bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of discharge events in the CMS GE1/1 GEM
detectors in presence of LHC beam
Authors: Calzaferri S. ,   the CMS Muon Group
Published: February 2024

In July 2022, the experiments installed on the Large Hadron Collider (LHC) accelerator ring started a new data taking phase, Run-3. Before this period, an upgrade campaign took place during the so called Long Shutdown 2 (2018–2022). In particular, the muon system of the CMS experiment has been upgraded with the installation of a new gas detector station, GE1/1, based on Gas Electron Multiplier technology (GEM). The CMS experiment has scheduled the installation of two additional GEM stations: GE2/1 and ME0. The aim of the GEM stations is to maintain the performance of the muon system, reached during the last data taking phase (Run-2), with the increase of instantaneous luminosity expected at the LHC. The installed GE1/1 station covers the pseudorapidity region 1.55 <|η|< 2.18. GE1/1 participated in the CMS Run-3 data taking from July to November 2022 and, in this period, its detectors were exposed for the first time to the radiation produced during the collisions of the LHC beams, with a center of mass energy of 13.6 TeV. Since the first days of Run-3, where only a few bunches collided in CMS, the GE1/1 detectors started to experience a significant number of discharges, affecting their smooth operation during the data taking. In this talk, we present an analysis of discharges, which started by simply counting the number of discharges occurring per detector. An interesting phenomenon observed was that the discharge rate can vary a lot among the installed detectors; this is due to the fact that the occurrence of discharges is driven by the manufacturing of the GEM foils used in the detectors. Imperfections in their manufacturing can lead to large variation in the discharge rate. In addition, the rate can vary in time, due to the fact that discharges can produce damage at the site generating them, deactivating a particular hole or, in the worst case, producing a short circuit in the GEM foil, deactivating a part of the foil amplification region. We present the evolution of the discharge rate in time and its dependence on the HV working point and on the luminosity delivered by the LHC beams. This contribution illustrates the actions taken to mitigate the discharge rate and to assure a smooth detector operation.
The XGIS instrument on-board THESEUS: detector principle and read-out electronics
Authors: Srivastava S. , Labanti C. , Amati L. , Campana R. , Virgilli E. , Marchesini E. , Borciani E. , Mele F. , Dedolli I. , Bertuccio G. , Demenev E. , Grassi M. , Malcovati P.
Published: February 2024

The functionality and experimental performance characterization of the latest four channel version of ORION ASIC, a very low noise multichip read out and processing electronics customized for the X and Gamma Imaging Spectrometer (XGIS) instrument onboard the Transient High-Energy Sky and Early Universe Surveyor (THESEUS) mission, is presented. XGIS is a set of two coded-masked wide field deep sky cameras using monolithic SDDs (Silicon Drift Detectors) and CsI:Tl (Thallium doped-Cesium Iodide) scintillator-based X-γ ray detectors. This paper highlights the design, working principle and the expected performances of the XGIS, on a small scale 2×2 prototype. Furthermore, the evolution timeline of different versions of ORION with detailed performance observations and analysis for spectroscopic resolution, electronic noise and the operational linear energy ranges of both X and the γ processors of the four-pixel ASIC version bonded to a 2×2 SDD array are emphasized. Each 2×2 SDD array element is electrically and dimensionally equivalent to single elements of the THESEUS 8×8 SDD array.
CaloScore v2: single-shot calorimeter shower simulation with diffusion models
Authors: Mikuni Vinicius , Nachman Benjamin
Published: February 2024

Diffusion generative models are promising alternatives for
fast surrogate models, producing high-fidelity physics
simulations. However, the generation time often requires an
expensive denoising process with hundreds of function evaluations,
restricting the current applicability of these models in a realistic
setting. In this work, we report updates on the CaloScore
architecture, detailing the changes in the diffusion process, which
produces higher quality samples, and the use of progressive
distillation, resulting in a diffusion model capable of generating
new samples with a single function evaluation. We demonstrate these
improvements using the Calorimeter Simulation Challenge 2022
dataset.
Accurate method based on data filtering for quantitative multi-element analysis of soils using CF-LIBS
Authors: HAN 韩 Weiwei 伟伟 , SUN 孙 Duixiong 对兄 , ZHANG 张 Guoding 国鼎 , DONG 董 Guanghui 光辉 , CUI 崔 Xiaona 小娜 , SHEN 申 Jincheng 金成 , WANG 王 Haoliang 浩亮 , ZHANG 张 Denghong 登红 , DONG 董 Chenzhong 晨钟 , SU 苏 Maogen 茂根
Published: February 2024

