bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Dispatch of Island Integrated Energy System Based on Ranking Group Learning Optimization Algorithm
Authors: Li Jian , Lu Yang
Published: October 2023

In order to improve the flexibility of the Island Integrated Energy System (IIES) and reduce operating costs, the Cooling Thermal and Electric three-load Demand Response (DR) are introduced into the IIES. Under the constraints of the output of each unit, this paper establishes a comprehensive energy economic dispatch model with the lowest total operating cost of the system as the objective function, and a Ranking Group Learning Optimization (RGSO) is proposed to optimize the output of each unit. In order to verify the effectiveness of the proposed model and algorithm, simulation experiments are carried out on the typical operating scenarios of the IIES in summer and winter, and the results are compared with those of the other five optimization algorithms. Experimental results show that the proposed algorithm has a good global convergence performance, and the computational cost is lower than the other five optimization algorithms.
Research on Orderly Charging Method of Electric Vehicles Based on Deep Reinforcement Learning
Authors: Wu Ning , Xiao Jing , Han Shuai , Wu Xiaorui , Gong Wenlan
Published: October 2023

Electric vehicle charging stations are vital for the integration of electric vehicles (EV) with the future energy internet. To minimize daily operating costs in the face of uncertain time-of-use pricing and user behavior, this paper proposes an ordered charging optimization strategy from the perspective of load aggregators. By modeling the optimization problem as a finite-horizon Markov Decision Process (MDP) and using a reward-penalty feedback function to extract high-quality experience, the optimal operating strategy can be obtained. Results show that the proposed strategy reduces daily operating costs, protects batteries, and meets the charging.
Method of Incomplete Leaf Recognition Based on Artificial Neural Network
Authors: Rao Zhimin , Li Yixiu , Mao Jiandong , Zhao Hu , Zhou Chunyan , Gong Xin
Published: October 2023

Plant classification is the basic work for plant research, and it is of great significance to explore the relationship among plants. It is the most direct, effective and simple method to classify and recognize plants by features of plant leaves. In this paper, the original photos of mulberry leaves, pear tree leaves, plum tree leaves, silver poplar tree leaves, spiraea leaves, willow leaves are collected, and an operation interface of the incomplete leaf recognition system was designed to process the original image of incomplete leaves. After various characteristic parameters of incomplete leaves are obtained, the species of incomplete leaves are recognized by artificial neural network. Experimental results show that this method can effectively identify incomplete leaves.
Non-spherical Particle Modelling Approach in Discrete Element Method and its Validations
Authors: Liu Cong , Wang Kang , Zhou Shen
Published: October 2023

The discrete element method (DEM) is widely used for investigating the mechanical behaviours of complex physical system consisting of particles. In nature, the physical system such as rock and soil system, sand or flour are all composed of particles with different shapes. The particle shape can considerably influence nature characteristics in DEM simulation. Developing an effective particle shapes representation approach is a valuable task to improve the DEM modelling techniques. In this study, a super-quadrics function is introduced to represent the non-spherical particle shape. Furthermore, the corresponding contact detection and calculation algorithm named “deepest point method” is also explained to describe the complex contact relationships and calculate the contact forces between two irregular particles. At last, sandpile collapse simulations were conducted to validate the accuracy of the proposed approach. The numerical results indicate that the non-spherical particle modelling approach in this study can easily simulate most nature shape of particle system.
Inequality and growth impacts of climate change—insights from South Africa
*
Authors: Dasgupta Shouro , Emmerling Johannes , Shayegh Soheil
Published: October 2023

The impact of climate change on economic growth has been the subject of numerous studies in recent years, with macro-econometric analyses estimating the effect of rising temperatures on gross domestic product (GDP) growth rates at the country-level. However, the distributional impact of warming on inequality and poverty at the micro-level remains relatively unexplored. In this paper, we investigate the relationship between temperature and inequality in South Africa at the national and sub-national level. Our analysis reveals a significant

∪

-shaped relationship between temperature and inequality indices, with inequality lowest at moderate temperatures (11 ∘C–18 ∘C) and increasing sharply as temperatures increase. We find that the optimal temperatures are lower for inequality measures than for income levels. This indicates that substantial increases in inequality are expected at higher temperatures compared to growth impacts. This effect is particularly noticeable for the poorer segments of the population, whose productivity and wages decline as temperatures increase, while the impact on the richer segments is less significant due to their greater adaptive capacity. In terms of mechanisms, we find that agricultural households are more likely to experience an increase in inequality due to warming. Our findings suggest that global warming has two adverse effects on hot countries: reducing average growth and increasing inequality. We compare the outcomes of the moderate RCP6.0 scenario to a reference scenario without warming and find that by the end of the century, the Gini coefficient in South Africa is expected to increase by 3–6 points, resulting in a potential welfare loss of approximately 50% when combined with the impact of warming on GDP (which alone can reach up to 43% by 2100 in South Africa). Our findings highlight the importance of investigating the distributional effects of climate change at the micro-level, particularly in low- or middle-income countries where vulnerable populations are more susceptible to its impacts.
Supersymmetry and integrability for a class of XY central spin models
Authors: van Tonder Jaco , Links Jon
Published: October 2023

