bluuebunny/crossref_metadata_2025 huggingface dataset:
Translating evidence: pain treatment in newborns, infants, and toddlers during needle-related procedures
Authors: Harrison Denise , Bueno Mariana
Published: February 2023

Introduction:

Treatment of pain in preterm, sick, and healthy newborns and infants and toddlers (up to 2 years of age) is consistently reported to be inadequate, and effective strategies are poorly implemented.

Objectives:

To present existing evidence of effective pain treatment strategies during needle-related procedures and to highlight initiatives focused on translating evidence into practice.

Methods:

This Clinical Update focuses on the 2022 International Association for the Study of Pain Global Year for Translating Pain Knowledge to Practice in the specific population of newborns, infants, and toddlers. Best evidence is reviewed, and existing knowledge translation strategies and programs available to implement evidence into practice are presented.

Results:

Effective strategies for newborn and young infants during frequently occurring needle procedures include small volumes of sweet solutions, breastfeeding, or skin-to-skin care when feasible and culturally acceptable. In addition, strategies such as nonnutritive sucking, positioning, swaddling, gentle touch, facilitated tucking, and secure holding can be used. For toddlers, the evidence is less robust, and discerning between pain and distress is challenging. However, strategies recommended for needle-related procedures include upright secure comfort holding by parents/caregivers, age-appropriate distraction, and topical anesthetics. Translation of effective pain management needs to involve the family, who need to be supported and empowered to comfort their child during painful procedures. Organizational, nationwide, and global initiatives aimed at improving implementation of effective pain treatments exist.

Conclusion:

There is evidence of effective pain management strategies for newborns, infants, and toddlers, and a great deal of effort is being made to translate knowledge into action.
Applicability of Artificial Societies to Evaluate Health Care Policies
Authors: Tolk Andreas , Rouse William B. , Pires Bianica S. , Cline Jon C. , Diallo Saikou Y. , Russell Sybil A.
Published: February 2023

Summary Statement

We propose the use of artificial societies to support health care policymakers in understanding and forecasting the impact and adverse effects of policies. Artificial societies extend the agent-based modeling paradigm using social science research to allow integrating the human component. We simulate individuals as socially capable software agents with their individual parameters in their situated environment including social networks. We describe the application of our method to better understand policy effects on the opioid crisis in Washington, DC, as an example. We document how to initialize the agent population with a mix of empiric and synthetic data, calibrate the model, and make forecasts of possible developments. The simulation forecasts a rise in opioid-related deaths as they were observed during the pandemic. This article demonstrates how to take human aspects into account when evaluating health care policies.
Risk Models for Developing Pancreatic Fistula After Pancreatoduodenectomy
Authors: Schouten Thijs J. , Henry Anne Claire , Smits Francina J. , Besselink Marc G. , Bonsing Bert A. , Bosscha Koop , Busch Olivier R. , van Dam Ronald M. , van Eijck Casper H. , Festen Sebastiaan , Groot Koerkamp Bas , van der Harst Erwin , de Hingh Ignace H.J.T. , Kazemier Geert , Liem Mike S.L. , de Meijer Vincent E. , Patijn Gijs A. , Roos Daphne , Schreinemakers Jennifer M.J. , Stommel Martijn W.J. , Wit Fennie , Daamen Lois A. , Molenaar Izaak Q. , van Santvoort Hjalmar C. ,   for the Dutch Pancreatic Cancer Group
Published: February 2023

Objective:

To evaluate the performance of published fistula risk models by external validation, and to identify independent risk factors for postoperative pancreatic fistula (POPF).

Background:

Multiple risk models have been developed to predict POPF after pancreatoduodenectomy. External validation in high-quality prospective cohorts is, however, lacking or only performed for individual models.

Methods:

A post hoc analysis of data from the stepped-wedge cluster cluster-randomized Care After Pancreatic Resection According to an Algorithm for Early Detection and Minimally Invasive Management of Pancreatic Fistula versus Current Practice (PORSCH) trial was performed. Included were all patients undergoing pancreatoduodenectomy in the Netherlands (January 2018–November 2019). Risk models on POPF were identified by a systematic literature search. Model performance was evaluated by calculating the area under the receiver operating curves (AUC) and calibration plots. Multivariable logistic regression was performed to identify independent risk factors associated with clinically relevant POPF.

Results:

Overall, 1358 patients undergoing pancreatoduodenectomy were included, of whom 341 patients (25%) developed clinically relevant POPF. Fourteen risk models for POPF were evaluated, with AUCs ranging from 0.62 to 0.70. The updated alternative fistula risk score had an AUC of 0.70 (95% confidence intervals [CI]: 0.69–0.72). The alternative fistula risk score demonstrated an AUC of 0.70 (95% CI: 0.689–0.71), whilst an AUC of 0.70 (95% CI: 0.699–0.71) was also found for the model by Petrova and colleagues. Soft pancreatic texture, pathology other than pancreatic ductal adenocarcinoma or chronic pancreatitis, small pancreatic duct diameter, higher body mass index, minimally invasive resection and male sex were identified as independent predictors of POPF.

