bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Biologics and Janus Kinase Inhibitors With Inflammatory Bowel Disease as Paradoxical Reactions: A Real‐World Assessment
Authors: Zhan Zhi‐Qing , Li Jia‐Xin , Chen Ying‐Xuan , Fang Jing‐Yuan
Published: December 2024

Background and Objective

With limited evidence connecting paradoxical inflammatory bowel disease (paradoxical IBD) to the newest biologics and Janus kinase inhibitors, our study aims to investigate the occurrence of paradoxical IBD induced by these agents in treating other immune‐mediated inflammatory diseases (IMIDs). We aim to identify associated risk signals, the primary affected population, and the risk profile changes over time.

Methods

We performed disproportionality analysis to evaluate paradoxical IBD risk signals using data from the FDA Adverse Event Reporting System. Stratification analyses according to IBD subtype, age, gender, and agents' indications were performed. Weibull shape parameter (WSP) test was conducted to assess paradoxical IBD risk changes over time. Linkage disequilibrium score regression and Mendelian Randomization were employed to evaluate genetic correlations and causality between these agents' indications (i.e., non‐IBD IMIDs) and IBD.

Results

This study included 3296 patients reporting 3407 occurrences of paradoxical IBD following using these agents as primary suspects. Among TNF blockers, consistent positive signals for paradoxical IBD were noted: Adalimumab (n = 1983, ROR [95%CI] = 1.55 [1.47–1.63]), Infliximab (n = 545, ROR [95%CI] = 2.12 [1.95–2.32]), Certolizumab Pegol (n = 342, ROR [95%CI] = 1.9 [1.71–2.12]), and Golimumab (n = 154, ROR [95%CI] = 1.64 [1.4–1.93]). Ustekinumab, an IL‐12 and IL‐23 antagonist, also showed a strong positive signal (n = 155, ROR [95%CI] = 2.03 [1.73–2.39]). Conversely, Upadacitinib, Tofacitinib (Janus kinase inhibitors), and Risankizumab (IL‐23 antagonist) exhibited insignificant associations with paradoxical IBD. Crohn's disease (CD) is the mainly developing form. WSP analysis identified two temporal patterns of paradoxical IBD: early failure and random failure types. Significant genetic correlations between three IMIDs and IBD were uncovered, with psoriasis specifically found to causally elevate CD risk.

Conclusions

This study identifies paradoxical IBD as a consistent positive signal across multiple IMID agents, predominantly manifesting as CD, potentially aiding in timely detection and therapeutic decision‐making.
Primary soft palate canine transmissible venereal tumour in a neutered Siberian husky dog (Canis lupus familiaris)
Authors: Hafezi Bahareh , Kazemi Mehrjerdi Hossein , Salari Sedigh Hamideh , Rajabioun Masoud , Mohri Mehrdad
Published: December 2024

Canine transmissible venereal tumour is a type of neoplasm that can be transmitted through sexual contact in dogs. The occurrence of secondary oral canine transmissible venereal tumour is well documented in dogs; however, primary oral canine transmissible venereal tumour is uncommon. This report presents a rare case of a 2.5‐year‐old, neutered, male Siberian husky dog with an ulcerated mass on the soft palate that was undetected by clinical and radiological examinations, which was later diagnosed as a canine transmissible venereal tumour based on cytology without any genital manifestations. Chemotherapy with vincristine sulfate (5 weeks) resulted in complete recovery of the tumour without recurrence after 6 months. Based on our findings, we emphasise the importance of considering canine transmissible venereal tumour as a possible cause of extragenital masses even in neutered dogs.
Myxoedema coma in a dog with a cervical abscess
Authors: Geijo Kaila Dolores Tavío , L'Eplattenier Henry , del Solar Bravo Raquel , Isaya Rosaria , Díaz Aldara Eiras
Published: December 2024

A 7‐year‐old, female, neutered Staffordshire bull terrier was referred with a 2‐month history of a ventral cervical mass, a recent development of generalised skin swelling and a history of sad facial expression for the last 4 years. Clinical examination revealed generalised non‐pitting oedema and depressed mentation. A tentative diagnosis of myxoedema coma was made based on clinical findings and laboratory results. Treatment with oral levothyroxine was administered, and a marked reduction of the non‐pitting oedema was observed after 48 hours. Total T4 (<6 nmol/L; reference interval: 10–45) and thyroid‐stimulating hormone (0.79 ng/mL; reference interval: 0.00–0.60) levels confirmed hypothyroidism. A migrating foreign body causing a cervical abscess was detected and removed by exploratory surgery. At 2‐month follow‐up, the clinical signs had resolved and total T4 levels were at the ideal level. This case emphasises the importance of early recognition and treatment of myxoedema in dogs presenting with non‐pitting oedema.
On the Correlation Between Large-Scale Structures in the Vicinity of Turbulent/Non-turbulent Interface and Wall Pressure Within the Turbulent Boundary Layer
Authors: Chen Langsheng , Ye Qingqing
Published: December 2024

