Broader Level Research Articles

Learning the Causal Structure of Networked Dynamical Systems under Latent Nodes and Structured Noise

This paper considers learning the hidden causal network of a linear networked dynamical system (NDS) from the time series data at some of its nodes -- partial observability. The dynamics of the NDS are driven by colored noise that generates spurious associations across pairs of nodes, rendering the problem much harder. To address the challenge of noise correlation and partial observability, we assign to each pair of nodes a feature vector computed from the time series data of observed nodes. The feature embedding is engineered to yield structural consistency: there exists an affine hyperplane that consistently partitions the set of features, separating the feature vectors corresponding to connected pairs of nodes from those corresponding to disconnected pairs. The causal inference problem is thus addressed via clustering the designed features. We demonstrate with simple baseline supervised methods the competitive performance of the proposed causal inference mechanism under broad connectivity regimes and noise correlation levels, including a real world network. Further, we devise novel technical guarantees of structural consistency for linear NDS under the considered regime.

Abstract 3522: Application of large language models to nucleotide sequences for profiling signaling pathway disruptions in ovarian cancer patients

Abstract Ovarian cancer is a challenging disease, often exhibiting recurrence after initial treatment. The complexity arises from simultaneous disruptions in multiple signaling pathways within tumor cells, rendering targeted inhibitors ineffective in providing sustained therapeutic impact. While targeted sequencing panels can identify specific therapeutically relevant events, they often fail to capture the complete picture of targetable tumor driving aberrations, and provide biomarkers relevant to disease resistance and/or recurrence. A potential solution lies in comprehensively defining the landscape of signaling pathway alterations by identifying molecular triggers underlying their dysregulation. While individual DNA mutations sometimes may not lead to carcinogenesis or changes in tumor cell behavior, combination of deactivating mutations in suppressor genes, can influence tumor development and prognosis, warranting a comprehensive delineation of their effect on the broad signaling network level. To this end, we propose the Large Language Models (LLMs), which have been successful in natural language processing, particularly in understanding context. Such tools are essential for discerning the effect of mutation combinations, their physical proximity to other mutations, and functional gene regions. We obtained mutation annotation files for 177 ovarian cancer patients from the TCGA database, reconstructing consensus nucleotide sequences using a reference genome. To input this data into LLMs, we generated embeddings for these sequences using the Nucleotide Transformer algorithm, pre-trained on 500 million variants of the reference genome. Additionally, we extracted data on detected disruptions in 10 signaling pathways (Cell Cycle, HIPPO, MYC, NOTCH, NRF2, PI3K, RTK RAS, TP53, TGF-Beta, WNT) for these patients from TCGA. Each pathway was associated with the percentage of its alteration. We trained a deep learning algorithm on these data to predict a combination of 10 numerical values, each corresponding to the percentage of disruption for a given signaling pathway. Our findings revealed that nearly half of the patients exhibited disruptions in 5 or more signaling pathways. The algorithm developed enables the determination of the extent of disruption in each pathway based on whole exome sequencing results. This approach facilitates more informed treatment strategy planning and enhances the efficient development of new drugs for ovarian cancer treatment. Citation Format: Dmitrii K. Chebanov, Nadezhda S. Tatevosova. Application of large language models to nucleotide sequences for profiling signaling pathway disruptions in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3522.

Antimicrobial resistance landscape in a metropolitan city context using open drain wastewater-based metagenomic analysis

One Health concept recognizes the inextricable interactions of diverse ecosystems and their subsequent effect on human, animal and plant health. Antimicrobial resistance (AMR) is a major One Health concern and is predicted to cause catastrophes if appropriate measures are not implemented. To understand the AMR landscape in a south Indian metropolitan city, metagenomic analysis of open drains was performed. The data suggests that in January 2022, macrolide class of antibiotics contributed the highest resistance of 40.1% in the city, followed by aminoglycoside- 24.4%, tetracycline- 11.3% and lincosamide- 6.7%. The ‘mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics’ were the major contributor of resistance with a prevalence of 39.7%, followed by ‘16s rRNA with mutation conferring resistance to aminoglycoside antibiotics’- 22.2%, ‘16S rRNA with mutation conferring resistance to tetracycline derivatives’- 9.2%, and ‘23S rRNA with mutation conferring resistance to lincosamide antibiotics’- 6.7%. The most prevalent antimicrobial resistance gene (ARG) ‘mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics’ was present in multiple pathogens including Escherichia coli, Campylobacter jejuni, Acinetobacter baumannii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Klebsiella pneumoniae and Helicobacter pylori. Most of the geographical locations in the city showed a similar landscape for AMR. Considering human mobility and anthropogenic activities, such an AMR landscape could be common across other regions too. The data indicates that pathogens are evolving and acquiring antibiotic resistance genes to evade antibiotics of multiple major drug classes in diverse hosts. The outcomes of the study are relevant not only in understanding the resistance landscape at a broader level but are also important for identifying the resistant drug classes, the mechanisms of gaining resistance and for developing new drugs that target specific pathways. This kind of surveillance protocol can be extended to regions in other developing countries to assess and combat the problem of antimicrobial resistance.