Conclusion:

Published risk models predicting clinically relevant POPF after pancreatoduodenectomy have a moderate predictive accuracy. Their clinical applicability to identify high-risk patients and guide treatment strategies is therefore questionable.
The Influence of Patient Preference on Surgeons’ Treatment Recommendations in the Management of Intraductal Papillary Mucinous Neoplasms
Authors: Sacks Greg D. , Shin Paul , Braithwaite R. Scott , Soares Kevin C. , Kingham T. Peter , D’Angelica Michael I. , Drebin Jeffrey A. , Jarnagin William R. , Wei Alice C.
Published: February 2023

Objective:

We aimed to determine whether surgeon variation in management of intraductal papillary mucinous neoplasms (IPMN) is driven by differences in risk perception and quantify surgeons’ risk threshold for changing their recommendations.

Background:

Surgeons vary widely in management of IPMN.

Methods:

We conducted a survey of members of the Americas HepatoPancreatoBiliary Association, presented participants with 2 detailed clinical vignettes and asked them to choose between surgical resection and surveillance. We also asked them to judge the likelihood that the IPMN harbors cancer and that the patient would have a serious complication if surgery was performed. Finally, we asked surgeons to rate the level of cancer risk at which they would change their treatment recommendation. We examined the association between surgeons’ treatment recommendations and their risk perception and risk threshold.

Results:

One hundred and fifty surgeons participated in the study. Surgeons varied in their recommendations for surgery [19% for vignette 1 (V1) and 12% for V2] and in their perception of the cancer risk (interquartile range: 2%–10% for V1 and V2) and risk of surgical complications (V1 interquartile range: 10%–20%, V2 20%–30%). After adjusting for surgeon characteristics, surgeons who were above the median in cancer risk perception were 22 percentage points (27% vs. 5%) more likely to recommend resection than those who were below the median (95% CI: 11.34%; P<0.001). The median risk threshold at which surgeons would change their recommendation was 15% (V1 and V2). Surgeons who recommended surgery had a lower risk threshold for changing their recommendation than those who recommended surveillance (V1: 10.0 vs. 15.0, P=0.06; V2: 7.0 vs. 15.0, P=0.05).

Conclusions:

The treatment that patients receive for IPMNs depends greatly on how their surgeons perceive the risk of cancer in the lesion. Efforts to improve cancer risk prediction for IPMNs may lead to decreased variations in care.
Primary Graft Dysfunction Is Associated With Development of Early Cardiac Allograft Vasculopathy, but Not Other Immune-mediated Complications, After Heart Transplantation
Authors: Han Jiho , Moayedi Yasbanoo , Henricksen Erik J. , Waddell Kian , Valverde-Twiggs Julien , Kim Daniel , Luikart Helen , Zhang Bing M. , Teuteberg Jeffrey , Khush Kiran K.
Published: February 2023

Background.

We investigated associations between primary graft dysfunction (PGD) and development of acute cellular rejection (ACR), de novo donor-specific antibodies (DSAs), and cardiac allograft vasculopathy (CAV) after heart transplantation (HT).

Methods.

A total of 381 consecutive adult HT patients from January 2015 to July 2020 at a single center were retrospectively analyzed. The primary outcome was incidence of treated ACR (International Society for Heart and Lung Transplantation grade 2R or 3R) and de novo DSA (mean fluorescence intensity >500) within 1 y post-HT. Secondary outcomes included median gene expression profiling score and donor-derived cell-free DNA level within 1 y and incidence of cardiac allograft vasculopathy (CAV) within 3 y post-HT.

Results.

When adjusted for death as a competing risk, the estimated cumulative incidence of ACR (PGD 0.13 versus no PGD 0.21; P = 0.28), median gene expression profiling score (30 [interquartile range, 25–32] versus 30 [interquartile range, 25–33]; P = 0.34), and median donor-derived cell-free DNA levels was similar in patients with and without PGD. After adjusting for death as a competing risk, estimated cumulative incidence of de novo DSA within 1 y post-HT in patients with PGD was similar to those without PGD (0.29 versus 0.26; P = 0.10) with a similar DSA profile based on HLA loci. There was increased incidence of CAV in patients with PGD compared with patients without PGD (52.6% versus 24.8%; P = 0.01) within the first 3 y post-HT.

Conclusions.

During the first year after HT, patients with PGD had a similar incidence of ACR and development of de novo DSA, but a higher incidence of CAV when compared with patients without PGD.
Effectiveness of a Smart Urinary Continence Care Assessment System for Nursing Home Residents
Authors: Rajabali Saima N. , Hunter Kathleen F. , Asaana Prosper , McCreary Megan L. , Nazari Sahar , Wagg Adrian S.
Published: February 2023

PURPOSE:

The purpose of this study was to compare the effect of use of an electronic urinary continence assessment system versus usual care on construction of care plans, resource use, and continence care for nursing home (NH) residents.