To obtain more stable spectral data for accurate quantitative analysis of multi-element, especially for the large-area in-situ elements detection of soils, we propose a method for a multi-element quantitative analysis of soils using calibration-free laser-induced breakdown spectroscopy (CF-LIBS) based on data filtering. In this study, we analyze a standard soil sample doped with two heavy metal elements, Cu and Cd, with a specific focus on the line of Cu I 324.75 nm for filtering the experimental data of multiple sample sets. Pre- and post- data filtering, the relative standard deviation for Cu decreased from 30% to 10%, The limits of detection (LOD) values for Cu and Cd decreased by 5% and 4%, respectively. Through CF-LIBS, a quantitative analysis was conducted to determine the relative content of elements in soils. Using Cu as a reference, the concentration of Cd was accurately calculated. The results show that post- data filtering, the average relative error of the Cd decreases from 11% to 5%, indicating the effectiveness of data filtering in improving the accuracy of quantitative analysis. Moreover, the content of Si, Fe and other elements can be accurately calculated using this method. To further correct the calculation, the results for Cd was used to provide a more precise calculation. This approach is of great importance for the large-area in-situ heavy metals and trace elements detection in soil, as well as for rapid and accurate quantitative analysis.
On a remark by Alan Weinstein
Authors: Androulidakis Iakovos
Published: February 2024

Alan Weinstein remarked that, working in the framework of diffeology, a construction from Noncommutative Differential Geometry might provide the non-trivial representations required for the geometric quantisation of a symplectic structure which is not integral. In this note we show that the construction we gave with P. Antonini does indeed provide non-trivial representations.
Elastic diffeological spaces
Authors: Blohmann Christian
Published: February 2024

We introduce a class of diffeological spaces, called elastic, on which the left Kan extension of the tangent functor of smooth manifolds defines an abstract tangent functor in the sense of Rosický. On elastic spaces there is a natural Cartan calculus, consisting of vector fields and differential forms, together with the Lie bracket, de Rham differential, inner derivative, and Lie derivative, satisfying the usual graded commutation relations. Elastic spaces are closed under arbitrary coproducts, finite products, and retracts. Examples include manifolds with corners and cusps, diffeological groups and diffeological vector spaces with a mild extra condition, mapping spaces between smooth manifolds, and spaces of sections of smooth fiber bundles.
Singular foliations through diffeology
Authors: Miyamoto David
Published: February 2024

A singular foliation is a partition of a manifold into leaves of perhaps varying dimension. Stefan and Sussmann carried out fundamental work on singular foliations in the 1970s. We survey their contributions, show how diffeological objects and ideas arise naturally in this setting, and highlight some consequences within diffeology. We then introduce a definition of transverse equivalence of singular foliations, following Molino’s definition for regular foliations. We show that, whereas transverse equivalent singular foliations always have diffeologically diffeomorphic leaf spaces, the converse holds only for certain classes of singular foliations. We finish by showing that the basic cohomology of a singular foliation is invariant under transverse equivalence.
Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial
Authors: Grekowitz Eva , Metz Martin , Altrichter Sabine , Bauer Andrea , Brockow Knut , Heine Guido , Lionnet Leonard , Saday Kadriye Kaplan , Hultsch Thomas , Søerensen Ole E , Maurer Marcus
Published: February 2024

Background

Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects.

Objectives

To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression.

Methods

This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability.

Results

Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R.