Several studies have exploited the integrable structure of central spin models to deepen understanding of these fundamental systems. In recent years, an underlying supersymmetry for systems with XX interactions has been uncovered. Here we report that a class of central spin models with XY interactions is also supersymmetric and integrable. The associated Bethe Ansatz solution is presented for the case where all particles are spin-1/2.
Toward understanding the microstructure characteristics, phase selection and magnetic properties of laser additive manufactured Nd-Fe-B permanent magnets
Authors: Yao Bo , Kang Nan , Li Xiangyu , Li Dou , Mansori Mohamed EL , Chen Jing , Yang Haiou , Tan Hua , Lin Xin
Published: October 2023

Highlights

Nd-Fe-B permanent magnets with different solidification conditions are prepared using vacuum induction melting (VIM), laser directed energy deposition (LDED) and laser powder bed fusion (LPBF) technologies, respectively.

The intrinsic relationship among the microstructure evolution, phase selection and magnetic properties of the Nd-Fe-B magnets under different solidification conditions is clarified in detail.

The solidification velocity (V) and cooling rate (R) are key factors in determining the phase selection of Nd-Fe-B magnets.

A coercivity of 656 kA m−1, a remanence of 0.79 T and maximum energy product of 71.5 kJ m−3 are achieved in the LPBF Nd-Fe-B magnet.
On the Hilbert-Samuel coefficients of Frobenius powers of an ideal
Authors: Banerjee Arindam , Goel Kriti , Verma J.
Published: October 2023

We provide suitable conditions under which the asymptotic limit of the Hilbert-Samuel coefficients of the Frobenius powers of an

m

\mathfrak {m}

-primary ideal exists in a Noetherian local ring

(
R
,

m

)

(R,\mathfrak {m})

with prime characteristic

p
>
0.

p>0.

This, in turn, gives an expression of the Hilbert-Kunz multiplicity of powers of the ideal. We also prove that for a face ring

R
R

of a simplicial complex and an ideal

J
J

generated by pure powers of the variables, the generalized Hilbert-Kunz function

ℓ
(
R

/

(

J

[
q
]

)
k

)

\ell (R/(J^{[q]})^k)

is a polynomial for all

q
,
k

q,k

and also give an expression of the generalized Hilbert-Kunz multiplicity of powers of

J
J

in terms of Hilbert-Samuel multiplicity of

J
.

J.

We conclude by giving a counter-example to a conjecture proposed by I. Smirnov which connects the stability of an ideal with the asymptotic limit of the first Hilbert coefficient of the Frobenius power of the ideal.
Sandwich groups and (strong) left 3-Engel elements in groups
Authors: Hadjievangelou Anastasia , Traustason Gunnar
Published: October 2023

In this paper we prove a group theoretic analogue of the well known local nilpotence theorem for sandwich Lie algebras due to Kostrikin and Zel’manov [Trudy Mat. Inst. Steklov. 183 (1990), pp. 106–111, 225]. We introduce the notion of a strong left

3
3

-Engel element of a group

G
G

and show that these are always in the locally nilpotent radical of

G
G

. This generalises a previous result of Jabara and Traustason [Proc. Amer. Math. Soc. 147 (2019), pp. 1921–1927] that showed that a left

3
3

-Engel element

a
a

of a group

G
G

is in the locally nilpotent radical of

G
G

whenever

a
a

is of odd order.
Domination of semigroups generated by regular forms
Authors: Arora Sahiba , Chill Ralph , Djida Jean-Daniel
Published: October 2023

We give a representation for regular forms associated with dominated

C
0

C_0

-semigroups which, in turn, characterizes the domination of

C
0

C_0

-semigroups associated with regular forms. In addition, we prove a relationship between the positivity of (dominated)

C
0

C_0

-semigroups and the locality of the associated forms.
Making and breaking rules with clay and code: iteration, glitch, and mathematical thinking
Authors: Tihanyi Timea
Published: October 2023

The present paper introduces 3D printing from the perspective of a visual artist’s practice. It considers mathematical ideas from basic geometry and trigonometry to computational theory for the creation of forms and textures, which otherwise would not be possible to create. 3D printing with clay is a recent development within a repertoire of available additive technologies. In ceramic craft, the process of building up a form coil by coil is one of the most ancient techniques. Clay printers revisit this process with unprecedented granularity, accessibility, and transparency. The digital-to-physical workflow creates limitless entry points for using mathematics in creating a design from scratch or hacking an existing design. I introduce several of my recent projects and collaborations with mathematicians and design researchers at Slip Rabbit Studio using the Rhinoceros/Grasshopper software for form giving, and using data physicalization, coding and machine manipulations.
Twenty-First-Century Learning Spaces and Pedagogical Change
Authors: Colton Jill
Published: October 2023