DESIGN:

Convergent mixed-methods study comprising a prospective, parallel arm–controlled phase, and concurrent qualitative component.

SUBJECTS AND SETTING:

The study setting was Alberta, a province in Western Canada. Residents requiring a continence assessment or reassessment in an NH with 2 units assigned to intervention (I) and 2 units to usual care (UC). One hundred one residents (I: n = 49; UC: n = 52) participated; 89 (I: n = 43; UC: n = 46) completed the study. The mean age of the UC group was 88.5 (SD = 6.9) years, whereas the mean age of the intervention group was 85.6 (SD = 7.5) years.

METHODS:

Quantitative data on assessment, resource use, resident quality of life, and continence care outcomes were collected at weeks 0, 2, and 8; plan adherence was assessed at week 16. Qualitative data were collected via interviews.

RESULTS:

Analysis revealed a significant change in the proportion of residents achieving a reduction in 24-hour pad absorbency (50.6% vs 39.1%, P = .034) at week 8. There were significant differences in between-group changes (total absorbency of pads used in 24 hours and total cost of night pads used). Both groups reported improved health-related quality of life. Analysis of qualitative data revealed 3 themes: resource use; quality of continence care; and system utility and limitations.

CONCLUSIONS:

A technological solution offering a standardized system of continence assessment provided benefit in terms of quality of care for residents and use of continence containment products; utility was validated by staff.
Effectiveness of Single Chest Tube vs Double Chest Tube Application Post Decortication: Prospective Randomized Controlled Study
Authors: Hart Jonathan Minagogo , Mohammed Anwar Hussien , Tesfaye Samuel , Nadamo Siyasebew Mamo , Feyissa Mekonnen Senbu , Fekadu Desalegn Wadaja , Tadesse Isreal Bacha , Gebeyehu Hiwot Tebeje
Published: February 2023

Background:

Draining the chest cavity with two tubes is a common practice amongst thoracic surgeons. This research was conducted in Addis Ababa from March 2021 to May 2022. A total of 62 patients were included.

Study Design:

This study was conducted to investigate the superiority of either single tube or double tubes insertion following decortication. Patients were randomized in a ratio of 1:1. In Group A two tubes were inserted; in Group B, single tube 32F tubes was inserted. Statistical analyses were performed using SPSS V.27, student’s t-test and Pearson chi-square test.

Results:

The age range 18 to 70 years; the mean of 44 ± 14.4434; male to female ratio of 2.9:1. The dominant underlying pathologies were TB and trauma (45.2% vs 35.5%); right side was more involved (62.3%). Drain output was 1465ml ± 1887.9751 in Group A vs 1018ml ± 802.5662 in Group B (p-value .00001); the duration of drains was 7.5498 ± 11.3137 days in Group A versus 3.8730 ± 1.4142 days in Group B [p-value .000042]. The degree of pain was 2.6458 ± 4.2426 vs 2.000 ± 2.1213 in Group A and Group B respectively (p-value 0.326757); The length of hospital stay was 21.5818 ± 11.9791 days in Group A vs 13.6091 ± 6.2048 days in Group B (p-value .00001). Group A had air leak of 90.3% vs 74.2% in Group B; subcutaneous emphysema was 9.7% in Group A and 12.9% in Group B. No fluid recollection and no patients required reinsertion tube.

Conclusions:

The placement of single tube following decortication is effective in reducing drain output; shorter time of drain; shorter hospital stay. There was no association of pain. No effect on other endpoints.
A multi-scale review of the dynamics of collective behaviour: from rapid responses to ontogeny and evolution
Authors: Ioannou Christos C. , Laskowski Kate L.
Published: February 2023

Collective behaviours, such as flocking in birds or decision making by bee colonies, are some of the most intriguing behavioural phenomena in the animal kingdom. The study of collective behaviour focuses on the interactions between individuals within groups, which typically occur over close ranges and short timescales, and how these interactions drive larger scale properties such as group size, information transfer within groups and group-level decision making. To date, however, most studies have focused on snapshots, typically studying collective behaviour over short timescales up to minutes or hours. However, being a biological trait, much longer timescales are important in animal collective behaviour, particularly how individuals change over their lifetime (the domain of developmental biology) and how individuals change from one generation to the next (the domain of evolutionary biology). Here, we give an overview of collective behaviour across timescales from the short to the long, illustrating how a full understanding of this behaviour in animals requires much more research attention on its developmental and evolutionary biology. Our review forms the prologue of this special issue, which addresses and pushes forward understanding the development and evolution of collective behaviour, encouraging a new direction for collective behaviour research.