Activity of Bambusa vulgaris extract in reducing silver nanoparticles: evaluation against methylene blue organic pollutant and microbial agents

This article presents an investigation focusing on successfully synthesising silver nanoparticles with zero valences. The synthesis involves utilising an extract from bamboo leaves, specifically those obtained from the Bambusa vulgaris species. X-ray diffraction, transmission electron microscopy, Fourier transform infrared, and ultraviolet–visible spectroscopy characterised the synthesised Ag nanomaterials. The X-ray diffraction pattern obtained from the collected samples confirms the presence of a face-centred cubic structure and a significant level of crystallinity. The studied materials had a spherical morphology, as determined by transmission electron microscopy analysis. The particle size was measured to be 22 nm. FT-IR analysis validates the presence of biomolecules in the leaf extract, which is accountable for the reduction of Ag+ ions and subsequent stabilisation of Ag nanoparticles. Without chemical agents, the reduction of Ag ions to Ag was confirmed using UV–Vis spectroscopy. This analytical technique revealed a peak at 450 nm, indicating surface plasmon resonance. Photogenerated electron carriers can be inferred from a distinct and diverse set of photoluminescence spectra. The study also includes an analysis of the photocatalytic effectiveness of the synthesised silver nanoparticles, specifically in the breakdown of methylene blue (MB) dye. The efficacy of the silver nanoparticle (Ag NP) photocatalyst was assessed by examining the degradation process of a methylene blue dye solution in an aqueous medium under direct sunlight exposure. The experiment also evaluated the impact of catalyst dosage and dye concentration on the efficient degradation of MB dye. The investigation findings indicate that the optimal catalyst dosage and dye concentration were determined to be 0.015 mg/mL and 10 µM, respectively. Notably, the photocatalytic degradation process exhibited remarkable efficacy, with a peak efficiency of 94% after 120 min under direct solar irradiation. The experimental results suggest that the synthesised particles demonstrate a disintegration rate of 96% over 120 min when exposed to visible light. The utilisation of bio-processed silver nanoparticles has exhibited the achievement of phase purity during the manufacturing process, as well as an enhancement in catalytic efficacy. It implies that the synthesised technique offers a more advantageous option for producing nanoparticles on a large scale, potentially applicable in wastewater treatment at a broad level.

Intraspecific trait variation modulates the temperature effect on elemental quotas and stoichiometry in marine Synechococcus.

Diverse phytoplankton modulate the coupling between the ocean carbon and nutrient cycles through life-history traits such as cell size, elemental quotas, and ratios. Biodiversity is mostly considered at broad functional levels, but major phytoplankton lineages are themselves highly diverse. As an example, Synechococcus is found in nearly all ocean regions, and we demonstrate contains extensive intraspecific variation. Here, we grew four closely related Synechococcus isolates in serially transferred cultures across a range of temperatures (16-25°C) to quantify for the relative role of intraspecific trait variation vs. environmental change. We report differences in cell size (p<0.01) as a function of strain and clade (p<0.01). The carbon (QC), nitrogen (QN), and phosphorus (QP) cell quotas all increased with cell size. Furthermore, cell size has an inverse relationship to growth rate. Within our experimental design, temperature alone had a weak physiological effect on cell quota and elemental ratios. Instead, we find systemic intraspecific variance of C:N:P, with cell size and N:P having an inverse relationship. Our results suggest a key role for intraspecific life history traits in determining elemental quotas and stoichiometry. Thus, the extensive biodiversity harbored within many lineages may modulate the impact of environmental change on ocean biogeochemical cycles.

End-user research into understanding perceptions of and reactions to a microarray patch (MAP) for contraception among women in Ghana, Kenya and Uganda.