The present work investigates the relation between large-scale coherent structures in the vicinity of turbulent/non-turbulent interface and corresponding pressure fluctuations within the turbulent boundary layer (TBL) close to the trailing edge of the NACA0012 airfoil. The planar particle image velocimetry (PIV) measurements were conducted to capture the instantaneous velocity fields, with simultaneous wall-pressure fluctuation measurement obtained by miniature transducers. Based on the identifications of high amplitude pressure peaks (HAPPs) in the pressure signal, the corresponding simultaneous measured velocity fields are conditionally averaged, revealing the dominance of high-speed large-scale motions (LSMs). The simultaneously measured pressure fluctuations are conditionally extracted based on the occurrence of low- and high-speed LSMs. Results show that high-speed LSMs induce high-energy positive pressure fluctuations, especially when located upstream of the reference wall pressure transducer. The correlation analysis between various scale velocities acquired by empirical modal decomposition (EMD) and the reference pressure signal is conducted. It is demonstrated that upstream high-speed motions with sweeps accompanied by downstream low-speed motions with ejections are responsible for the positive pressure fluctuations, while the negative pressure fluctuations are attributed to the adverse arrangement. It is also observed that the sourced coherent structures of pressure fluctuations can expand outside the TBL, with significant momentum exchange across the turbulent/non-turbulent interface (TNTI).
Conditional Mean Velocity and Vorticity Fields in the Vicinity of the Turbulent/Turbulent Interface of a Planar Wake
Authors: Chen Jiangang , R. H. Buxton Oliver
Published: December 2024

This work reports an experimental investigation of the spatial evolution of the conditionally-averaged velocity and vorticity fields in the vicinity of the turbulent/turbulent interface (TTI) in the planar wake of a circular cylinder. The wake was exposed to various turbulent backgrounds featuring different turbulence intensities and integral length scales. Combined simultaneous particle image velocimetry (PIV) and planar laser induced fluorescence (PLIF) measurements were conducted at an inlet Reynolds number of 3800 to capture the velocity and vorticity fields close to the interface. The result implies that TTIs can establish two layers when the background turbulence is sufficiently intense, which distinguishes TTIs from the turbulent/non-turbulent interface (TNTI). The two layers in TTIs have equal thickness of about 13 local Kolmogorov length scales, which is approximately equal to the thickness of the turbulent sublayer in a TNTI at sufficiently high Reynolds number and suggests that there is no viscous superlayer in TTIs.
Experimentally Detecting the Turbulent/ Non-turbulent Interface in Wall-Bounded Flows
Authors: Parikh Agastya , Kähler Christian J.
Published: December 2024

In experimental studies of the turbulent/ non-turbulent interface (TNTI) of wall-bounded flows, a significant challenge is accurate detection of the interface in 2D and 3D. Detection criteria based on turbulent kinetic energy (TKE) and homogeneity of the flowfield have been applied to PIV measurements of TBLs [2, 15]. The use of local seeding (LS) as a passive tracer was also investigated to decouple TNTI detection from the reduced spatial resolution associated with velocimetric methods. This yielded the simple and robust particle image density detection method, which has good spatial resolution but lacks access to velocimetry in the potential flow [15]. With recent development of fluorescent DEHS and its application to tag the TBL, it is possible to obtain the entire flowfield in addition to segregating the flow into its turbulent and non-turbulent parts in air flows [8–10]. Finally, 3D reconstruction of the TNTI with imaging of the TBL at an oblique angle opens the door to more complex investigation and new insights of the interface [14].
Local Properties of the Turbulent/Non-turbulent Interface
Authors: Er Sarp , Laval Jean-Philippe , Vassilicos Christos
Published: December 2024

The effect of spatial resolution on local propagation velocity of the Turbulent/Non-Turbulent Interface (TNTI) is documented. A TNTI-local coordinate system and a Reynolds decomposition based on a TNTI-conditional averaging operation are introduced and used to assess the local velocity field and the mass and momentum balances at the TNTI layer. A clear jump of the TNTI-averaged Reynolds shear stress exists through the TNTI layer and the TNTI-averaged fluid velocity normal to the TNTI is determined by the correlation between the TNTI normal vector and the fluid velocity fluctuations around the TNTI-average fluid velocity. The TNTI-local fluid velocity field is compressive normal to the TNTI and stretching in the direction tangent to the TNTI, a structure that has important consequences.
Entrainment Mechanism Analysis of Oblique Shock-Wave/Boundary-Layer Interactions
Authors: Meng Fanzhao , Han Wang , Yang Lijun
Published: December 2024