This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Lekking as collective behaviour
Authors: Rathore Akanksha , Isvaran Kavita , Guttal Vishwesha
Published: February 2023

Lekking is a spectacular mating system in which males maintain tightly organized clustering of territories during the mating season, and females visit these leks for mating. Various hypotheses—ranging from predation dilution to mate choice and mating benefit—offer potential explanations for the evolution of this peculiar mating system. However, many of these classic hypotheses rarely consider the spatial dynamics that produce and maintain the lek. In this article, we propose to view lekking through the perspective of collective behaviour, in which simple local interactions between organisms, as well as habitat, likely produce and maintain lekking. Further, we argue that interactions within the leks change over time, typically over a breeding season, to produce many broad-level as well as specific collective patterns. To test these ideas at both proximate and ultimate levels, we argue that the concepts and tools from the literature on collective animal behaviour, such as agent-based models and high-resolution video tracking that enables capturing fine-scale spatio-temporal interactions, could be useful. To demonstrate the promise of these ideas, we develop a spatially explicit agent-based model and show how simple rules such as spatial fidelity, local social interactions and repulsion among males can potentially explain the formation of lek and synchronous departures of males for foraging from the lek. On the empirical side, we discuss the promise of applying the collective behaviour approach to blackbuck (
Antilope cervicapra
) leks—using high-resolution recordings via a camera fitted to unmanned aerial vehicles and subsequent tracking of animal movements. Broadly, we suggest that a lens of collective behaviour may provide novel insights into understanding both the proximate and ultimate factors that shape leks.

This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Towards an integrative approach to understanding collective behaviour in caterpillars
Authors: McLellan Callum F. , Montgomery Stephen H.
Published: February 2023

To evolve, and remain adaptive, collective behaviours must have a positive impact on overall individual fitness. However, these adaptive benefits may not be immediately apparent owing to an array of interactions with other ecological traits, which can depend on a lineage's evolutionary past and the mechanisms controlling group behaviour. A coherent understanding of how these behaviours evolve, are exhibited, and are coordinated across individuals, therefore requires an integrative approach spanning traditional disciplines in behavioural biology. Here, we argue that lepidopteran larvae are well placed to serve as study systems for investigating the integrative biology of collective behaviour. Lepidopteran larvae display a striking diversity in social behaviour, which illustrates critical interactions between ecological, morphological and behavioural traits. While previous, often classic, work has provided an understanding of how and why collective behaviours evolve in Lepidoptera, much less is known about the developmental and mechanistic basis of these traits. Recent advances in the quantification of behaviour, and the availability of genomic resources and manipulative tools, allied with the exploitation of the behavioural diversity of tractable lepidopteran clades, will change this. In doing so, we will be able to address previously intractable questions that can reveal the interplay between levels of biological variation.

This article is part of a discussion meeting issue ‘Collective behaviour through time’.
A study of transfer of information in animal collectives using deep learning tools
Authors: Romero-Ferrero Francisco , Heras Francisco J. H. , Rance Dean , de Polavieja Gonzalo G.
Published: February 2023

We studied how the interactions among animals in a collective allow for the transfer of information. We performed laboratory experiments to study how zebrafish in a collective follow a subset of trained animals that move towards a light when it turns on because they expect food at that location. We built some deep learning tools to distinguish from video which are the trained and the naïve animals and to detect when each animal reacts to the light turning on. These tools gave us the data to build a model of interactions that we designed to have a balance between transparency and accuracy. The model finds a low-dimensional function that describes how a naïve animal weights neighbours depending on focal and neighbour variables. According to this low-dimensional function, neighbour speed plays an important role in the interactions. Specifically, a naïve animal weights more a neighbour in front than to the sides or behind, and more so the faster the neighbour is moving; and if the neighbour moves fast enough, the differences coming from the neighbour’s relative position largely disappear. From the lens of decision-making, neighbour speed acts as confidence measure about where to go.

This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Lower risks of sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors for new-onset hip fracture risks in patients with type-2 diabetes: A propensity score-matched study with competing risk analysis
Authors: In Chou Oscar Hou , Zhou Jiandong , Satti Danish Iltaf , Mui Jonathan V , Lin Karen , Lee Sharen , Wong Wing Tak , Chung Wai Abraham Ka , Liu Tong , Yung Cheung Bernard Man , Jing Fengshi , Tse Gary
Published: February 2023

Purpose

This study aimed to compare the effects of sodium glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset hip fractures.

Methods

This was a retrospective population-based cohort study including type-2 diabetes mellitus patients treated with either SGLT2I or DPP4I between January 1st2015 and December 31st2020 in Hong Kong. The primary outcome was new-onset hip fracture and the secondary outcome was all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regression were applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed.