Many organizations are developing new contraceptive products and approaches that promote self-care including a microarray patch (MAP) that has the potential for self-administration with appropriate training. We studied women's perceptions of the MAP technology with the primary goal of providing feedback on product attributes to inform early technical design decisions regarding various MAP contraceptive products in development by MAP developers. Our study consisted of a qualitative phase with in-person In-Depth Interviews (IDIs) with a total of 60 women of reproductive age (WRA) and quantitative surveys, via face-to-face computer-assisted interviews of a total of 927 women in Ghana, Kenya and Uganda. Women's perceptions on 12 attributes of the MAP were assessed through written descriptions, a profile, and visual stimuli such as graphics and images. Overall, the most widely preferred attribute set included: a hand-applied MAP, utilizing one circular patch, with a sticky backing, no larger than 2 cm diameter in size, applied by self, to the arm, offering sensory feedback (clicking sound and/or color change signals) to confirm enough pressure, successful application and removal, lasting 6 months with up to 12 months return to natural state of fertility. There is space to allow for variation in MAP designs (including the use of an applicator or provider administered MAP) if the design promotes and reflects the needs and expectations of users and providers. The contraceptive MAP had a high and broad level of appeal amongst all groups of women who participated in the study and has a strong value proposition around important contraceptive needs such as ease of use, convenience, and discretion.

Exploring Superstitious Beliefs Among Educated Urban Population

Technical revolutions and scientific advancements are conspicuous, but still, false beliefs and superstitious behaviour are quite commonplace. It could be believed that these beliefs are held by less educated people. Therefore, the present study investigated superstitions among educated urban people. Using a qualitative research method, data was collected through interviews and analyzed through thematic analysis. A total of 8 participants (i.e., 2 males and 6 females) participated in the study. All of the participants were highly educated (16 years’ education or above). A purposive sampling technique was used to include participants in this research. Detailed semi-structured interviews were conducted with each participant with their consent. Seven themes were derived including brooming, marriage fixing, palm itching, eye blink, glass break, lucky stones, and lucky numbers. The study recommends inculcating scientific knowledge on a broader level in Pakistan.

Hybrid Rice Production: A Worldwide Review of Floral Traits and Breeding Technology, with Special Emphasis on China.

Rice is an important diet source for the majority of the world's population, and meeting the growing need for rice requires significant improvements at the production level. Hybrid rice production has been a significant breakthrough in this regard, and the floral traits play a major role in the development of hybrid rice. In grass species, rice has structural units called florets and spikelets and contains different floret organs such as lemma, palea, style length, anther, and stigma exsertion. These floral organs are crucial in enhancing rice production and uplifting rice cultivation at a broader level. Recent advances in breeding techniques also provide knowledge about different floral organs and how they can be improved by using biotechnological techniques for better production of rice. The rice flower holds immense significance and is the primary focal point for researchers working on rice molecular biology. Furthermore, the unique genetics of rice play a significant role in maintaining its floral structure. However, to improve rice varieties further, we need to identify the genomic regions through mapping of QTLs (quantitative trait loci) or by using GWAS (genome-wide association studies) and their validation should be performed by developing user-friendly molecular markers, such as Kompetitive allele-specific PCR (KASP). This review outlines the role of different floral traits and the benefits of using modern biotechnological approaches to improve hybrid rice production. It focuses on how floral traits are interrelated and their possible contribution to hybrid rice production to satisfy future rice demand. We discuss the significance of different floral traits, techniques, and breeding approaches in hybrid rice production. We provide a historical perspective of hybrid rice production and its current status and outline the challenges and opportunities in this field.

When rules turn into tools: An activity theory-based perspective on implementation processes and unintended consequences.

The idea that actions of people, organizations or governments may lead to Unintended Consequences (UICs) is not new. In health, UICs have been reported as a result of various interventions including quality improvement initiatives, health information technology implementation, and knowledge translation, especially those involving translation of broad policies (evidence-based medicine and patient-centred care) or system level improvement into actionable items or tools. While some unintended consequences cannot be anticipated, others may be predictable. In this article, we present a model based on cultural historical activity theory, which may help policy-makers, health leaders, and researchers better anticipate UICs resulting from implementation of new programs or technologies and take action to address them or mitigate their risk of occurrence. We support this model using examples of UICs of implementing family centred care principles, electronic health records, and computerized templates for quality improvement in chronic disease management.