Twenty-first-century learning spaces are designed to enable students to develop the skills and dispositions required for uncertain and transformed futures. They are characterized by flexibility and openness, with architectural and technological features that allow for variable arrangements and digitally enhanced learning. Flexibility is achieved through the provision of features such as sliding doors, moveable furniture, open spaces, and smaller breakout rooms, which may be used by teachers and students in different ways. The flexibility and openness of these spaces are considered to enhance the collaborative, self-directed and inquiry- or project-based learning that are regarded as crucial for an education that prepares students for work and citizenship in the 21st century. The integration of networked digital tools and applications is a key aspect of 21st-century learning spaces and of the pedagogical changes that shape and are shaped by these spaces. Sociomaterial theoretical perspectives offer a way of interpreting and analyzing 21st-century learning spaces in relation to pedagogical change. The flexibility of these spaces is implicated in the flexibility of pedagogical approaches, and the opportunities for movement and varied arrangements in physical and digital spaces are correspondent with the self-managing, digitally literate learner. Links between learning spaces that are flexible, open, and digitally networked and the pedagogies enacted in those spaces have been the subject of empirical studies in Australia, the United Kingdom, Europe, Scandinavia, the United States, and New Zealand. These studies illustrate the importance of considering theoretical perspectives in research that investigates pedagogical change and learning space design.
Racism and Accountable Policing for Black Adults in the United States
Authors: Motley Jr. Robert O. , Baidoo Christopher
Published: October 2023

Racism is a public health concern for Black adults in the United States given its prevalence and association with adverse health outcomes for this population. The frequency of high-profile cases involving police use of gratuitous violence against Black adults has raised concerns regarding racially discriminatory law enforcement practices. In this article, racism is defined and a discussion is offered on its impact on the health and well-being of Black adults in the United States; the intersection of racism and policing; contemporary racialized policing practices; emerging evidence on prevalence rates for exposure (direct and indirect) to perceived racism-based police violence and associated mental and behavioral health outcomes; and police accountability through executive, legislative, legal, and other remedies.
DMFDDI: deep multimodal fusion for drug–drug interaction prediction
Authors: Gan Yanglan , Liu Wenxiao , Xu Guangwei , Yan Cairong , Zou Guobing
Published: October 2023

Drug combination therapy has gradually become a promising treatment strategy for complex or co-existing diseases. As drug–drug interactions (DDIs) may cause unexpected adverse drug reactions, DDI prediction is an important task in pharmacology and clinical applications. Recently, researchers have proposed several deep learning methods to predict DDIs. However, these methods mainly exploit the chemical or biological features of drugs, which is insufficient and limits the performances of DDI prediction. Here, we propose a new deep multimodal feature fusion framework for DDI prediction, DMFDDI, which fuses drug molecular graph, DDI network and the biochemical similarity features of drugs to predict DDIs. To fully extract drug molecular structure, we introduce an attention-gated graph neural network for capturing the global features of the molecular graph and the local features of each atom. A sparse graph convolution network is introduced to learn the topological structure information of the DDI network. In the multimodal feature fusion module, an attention mechanism is used to efficiently fuse different features. To validate the performance of DMFDDI, we compare it with 10 state-of-the-art methods. The comparison results demonstrate that DMFDDI achieves better performance in DDI prediction. Our method DMFDDI is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/DHUDEBLab/DMFDDI.git.
The effect of the COVID-19 pandemic on life expectancy in the USA: An application of hybrid life expectancy
Authors: Sanderson Warren C , Scherbov Sergei
Published: October 2023

Pandemics are, by definition, temporary intervals of substantially increased mortality rates experienced across a wide geographic area. One way of assessing the magnitude of the COVID-19 pandemic in the USA has been to compute the differences in life expectancy at birth during a pandemic year and the year before the pandemic. Such comparisons are misleading because they do not account for the duration of the pandemic. The computation of life expectancy in 2019 assumes that people spend their entire lives experiencing prepandemic mortality rates. The computation of life expectancy in 2021 assumes that people live their entire lives in a permanent pandemic. However, people do not live their entire lives experiencing the elevated mortality rates of 2021. This article introduces a method for calculating life expectancy that reflects the experience of people enduring pandemic-level mortality rates for fixed durations. We call the new quantity hybrid life expectancy because it integrates both pandemic and prepandemic mortality rates. The difference in life expectancy at birth in the USA in 2019 with and without a 3-year-long pandemic is 0.01 years. This is because mortality rates at ages 0, 1, and 2 in the pandemic were essentially unchanged from their prepandemic levels. Life expectancy at age 65 incorporating a 3-year pandemic is 0.18 years lower than life expectancy would have been without it. Reductions in life expectancy due to the COVID-19 pandemic using hybrid life expectancy are dramatically lower than differences in life expectancy that do not take the duration of the pandemic into account.
Low-voltage ride-through capability improvement of Type-3 wind turbine through active disturbance rejection feedback control-based dynamic voltage restorer
Authors: Boulaoutaq El Mahfoud , Aziz Asma , El Magri Abdelmounime , Abbou Ahmed , Ajaamoum Mohamed , Rachdy Azeddine
Published: October 2023