The interaction between shock waves and boundary layers impacts hypersonic vehicles’ aerodynamic structure, internal turbulent mixing, and combustion processes. Direct numerical simulations (DNSs) of the hypersonic boundary layer have been performed to study the turbulent/non-turbulent interface (TNTI) entrainment mechanism and the impact of shock waves. Two cases are analyzed with and without the shock-wave and boundary layer interaction. A novel approach is proposed to identify TNTI by integrating the vorticity threshold and fuzzy clustering method. To account for the influence of increasing Reynolds number in the flow direction on the vorticity threshold analysis, vorticity is normalized using the local boundary layer thickness and friction velocity. Two entrainment mechanisms are quantitatively described and compared using TNTI local entrainment velocity and the mass conservation equation. The results demonstrate that the entrainment process within the hypersonic boundary layer TNTI is predominantly governed by large-scale engulfment, and under the influence of shock waves, the dominance of large-scale ingestion is notably enhanced.
Effect of restrictive versus liberal fluid therapy for laparoscopic gastric surgery on postoperative complications: a randomized controlled trial
Authors: Kusaka Yusuke , Ueno Takeshi , Minami Toshiaki
Published: December 2024

Purpose

Currently, laparoscopic surgery is a standard technique in the field of abdominal surgery. However, the most adequate fluid regimen during laparoscopic surgery remains unclear. The aim of this trial is to compare a restricted fluid therapy with a liberal fluid therapy for laparoscopic abdominal surgery. Our hypothesis was that restrictive fluid therapy would reduce postoperative complications better than liberal fluid therapy.

Method

In this randomized controlled trial, patients scheduled for laparoscopic gastric surgery were randomized to either the liberal group (receiving 7–10 ml/kg/h of crystalloid) or the restrictive group (receiving 1–2 ml/kg/h of crystalloid) for each stratum of surgical procedure from April 2017 to March 2019. For both groups, blood loss was replaced by an equal volume of hydroxyethyl starch. The primary endpoint was postoperative complications up to 30 days after surgery, according to the Clavien–Dindo classification.

Results

We enrolled 148 patients, and 140 of these were randomized to either the liberal or the restrictive group after exclusion. As a result, 69 cases were included in the liberal group for analysis, and 67 patients composed the restrictive group. Median fluid administration for the liberal and restrictive groups was 2950 ml and 800 ml, respectively. As well, overall complications in the liberal and restrictive groups were 27.5% and 19.4%, respectively (risk ratio 0.71, 95% confidence interval 0.38–1.31, p value = 0.264).

Conclusion

Restricted fluid therapy and liberal fluid therapy did not show any statistical differences in postoperative complications after laparoscopic gastric surgery.
How do gender and age similarities with a potential social engineer influence one’s trust and willingness to take security risks?
Authors: Abuelezz Israa , Barhamgi Mahmoud , Alshakhsi Sameha , Yankouskaya Ala , Nhlabatsi Armstrong , Khan Khaled M. , Ali Raian
Published: December 2024

This study investigates how age and gender similarity between individuals and potential social engineers affect the individuals’ trust and risk-taking behaviors. We crafted and face validated 16 personas, varying in demographics and visual cues, and inquired whether participants would agree to use each persona’s offer to connect to the internet via their personal mobile hotspot, as well as the degree of trust they placed in the persona’s intentions. Individuals were informed about the potential risks associated with using another person’s mobile hotspot and that the person offering can be, but not necessarily, malicious. Data from 635 participants (322 Arabs and 313 British) were collected through an online survey. Participants were categorized by gender into male and female groups, and by age into two groups: early adulthood (18–35 years) and middle adulthood (36–59 years). Our results showed a correlation between trust and offer acceptance across all participant groups except for British females in middle adulthood. Additionally, participants, regardless of their gender and age groups, exhibited greater trust and acceptance towards personas who were female or older. Arab sample did not indicate a significant gender preference in aged personas; however, the British early adulthood group displayed a significant inclination towards accepting the offer from aged female personas over aged male personas. While demographic similarity between the potential manipulator personas and participants did not significantly impact the participants trust and risk-taking, our study uncovered differences in trust and offer acceptance when both age and gender demographics were considered together, suggesting nuanced effects of demographic matching and mismatching on taking security risks. These findings underscore the importance of incorporating bias awareness and debiasing techniques to reduce high reliance on demographic or cultural stereotypes.
Hiking trails extending from high elevations aid further spread of alien plant species in subalpine and alpine zones
Authors: Koyama Asuka , Egawa Chika , Akasaka Munemitsu
Published: December 2024

Hiking trails, as anthropogenic linear habitats in highly protected mountain areas, allow the spread of alien plant species. Here, we focused on hiking trails extending away from high-elevation ropeway termini in Japan and assessed whether alien plant species that invaded the termini (i.e., trail heads) have spread along the trails. We recorded alien plant species along hiking trails leading from ropeway termini on seven mountains and analyzed the plant characteristics that influence their occurrence. The number of alien plant species along the trails and the number of records of their occurrence were positively affected by the number of species around the trail heads, and were negatively affected by the elevation of the trail head. A species-level analysis indicated that the number of records of each species’ occurrence on trails was higher with the presence of each species around the trail head, with perennial life-span, and with a smaller seed mass. Our results show that hiking trails leading away from high-elevation ropeway termini can spread alien plant species up to a distance of ca. 700 m into alpine communities. This study provides evidence of the role of hiking trails in the spread of alien plant species into subalpine and alpine zones.
Prioritizing US Geological Survey science on salinization and salinity in candidate and selected priority river basins
Authors: Conaway Christopher H. , Baker Nancy T. , Brown Craig J. , Green Christopher T. , Kent Douglas B.
Published: December 2024

