To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This study examines how internal CEO alliances, defined as social and structural ties between CEOs, subordinate executives, and board members, influence corporate carbon performance. Drawing on data from 36 countries over the period 2002–2023, we find that strong internal alliances are associated with weaker carbon performance, suggesting that concentrated internal power may hinder firms’ emission reduction efforts. However, this adverse effect is significantly moderated by various organizational and institutional factors. Specifically, it is attenuated in contexts characterized by stringent environmental regulation, robust media oversight, high regulatory quality, and greater board gender diversity. At the individual level, CEO characteristics such as hometown affiliation and older age also appear to reduce the negative influence of internal alliances. These findings advance our understanding of how CEO power dynamics interact with external and internal governance mechanisms to influence firms’ climate-related outcomes.
Design Science is the discipline that studies the creation of artifacts – products, services, and systems and their embedding in our physical, virtual, psychological, economic, and social environments. This editorial is a collective effort of the Design Science Journal’s editorial board members, past and present. The journal’s inaugural 2015 editorial, “Design Science: Why, What and How,” reflected the thoughts and vision of that first editorial board for the new journal and the discipline it represented. The present contribution offers the reflections of editors who served the journal in the past 10 years. The individual contributions were not primed and are presented here unedited for conformity or consistency. Differently from the 2015 editorial, there is no effort to synthesize the individual contributions, leaving the task to our readers, who can draw their own conclusions about the Design Science Journal and community accomplishments to date, and the challenges ahead.
Extant literature indicated that glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may potentially reduce risk of opioid overdose in persons with opioid use disorders (OUDs). Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on OUDs.
Methods:
We examined preclinical and clinical paradigms examining the effects of GLP-1 and GLP-1 RAs on OUD and OUD-associated behaviours (i.e. opioid self-administration, opioid-seeking behaviour). Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, and JBI EBP Database), PubMed, and Web of Science from database inception to 1 May 2025. Primary studies (n = 10) examining the aforementioned effects associated with GLP-1 and GLP-1 RA administration were retrieved for analysis.
Results:
GLP-1 RAs (i.e. exenatide, liraglutide) reduced opioid-seeking behaviour (p < 0.05) and self-administration of opioid drugs (p < 0.05) in preclinical paradigms. In addition, results from human studies indicate that GLP-1 administration was associated with reducing the risk of opioid overdose in human studies (aIRR = 0.60, 95% CI [0.43, 0.83]).
Conclusion:
GLP-1 RAs may affect opioid self-administration as well as the risk for overdose as evidenced by both preclinical and clinical data. There is a need for adequate well-controlled studies to determine whether GLP-1 RAs may provide clinically meaningful improvement and risk reduction in persons living with OUDs.
Background: Electroencephalography (EEG) has emerged as a minimally invasive technique to quantify functional changes in neural activity associated with neurodegenerative disorders such as Alzheimer’s Disease (AD). Given its non-invasive approach, EEG has the potential to fill the pressing gap forearly, accurate, and accessible methods to detect and characterize disease progression in AD. Methods: To address these challenges, we conducted a pilot analysis of a custom machine learning-based automated preprocessing and feature extraction pipeline to identify indicators of AD and correlates of disease progression. Results: Our pipeline successfully detected several new and previously established EEG-based measures indicative of AD status and progression. Key findings included alterations in delta and theta band power, network connectivity disruptions, and increased slowing of brain rhythms. Additionally, we observed strong correlations between EEG-derived metrics and clinical measures such as Mini-Mental State Examination (MMSE) scores, supporting the external validity of our approach. These findings highlight the sensitivity of EEG biomarkers in differentiating between early and late stages of AD. Conclusions: Our findings suggest that this automated approach provides a promising initial framework for implementing EEG biomarkers in the AD patient population, paving the way for improved diagnostic and monitoring strategies.