Disconnections due to voltage drops in the grid cannot be permitted if wind turbines (WTs) contribute significantly to electricity production, as this increases the risk of production loss and destabilizes the grid. To mitigate the negative effects of these occurrences, WTs must be able to ride through the low-voltage conditions and inject reactive current to provide dynamic voltage support. This paper investigates the low-voltage ride-through (LVRT) capability enhancement of a Type-3 WT utilizing a dynamic voltage restorer (DVR). During the grid voltage drop, the DVR quickly injects a compensating voltage to keep the stator voltage constant. This paper proposes an active disturbance rejection control (ADRC) scheme to control the rotor-side, grid-side and DVR-side converters in a wind–DVR integrated network. The performance of the Type-3 WT with DVR topology is evaluated under various test conditions using MATLAB®/Simulink®. These simulation results are also compared with the experimental results for the LVRT capability performed on a WT emulator equipped with a crowbar and direct current (DC) chopper. The simulation results demonstrate a favourable transient and steady-state response of the Type-3 wind turbine quantities defined by the LVRT codes, as well as improved reactive power support under balanced fault conditions. Under the most severe voltage drop of 95%, the stator currents, rotor currents and DC bus voltage are 1.25 pu, 1.40 pu and 1.09 UDC, respectively, conforming to the values of the LVRT codes. DVR controlled by the ADRC technique significantly increases the LVRT capabilities of a Type-3 doubly-fed induction generator-based WT under symmetrical voltage dip events. Although setting up ADRC controllers might be challenging, the proposed method has been shown to be extremely effective in reducing all kinds of internal and external disturbances.
Genetic testing in the management of inherited cardiac disorders: two cases of Filamin-C arrhythmogenic left ventricular cardiomyopathy
Authors: Abela Mark , Grech Neil , Debattista Jessica , Felice Tiziana
Published: October 2023

Background

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a left ventricle–dominant arrhythmogenic cardiomyopathy (ACM) subtype often associated with malignant ventricular arrhythmias, left ventricular (LV) scar and sudden cardiac death. Awareness about LV involvement is now on the rise. The diagnosis relies on structural abnormalities on cardiac magnetic resonance (CMR) imaging and known ACM-causing genetic mutations.

Case summary

A 28-year-old lady (Case 1) was referred for cardiac screening after her father passed away suddenly. Her paternal uncle (Case 2) had been diagnosed with supposed dilated cardiomyopathy prior to referral. Both cases were worked up extensively with an electrocardiogram (ECG), 24-h ambulatory ECG monitor, exercise testing, and CMR imaging. Investigations of Case 1 showed T-wave inversion in the infero-lateral leads and a ventricular ectopic burden of 3% on ambulatory monitoring. Cardiac magnetic resonance imaging revealed moderately reduced LV systolic function (ejection fraction of 40%) with circumferential macroscopic fibrosis. Her uncle (Case 2) also had an impaired and dilated ventricle with extensive scar on CMR. Following the recent introduction of a cardiogenetic service in our unit, both were heterozygous for a pathogenic Filamin-C variant (c.7384+1G>A). Based on CMR findings and genetic results, the diagnosis of both patients was deemed to be ALVC. After years of surveillance, Patient 1 now has an implantable cardioverter defibrillator (ICD) indication.

Discussion

The importance of diagnosing patients with ACM lies in the predisposition to sudden cardiac death. Gene-specific treatment algorithms in ACM may alter management strategies, including ICD implantation as primary prevention. An in-depth multidisciplinary discussion and respecting patient autonomy are key factors in any decision pertaining to ICD implantation.
A case of a systemic cancer-associated thrombosis successfully treated with multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy
Authors: Yoneda Fumiya , Yamashita Yugo , Watanabe Shin , Ono Koh
Published: October 2023

Background

Cancer-associated thrombosis (CAT) is one of the major complications during the treatment course of cancer, which often challenges clinicians in daily clinical practice despite anticoagulation therapy.

Case summary

A 57-year-old man with a history of a liver transplantation was diagnosed with post-transplant lymphoproliferative disorders. He developed severe systemic thromboses including a massive pulmonary embolism and was treated with anticoagulation therapy including a factor Xa inhibitor. However, the systemic thromboses worsened despite the anticoagulation therapy. During the acute treatment course of the thromboses, we administered anticancer drug therapy in hopes of an improvement in the activity of the cancer status leading to a favourable effect on the thrombosis status. Multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy successfully improved the systemic thrombosis.