Conclusions

This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.
A comprehensive list of genes required for the efficient conjugation of plasmid Rts1 was determined by systematic deletion analysis
Authors: Murata Takahiro , Gotoh Yasuhiro , Hayashi Tetsuya
Published: February 2024

While conjugation-related genes have been identified in many plasmids by genome sequencing, functional analyses have not yet been performed in most cases, and a full set of conjugation genes has been identified for only a few plasmids. Rts1, a prototype IncT plasmid, is a conjugative plasmid that was originally isolated from Proteus vulgaris. Here, we conducted a systematic deletion analysis of Rts1 to fully understand its conjugation system. Through this analysis along with complementation assays, we identified 32 genes that are required for the efficient conjugation of Rts1 from Escherichia coli to E. coli. In addition, the functions of the 28 genes were determined or predicted; 21 were involved in mating-pair formation, three were involved in DNA transfer and replication, including a relaxase gene belonging to the MOBH12 family, one was involved in coupling, and three were involved in transcriptional regulation. Among the functionally well-analysed conjugation systems, most of the 28 genes showed the highest similarity to those of the SXT element, which is an integrative conjugative element of Vibrio cholerae. The Rts1 conjugation gene set included all 23 genes required for the SXT system. Two groups of plasmids with conjugation systems nearly identical or very similar to that of Rts1 were also identified.
Digest: A model for speciation in island systems
Authors: Cornu Lydia
Published: February 2024

Ecological pulses, marked by rapid environmental shifts, shape species dynamics such as speciation. Princepe et al. 2024 explore how intermittent migration, seabed depth, and sea-level changes influence species richness in islands. Their model, revealing nuanced richness patterns and migration impacts, contributes to understanding island evolution and offers insights into real-world cases. Examining the Philippines Archipelago, known for rich biodiversity, parallels emerge, showcasing the complex interplay of isolation, land bridges, and sea-level shifts in shaping genetic diversity. Overall, the findings enhance our understanding of population evolution in dynamic island environments.
Do Parties Matter? Party Positions and European Voters’ Attitudes toward Economic and Political Globalization
Authors: Honeker Alex
Published: February 2024

To what extent do party positions influence voters’ attitudes toward the economic and political aspects of globalization? Initially an issue following a left-right dimension of conflict, globalization increasingly divides mainstream from nonmainstream parties. In this study, I argue that parties help citizens form opinions on globalization issues. I then use data on voters’ attitudes and party positions on globalization to test this supply-side theory of globalization attitudes on both economic and political dimensions. Holding demand-side factors such as economic self-interest and predispositions/values constant, I find that party positions strongly affect voters’ views on economic and political globalization, with the effect being similar to that of education. Moreover, I find that the effect of cues from left- and right-populist parties is much more negative than that of mainstream parties, replicating previous elite-level findings on the positioning of these party families. Finally, green party cues show conflicting results for the economic and political dimensions, with green cues affecting voters negatively on economic globalization but positively on political globalization. The findings in this study call for a deeper exploration of the supply-side determinants of globalization attitudes.
Association between Child Tax Credit advance payments and food insufficiency in households experiencing economic shocks
Authors: McCann Nicole C , Dean Lorraine T , Bovell-Ammon Allison , Ettinger de Cuba Stephanie , Green Tiffany , Shafer Paul R , Raifman Julia
Published: February 2024

The COVID-19 pandemic brought increases in economic shocks due to poor health and lost employment, which reduced economic well-being, especially in households with children. The American Rescue Plan Act of 2021 expanded Child Tax Credit (CTC) payments to include eligibility for the lowest income households, boosted benefit levels, and provided monthly advance payments to households with children. Using Census Household Pulse Survey respondent data from January 2021 to July 2022, we evaluated the association between these advance CTC monthly payments and food insufficiency among households with children experiencing health- or employment-related economic shocks (defined as missed work due to COVID-19/other illness or COVID-19–related employer closure/layoff/furlough). Using a triple difference design, we found that the advance CTC was associated with greater reductions in food insufficiency among households with children experiencing economic shocks both compared with households without children and with households with children not experiencing economic shocks. Permanently expanding the advance CTC could create resilience to economic shocks during disease outbreaks, climate disasters, and recessions.
Capacity configuration strategy for wind-photovoltaic-battery system based on optimized simulated annealing
Authors: Huang Haoru , Hu Zhijie , Xu Shuaishuai , Wang Xiaoling
Published: February 2024