Results

This cohort included 56393 patients with type-2 diabetes mellitus (median age: 62.1 years old [interquantile range, IQR]: 54.2-71.1; 57.45% males), of which 20432 patients ([incidence rate, IR]: 36.23%) used SGLT2I and 35961 patients (IR: 63.77%) used DPP4I. After the 1:1 propensity score matching, 449 (IR: 1.09%) patients had hip fractures, and 2012 patients (IR: 4.92%) died. SGLT2I was associated with significantly lower risks of hip fractures after adjusting for the demographics, past comorbidities, non-SGLT2I/DPP4I medications and laboratory results (hazard ratio: 0.55; 95% confidence interval: 0.42-0.89; P=0.0036). The results were consistent in the competing risk models and the different propensity matching approaches.

Conclusions

SGLT2I was associated with lower risks of new-onset hip fractures after propensity score matching and adjustments.

This study compared the risks of hip fractures in between users of sodium glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors in type-2 diabetes mellitus. After propensity score matching, SGLT2I was associated with lower risks of hip fractures adjusting for confounders (hazard ratio: 0.55; 95% confidence interval: 0.42-0.89; P=0.0036).
Transcriptomic analysis of diverse organisms reveals the rareness of genetic assimilation in environmental adaptations
Authors: Chen Piaopiao , Zhang Jianzhi
Published: February 2023

Genetic assimilation is the evolutionary process by which an environmentally induced phenotype becomes genetically encoded and constitutive. Genetic assimilation has been proposed as the concluding step in the plasticity-first model of environmental adaptation and has been observed in multiple species, but its prevalence has not been systematically investigated. By analyzing transcriptomic data collected upon reciprocal transplant, we address this question in the experimental evolution, domestication, or natural evolution of a bacterial, a fungal, a plant, and four animal species. We find that genetic assimilation of environment-induced gene expression is the exception rather than the rule and that substantially more genes retain than lose their expression plasticity upon organismal adaptations to new environments. The probability of genetic assimilation varies among genes and decreases with the number of transcription factors controlling the gene and the expression level of the gene, supporting the hypothesis that genetic assimilation results primarily from passive losses of gene regulations that are not mutationally robust. Therefore, at the level of gene expression, our findings argue against the purported importance of genetic assimilation to environmental adaptation.
Acetylation-dependent coupling between G6PD activity and apoptotic signaling
Authors: Wu Fang , Muskat Natali H. , Dvilansky Inbar , Koren Omri , Shahar Anat , Gazit Roi , Elia Natalie , Arbely Eyal
Published: February 2023

Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling
Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma
Authors: Machour Feras E. , Abu-Zhayia Enas , Kamar Joyce , Barisaac Alma Sophia , Simon Itamar , Ayoub Nabieh
Published: February 2023

The splicing factor RBM10 is frequently mutated in lung adenocarcinoma (LUAD) (9-25%). Most RBM10 cancer mutations are loss-of-function, correlating with increased tumorigenesis and limiting targeted therapy efficacy in EGFR-mutated lung cancer. Notably, therapeutic strategies leveraging RBM10 deficiency remain unexplored. Hence, we conducted RBM10 CRISPR-Cas9 synthetic lethality (SL) screen and identified ∼250 RBM10 SL genes, including WEE1 kinase. WEE1 inhibition sensitized RBM10-deficient LUAD cellsin-vitroandin-vivo. Mechanistically, we identified a splicing-independent role of RBM10 in promoting replication fork progression that underpins RBM10-WEE1 SL. Also, we revealed that RBM10 is associated with active replication forks, which is reliant on PRIM1, an enzyme synthesizing RNA primers for Okazaki fragments. Functionally, we demonstrated that RBM10 serves as an anchor for recruiting HDAC1 and facilitates H4K16 deacetylation to maintain replication fork stability. Collectively, our data revealed a hitherto unrecognized function of RBM10 in fine-tuning DNA replication, and provide therapeutic arsenal for targeting RBM10-deficient tumors.
The role of the topical nasal decongestant oxymetazoline as a novel therapeutic option for post‐acne erythema: A split‐face, double‐blind, randomized, placebo‐controlled trial
Authors: Washrawirul Chanudda , Puaratana‐arunkon Thanaporn , Chongpison Yuda , Noppakun Nopadon , Asawanonda Pravit , Kumtornrut Chanat
Published: February 2023

