had no fracture line or elevated posterior fat pad on radiography but demonstrated lipohemarthrosis on POCUS. POCUS may elicit evidence of fracture even after normal radiography, and POCUS findings suggesting occult fracture may allow for more effective guidance on discharge.

We report a high-speed low dark current near-infrared (NIR) organic photodetector (OPD) on a silicon substrate with amorphous indium gallium zinc oxide (a-IGZO) as the electron transport layer (ETL). In-depth understanding of the origin of dark current is obtained using an elaborate set of characterization techniques, including temperature-dependent current-voltage measurements, current-based deep-level transient spectroscopy (Q-DLTS), and transient photovoltage decay measurements. These characterization results are complemented by energy band structures deduced from ultraviolet photoelectron spectroscopy. The presence of trap states and a strong dependency of activation energy on the applied reverse bias voltage point to a dark current mechanism based on trap-assisted field-enhanced thermal emission (Poole–Frenkel emission). We significantly reduce this emission by introducing a thin interfacial layer between the donor: acceptor blend and the a-IGZO ETL and obtain a dark current as low as 125 pA/cm2at an applied reverse bias of −1 V. Thanks to the use of high-mobility metal-oxide transport layers, a fast photo response time of 639 ns (rise) and 1497 ns (fall) is achieved, which, to the best of our knowledge, is among the fastest reported for NIR OPDs. Finally, we present an imager integrating the NIR OPD on a complementary metal oxide semiconductor read-out circuit, demonstrating the significance of the improved dark current characteristics in capturing high-quality sample images with this technology.

The positions of Abrikosov vortices have long been considered as means to encode classical information. Although it is possible to move individual vortices using local probes, the challenge of scalable on-chip vortex-control remains outstanding, especially when considering the demands of controlling multiple vortices. Realization of vortex logic requires means to shuttle vortices reliably between engineered pinning potentials, while concomitantly keeping all other vortices fixed. We demonstrate such capabilities using Nb loops patterned below a NbSe2layer. SQUID-on-Tip (SOT) microscopy reveals that the loops localize vortices in designated sites to a precision better than 100 nm; they realize “push” and “pull” operations of vortices as far as 3 μm. Successive application of such operations shuttles a vortex between adjacent loops. Our results may be used as means to integrate vortices in future quantum circuitry. Strikingly, we demonstrate a winding operation, paving the way for future topological quantum computing and simulations.

Lotteries are a common way to resolve ties in assignment mechanisms that ration resources. We consider a model with a continuum of agents and a finite set of resources with heterogeneous qualities, where the agents' preferences are generated from a multinomial‐logit (MNL) model based on the resource qualities. We show that all agents prefer a common lottery to independent lotteries at each resource if every resource is popular, meaning that the mass of agents ranking that resource as their first choice exceeds its capacity. We then prove a stronger result where the assumption that every resource is popular is not required and agents' preferences are drawn from a (more general) nested MNL model. By appropriately adapting the notion of popularity to resource types, we show that a hybrid tie‐breaking rule in which the objects in each popular type share a common lottery dominates independent lotteries at each resource.