Discussion

Anticoagulation therapy is a standard treatment for CAT; however, some cases of CAT do not successfully improve despite anticoagulation therapy, partly due to a highly active cancer status. Anticancer drug therapy might increase the risk of a thrombosis, whereas it could improve the activity of the cancer status leading to a decreased risk of a thrombosis. A multi-disciplinary therapy might be a reasonable option especially for CAT with a highly active cancer status.
Surgical removal of multiple left ventricular thrombi with video-assisted cardioscopy: a case report
Authors: Mitsuishi Atsuyuki , Miura Yujiro , Furukawa Atsuko , Yoshida Keisuke , Fukunaga Yukiko
Published: October 2023

Background

Left ventricular (LV) thrombus is a lethal complication of coronary artery disease that can lead to embolization and sudden death. There is no clear consensus on the optimal treatment for LV thrombi. There is a paucity of case series about surgical excision of LV thrombus in patients with coronary vessel disease. For that, there is insufficient evidence to support surgical excision of LV thrombus and recommend the optimal timing of this procedure.

Case summary

We report a case of a 52-year-old man with a history of percutaneous catheter intervention for mid-right coronary artery lesion 3 years ago. He presented with two-vessel coronary artery disease with three LV thrombi. The thrombi were mobile and protuberant. We performed coronary artery bypass grafting in both vessels and LV thrombectomy with video-assisted cardioscopy.

Discussion

Mobile or protuberant thrombus is the most important risk factor for embolization of LV thrombus. On the other hand, LV thrombus size rarely appears in studies as a risk factor for embolization, and when it does, it is a lesser risk factor. There are no case reports describing simultaneous formation of three LV thrombi after myocardial infarction, and it is not known if the risk of embolism is high in such cases. Our patient had very fragile thrombi, and thrombectomy was performed along with coronary artery bypass grafting due to the high risk of embolism.
Large-bore suction thrombectomy for sub-massive pulmonary embolism during second trimester of pregnancy: a case report
Authors: Kojodjojo Pipin , Ng Chin Hin , Ong Kymin Cayla , Zuzarte-Ng Regina , Chan Wan Xian
Published: October 2023

Background

Pregnancy-associated pulmonary embolism (PAPE) remains a significant cause of maternal mortality. Anticoagulation remains the mainstay of therapy for most pulmonary embolism (PE)-related pregnancies. However, in patients with haemodynamic compromise or those refractory to anticoagulation, management is challenging. Systemic thrombolysis is associated with a substantial risk of maternal bleeding and fetal loss. In non-pregnant PE patients, large bore catheter-directed suction thrombectomy is a proven and important technique to manage intermediate or high-risk PE, allowing for normalization of pulmonary pressures, avoidance of haemodynamic deterioration, without the need for thrombolytics, major surgery, significant blood loss, or prolonged hospitalization.

Case summary

A primigravid patient in her second trimester of pregnancy, initially diagnosed with a deep vein thrombosis refractory to heparin, presents with near-syncope due to sub-massive pulmonary embolism. The various management options including thrombolysis and surgical embolectomy etc. were discussed in detail by a multi-disciplinary PE team. She underwent large bore suction thrombectomy with complete thrombi removal, normalization of right heart strain, without the need for thrombolytics or surgery, minimal blood loss and was discharged after a short length of stay. She gave birth at term to a healthy infant.

Conclusion

Suction thrombectomy is an important consideration for physicians managing high-risk PAPE and is likely to be associated with much a lower risk of maternal and fetal mortality compared to thrombolysis or surgery.
Optimal interlesion distance for 90 and 50 watt radiofrequency applications with low ablation index values: experimental findings in a chronic ovine model
Authors: Bortone Agustín Alfonso , Ramirez F Daniel , Constantin Marion , Bortone Clara , Hébert Caroline , Constantin Justine , Bialas Patric , Limite Luca Rosario
Published: October 2023

Aims

The optimal interlesion distance (ILD) for 90 and 50 W radiofrequency applications with low ablation index (AI) values in the atria has not been established. Excessive ILDs can predispose to interlesion gaps, whereas restrictive ILDs can predispose to procedural complications. The present study sought, therefore, to experimentally determine the optimal ILD for 90 W–4 s and 50 W applications with low AI values to optimize catheter ablation outcomes in humans.

Methods and results

Posterior intercaval lines were created in eight adult sheep using CARTO and the QDOT-MICRO catheter in a temperature-controlled mode. In four animals, the lines were created with 50 W applications, a target AI value ≥350, and ILDs of 6, 5, 4, and 3 mm, respectively. In the other four animals, the lines were created with 90 W–4 s applications and ILDs of 6, 5, 4, and 3 mm, respectively. Activation maps were created immediately after ablation and at 21 days to assess linear block prior to gross and histological analyses. All eight lines appeared transmural and continuous on histology. However, for 50 W-only applications with an ILD of 3 mm resulted in durable linear electrical block, whereas for 90 W applications, only the lines with ILDs of 4 and 3 mm were blocked. No complications were detected during ablation procedures, but all power and ILD combinations except 50 W–6 mm resulted in asymptomatic shallow lung lesions.