Photovoltaic (PV) and wind power are very promising renewable energy sources. Wind-PV has good complementarity, and the battery can better smooth the power fluctuation of wind-PV, so the wind-PV-battery system has been widely used. The capacity configuration of the wind-PV-battery system is a complex issue because many factors affect it. Unlike other studies that focus on many meaningless parameters, the contribution of this paper is that we focus on three key elements, system reliability, cost, and wind-PV energy discard rate (EDR), which are the key factors affecting the capacity configuration of the system because system reliability and cost are factors that cannot be ignored during system operation. At the same time, the EDR is the government’s minimum requirement for system operation. Based on this, this paper establishes an optimization function to minimize the loss of power supply probability (LPSP), cost, and EDR, and then optimizes a simulated annealing (SA) algorithm to improve its optimization speed as well as accuracy, and finally verifies through simulation, that the optimized SA has better performance and can obtain a satisfactory reference configuration for wind-PV-battery capacity. Further, we have also analyzed the effectiveness obtained by applying retired batteries to the energy storage system. In our example, the cost of the system after using retired batteries is only about 61% of the cost of using new batteries, which suggests that utilizing retired batteries instead of new batteries has a better cost performance.
Racial (In)justice in Brazil: Reconstructing the Subaltern Memories of Poor and Black Women in the Brazilian Dictatorship
Authors: Pamplona Pablo , Besen Beatriz , de Wolff Kaya , Ansara Soraia , Galeão-Silva Luis
Published: February 2024

The Brazilian military-corporate dictatorship faced the resistance and mobilization of several marginalized groups. In this article, we reconstruct the subaltern memories of Black and poor women from the outskirts of São Paulo who participated in Christian Base Communities and the Cost-of-Living Movement, and we show how their mobilization was supported by social movements across the country. Despite their dimension and impact, a report by the Brazilian National Truth Commission fails to recognize their role in the country’s democratic transition and the violence suffered by marginalized groups. These memories support a reflection on the myth of ‘racial democracy’ in Brazil as a general denial of racial violence throughout the country’s history, which leaves intact its structures of injustice. We argue that the reconstruction of subaltern memories can have a significant impact on transitional justice and recover their critical role in democracy.
When the Background Looms Large over the Foreground: Medical Professionals, Diplomats, and Co-Managing SARS-CoV-2
Authors: Kornprobst Markus , Strobl Stephanie
Published: February 2024

The Public Health Emergency of International Concern (PHEIC) is the highest alert that the World Health Organization (WHO) can issue. Even though the International Health Regulations (IHR 2005) prescribe tight deadlines and an expeditious decision-making process to determine such a PHEIC, it took many weeks for the alert to be declared to counter the spread of SARS-CoV-2 (coronavirus). What explains the delay? Drawing from recent advances in the literature on international orders, our argument zooms in on the troubled relations between medical professionals and diplomats. Practices enacting a hierarchical relationship between the medical and diplomatic communities of practice (background) undermined crucial parts of the decision-making mechanism laid out in the IHR, which puts medical professionals in a strong position (foreground). This study contributes to a better understanding of PHEICs, global health governance, and, beyond this, to how actors employing different lenses to make sense of the world fail or succeed to manage crises together. Our findings also have important policy implications for discussions about a Pandemic Treaty.
Effect of water sulfate and dietary bismuth subsalicylate on feed and water intake, ruminal hydrogen sulfide concentration, and trace-mineral status of growing beef heifers
Authors: Evans Mikaela G , Campbell John C , Ribeiro Gabriel O , Henry Darren H , Waldner Cheryl , Penner Gregory B
Published: February 2024