The US Geological Survey (USGS) is selecting and prioritizing basins, known as Integrated Water Science basins, for monitoring and intensive study. Previous efforts to aid in this selection process include a scientifically defensible and quantitative assessment of basins facing human-caused water resource challenges (Van Metre et al. in Environmental Monitoring and Assessment, 192(7), 458 2020). In the present work, we explore this ranking process based on water quality considerations, specifically salinity and salinization. We selected top candidate basins to study salinity and salinization issues in 18 hydrologic regions that include 163 candidate basins. Our prioritization is based on quantitative assessment of sources of salinity, drivers of change, and receptors that must respond to those sources and drivers. Source terms represented in the prioritization include geology, depth to brackish groundwater, stream conductivity, chloride in precipitation, urban and agricultural land use, application of road salt as a deicer, and irrigation. Drivers represented in prioritization include changes in chemical weathering as a result of changes in rainwater chemistry. Receptors include measures of water stress, measurements of stream ecological health, and socioeconomic factors. In addition, we present research activities for the USGS on salinity and salinization that can be pursued in these basins including assessment of sources, pathways, and loadings; predicting and understanding changes in sources, peaks, and trends; understanding the components of salinity and mobilization of contaminants; understanding the relationship between salinization and changing ecosystems; and developing knowledge on the causes and distribution of groundwater salinity, brackish water resources, and challenges related to desalination.
Optimizing separation: Utilizing Aspergillus oryzae for bioflocculation of marine Tetraselmis subcordiformis on agricultural residues
Authors: Tölle Marius , Kuenz Anja
Published: December 2024

Microalgae are a promising source of high-quality nutrients for the growing population. They contain high concentrations of protein, unsaturated fatty acids and carbohydrates, as well as vitamins and antioxidants. However, conventional separation methods are too high in cost or cause contamination in the end product. Thus, fungal bioflocculation has gained traction as a promising separation method. This is a process in which microalgae adhere to mycelial surfaces. Problematically, previous studies often investigated the bioflocculation process via inedible and possibly harmful fungal species. In this study, the safe and edible fungus Aspergillus oryzae was investigated for the bioflocculation of marine microalga Tetraselmis subcordiformis on the basis of agricultural residues. Fungal growth conditions were optimized to achieve a maximum separation of 99.5% and dry mass ratio (algal to fungal) of 0.48 g g−1. This efficacy was achieved with the fungal culture conditions of 25 °C, 75 rpm, 105 spores mL−1 and an addition of 800 mg L−1 urea. Additionally, field emission scanning electron microscopy and microscopy of thin sections of paraffin embedded biomass revealed that the mycelial structure played a critical role in microalgal separation. The nitrogen addition resulted in a denser mycelial network, aiding the capture of microalgal cells, thus enhancing bioflocculation. Overall, the above-described process was able to produce biomass suitable for human consumption while exclusively utilizing agricultural residues as media components. These findings open possibilities for scalable, cost-effective microalgae harvesting systems, which can be integrated into sustainable food production. Future research could focus on optimizing the system for other microalgal species and exploring industrial scale applications in food and feed sectors.
Women, Gender, and Rebel Governance during Civil Wars
Authors: Loken Meredith Maloof
Published: December 2024

How is rebel governance gendered, and how does women's participation in rebellion affect the development and execution of governance programs? The author develops a framework for evaluating and explaining rebel governance's gendered dynamics, identifying four areas where attention to women and to gender helps us better understand these institutions: recruitment and internal organization, program expansion, development of new projects, and multi-layered governance relationships. They explore the context and significance of these dynamics using cross-conflict data on rebel governance institutions and women's participation as well as qualitative evidence from three diverse organizations. They suggest that it is not only the fact of women's participation that matters but the gendered nature of social and political relationships that help explain how rebels govern during civil wars. They show how women's involvement can shape governance content and implementation and how their participation may help rebel groups expand projects and engage with civilian communities.
Liability for Greenwashing in Company Sustainability Reports: A Novel Application of the English Tort Law Doctrine of Assumption of Responsibility
Authors: Morgandi Tibisay
Published: December 2024

The publication of annual sustainability reports—in which companies describe their sustainability performance and strategies—is now a routine part of doing business, especially for multinational companies. This essay examines the legal implications of inflated, misleading—or even plain false—statements made by UK companies in their sustainability reports regarding their operations and those of their subsidiaries, as well as those of entities in their supply chains. It argues that even when they are not legally mandated, these statements can carry legal significance under English tort law. It explains how in Vedanta the UK Supreme Court, applying the doctrine of “assumption of responsibility,” held that a company that states in a sustainability report that it is undertaking a specific task to prevent harm caused by a separate entity may thereby incur a duty to perform that task. Should the company fail to perform that task, and harm occur as a result, the company may incur tortious liability for its omission. This ruling has important implications for UK companies that, for both reputational and legal reasons, make statements concerning their responsibility for the conduct of entities in their supply chains. In practice, as a result of this lesser-known aspect of Vedanta, the legal position of UK companies with respect to entities in their supply chains may not be very different from that of their EU counterparts subject to the EU Corporate Sustainability Due Diligence Directive (CSDDD).
The Unintended Consequences of the EU Corporate Sustainability Due Diligence Directive
Authors: Mieszkowska Jowita
Published: December 2024