Conclusion

In the intercaval region in sheep, for 50 W applications with an AI value of ∼370, the optimal ILD is 3 mm, whereas for 90 W–4 s applications, the optimal ILD is 3–4 mm.
Some Certainties and Some Uncertainties in European Union Trade Mark Law
Authors: García-Pérez Rafael
Published: October 2023

Thirty-five years have passed since the entry into force of the First Trade Mark Directive (First Council Directive 89/104/EEC of 21 December 1988 to approximate the laws of the Member States relating to trade marks). The purpose of this article is to reflect on the journey thus far and the road ahead. This article does this in two ways. The first part of the article identifies some aspects of European Union trade mark law that can be regarded as uncontroversial. The second part explores a number of issues of a more speculative nature as well as some trends that may shape the evolution of European Union trade mark law in the years to come.
Efficacy and Safety of Anti-Tumor Necrosis Factor Alpha in Very Early Onset Inflammatory Bowel Disease
Authors: Collen Lauren V , Mitsialis Vanessa , Kim David Y , Bresnahan Mairead , Yang Jessica , Tuthill Margaret , Combs Abigail , Barends Jared , Field Michael , Liu Enju , Bearup Richelle , Okoroafor Ibeawuchi , Klein Christoph , Muise Aleixo M , Bousvaros Athos , Ouahed Jodie , Snapper Scott B
Published: October 2023

Background

Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD.

Methods

Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression.

Results

In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn’s disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed.

Conclusions

Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.
Notes from the Front: The Casebook of a Renaissance Hospital Surgeon
Authors: Strocchia Sharon
Published: October 2023

This essay uses the unpublished casebook kept by the Tuscan surgeon Giovanbattista Nardi to examine the provision of urgent medical care in sixteenth-century Italian hospitals. Most major hospitals on the peninsula maintained separate therapeutic spaces known as medicherie for this purpose. Written in the 1580s while Nardi worked as a staff surgeon at a Florentine civic hospital, this rare surgical casebook provides insight into the types of institutional resources devoted to acute medical problems; the clientele seeking immediate assistance and the situations that brought them there; the treatments used to achieve short-term “cures”; and the clinical experiences of hospital surgeons who served as frontline healers. A close analysis of the seventy-nine cases recorded sheds new light on everyday surgical treatments for conditions ranging from serious head injuries requiring trephination to syphilitic lesions and genital trauma. Casebook entries also reveal Nardi’s deep engagement with the composition and use of topical remedies as both practitioner and experimenter. Intended as a memory aid for future reference, the casebook shows material traces of the author’s shifting occupational identity as he matured from hospital surgeon to university-trained physician. Viewed through multiple lenses, this richly layered source expands our understanding of both the practice and profession of early modern surgery.
Operative technique for a successful laparoscopic en-bloc resection of gastrogastric fistula following roux-en-Y gastric bypass
Authors: Patel Krishna , Perdue Jordyn , Varre Jaya , Serapiglia Vinnie , Rizzo Anthony , Sonnanstine Thomas
Published: October 2023

Gastrogastric fistulas are rare complications following Roux-en-Y gastric bypass surgery and are characterized by a fistulous connection between the gastric pouch and the remnant stomach. The presentation is often variable and a high-index of suspicion must be maintained for accurate and timely diagnosis. In this case report, we provide a detailed review of the technical steps taken to successfully resect a gastrogastric fistula en-bloc laparoscopically with an unremarkable post-operative course.
The role of radiation and halo mergers in Pop III star formation
Authors: Correa Magnus Lilia , Smith Britton D , Khochfar Sadegh , O’Shea Brian W , Wise John H , Norman Michael L , Turk Matthew J
Published: October 2023

We present a study of the co-evolution of a population of primordial star-forming minihaloes at Cosmic Dawn. In this study, we highlight the influence of individual Population III stars on the ability of nearby minihaloes to form sufficient molecular hydrogen to undergo star formation. In the absence of radiation, we find the minimum halo mass required to bring about collapse to be ∼105 M⊙, this increases to ∼106 M⊙ after two stars have formed. We find an inverse relationship between halo mass and the time required for it to recover its molecular gas after being disrupted by radiation from a nearby star. We also take advantage of the extremely high resolution to investigate the effects of major and minor mergers on the gas content of star-forming minihaloes. Contrary to previous claims of fallback of supernova ejecta, we find minihaloes evacuated after hosting Pop III stars primarily recover gas through mergers with undisturbed haloes. We identify an intriguing type of major merger between recently evacuated haloes and gas-rich ones, finding that these ‘mixed’ mergers accelerate star formation instead of suppressing it like their low-redshift counterparts. We attribute this to the gas-poor nature of one of the merging haloes resulting in no significant rise in temperature or turbulence and instead inducing a rapid increase in central density and hydrostatic pressure. This constitutes a novel formation pathway for Pop III stars and establishes major mergers as potentially the primary source of gas, thus redefining the role of major mergers at this epoch.
Aluminium-26 production in low- and intermediate-mass binary systems
Authors: Osborn Zara , Karakas Amanda I , Kemp Alex J , Izzard Robert G
Published: October 2023