This paper presents a low-profile miniaturized dual-band antenna utilizing the quarter-mode substrate integrated waveguide (QMSIW) structure. The two modes of TE110 and TE220 of a single QMSIW structure are employed, enabling a dual-band operation. The frequency ratio between the two bands can be tuned by loading a capacitive structure, which is comprised of a capacitive-loaded patch and a short circuit post, inside the QMSIW structure. By introducing parasitic QMSIW structures through magnetic coupling, a dual-band antenna with enhanced bandwidths is achieved. The antenna has dimensions of smaller than 400 mm2 (0.048λL2) with a uniform height of 1.4 mm (0.016λL). Measurement results indicate that the −6 dB impedance bandwidths of the antennas can cover the 5G N78 (3.3–3.6 GHz) and N79 (4.8–5 GHz) bands, and the average efficiencies is better than −2.5 dB. To the authors’ knowledge, the proposed designs offer dual-wideband operation while having the smallest planar dimension compared to the previously reported antennas. Furthermore, an extended electric coupling dual-band antenna configuration is also described and measured, which achieves similar bandwidth extension as the proposed antenna.
Connecting individual robots to form an inter-reconfigurable system with a flexible base size enhances the ability to access and cover areas for cleaning and maintenance tasks. Given that increased configuration complexity expands the search space dimension, an optimal routing solution ensuring efficiency is essential. In this paper, we present an inter-reconfigurable multi-robot system capable of adjusting the bases of its two units, along with an optimal path planning approach for confined spaces based on a modified informed rapidly-exploring random tree algorithm by a greedy set (RIRRT*). We validate the navigation of the proposed inter-reconfigurable platform using RIRRT* for four informed dimensional search spaces as a case study in both simulated and real-world environments. The proposed path planning method for the inter-reconfigurable system outperformed conventional strategies, achieving significant reduction in both execution time and energy utilization.
Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.
To evaluate one-stage thyroid cartilage laryngotracheal reconstruction in children less than one year of age with congenital subglottic stenosis.
Methods
Congenital subglottic stenosis children less than one year old who underwent one-stage thyroid cartilage laryngotracheal reconstruction between 2016 and 2020 in our department were retrospectively reviewed. Their clinical characteristics, treatments and prognoses were assessed.
Results
Eleven congenital subglottic stenosis children (6–11 months) were included: seven with Myer–Cotton grade II, and four with Myer–Cotton grade III. Their tracheal diameters were corrected to normal size using thyroid cartilage, and they were intubated under sedation for two weeks after surgery. Moreover, all of them received anti-infection and anti-reflux therapies during hospitalisation. No breathing difficulty, aspiration, hoarseness or laryngitis was observed during the follow-up period (10–30 months), and their growth and development were age appropriate.
Conclusion
The one-stage thyroid cartilage laryngotracheal reconstruction is a good treatment option for congenital subglottic stenosis children less than one year old with Myer–Cotton grade II–III.