On March 15, 2024, the Corporate Sustainability Due Diligence Directive (CSDDD or Directive) was adopted by the EU Council.1 This Directive represents the EU's first piece of mandatory due diligence legislation governing the responsibilities of companies for human rights due diligence and transition plans for climate mitigation. It also codifies the principle that “all businesses have a responsibility to respect human rights, which are universal, indivisible, interdependent and interrelated.”2 The Directive broadly follows the framework of the non-binding UN Guiding Principles on Business and Human Rights (UNGPs) which first introduced the concept of human rights due diligence.3 The CSDDD requires that businesses incorporate human rights due diligence into policies,4 identifying, assessing, preventing, mitigating, and ending actual and potential adverse human rights impacts,5 remedying any impacts and monitoring the effectiveness of these processes.6 The Directive also introduces significant sanctions for non-compliance.7
The UN Supply Chain Treaty Negotiations: Between Transnational Civil Litigation and Public Law Beyond Borders
Authors: Cantú Rivera Humberto
Published: December 2024

The negotiations on a treaty to regulate global supply chains and their impact on human rights will hold its tenth session in December 2024. The question the negotiations address is not completely new: previous efforts, starting in the 1970s at the United Nations,1 tried to establish international obligations for “transnational corporations” (TNC), but found the issue of defining the subject to be regulated challenging. Academia and civil society also took turns defining the concept, although much of the focus equally revolved around the issues surrounding or caused by transnational corporations (i.e., the resource curse, regulatory chill, etc.). However, the current debate in the intergovernmental working group established by the Human Rights Council has focused, among other important elements, on defining the object of regulation—transnational corporations or transnational business activities—as well as the specific forms of liability under domestic law that could be used in cases of human rights harms or environmental degradation caused by business enterprises. This contribution addresses these two issues, considering some of the debates during the ninth session, and exploring aspects that need to be considered as the process moves forward.
A note on continuity and asymptotic consistency of measures of risk and variability
Authors: Gao Niushan , Xanthos Foivos
Published: December 2024

In this short note, we show that every convex, order-bounded above functional on a Fréchet lattice is automatically continuous. This improves a result in Ruszczyński and Shapiro ((2006) Mathematics of Operations Research31(3), 433–452.) and applies to many deviation and variability measures. We also show that an order-continuous, law-invariant functional on an Orlicz space is strongly consistent everywhere, extending a result in Krätschmer et al. ((2017) Finance and Stochastics18(2), 271–295.).
Process, rationality and human wellbeing
Authors: Dold Malte , Harper David , Rajagopalan Shruti , Whitman Glen
Published: December 2024

This special issue explores foundational questions in behavioral economics and behavioral public policy, drawing on the work of Mario Rizzo, a critical voice in the debate on behavioral paternalism. Behavioral economics has offered significant insights into decision-making, often challenging traditional economic models. However, it has also introduced normative frameworks into policy analysis, such as preference purification, that critics argue oversimplify human decision-making and risk imposing external values. Contributions to this issue examine themes including the tension between standard rationality and inclusive rationality, the epistemological limitations of paternalistic interventions, and the role of tacit knowledge and dynamic learning in policymaking. By engaging perspectives from economics, psychology, philosophy, and law, the issue discusses process-based approaches to policy analysis that respect individual agency and accommodate uncertainty. It also highlights the political economy dimensions of behavioral public policy, emphasizing the need for institutional reforms that enable learning and systematic change rather than narrowly focusing on individual cognitive biases. This issue serves as both a tribute to Mario Rizzo’s intellectual contributions and a call for a deeper reflection on the methodological and normative foundations of behavioral public policy.
Biopreserving Pathogens: Promise & Peril
Authors: Jaskiewicz Justyna , Wolf Susan M. , Toner Mehmet , Sandlin Rebecca D.
Published: December 2024

The development of technologies for the biopreservation of infectious organisms requires careful analysis of benefits and risks. This article reviews the regulatory landscape and oversight responsibilities in the United States in respect to pathogen biopreservation. Focused on two globally significant pathogens, Cryptosporidium and Plasmodium, the article explores advantages and potential risks of biopreservation concerning biosafety, biosecurity and biocontainment.
Successfully Bridging Innovation and Application: Exploring the Utility of a Risk Innovation Approach in the NSF Engineering Research Center for Advanced Biopreservation Technologies (ATP-Bio)
Authors: Maynard Andrew D. , Oye Kenneth A. , Scragg Marissa , Tripp Tim , Wolf Susan M.
Published: December 2024