Aluminium-26 is a radioactive isotope which can be synthesized within asymptotic giant branch (AGB) stars, primarily through hot bottom burning. Studies exploring 26Al production within AGB stars typically focus on single-stars; however, observations show that low- and intermediate-mass stars commonly exist in binaries. We use the binary population synthesis code binary_c to explore the impact of binary evolution on 26Al yields at solar metallicity both within individual AGB stars and a low/intermediate-mass stellar population. We find the key stellar structural condition achieving most 26Al overproduction is for stars to enter the thermally pulsing AGB (TP-AGB) phase with small cores relative to their total masses, allowing those stars to spend abnormally long times on the TP-AGB compared to single-stars of identical mass. Our population with a binary fraction of 0.75 has an 26Al weighted population yield increase of 25 per cent compared to our population of only single-stars. Stellar-models calculated from the Mt Stromlo/Monash Stellar Structure Program, which we use to test our results from binary_c and closely examine the interior structure of the overproducing stars, support our binary_c results only when the stellar envelope gains mass after core-He depletion. Stars which gain mass before core-He depletion still overproduce 26Al, but to a lesser extent. This introduces some physical uncertainty into our conclusions as 55 per cent of our 26Al overproducing stars gain envelope mass through stellar wind accretion onto pre-AGB objects. Our work highlights the need to consider binary influence on the production of 26Al.
Interface of equation of state, atomic data, and opacities in the solar problem
Authors: Pradhan Anil K
Published: October 2023

The dependence of the Rosseland Mean Opacity (RMO) on the equation of state and the number of included atomic levels of iron ions prevalent at the solar radiative/convection boundary is investigated. The ‘chemical picture’ Mihalas–Hummer–Däppen (MHD) equation-of-state (EOS), and its variant QMHD–EOS, are studied at two representative temperature–density sets at the base of the convection zone and the Sandia Z experiment: (2 × 106 K, 1023/cc) and (2.11 × 106 K, 3.16 × 1022/cc), respectively. It is found that whereas the new atomic data sets from accurate R-matrix calculations for opacities (RMOP) are vastly overcomplete, involving hundreds to over a thousand levels of each of the three Fe ions considered – Fe xvii, Fe xviii, Fe xix – the EOS constrains contributions to RMOs by relatively fewer levels. The RMOP iron opacity spectrum is quite different from the Opacity Project distorted wave model and shows considerably more plasma broadening effects. This work points to possible improvements needed in the EOS for opacities in high-energy–density plasma sources.
Tumor-specific polycistronic miRNA delivered by engineered exosomes for the treatment of glioblastoma
Authors: McDonald Malcolm F , Hossain Anwar , Momin Eric N , Hasan Irtiza , Singh Sanjay , Adachi Satoshi , Gumin Joy , Ledbetter Daniel , Yang Jing , Long Lihong , Daou Marc , Gopakumar Sricharan , Phillips Lynette M , Parker Kerrigan Brittany , Lang Frederick F
Published: October 2023

Background

Glioblastoma (GBM) has poor prognosis due to ineffective agents and poor delivery methods. MicroRNAs (miRs) have been explored as novel therapeutics for GBM, but the optimal miRs and the ideal delivery strategy remain unresolved. In this study, we sought to identify the most effective pan-subtype anti-GBM miRs and to develop an improved delivery system for these miRs.

Methods

We conducted an unbiased screen of over 600 miRs against 7 glioma stem cell (GSC) lines representing all GBM subtypes to identify a set of pan-subtype-specific anti-GBM miRs and then used available TCGA GBM patient outcomes and miR expression data to hone in on miRs that were most likely to be clinically effective. To enhance delivery and expression of the miRs, we generated a polycistronic plasmid encoding 3 miRs (pPolymiR) and used HEK293T cells as biofactories to package pPolymiR into engineered exosomes (eExos) that incorporate viral proteins (Gag/VSVg) in their structure (eExos+pPolymiR) to enhance function.

Results

Our stepwise screen identified miR-124-2, miR-135a-2, and let-7i as the most effective miRs across all GBM subtypes with clinical relevance. Delivery of eExos+pPolymiR resulted in high expression of all 3 miRs in GSCs, and significantly decreased GSC proliferation in vitro. eExos+pPolymiR prolonged survival of GSC-bearing mice in vivo when compared with eExos carrying each of the miRs individually or as a cocktail.