In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ± 13) or HS (4,778 ± 263 mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ± 41 kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days −13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58 mg/L more (P < 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08 mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P < 0.001). The liver concentration of selenium was reduced (P < 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration.
Male Lrp5A214V mice maintain high bone mass during dietary calcium restriction by altering the vitamin D endocrine system
Authors: Ozgurel Serra Ucer , Reyes Fernandez Perla C , Chanpaisaeng Krittikan , Fleet James C
Published: February 2024

Environmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations in the Lrp5 gene (Lrp5A214V) altered the sensitivity of mice to an environment of inadequate dietary calcium (Ca) intake. Weanling male Lrp5A214V mice and wildtype littermates (control) were fed AIN-93G diets with 0.125%, 0.25%, 0.5% (reference, basal), or 1% Ca from weaning until 12 weeks of age (ie, during bone growth). Urinary Ca, serum Ca, Ca regulatory hormones (PTH, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)), bone parameters (μCT, ash), and renal/intestinal gene expression were analyzed. As expected, low dietary Ca intake negatively impacted bones and Lrp5A214V mice had higher bone mass and ash content. Although bones of Lrp5A214V mice have more matrix to mineralize, their bones were not more susceptible to low dietary Ca intake. In control mice, low dietary Ca intake exerted expected effects on serum Ca (decreased), PTH (increased), and 1,25(OH)2D3 (increased) as well as their downstream actions (ie, reducing urinary Ca, increasing markers of intestinal Ca absorption). In contrast, Lrp5A214V mice had elevated serum Ca with a normal PTH response but a blunted 1,25(OH)2D3 response to low dietary Ca that was reflected in the renal 1,25(OH)2D3 producing/degrading enzymes, Cyp27b1 and Cyp24a1. Despite elevated serum Ca in Lrp5A214V mice, urinary Ca was not elevated. Despite an abnormal serum 1,25(OH)2D3 response to low dietary Ca, intestinal markers of Ca absorption (Trpv6, S100g mRNA) were elevated in Lrp5A214V mice and responded to low Ca intake. Collectively, our data indicate that the Lrp5A214V mutation induces changes in Ca homeostasis that permit mice to retain more Ca and support their high bone mass phenotype.
Electoral Campaigns as Dynamic Contests
Authors: Acharya Avidit , Grillo Edoardo , Sugaya Takuo , Turkel Eray
Published: February 2024

We develop a model of electoral campaigns in which two office-motivated candidates allocate their budgets over time to affect their odds of winning. We measure the candidates’ evolving odds of winning using a state variable that tends to decay over time, and we refer to it as the candidates’ “relative popularity.” In our baseline model, the equilibrium ratio of spending by each candidate equals the ratio of their initial budgets; spending is independent of past realizations of relative popularity; and there is a positive relationship between the strength of decay in the popularity process and the rate at which candidates increase their spending over time as election day approaches. We use this relationship to recover estimates of the perceived decay rate in popularity leads in U.S. subnational elections.
Challenging the existing order of knowledge sharing governance with digital sequence information on genetic resources
Authors: Lawson Charles , Humphries Fran , Rourke Michelle
Published: February 2024

The Conference of the Parties to the Convention on Biological Diversity (CBD) have begun work on establishing a distinct multilateral mechanism to access and share the benefits (ABS) from digital sequence information on genetic resources (DSI), with the expectation of new monetary benefits. Regulating DSI for benefit sharing is problematic because efficiently and effectively regulating information requires defining DSI and identifying a suitable material proxy for the information because it is itself intangible (probably a levy or tax to access or use a database of information). More problematic is finding a compromise to the competing information governance frameworks: a dominant international intellectual property order that favours the free exchange of resources and information (generally favoured by the technology rich North); the taking of nature by States and re-ordering of biological resources to deliver benefits (generally favoured by the technology poor South); and, the claims of Indigenous Peoples according to their emerging rights in international law.
Clinical Outcomes Associated with Amoxicillin Treatment for Acute Otitis Media in Children
Authors: Frost Holly M , Keith Amy , Fletcher Dana R , Sebastian Thresia , Dominguez Samuel R , Kurtz Melanie , Parker Sarah K , Wilson Michael L , Jenkins Timothy C
Published: February 2024

Background

Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production.