This exploratory study set out to pilot use of a Risk Innovation approach to support the development of advanced biopreservation technologies, and the societally beneficial development of advanced technologies more broadly. This is the first study to apply the Risk Innovation approach — which has previously been used to help individual organizations clarify areas of value and threats — to multiple entities involved in developing an emerging technology.
Can Medical Licensing Boards Swing the Pendulum Towards Judicious Opioid Prescribing Practices?
Authors: Nelson Lewis S. , Perrone Jeanmarie
Published: December 2024

In the initial wave of the opioid crisis, uninformed prescribing practices and lax oversight were the drivers of opioid addiction and death. Although opioid prescriptions have decreased by 44.4 percent between 2011-2020,1 the number of deaths linked to prescription opioids has decreased only marginally.2 The marked fall in opioid prescribing without a concomitant reduction in opioid-related deaths suggests that an at-risk population continued to receive prescription opioids, whether directly or indirectly, from a medical professional. Currently, illicitly manufactured fentanyl (IMF) is the culprit for the majority of the approximately 81,000 annual opioid-related deaths.3 This finding has been misleadingly used to suggest that prescription opioids for chronic pain are no longer (and never were) a relevant concern,4 while the reality is that their lethal consequences are simply dwarfed by the marked rise in IMF deaths.5
Out of Bounds: Physician Licensing Board Disciplinary Cases related to Opioid Prescribing
Authors: Galletly Carol L. , Christenson Erika A. , Ohlrich Jessica , Dickson-Gomez Julia
Published: December 2024

Physician prescribing practices contributed to the US opioid epidemic, leading to increased regulation of opioid prescribing. In some instances, prescribers are unscrupulous or corrupt. They are criminally investigated and subject to prosecution. Less egregious opioid prescribing infractions are addressed through state medical licensing boards. At stake are physicians’ licenses to practice medicine.
Ethical Issues in Emerging Technologies to Extend the Viability of Biological Materials Across Time and Space
Authors: Childress James F. , Brister Evelyn , Thompson Paul B. , Wolf Susan M. , Callier Shawneequa L. , Capron Alexander M. , Pruett Timothy L. , Zuchowicz Nikolas
Published: December 2024

This article presents a framework of ethical analysis for anticipatory evaluation of advanced biopreservation technologies and employs the framework illustratively in three domains. The framework features four clusters of general ethical considerations: (1) Producing Benefits, Minimizing Harms, Balancing Benefits, Risk, and Costs; (2) Justice, Fairness, Equity; (3) Respect for Autonomy; and (4) Transparency, Trustworthiness, and Public Trust.
Biopreservation Beyond the Biosphere: Exploring the Ethical, Legal & Social Implications of Suspended Animation in Space
Authors: Feys Roel , Uygun Korkut , Filz von Reiterdank Irina , Wolf Susan M. , Isasi Rosario
Published: December 2024

In the evolving field of advanced biopreservation technologies, the development of suspended animation (SA) is inspired by real-world challenges. In the context of space exploration, SA is seen as a solution to enable humans to undertake missions far beyond low Earth orbit, including routine travel to other planets in our solar system and beyond. While work on the socio-ethical and legal implications (ELSI) of space exploration continues to evolve, NASA has committed to make ethics a priority issue, making this a fruitful field for further examination.
An “Amazon of Living Things”? The History & Horror of Commodifying Life
Authors: Bratcher Goodwin Michele
Published: December 2024

This article argues that beneath the veneer of legitimacy in the organ, tissue, and body part transplantation systems exists a horrifying history of human commodification whose vestiges surprisingly linger in contemporary supply and allocation systems. This history, as the Article demonstrates, dates back to the colonial period in the United States, where “grave robbing” became an important feature in the advancement of medicine. This legacy lives on.
Intranight optical monitoring of the rare quasar J0950+5128, the brightest known candidate for transition from radio-quiet to radio-loud state
Authors: Chand Krishan , Gopal-Krishna  , Chand Hum
Published: December 2024

We report a novel pilot project to characterise intra-night optical variability (INOV) of an extremely rare type of quasar, which has recently been caught in the act of transiting from a radio-quiet to radio-loud state, on a decadal time scale. Such rare transitions may signify a recurrence, or conceivably the first switch-on of jet activity in optically luminous quasars. The newly formed jet could well be jittery and unsteady, both in power and direction. The optically brightest among such radio-state transition candidates, the quasar J0950+5128 (

$z = 0.2142$

), was monitored by us with dense sampling in the R-band, during 2020-21 in 6 sessions, each lasting

$ \gt $

4 hours. This is the first attempt to characterise the INOV properties associated with this recently discovered, extremely rarely observed phenomenon of quasar radio-state transition. The non-detection of INOV in any of the 6 sessions, down to the 1-2% level, amounts to a lack of evidence for a blazar-like optical activity,

$\sim$

2 years after its transition to radio-loud state was found. The only INOV feature detected in J0950+5128 during our observational campaign was a