Post‐acne erythema (PAE) is one of the most common sequelae of acne inflammation. Unfortunately, the treatment of PAE remains challenging due to limited effective topical treatments. The objectives of this study were to evaluate the efficacy and safety of topical oxymetazoline hydrochloride (OxH) 0.05% solution for PAE. This study was a split‐face, participants‐and investigators‐blinded, randomized, placebo‐controlled trial conducted between December 2021 and March 2022 in Bangkok, Thailand. Healthy adults aged from 18 to 45 years with mild to severe PAE, according to the Clinician's Erythema Assessment (CEA), on both sides of the face were eligible. After randomization, each participant applied the OxH to one side of their face and a placebo to the contralateral face twice daily for 12 weeks. The primary outcome was PAE lesion counts. The secondary outcomes were erythema index, clinical response rate at week 12 (“clear,” “almost clear,” or “at least two‐grade improvement” by CEA), and patient satisfaction scores. A total of 30 participants were enrolled. The OxH‐treated skin showed a significantly greater mean difference (MD) reduction in PAE lesion counts than the placebo after 8 weeks of treatment (4.30, 95% confidence interval [CI] 1.42–7.18). Similarly, the MD reduction of the erythema index was higher in the OxH‐treated skin from the second week (11.82, 95% CI 8.48–15.15). Additionally, the OxH‐treated side also achieved a higher clinical response rate after 8 weeks of treatment (40.00% vs. 6.67%; p = 0.002) and rated higher satisfaction than those using the placebo at the end of the study (mean [standard deviation] satisfaction score 8.30 [0.18] vs 7.40 [0.18], P < 0.001). There were no serious adverse events or flares of erythema during the study. In conclusion, our study demonstrated that the topical OxH 0.05% solution was effective, well‐tolerated, and safe for reducing PAE without a rebound effect. It could be a choice of PAE management. Trial Registration: Thai Clinical Trials Registry No. TCTR20211207004.
Boundedly Rational Decisions on Exploration Versus Exploitation in Alliance Portfolios: Problemistic and Slack Searches Under CEO Overconfidence
Authors: Zhang Fen , Yang Xiaotian , Yuan Changhong , Fan Weiguo
Published: February 2023

How do firms configure exploration versus exploitation in alliance portfolios under the premise of bounded rationality? From the behavioural perspective, problemistic and slack searches can be used as behavioural explanations for their configurations. Furthermore, the boundedly rational decision‐maker's limited cognitive capability in the form of CEO overconfidence also causes the subjective interpretation of information. This study investigates the links between below‐aspiration performance, slack, and firms’ boundedly rational decisions under the influence of CEO overconfidence in alliance portfolio configurations. A feasible generalized least‐squares regression is performed to test the model empirically using data from 224 publicly traded high‐tech firms in the United States. We find that below‐aspiration performance and slack both play roles in emphasizing exploration relative to exploitation in alliance portfolios. Further, CEO overconfidence intensifies the positive roles of below‐aspiration levels and slack in preference for exploration alliances. This study contributes to the bounded rationality literature by extending the implications of the behavioural theory of the firm to firms’ preference in alliance portfolio configurations in terms of the exploration‐to‐exploitation ratio. Furthermore, our findings deepen the understanding of the role of overconfidence in CEOs’ subjective interpretations, thus filling a critical research gap in extant behavioural research.
Presumptions of Legislative Intent in R (Coughlan) v Minister for the Cabinet Office
Authors: Morón Luciana
Published: February 2023

In R (Coughlan) v Minister for the Cabinet Office, the UK Supreme Court held that the Minister for the Cabinet Office acted lawfully when making orders which introduced, as a pilot scheme, a requirement for voter identification in local government elections in certain local authority areas. The case turned on the interpretation of section 10 of the Representation of the People Act 2000, pursuant to which the orders were made. This note argues that the Court erred when it concluded that the intended scope of the power created by section 10 was clear without first analysing the prior question of whether that power had to be interpreted restrictively. The Court's reasoning appears to misunderstand the operation of the presumptions in favour of a restrictive interpretation of interferences with fundamental rights and of ‘Henry VIII powers’. This note submits that, ultimately, the Court's approach threatens to erode the principle of legality.
Instream sensor results suggest soil–plant processes produce three distinct seasonal patterns of nitrate concentrations in the Ohio River Basin
Authors: Gerlitz Morgan , Fox Jimmy , Ford William , Husic Admin , Mahoney Tyler , Armstead Mindy , Hendricks Susan , Crain Angela , Backus Jason , Pollock Erik , Ren Wei , Tao Bo , Riddle Brenden , White David
Published: February 2023