OBJECTIVES/GOALS: RETgene fusions in sarcoma are rare and their impact on pathogenicity is unknown. Malignant peripheral nerve sheath tumors (MPNST) are a deadly, genomically heterogenous soft tissue sarcoma rarely harboring targetable aberrations. We present a case of a CCDC6-RET fusion MPNST sensitive to RET-inhibitor therapy in a xenograft model. METHODS/STUDY POPULATION: Lung tumor tissue was obtained per an approved collection protocol from a 21yo male patient with a spontaneous MPNST harboring an inactivating mutation in NF-1 and a CCDC6-RET gene fusion detected by a commercially available sequencing panel (Signatera). To confirm pathogenicity of the RET fusion, fresh tumor tissue was engrafted into immunocompromised NSG mice in the anterior and posterior flanks, harvested at ~10 weeks, and re-transplanted into bilateral flanks. When tumor diameters reached 0.5-1cm (~4 weeks), mice were randomized into 3 groups (n=6/group) and treated with either vehicle (V) (PBS), the RET-specific inhibitor selpercatinib (S) (20mg/kg twice daily), or the multi-kinase inhibitor cabozantinib (C) (30mg/kg daily) by oral gavage. Mice were monitored weekly for weight and tumor size. RESULTS/ANTICIPATED RESULTS: 92% (33/36) of implanted tumors were evaluable for treatment response. Pre-treatment tumor volumes (mm3) across all three groups were similar (mean/Std Dev – V: 230/111, S: 271/132, C: 230/123). At day 7, tumor growth was significantly inhibited by S and C versus V (ANOVA p < 0.001, post-hoc Tukey’s V vs S p= 0.0178, V vs C p< 0.0001, S vs C p= 0.0005). V-treated tumors increased in volume by 60% while S reduced tumor volume by ~80% and C reduced tumor volume by ~20%. S and C treatments were tolerated well. and S improved survival with 100% of mice alive at day 63 vs 0% in V and C groups. 6 of the 12 implanted tumors treated with S, 50% increased in size after ~6-weeks following a >90% initial tumor reduction in tumor volume. Follow-on molecular studies in S-resistant tumors are ongoing. DISCUSSION/SIGNIFICANCE: Targetable genomic changes in MPNST, especially in RET, are infrequent and often considered stochastic. Our findings suggest that precision medicine approaches pairing genomic sequencing and in vivotesting of target gene pathogenicity may guide treatment planning and novel discovery for rare, difficult to treat sarcomas.
Initial microbial colonization plays an important role in neonatal gut health. However, studies on gut microbial composition at birth are challenging, due to the limited access to accurate sampling. Here, we characterized the jejunal and ileal bacterial composition (epimural and luminal) of neonatal calves within 30 minutes after birth, and compared it with maternal (birth canal and rectum) and birth environments. RNA-based quantification along with amplicon sequencing revealed the colonization of active, dense (1.1–9.4 × 108 16S rRNA copy/g of sample), and diverse bacteria in the calf small intestine at birth. Pseudomonadaceae and Propionibacteriaceae dominated epimural communities, while Propionibacteriaceae, Prevotellaceae, Ruminococcaceae, and Lachnospiraceae dominated luminal communities. The composition of calf gut bacteria at birth was significantly different from maternal bacteria, especially for beneficial bifidobacteria. The bacterial communities of calf body habitats were similar to those of the birth environment, which was again divergent from gut microbiota. This study suggests an establishment of small intestinal-specific microbiota from birth, which is considerably deviated from maternal microbiota. In corollary, we further propose that small intestinal microbiota colonization could be mainly modulated by host selection.
The efficient separation of hexane isomers from the light naphtha fraction is a significant challenge in the petrochemical industry. 5A zeolite adsorbent is used commercially to sieve alkane isomers. In this study, 5A zeolites were synthesized using a low-cost natural clay mineral precursor, i.e. palygorskite (PAL), with the addition of crystallization directing agent (CDA). By varying the mass ratio of CDA/deionized water, 5A zeolites were obtained as CDA-5%, CDA-7.5%, and CDA-10%. All products were submicron particles with an average particle size of 400–800 nm. A sieving test of CDA-induced 5A zeolites was carried out on hexane adsorbates including n-hexane (nHEX), 2-methylpentane (2MP), and 3-methylpentane (3MP). According to vapor-phase batch adsorption experiments, a significant equilibrium amount (0.149 g/g) of nHEX and only 0.0321 g/g 2MP and 0.0416 g/g 3MP were adsorbed on the 5A zeolite product with CDA-5%. The dynamic adsorption performance of 5A zeolite (CDA-5%) was evaluated by breakthrough curves of binary mixtures of nHEX/2MP and nHEX/3MP. Palygorskite 5A (PAL 5A) zeolite achieved maximum dynamic adsorption capacities of nHEX (0.16 g/g in both cases) at 200°C and 1.2 MPa total pressure. This work provided an economic alternative for the synthesis of 5A zeolites using natural clay minerals instead of chemical raw materials.
Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).
Participants and Methods:
Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.
Results:
Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.
Conclusions:
Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.
Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear.
Methods
One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed.
Results
Cognitive impairment (global cognition, verbal memory, language, visual–spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS.
Conclusions
Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.
Depressive symptoms, functional impairment, and decreased quality of life (QOL) are three important domains of major depressive disorder (MDD). However, the possible causal relationship between these factors has yet to be elucidated. Moreover, it is not known whether certain symptoms of MDD are more impairing than others. The network approach is a promising solution to these shortfalls.
Methods
The baseline data of a multicenter prospective project conducted in 11 governances of China were analyzed. In total, 1385 patients with MDD were included. Depressive symptoms, functioning disability, and QOL were evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17), the Sheehan Disability Scale (SDS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). The network was estimated through the graphical Least Absolute Shrinkage and Selection Operator (LASSO) technique in combination with the directed acyclic graph.
Results
Three centrality metrics of the graphical LASSO showed that social life dysfunction, QOL, and late insomnia exhibited the highest strength centrality. The network accuracy and stability were estimated to be robust and stable. The Bayesian network indicated that some depressive symptoms were directly associated with QOL, while other depressive symptoms showed an indirect association with QOL mediated by impaired function. Depressed mood was positioned at the highest level in the model and predicted the activation of functional impairment and anxiety.
Conclusions
Functional disability mediated the relationship between depressive symptoms and QOL. Family functionality and suicidal symptoms were directly related to QOL. Depressed mood played the predominant role in activating both anxiety symptom and functional impairment.
Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case–control study of 260 AMD cases and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95 % confidence interval (CI) of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs (95 % CI) were 0·30 (0·10, 0·88) for lutein and 0·28 (0·11, 0·74) for β-cryptoxanthin. The associations for other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD. ORs (95% CIs) comparing extreme categories were 0·42 (0·20, 0·88) for spinach and 0·52 (95% CI: 0·27, 0·98) for egg. Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0·23; 95% CI: 0·08, 0·71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
For each recollement of triangulated categories, there is an epivalence between the middle category and the comma category associated with a triangle functor from the category on the right to the category on the left. For a morphic enhancement of a triangulated category $\mathcal {T}$, there are three explicit ideals of the enhancing category, whose corresponding factor categories are all equivalent to the module category over $\mathcal {T}$. Examples related to inflation categories and weighted projective lines are discussed.
We present here the first study on the stability of plane Poiseuille flow when the fluid is stratified in density perpendicularly to the plane of horizontal shear. Using laboratory experiments, linear stability analyses and direct numerical simulations, we describe the appearance of an instability that results from a resonance of internal gravity waves and Tollmien–Schlichting waves carried by the flow. This instability takes the form of long meanders confined in thin horizontal layers stacked along the vertical axis.
Prior research in the behavioral sciences has demonstrated that reminders can be an effective tool for encouraging health-related behavior changes. This article extends that literature by reporting the outcome of a randomized controlled trial of mailed vaccination reminders. In addition to making a substantive contribution regarding the efficacy of mailed reminders, this article also makes a methodological contribution: it illustrates how researchers can study the causal impact of an intervention even when a pure parallel trial is not possible. In this study, the Louisiana Department of Health sent postcard reminders regarding four recommended vaccinations (influenza, tetanus, shingles and pneumonia) to 208,867 senior residents of Louisiana. We used block randomization and a stepped wedge design to assess the efficacy of the intervention. Individuals were blocked by their prior vaccine record and randomized to receive the postcard in one of four consecutive months (October–January). The reminder postcard had an overall positive effect on vaccination rates. The statistically significant and substantively small increase in overall vaccination rates was driven by participants who received the postcard reminder early in the intervention period.
This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.