Methods

205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE).

Results

8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05).

Conclusions

Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria.
Fit for duty
Authors: Prats Jordi
Published: February 2024

In the second of a two-part series, Jordi Prats looks at the mass production of clothing, including uniforms, through a statistical lens
Down the Victorian data mine
Authors: Hanley James , Turner Elizabeth
Published: February 2024

We tend to think of data mining as having originated in the late twentieth century, prompted in large part by e-commerce. But, here, James Hanley and Elizabeth Turner tell the story of an eighteenth-century customer loyalty programme later “quarried” for a 1884 article whose statistical ingenuity and overreach won it international media reaction
The inadvertently revealing statistic: A systemic gap in statistical training?
Authors: Derrick Ben , Green Elizabeth , Ritchie Felix , Smith Jim , White Paul
Published: February 2024

While concerns around data privacy are well-known, there's a lack of awareness and training when it comes to the confidentiality risk of published statistics, argue Ben Derrick, Elizabeth Green, Felix Ritchie, Jim Smith, Paul White
The path to success is about more than grades
Authors: Mitra Sinjini , Zhang Yi
Published: February 2024

Family responsibilities, work commitments and financial stress are among the reasons why students might drop out of university. Sinjini Mitra and Yi Zhang used statistics at their minority-serving institution to explore the role of non-academic factors in student success
Iatrogenic wandering spleen causing gastric outlet obstruction and perforation
Authors: Lieb K R , Beaulieu D , Dhir M
Published: February 2024

The phenomenon of a wandering spleen is rare with few published case reports. The cases published in the literature mainly result from acquired or congenital laxity of the spleen’s anchoring ligaments. Our case demonstrates an uncommon complication and possibly the first reported case of an iatrogenic wandering spleen. We present an interesting case of a 51-year-old female patient with congenital adrenal hyperplasia, fibromyalgia, and rheumatoid arthritis who underwent robotic-assisted left adrenalectomy for a 10-cm adrenal mass. Postoperatively, she developed uncontrolled pain and gastric distension due to spleen entrapment, leading to an open laparotomy and splenectomy with gastric perforation repair. She made an uneventful recovery. The rarity of iatrogenic wandering spleen as well as our patient’s complex medical history, including chronic steroid use, presented unique challenges in postoperative management. This case highlights the importance of thorough perioperative evaluation and careful surgical planning in patients with underlying conditions.
Nanotechnology in sexual medicine
Authors: Podlasek Carol A
Published: February 2024

Statement of Significance: There is significant potential for improvement in erectile function and prevention of erectile dysfunction if these diverse and novel nanotherapies can be translated to the clinic.
The Fascial Distortion Model in Military Aircrew with Chronic Neck Pain: A Case Study
Authors: Fullenkamp Allison J
Published: February 2024

Musculoskeletal pain can be a significant safety risk to aircrew. Flight surgeons are the primary care providers for aircrew and are responsible for safely treating musculoskeletal pain. Certain medical interventions can be used to treat pain while maintaining the ability to fly safely. A previous F-18 Naval Flight Officer presented to the flight surgeon with chronic neck pain seeking noninvasive and nonpharmacological therapy. After one Osteopathic Manual Treatment session using the Fascial Distortion Model (FDM), the patient had improved pain and function. The aircrewman reported an 83% reduction in pain and a 200% improvement in cervical Range of Motion (ROM) immediately following treatment. Neck pain is a common complaint in aircrew. This pain can become an in-flight distraction, thus increasing the risk of aviation mishaps. FDM can decrease pain and increase ROM quickly, without equipment or a large amount of space and without the use of medications that may prohibit an aircrew member from flying. This case study shows the ability to treat a uniformed aircrewman with neck pain while onboard an aircraft. FDM is a technique that can be taught to all flight surgeons. Teaching future flight surgeons FDM techniques can improve the U.S. Navy’s resources by decreasing time away from work along with decreasing medical costs. The use of osteopathic manipulation treatment significantly reduced an aircrewman’s pain and increased ROM with one treatment while maintaining flight status per current aeromedical waiver guidelines.
Substitution Models of Protein Evolution with Selection on Enzymatic Activity
Authors: Ferreiro David , Khalil Ruqaiya , Sousa Sergio F , Arenas Miguel
Published: February 2024

Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity. Here, we present a substitution model of protein evolution with selection on both protein structure and enzymatic activity, and that can be applied to phylogenetics. In particular, the model considers the binding affinity of the enzyme–substrate complex as well as structural constraints that include the flexibility of structural flaps, hydrogen bonds, amino acids backbone radius of gyration, and solvent-accessible surface area that are quantified through molecular dynamics simulations. We applied the model to the HIV-1 protease and evaluated it by phylogenetic likelihood in comparison with the best-fitting empirical substitution model and a structurally constrained substitution model that ignores the enzymatic activity. We found that accounting for selection on the protein activity improves the fitting of the modeled functional regions with the real observations, especially in data with high molecular identity, which recommends considering constraints on the protein activity in the development of substitution models of evolution.
Comparison of different target volume delineation strategies based on recurrence patterns in adjuvant radiotherapy for glioblastoma
Authors: Yilmaz Melek Tugce , Kahvecioglu Alper , Yedekci Fazli Yagiz , Yigit Ecem , Ciftci Gokcen Coban , Kertmen Neyran , Zorlu Faruk , Yazici Gozde
Published: February 2024

Background

Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) recommendations are commonly used guidelines for adjuvant radiotherapy in glioblastoma. In our institutional protocol, we delineate T2-FLAIR alterations as gross target volume (GTV) with reduced clinical target volume (CTV) margins. We aimed to present our oncologic outcomes and compare the recurrence patterns and planning parameters with EORTC and RTOG delineation strategies.

Methods

Eighty-one patients who received CRT between 2014 and 2021 were evaluated retrospectively. EORTC and RTOG delineations performed on the simulation computed tomography and recurrence patterns and planning parameters were compared between delineation strategies. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for statistical analyses.

Results

Median overall survival and progression-free survival were 21 months and 11 months, respectively. At a median 18 month follow-up, of the 48 patients for whom recurrence pattern analysis was performed, recurrence was encompassed by only our institutional protocol’s CTV in 13 (27%) of them. For the remaining 35 (73%) patients, recurrence was encompassed by all separate CTVs. In addition to the 100% rate of in-field recurrence, the smallest CTV and lower OAR doses were obtained by our protocol.

Conclusions

The current study provides promising results for including the T2-FLAIR alterations to the GTV with smaller CTV margins with impressive survival outcomes without any marginal recurrence. The fact that our protocol did not result in larger irradiated brain volume is further encouraging in terms of toxicity.
Cross-State Border Nicotine Vaping Products Purchase—Early Evidence From State Emergency Sales Restrictions in 2019
Authors: Cheng Kai-Wen , Liber Alex C , Levy David T
Published: February 2024

Introduction

While retail sales and retailer inspection studies generally indicate high compliance with state sales restrictions on Nicotine Vaping Products (NVPs) within the restricted area, studies using survey data generally indicate that most users could readily continue gaining access to restricted NVPs. Our study bridges a gap in the current literature and investigates the potential role of cross-state border purchases to evade state emergency NVP sales restrictions in 2019.

Aims and Methods

The study sample was restricted to NVP sales from the states neighboring Massachusetts, Rhode Island, and Washington, three states that implemented all NVP or flavored NVP sales restrictions in 2019. Among these neighboring states, the 2019 weekly county-level NVP sales by flavors (tobacco, mint/menthol, and other flavors) were compiled using Nielsen Scanner data. A quasi-experimental, comparison group pre–post study design was used to study the impacts of NVP sales restrictions on cross-state border NVP purchases.

Results

Weekly NVP sales for border counties significantly increased in response to the MA, RI, and WA bans for tobacco flavored (56%, 45%, 14%, respectively), menthol/mint flavored (51%, 2%, 41%, respectively), and other flavored (79%, 3%, 4%, respectively) products, compared to sales for non-border counties (all p-values < .01).