Evaluation of Genetic Parameters and Comparison of Stress Tolerance Traits in Different Strains of Litopenaeus vannamei.

Litopenaeus vannamei stands out globally in aquaculture for its fast growth, broad salt tolerance, disease resistance, and high protein levels. Selective breeding requires the precise estimation of the variance components and genetic parameters for important traits. This study formed lineages from 20 full sibling families of L. vannamei, with progenitors from Thailand and the USA. We then assessed the genetic resilience traits of juvenile shrimp from these families to high ammonia-N, high pH, and low salinity by performing a 96 h acute toxicity test. Mortality rates for the families under 96 h exposure to high ammonia-N, high pH, and low salinity were 19.52-92.22%, 23.33-92.22%, and 19.33-80.00%, respectively, showing significant variance in stress tolerance among families (p < 0.05). Survival heritability estimates, using threshold male and female models, were 0.44 ± 0.12 in high ammonia-N, 0.41 ± 0.12 in high pH, and 0.27 ± 0.08 in low salinity, respectively. Genetic correlations between growth and stress resistance traits varied from 0.0137 ± 0.2406 to 0.8327 ± 0.0781, and phenotypic correlations ranged from 0.0019 ± 0.0590 to 0.6959 ± 0.0107, indicating a low-to-high positive correlation significant at (p < 0.05). It was found that the survival rate of families No. 2 and No. 9 was higher under high ammonia-N and high pH stresses, while the survival rate of family No. 10 was higher under low salinity stress after comparing two selection criteria, the breeding values and phenotypic values. Thus, these three families are identified as potential breeding program candidates. Through the creation of a genetic parameter estimation model, the genetic variances across mating combinations for stress resistance traits were obtained and families with heightened stress resistance were identified, laying the groundwork for enhanced genetic selection of L. vannamei.

Dynamical interplay between superconductivity and pseudogap in cuprates as revealed by terahertz third-harmonic generation spectroscopy

We report on nonlinear terahertz third-harmonic generation (THG) measurements on YBa 2 Cu 3 O 6+ x thin films. Different from conventional superconductors, the THG signal starts to appear in the normal state, which is consistent with the crossover temperature T * of pseudogap over broad doping levels. Upon lowering the temperature, the THG signal shows an anomaly just below T c in the optimally doped sample. Notably, we observe a beat pattern directly in the measured real-time waveform of the THG signal. We elaborate that the Higgs mode, which develops below T c , couples to the mode already developed below T * , resulting in an energy level splitting. However, this coupling effect is not evident in underdoped samples. We explore different potential explanations for the observed phenomena. Our research offers valuable insight into the interplay between superconductivity and pseudogap.

Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development

BackgroundThe common house spider Parasteatoda tepidariorum represents an emerging new model organism of arthropod evolutionary and developmental (EvoDevo) studies. Recent technical advances have resulted in the first single-cell sequencing (SCS) data on this species allowing deeper insights to be gained into its early development, but mid-to-late stage embryos were not included in these pioneering studies.ResultsTherefore, we performed SCS on mid-to-late stage embryos of Parasteatoda and characterized resulting cell clusters by means of in-silico analysis (comparison of key markers of each cluster with previously published information on these genes). In-silico prediction of the nature of each cluster was then tested/verified by means of additional in-situ hybridization experiments with additional markers of each cluster.ConclusionsOur data show that SCS data reliably group cells with similar genetic fingerprints into more or less distinct clusters, and thus allows identification of developing cell types on a broader level, such as the distinction of ectodermal, mesodermal and endodermal cell lineages, as well as the identification of distinct developing tissues such as subtypes of nervous tissue cells, the developing heart, or the ventral sulcus (VS). In comparison with recent other SCS studies on the same species, our data represent later developmental stages, and thus provide insights into different stages of developing cell types and tissues such as differentiating neurons and the VS that are only present at these later stages.

Acylation of MLKL Impacts Its Function in Necroptosis.