The Ohio River Basin (ORB) is responsible for 35% of total nitrate loading to the Gulf of Mexico yet controls on nitrate timing require investigation. We used a set of submersible ultraviolet nitrate analyzers located at 13 stations across the ORB to examine nitrate loading and seasonality. Observed nitrate concentrations ranged from 0.3 to 2.8 mg L−1 N in the Ohio River's mainstem. The Ohio River experiences a greater than fivefold increase in annual nitrate load from the upper basin to the river's junction with the Mississippi River (74–415 Gg year−1). The nitrate load increase corresponds with the greater drainage area, a 50% increase in average annual nitrate concentration, and a shift in land cover across the drainage area from 5% cropland in the upper basin to 19% cropland at the Ohio River's junction with the Mississippi River. Time‐series decomposition of nitrate concentration and nitrate load showed peaks centered in January and June for 85% of subbasin‐year combinations and nitrate lows in summer and fall. Seasonal patterns of the terrestrial system, including winter dormancy, spring planting, and summer and fall growing‐harvest seasons, are suggested to control nitrate timing in the Ohio River as opposed to controls by river discharge and internal cycling. The dormant season from December to March carries 51% of the ORB's nitrate load, and nitrate delivery is high across all subbasins analyzed, regardless of land cover. This season is characterized by soil nitrate leaching likely from mineralization of soil organic matter and release of legacy nitrogen. Nitrate experiences fast transit to the river owing to the ORB's mature karst geology in the south and tile drainage in the northwest. The planting season from April to June carries 26% of the ORB's nitrate and is a period of fertilizer delivery from upland corn and soybean agriculture to streams. The harvest season from July to November carries 22% of the ORB's nitrate and is a time of nitrate retention on the landscape. We discuss nutrient management in the ORB including fertilizer efficiency, cover crops, and nitrate retention using constructed measures.
Higher Education in the United States:Laissez‐Faire, Differentiation, and Research
Authors: Urquiola Miguel
Published: February 2023

The U.S. higher education system stands out in three dimensions. First, it has the highest number of leadingresearchuniversities. Second, it displays significantdifferentiation: multiple types of institutions offer services that differ in cost, prestige, etc. Third, it has alaissez‐faire/free‐market orientation: private and public entities are free to open schools and compete; essentially all schools enjoy substantial autonomy. This paper makes the case that these features are systematically related. The development of the American higher education market—which allowed market forces to operate and lacked centralized planning—contributed to the emergence of differentiation and a set of leading research universities.
Japan's Higher Education Policies under Global Challenges
Authors: Yonezawa Akiyoshi
Published: February 2023

Over the past 20 years, Japan's higher education policy has been strongly influenced by national policies for achieving world‐class excellence as a tool for economic and social development. However, Japan's universities, especially the top universities, have faced difficulties in maintaining an international presence, both in terms of academic excellence and the development of globally competitive human resources. This paper reflects on how national policies, especially economic and fiscal policies, have intervened in higher education since the beginning of the 21st century, and then investigates the impact of these policies and discusses the future perspective on Japan's higher education given the current global challenges.
The Evolution of University–Industry Linkages in Thailand
Authors: Intarakumnerd Patarapong , Jutarosaga Anittha
Published: February 2023

This paper aims to examine the evolution and major transition of Thailand's higher education system and its contribution to deepening and broadening local university‐industry linkages (UILs), especially in Thailand's high‐tech, mid‐tech, and science‐based industries. The ties with universities were deployed differently across sectors. Key driving factors are individual firms' strategies and efforts to upgrade their production bases in Thailand and sector‐specific government initiatives to facilitate university‐industry collaboration. While the UILs in the automotive sector are limited, the pharmaceuticals and electronics have shown collective effort in establishing sector‐wide UILs.
Does private sector involvement improve the distribution efficiency of subsidized fertilizer? A natural experiment from Nepal
Authors: Thapa Ganesh , Gaihre Yam Kanta , Choudhary Dyutiman , Gautam Shriniwas
Published: February 2023

Despite the government spending significant amounts on fertilizer subsidies, Nepal's average fertilizer application rate is lower than in other South Asian countries. The low application is attributed to poor access to fertilizer and an inefficient distribution system. The government of Nepal issued a “Fertilizer Distribution Directive (FDD) 2020” to improve the distribution system. We assessed the impacts of involving the private sector in selling fertilizer to farmers. We examined whether the market transaction cost proxied by farmers’ search cost (communication and travel cost), travel time to visit the stores, and the opportunity cost of time spent in purchasing fertilizer have been reduced by FDD 2020. A difference‐in‐difference approach refined with propensity score matching was used to estimate the fertilizer distribution efficiency using survey data from 619 households across six districts. Private sector involvement was found to reduce travel time to fertilizer retailers by about 10 min and transaction costs to purchase subsidized fertilizer by about 20 Nepalese Rupees (NPR) per season, compared to the conventional approach of sale by farmer cooperatives. Implementation of the directive has removed the bias of cooperatives selling fertilizer only to members, especially medium and large‐scale farmers. The directive and private sector involvement have led to a more equitable and efficient distribution of subsidized fertilizer. However, the government should routinely monitor and regulate the fertilizer mainly targeted to the private fertilizer retailers.
Derivation and validation of a risk prediction score for nonsteroidal anti‐inflammatory drug‐related serious gastrointestinal complications in the elderly
Authors: Lee Suhyun , Heo Kyu‐Nam , Lee Mee Yeon , Ah Young‐Mi , Shin Jaekyu , Lee Ju‐Yeun
Published: February 2023

Aims

Few studies have quantified the impact of risk factors on GI complications in elderly nonsteroidal anti‐inflammatory drug (NSAID) users. This study aimed to develop and validate a risk prediction score for severe GI complications to identify high‐risk elderly patients using NSAID.