$\sim$

0.15-mag spike lasting < 6 minutes, seen at 13.97 UT on 18-March-2021. We also report the available optical light curves of this quasar from the Zwicky Transient Facility survey, which indicate that it had experienced a phase of INOV activity around the time its transition to the radio-loud state was detected, however that phase did not sustain until the launch of our INOV campaign

$\sim$

2 years later.
OF ARMS AND THE GENTLEMAN: ROBERT FAYRFAX AND HIS FAMILY
Authors: Sandon Nicholas
Published: December 2024

This paper appraises the current reception of the early Tudor church musician and composer Robert Fayrfax and the information upon which it is based. The first section summarily introduces Robert and traces how the image of him developed. The second assesses this image in the light of armorial and other evidence. The third explores further material about Robert and his family contained in an important document. The fourth relates the findings to a wider context. The fifth investigates the interrelationship of two manuscripts once owned by Robert’s father.
When Scottish medicine hospitalized Indian magic: Dr James Esdaile's mesmeric surgery in mid-nineteenth-century Bengal
Authors: Raj Kapil
Published: December 2024

In order to explore the ways knowledge travels across spatial and cultural boundaries, this article focuses on the intriguing case of the Edinburgh-trained Scottish surgeon James Esdaile (1808–59), who, after practising conventional surgery for almost fifteen years in British colonial India, quite unexpectedly turned to mesmeric anaesthesia in the last five years of his service. By following his career and his mesmeric turn, the article describes Esdaile's subsequent public experiments in mesmeric anaesthesia in collaboration with indigenous practices and practitioners of trance induction in the 1840s which led to the creation of a special mesmeric hospital in Calcutta. Although very successful, it eventually ceased to function, apparently victim to new and cheaper chemical anaesthetics. Mobilizing the insights of science studies scholarship into the processes of scientific experimentation, this article seeks to shed new light on the necessary professional, social and political investments for the making and mobility of scientific knowledge across social and cultural boundaries in a colonial setting.
Essay review: Why we fight about science
Authors: Thomas William
Published: December 2024

The concept of ‘science’ occupies a distinctive place within our rhetorical inheritance. Tangential to science's actual practices and institutions, this rhetoric holds that science comprises an arsenal of techniques, or a pervasive mentality, that have broadly shaped and even defined modern society. Such notions have been the subject of more or less constant discussion for two or three centuries, with early critics of scientific thought targeting its links to the religious and political radicalism of the Enlightenment and the troubles of industrialization.
The final closure time of the eastern segment of the Paleo-Asian Ocean: Insights from geochronology and geochemistry of Permian-Triassic sedimentary sequence in Wangqing, Jilin Province, China
Authors: Yin Junzhe , Liang Chenyue , Zheng Changqing , Song Zhiwei , Jia Xianghe , Chen Long
Published: December 2024

The Central Asian Orogenic Belt is the world’s largest accretionary orogenic belt, associated with the closure of the Paleo-Asian Ocean (PAO). However, the final closure timing of the eastern PAO remains contentious. The Permian-Triassic sedimentary sequences in the Wangqing area along the Changchun-Yanji suture zone offer important clues into this final closure. New data on petrology, whole-rock geochemistry, zircon U-Pb geochronology and zircon Hf isotopes of sedimentary rocks from the Miaoling Formation and Kedao Group in Wangqing area provide new insights into the final closure of the eastern end of the PAO. The maximum deposition ages of the Miaoling Formation and Kedao Group have been constrained to the Late Permian (ca. 253 Ma) and early Middle Triassic (ca. 243 Ma), respectively. These sedimentary rocks exhibit similar geochemical characteristics, showing low textural and compositional maturities, implying short sediment transport, with all detrital zircons suggesting their origins from felsic igneous rocks. The εHf(t) values of the Miaoling Formation range from −6.09 to 12.43 and from −2.20 to 7.59 for the Kedao Group, implying these rocks originated from NE China. Considering our new data along with previously published data, we propose that a reduced remnant ocean remained along the Changchun-Yanji suture zone in the early Middle Triassic (ca. 243 Ma), suggesting the final closure of the eastern PAO likely occurred between the latest Middle Triassic and early Late Triassic.
Promoting Digitalization of Electronic Trade Documents in Nigeria through the Model Law on Electronic Transferable Records
Authors: Anyamele Uchenna
Published: December 2024

Given the increasing use of technology and the digitalization of international trade through electronic documents, there is a need for a globally harmonized standard that caters for the legal aspects of digitalization. The Model Law on Electronic Transferable Records (MLETR) is one such law. Yet, it has not been adopted in Nigeria or several other jurisdictions. This article considers the possibility of Nigeria adopting the MLETR. To do this, the article considers the meaning of electronic transferable documents and the legal implications of digitalizing them. The article also examines the barriers and challenges to digitalizing electronic transferable records. It then considers some of the laws in Nigeria that would support electronic and digital trade transactions. Subsequently, the article highlights the benefits, challenges and hindrances to the adoption of the MLETR in Nigeria. It recommends an approach to adopting the MLETR, drawing from jurisdictions that have adopted it.
What is shared and what is not: How the Cold War era in northeastern Thailand is remembered on social media
Authors: Pholsena Vatthana
Published: December 2024