Mixed lineage kinase domain-like (MLKL) is a key signaling protein of necroptosis. Upon activation by phosphorylation, MLKL translocates to the plasma membrane and induces membrane permeabilization, which contributes to the necroptosis-associated inflammation. Membrane binding of MLKL is initially initiated by electrostatic interactions between the protein and membrane phospholipids. We previously showed that MLKL and its phosphorylated form (pMLKL) are S-acylated during necroptosis. Here, we characterize the acylation sites of MLKL and identify multiple cysteines that can undergo acylation with an interesting promiscuity at play. Our results show that MLKL and pMLKL undergo acylation at a single cysteine, with C184, C269, and C286 as possible acylation sites. Using all-atom molecular dynamic simulations, we identify differences that the acylation of MLKL causes at the protein and membrane levels. Through investigations of the S-palmitoyltransferases that might acylate pMLKL in necroptosis, we showed that zDHHC21 activity has the strongest effect on pMLKL acylation, inactivation of which profoundly reduced the pMLKL levels in cells and improved membrane integrity. These results suggest that blocking the acylation of pMLKL destabilizes the protein at the membrane interface and causes its degradation, ameliorating the necroptotic activity. At a broader level, our findings shed light on the effect of S-acylation on MLKL functioning in necroptosis and MLKL-membrane interactions mediated by its acylation.

Efficient color image steganography based on new adapted chaotic dynamical system with discrete orthogonal moment transforms

In today's rapidly evolving digital landscape, safeguarding the secure transmission of sensitive information is paramount. Traditional steganography methods, while effective at data concealment, have grown vulnerable to brute force attacks in our age of powerful computing. This paper addresses the pressing need to bolster data transmission security. To address the challenges posed by limited key space and security concerns associated with 1-D chaotic maps in data transmission, we introduce a novel 1-D chaotic map, the Multi-Parameter Chebyshev Map (MCM). The MCM boasts four control parameters, each with a broad chaotic range and high chaos level, significantly enhancing security. Furthermore, we present an innovative steganography technique for color images that leverages the MCM in conjunction with discrete moment transforms. This method chaotically embeds the secret message within the moment coefficients of a cover color image using MCM and quantization rules. The expansive chaotic range and high chaos level of the MCM substantially reinforce the security of this approach. The considered moment transforms include Tchebichef, Krawtchouk, Hahn, Charlier, Meixner, Shmaliy, Racah, and Dual-Hahn. The performance of the proposed steganography method is thoroughly evaluated and compared with other state-of-the-art methods in terms of hiding capacity and image quality in both spatial and transform domains. The quantization of moment coefficients demonstrates its superior performance. This method holds crucial implications for practical applications requiring secure communication of color images, such as military and medical contexts. The combination of MCM and moment transforms in this method presents a promising avenue for future research in the field of information hiding.

Nanopore Direct RNA Sequencing for Modified Uridine Nucleotides Yields Signals Dependent on the Physical Properties of the Modified Base

AbstractSequencing for RNA modifications with the nanopore direct RNA sequencing platform provides ionic current levels, helicase dwell times, and base call data that differentiate the modifications from the canonical form. Herein, model RNAs were synthesized with site‐specific uridine (U) base modifications that enable the study of increasing an alkyl group size, halogen identity, or a change in base acidity to impact the nanopore data. The analysis concluded that increases in alkyl size trend with greater current blockage but a similar change in base‐call error was not found. The addition of a halogen series to C5 of U revealed that the current levels recorded a trend with the water‐octanol partition coefficient of the base, as well as the base call error. Studies with U modifications that are deprotonated (i. e., anionic) under the sequencing conditions gave broad current levels that influenced the base call error. Some modifications led to helicase dwell time changes. These insights provide design parameters for modification‐specific chemical reagents that can shift nanopore signatures to minimize false positive reads, a known issue with this sequencing approach.

Nasal Vowels in Solor Dialect of Lamaholot Language and Their Morpho-Syntactic Significance