Methods

We used the following two Korean claims datasets: customized data with an enrolment period 2016–2017 for model development, and the sample data in 2019 for external validation. We conducted a nested case–control study for model development and validation. NSAID users were identified as the elderly (≥65 years) who received NSAIDs for more than 30 days. Serious GI complications were defined as hospitalizations or emergency department visits, with a main diagnosis of GI bleeding or perforation. We applied the logistic least absolute shrinkage and selection operator (LASSO) regression model for variable selection and model fitting.

Results

We identified 8176 cases and 81 760 controls with a 1:10 matched follow‐up period in the derivation cohort. In the external validation cohort, we identified 372 cases from 254 551 patients. The risk predictors were high‐dose NSAIDs, nonselective NSAID, complicated GI ulcer history, male sex, concomitant gastroprotective agents, relevant co‐medications, severe renal disease and cirrhosis. Area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.77–0.81) in the external validation dataset.

Conclusions

The prediction model may be a useful tool for reducing the risk of serious GI complications by identifying high‐risk elderly patients.
DROID: Dose-Ranging Approach to Optimizing Dose in Oncology Drug Development
Authors: Guo Beibei , Yuan Ying
Published: February 2023

In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the “more is better” paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose-ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well-established dose-ranging study framework, which has been routinely used to develop non-oncology drugs for decades, and bridges it with established oncology dose-finding designs to optimize the dose of oncology drugs. DROID consists of two seamlessly connected stages. In the first stage, patients are sequentially enrolled and adaptively assigned to investigational doses to establish the therapeutic dose range (TDR), defined as the range of doses with acceptable toxicity and efficacy profiles, and the recommended phase 2 dose set (RP2S). In the second stage, patients are randomized to the doses in RP2S to assess the dose–response relationship and identify the optimal dose. The simulation study shows that DROID substantially outperforms the conventional approach, providing a new paradigm to efficiently optimize the dose of targeted oncology drugs. DROID aligns with the approach of a randomized, parallel dose-response trial design recommended by the FDA in the Guidance on Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.
Homogeneity Tests of Covariance for High-Dimensional Functional Data with Applications to Event Segmentation
Authors: Zhong Ping-Shou
Published: February 2023

We consider inference problems for high-dimensional (HD) functional data with a dense number of T repeated measurements taken for a large number of p variables from a small number of n experimental units. The spatial and temporal dependence, high dimensionality, and dense number of repeated measurements pose theoretical and computational challenges. This paper has two aims; our first aim is to solve the theoretical and computational challenges in testing equivalence among covariance matrices from HD functional data. The second aim is to provide computationally efficient and tuning-free tools with guaranteed stochastic error control. The weak convergence of the stochastic process formed by the test statistics is established under the “large p, large T, and small n” setting. If the null is rejected, we further show that the locations of the change points can be estimated consistently. The estimator's rate of convergence is shown to depend on the data dimension, sample size, number of repeated measurements, and signal-to-noise ratio. We also show that our proposed computation algorithms can significantly reduce the computation time and are applicable to real-world data with a large number of HD-repeated measurements (e.g., functional magnetic resonance imaging (fMRI) data). Simulation results demonstrate both the finite sample performance and computational effectiveness of our proposed procedures. We observe that the empirical size of the test is well controlled at the nominal level, and the locations of multiple change points can be accurately identified. An application to fMRI data demonstrates that our proposed methods can identify event boundaries in the preface of the television series Sherlock. Code to implement the procedures is available in an R package named TechPhD.
Practitioners' perspectives on spatial reasoning in educational practice from birth to 7 years
Authors: Bates Kathryn E. , Williams Ashley Y. , Gilligan‐Lee Katie A. , Gripton Catherine , Lancaster Andrea , Williams Helen , Borthwick Alison , Gifford Sue , Farran Emily K.
Published: February 2023

Background

There is a growing evidence base for the importance of spatial reasoning for the development of mathematics. However, the extent to which this translates into practice is unknown.

Aims

We aimed to understand practitioners' perspectives on their understanding of spatial reasoning, the extent to which they recognize and implement spatial activities in their practice, and the barriers and opportunities to support spatial reasoning in the practice setting.

Sample

Study 1 (questionnaire) included 94 participants and Study 2 (focus groups) consisted of nine participants. Participants were educational practitioners working with children from birth to 7 years.

Methods

The study was mixed methods and included a questionnaire (Study 1) and a series of focus groups (Study 2).

Results

We found that whilst practitioners engage in a variety of activities that support spatial reasoning, most practitioners reported little confidence in their understanding of what spatial reasoning is.

Conclusion

Informative and accessible resources are needed to broaden understanding of the definition of spatial reasoning and to outline opportunities to support spatial reasoning.