Conclusions

Our study identified significant cross-state border NVP purchases in all studied states to circumvent NVP emergency sales restrictions in response to the EVALI outbreak. Policymakers should factor in these purchasing behaviors to evade sales restrictions when evaluating any future potential policies at the state or local levels.

Implications

While retail sales data and retailer inspections indicate high compliance with Nicotine Vaping Product (NVP) flavor sales restrictions from major retail outlets, survey data obtain mixed findings on the effects of sales restrictions on vaping behaviors. Our study identified a significant increase in cross-state border NVP purchases to circumvent NVP sales restrictions in 2019, consistent across all three settings of Massachusetts, Rhode Island, and Washington. Policymakers should factor in these cross-state border NVP purchases in response to sales restrictions when evaluating any future potential NVP sales restrictions.
The Rise of Public–Private Religious Partnerships: Arguing Church Autonomy in the Era of Public Funding of Religion
Authors: Perez Nahshon
Published: February 2024

Religion and government, following the influence of Locke and Madison are often considered two different institutions. As such, they function under different sets of rules. We argue that the ‘two institutions’ image and institutional reality are increasingly untenable. Rather, religion and government are intertwined in many democratic countries, including, growingly, in the US, that it would be more accurate to speak of the new norm of governmental–religious hybridity. Advances in data collected regarding religion–state relations, and the accumulation of court decisions in the US bring to the fore a new norm of religious–governmental hybridity. Such hybrid institutions are typically functionally religious associations; however, their funding is sourced in the government to create ‘public private religious partnerships’. If such a re-classification is justified, then norms of public law should apply to such religious associations. This bears substantial implications vis-a-vis central concepts used in political and legal circles regarding religious freedom; furthermore, this reclassification also bears upon an ongoing intellectual debate between scholars such as Chiara Cordelli—advocating democratization of religion, and Michael W. McConnell who advocated an opposing view: a strong version of church autonomy. So, this reclassification bears important implications for both scholarly debates and political issues.
First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors
Authors: Piha-Paul Sarina A , Xu Binghe , Dumbrava Ecaterina E , Fu Siqing , Karp Daniel D , Meric-Bernstam Funda , Hong David S , Rodon Jordi A , Tsimberidou Apostolia M , Raghav Kanwal , Ajani Jaffer A , Conley Anthony P , Mott Frank , Fan Ying , Fan Jean , Peng Peng , Wang Hui , Ni Shumao , Sun Caixia , Qiang Xiaoyan , Levin Wendy J , Ngo Brenda , Ru Qinhua Cindy , Wu Frank , Javle Milind M
Published: February 2024

Purpose

This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors.

Patients and Methods

Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy.

Results

Forty-eight patients were enrolled (dose escalation, n = 40; dose expansion, n = 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, n = 1) and hypertension (15 mg, n = 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; n = 7) or stable disease (SD) ≥ 24 weeks (n = 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR n = 3; SD ≥ 24 weeks n = 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR n = 2; SD ≥ 24 weeks n = 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR n = 1; SD ≥ 24 weeks n = 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib’s half-life was 28-34 hours.

Conclusions

Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials.
Tissue-Matched IgH Gene Rearrangement of Circulating Tumor DNA Shows Significant Value in Predicting the Progression of Diffuse Large B Cell Lymphoma
Authors: Zhao Kewei , Zheng Xin , Liu Xinxiu , Liu Tao , Ke Zhonghe , Zhu Fang , Wen Qiuyue , Xin Beibei , Li Qiuhui , Zhang Liling
Published: February 2024

Background

Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression.

Methods

Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the “dominant circulating clonotype,” whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the “dominant tissue-matched clonotype.” The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of “dominant tissue-matched clonotype” proportion or “dominant circulating clonotype” proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and β2-microglobulin.

Results

A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of “dominant circulating clonotype” and “dominant tissue-matched clonotype” was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and “dominant circulating clonotype” proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the “dominant tissue-matched clonotype” and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64).

Conclusion

IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.