The Lamaholot language spoken in East Flores and Lembata has several interesting distinctive features, compared to its neighboring languages. One of these features is nasal vowels. Nasal vowels in this language are phonemic, in that they show distinct meanings in contrasted minimal-pair words. Because of this phonemic characteristic, the nasal vowels in the dialect have significant influences on the Lamaholot linguistics. This research will examine the importance of nasal vowels in Solor dialect of Lamaholot morphologically and syntactically. Two research problems this study has tried to answer are (1) what are the morphologic and syntactic significances of the nasal vowels of Solor Dialect of Lamaholot Language, and (2) what meanings do these nasal vowels indicate when they involve in morphological processes? Apart from being an additional linguistic reference for the study of languages in eastern Indonesia in particular, and Austronesian languages at a broader level, this research also contributes to the efforts to maintain regional languages in East Nusa Tenggara. The approach to be used in this study is descriptive. The theory referred to is functional typology with the concepts of Basic Linguistic Theory based on generative structural grammar. References to the theory can be read, among others, in Payne (1997), Dixon (2010a), Comrie (1989) and Sophen (2007a, 2007b, 2007c). Data for this study was collected through recording and elicitation from the native speakers of Solor dialect. The collected corpus in the form of audio data is analyzed and stored electronically with the Praat application, and then transcribed into text form. The text data is sorted, then analyzed and stored electronically with the Toolbox application, which can later be used as additional data for the Solor – Lamaholot dialect dictionary database, which the author is currently working on. The research results show that the presence of nasal vowels in the Solor dialect of the Lamaholot language gives very significant and influential contribution to the communication and speech of speakers of this dialect. This grammatical feature is so important that its presence can give rise to different interpretations by listeners. Morphosyntactically, the nasal vowels in Solor dialect of the Lamaholot language express five functions, namely (1) to express the pronominal form of ownership; (2) to express the form of alienable ownership; (3) to express the enclitic form of third person singular possession in common nouns; (4) to state the participial function derived from the verb; and (5) to express the attributive function of adjectives in the Solor dialect of the Lamaholot language.

P734 Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD study

Abstract Background The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy. Methods This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response. Results Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories. Conclusion Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.

Advancing environmental assessment of the circular economy: Challenges and opportunities

The lifecycle assessment (LCA) framework is widely applied to comprehensively evaluate and improve the environmental performance of a circular economy (CE). The advances and application of LCA has been primarily restricted to evaluate the environmental performance of the CE at a micro-level, wherein the CE is implemented for a single product system.However, the CE can be operationalized at two broader levels: the meso–level (for eco-industrial parks) and the macro-level (for a city, state, or nation). Six methodological challenges emerge when applying LCA to a meso‑ or macro-level CE and remain unaddressed in the existing literature. This includes: selecting a relevant system boundary and functional unit, addressing data paucity and uncertainty, accounting for stakeholder behavior, assessing the trade-offs from renewable energy (RE) use, accounting for manufacturing and technology evolution, and quantifying displacement and rebound. This article proposes potential solutions and research priorities to address the above challenges.

Longitudinal Effects of Employees’ Big Five Personality Traits on Internal Promotions Differentiated by Job Level in a Multinational Company

Promotions are central to individual career success. For organisations, it is crucial to identify and develop employees capable of higher-level responsibility. Previous research has shown that personality traits as inter-individual differences predict promotions. However, effects have mostly been examined on a broad factor level. This study investigated longitudinal effects of Big Five personality traits on both factor (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness) and more detailed facet levels on promotions in employees of a multinational wholesale company (N = 1774, n = 343 promoted). We also explored how personality differentially impacts promotional likelihood as a matter of target job level (individual contributor vs. first- or senior-level manager roles). Overall, associations with promotions were detected for neuroticism (negative) and conscientiousness (positive). At the more nuanced facet level, all Big Five factors had at least one personality facet that was significantly related to promotions. Additionally, personality-promotion relationships were generally stronger for lower- rather than higher-level promotions. Taken together, our findings demonstrate that employee personality traits have a meaningful impact on who will be promoted and should hence be considered in organisational personnel selection, personnel development, and performance management practices.

Rationalising development of classification systems describing livestock production systems for disease burden analysis within the Global Burden of Animal Diseases programme

The heterogeneity that exists across the global spectrum of livestock production means that livestock productivity, efficiency, health expenditure and health outcomes vary across production systems. To ensure that burden of disease estimates are specific to the represented livestock population and people reliant upon them, livestock populations need to be systematically classified into different types of production system, reflective of the heterogeneity across production systems.This paper explores the data currently available of livestock production system classifications and animal health through a scoping review as a foundation for the development of a framework that facilitates more specific estimates of livestock disease burdens. A top-down framework to classification is outlined based on a systematic review of existing classification methods and provides a basis for simple grouping of livestock at global scale.The proposed top-down classification framework, which is dominated by commodity focus of production along with intensity of resource use, may have less relevance at the sub-national level in some jurisdictions and will need to be informed and adapted with information on how countries themselves categorize livestock and their production systems. The findings in this study provide a foundation for analysing animal health burdens across a broad level of production systems. The developed framework will fill a major gap in how livestock production and health are currently approached and analysed.