This article investigates memories of the Cold War era in Thailand, through online practices on Facebook pages administered by residents of a borderland province in the Northeast that was a key front line during the conflict. The possibilities for greater access to, and dissemination of, information afforded by digital media technologies have created a new environment for the production of shared knowledge about the past. However, on these pages, instead of converging plural memories, participatory online culture and the use of the language of memory have enabled the creation of distinct and separated memory spaces. This article calls attention in particular to what is silenced and absent in what people are sharing online. It argues that the deep-seated ethnic politics of the Cold War have an afterlife in Thai society—especially in the country's ‘margins’ where the conflict was most violent—that is reflected as much by what is not said as by what is said online.
Causal mechanisms of quadruple networks in pediatric bipolar disorder
Authors: Wang Rong , Wang Chun , Zhang Gui , Mundinano Inaki-Carril , Zheng Gang , Xiao Qian , Zhong Yuan
Published: December 2024

Background

Pediatric bipolar disorder (PBD) is characterized by abnormal functional connectivity among distributed brain regions. Increasing evidence suggests a role for the limbic network (LN) and the triple network model in the pathophysiology of bipolar disorder (BD). However, the specific relationship between the LN and the triple network in PBD remains unclear. This study aimed to investigate the aberrant causal connections among these four core networks in PBD.

Method

Resting-state functional MRI scans from 92 PBD patients and 40 healthy controls (HCs) were analyzed. Dynamic Causal Modeling (DCM) was employed to assess effective connectivity (EC) among the four core networks. Parametric empirical Bayes (PEB) analysis was conducted to identify ECs associated with group differences, as well as depression and mania severity. Leave-one-out cross-validation (LOOCV) was used to test predictive accuracy.

Result

Compared to HCs, PBD patients exhibited primarily excitatory bottom-up connections from the LN to the salience network (SN) and bidirectional excitatory connections between the default mode network (DMN) and SN. In PBD, top-down connectivity from the triple network to the LN was excitatory in individuals with higher depression severity but inhibitory in those with higher mania severity. LOOCV identified dysconnectivity circuits involving the caudate and hippocampus as being associated with mania and depression severity, respectively.

Conclusions

Disrupted bottom-up connections from the LN to the triple network distinguish PBD patients from healthy controls, while top-down disruptions from the triple network to LN relate to mood state differences. These findings offer insight into the neural mechanisms of PBD.
Familial co-aggregation and shared familiality among neurodevelopmental problems and with aggressive behavior, depression, anxiety, and substance use
Authors: Vos Melissa , Wang Rujia , Rommelse Nanda N. J. , Snieder Harold , Larsson Henrik , Hartman Catharina A.
Published: December 2024

Objective

To refine the knowledge on familial transmission, we examined the (shared) familial components among neurodevelopmental problems (i.e. two attention-deficit/hyperactivity–impulsivity disorder [ADHD] and six autism spectrum disorder [ASD] subdomains) and with aggressive behavior, depression, anxiety, and substance use.

Methods

Data were obtained from a cross-sectional study encompassing 37 688 participants across three generations from the general population. ADHD subdomains, ASD subdomains, aggressive behavior, depression, anxiety, and substance use were assessed. To evaluate familial (co-)aggregation, recurrence risk ratios (λR) were estimated using Cox proportional hazards models. The (shared) familiality (f2), which is closely related to (shared) heritability, was assessed using residual maximum likelihood-based variance decomposition methods. All analyses were adjusted for sex, age, and age2.

Results

The familial aggregation and familiality of neurodevelopmental problems were moderate (λR = 2.40–4.04; f2 = 0.22–0.39). The familial co-aggregation and shared familiality among neurodevelopmental problems (λR = 1.39–2.56; rF = 0.52–0.94), and with aggressive behavior (λR = 1.79–2.56; rF = 0.60–0.78), depression (λR = 1.45–2.29; rF = 0.43–0.76), and anxiety (λR = 1.44–2.31; rF = 0.62–0.84) were substantial. The familial co-aggregation and shared familiality between all neurodevelopmental problems and all types of substance use were weak (λR = 0.53–1.57; rF = −0.06–0.35).

Conclusions

Neurodevelopmental problems belonging to the same disorder were more akin than cross-disorder problems. That said, there is a clear (shared) familial component to neurodevelopmental problems, in part shared with other psychiatric problems (except for substance use). This suggests that neurodevelopmental disorders, disruptive behavior disorders, and internalizing disorders share genetic and environmental risk factors.
Neural activity during working memory predicts clinical response to computerized executive function training prior to cognitive processing therapy
Authors: Davey Delaney , Caudle Morgan M. , Hoffman Samantha N. , Jak Amy J. , Bomyea Jessica , Crocker Laura D.
Published: December 2024

Background

Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Methods

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Conclusions

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.