Conclusion

eExos+pPolymiR, which includes a pan-subtype anti-glioma-specific miR combination encoded in a polycistronic plasmid and a novel exosome delivery platform, represents a new and potentially powerful anti-GBM therapeutic.
Distribution of suspected tick vectors and reported cases of Rocky Mountain spotted fever in California
Authors: Rotramel George L. , Schwan Tom G. , Doty Robert E.
Published: October 2023

Evidence is presented for an area of human risk to Rocky Mountain spotted fever (RMSF) in California extending beyond the range of its classic tick vector, Dermacentor andersoni. Geographic, seasonal, and host distributions of Dermacentor variabilis and Dermacentor occidentalis suggest these species as potential vectors of RMSF in California outside the range of Dermacentor andersoni.
Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis
Authors: Ghanem Joseph , Orri Massimiliano , Moro Laura , Lavigne Katie M , Raucher-Chéné Delphine , Malla Ashok , Joober Ridha , Lepage Martin
Published: October 2023

Background and Hypothesis

Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups.

Study Design

In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS).

Study Results

Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms.

Conclusion

We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.
Comparison of growth performance and tissue cobalt concentrations in beef cattle fed inorganic and organic cobalt sources
Authors: Raths Rachel , Rodriguez Brandon , Holloway Joseph W , Waite Audie , Lawrence Ty , van de Ligt Jennifer L G , Purvis Heb , Doering-Resch Heidi , Casper David P
Published: October 2023

Cobalt is an essential trace mineral required for ruminal vitamin B12 synthesis, but sources differ in ruminal microbial utilization, i.e., cobalt carbonate is poorly water soluble, whereas acetate and lactate forms are water soluble. Reports comparing organic cobalt lactate to other cobalt salts are lacking. The study objective was to determine if feeding cobalt lactate at two inclusion rates resulted in similar growth performance and tissue cobalt concentrations as the carbonate and acetate forms used in feeds. One hundred Angus cross bred steers weighing 385 ± 20 kg were randomly assigned to one of five treatments. Cattle were fed a basal diet plus: 1) cobalt carbonate to supply cobalt at 30 mg/steer/d, 2) cobalt acetate to supply cobalt at 30 mg/steer/d, 3) cobalt acetate to supply cobalt at 60 mg/steer/d, 4) cobalt lactate to supply cobalt at 30 mg/steer/d, and 5) cobalt lactate to supply cobalt at 60 mg/steer/d. Cattle were fed according to industry standards until body fat deposition was visually deemed to grade USDA Choice, which was 92 and 117 d for each of the 2 blocks, respectively. Steers were harvested and carcass measurements recorded along with sampling of adipose, heart, kidney, liver, and muscle for tissue cobalt concentrations. Three statistical contrasts consisted of: 1: inorganic (cobalt carbonate) vs. organic (cobalt acetate and lactate); 2: cobalt acetate vs. cobalt lactate; and 3: feeding rate of 30 vs. 60 mg/steer/d cobalt. Body weight gains, average daily gains, dry matter intake, and feed conversions were similar (P > 0.10) for steers fed all cobalt sources and feeding rates. Hot carcass weight, yield grade, back fat thickness, and ribeye area were similar (P > 0.10) among steers fed all cobalt sources and inclusion rates. Liver, kidney, muscle, and adipose cobalt concentrations were similar (P > 0.08) for steers fed inorganic vs. organic cobalt sources. Feeding cobalt lactate compared with cobalt acetate did not affect (P > 0.10) liver, kidney, heart, muscle, and adipose tissue cobalt concentrations. Feeding 60 mg/steer/d cobalt compared with 30 mg/steer/d increased (P < 0.01) liver, kidney, heart, and adipose tissue cobalt concentrations, while muscle was a tendency (P < 0.06). The study demonstrated that feeding soluble cobalt lactate, a new cobalt source, resulted in similar growth performance, carcass characteristics, and tissue cobalt concentrations when compared with cobalt acetate and carbonate.
Derivation and Validation of a New Equation for Estimating Free Valproate Concentration in Critically Ill Adult Patients
Authors: Liu Ji Tong , Brown Caitlin S. , Mara Kristin C. , Riker Richard R. , Rabinstein Alejandro A. , Fraser Gilles L. , May Teresa L. , Armstrong Kaitlin J. , Seder David B. , Gagnon David J.
Published: October 2023

IMPORTANCE:

Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients.

OBJECTIVES:

We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations.

DESIGN:

Retrospective cohort study.

SETTING:

Two academic medical centers.

PARTICIPANTS:

Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022.

MAIN OUTCOMES AND MEASURES:

Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared.

RESULTS:

Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, –13.6 to 14.2]) than the Nasreddine (–9.2 [–26.5 to 8.2]), Kodama (–9.7 [–30.0 to 10.7]), Conde Giner (–7.9 [–24.9 to 9.1]), and Parent (–9.9 [–30.7 to 11.0]) equations, and similar to Doré (–2.0 [–16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%).

CONCLUSIONS AND RELEVANCE:

For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness.