bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and initial condensation characteristics of superhydrophobic coating based on nano-SiO2 particles
Authors: Pan Shishun , Sheng Wei , Zheng Haikun , Bayizi Maierzukejiang , Liu Sikai , Wang Yunpeng , Guo Huazheng
Published: January 2025

Superhydrophobic surfaces can effectively inhibit the growth of droplets and reduce attachment, thus inhibiting the formation of frost. In this paper, using dimethyldimethoxysilane-modified silica nanoparticles, a superhydrophobic coating with a contact angle of 165.73 ± 1° and a rolling angle of 2 ± 1° was successfully prepared by the secondary spraying method, and the chemical composition of the substrate and the surface morphology of the coating were characterized by means of FT-IR, EDS, and SEM. A visualization test rig was constructed to investigate the condensation droplet growth characteristics on the superhydrophobic surface across various tilt angles (0°to 90°), cold surface temperatures (-1 ℃ to 5 ℃), and humidity levels (45% to 75%). The experimental results revealed that as the tilt angle increases, the forces acting on the condensed droplets change, resulting in a higher frequency of droplet merging, jumping, and slipping. Furthermore, a decrease in cold surface temperature accelerates the growth of condensed droplets. Under varying humidity conditions, droplets on the superhydrophobic surface nucleate and grow more rapidly in high humidity environments, where they exhibit a larger coverage area despite having a relatively small mean radius.
Jacob van Ruisdael's Ecological Landscapes
Authors: Levesque Catherine
Published: January 2025

This book examines Jacob van Ruisdael's treatment of five subjects - dunes, grainfields, ruins, rushing water, and woodlands - that recur throughout his career. The paintings, though fictive, show close attention to the complexities of particular environments that can be fruitfully considered 'ecological'. The pattern of Ruisdael's reworking each environment and associated phenomena shows him as laboring over these themes. His work across media conveys something of his demanding and methodical procedure as he sought to achieve pictorially the force, temporality, vitality, and motion of nature. Ruisdael's paintings decenter humankind within familiar yet reimagined landscapes. His ability to depict nature's dynamism provided an alternative vision at a foundational moment when landscape, increasingly manipulated and controlled, was most often considered property and investment. His focus on the techniques and processes of his own work to render these entities was essential to his ecological perspective and invites a similar recognition from an attentive viewer.
Will It Be FINE-for-EU? A Proposal for a Mechanism Funding Pan-European Green Investment to Promote the EU (Still) Meeting Its Climate Goals
Authors: Scherleitner Moritz , Traversa Edoardo
Published: January 2025

Addressing climate change is a global priority. There is broad, science-based consensus that efficient environmental policy requires significant and rapid investments aimed at accelerating energy transition and safeguarding biodiversity. Yet, despite valuable improvements such as NextGenerationEU and the ETS, the EU and its Member States are still in search of extra financial resources. Here, we establish the FINE-for-EU mechanism to provide finance for pan-European green investment projects. We propose setting up a Pan-European Climate Fund to create a financial link between the benefits businesses derive from the cross-border legal framework and the specific responsibilities they have towards supporting climate objectives.
Evaluation of Claytone-ER as a novel rheological additive for enhancing oil-based drilling fluid performance under high-pressure high-temperature conditions
Authors: Mahmoud Ali , Gajbhiye Rahul , Elkatatny Salaheldin
Published: January 2025

Conventional oil drilling fluids often fail under extreme (high-pressure high-temperature, HPHT) conditions, leading to wellbore instability and formation damage, causing substantial economic losses in the drilling industry. The objective of this study was to evaluate the performance of Claytone-ER, a novel rheological additive for oil-based drilling fluids (OBDF), compared with a conventional organoclay (OC). Claytone-ER improved the drilling fluid performance significantly, including enhancement of the emulsion stability by 3% (863 V to 891 V), mitigation of sagging behavior, and substantial improvement in key rheological parameters such as plastic viscosity (PV) by 26.5%, yield point (YP) by 98%, and apparent viscosity (AV) by 36.5%. Additionally, Claytone-ER enhanced gel strength (GS) and improved filtration properties, reducing filtrate volume by 8% (5.0 cm3 to 4.6 cm3) and filter cake thickness by 6% (2.60 mm to 2.45 mm). These results demonstrated the potential of Claytone-ER to enhance the stability and performance of OBDFs under extreme HPHT conditions, leading to improved drilling efficiency, reduced non-productive time, and cost savings for drilling operations. Furthermore, the enhanced rheological properties, sag resistance, and filtration control contribute to better wellbore stability and minimize the risk of formation damage, ensuring long-term well productivity. This study represents a significant advancement in drilling fluid technology, paving the way for safer and more efficient drilling operations in challenging HPHT environments. Future research will focus on field trials to validate the efficacy of Claytone-ER in real-world HPHT drilling scenarios.
Early-stage investigators’ experiences with an National Institutes of Health Pilot Award Program
Authors: Collins Cyleste C. , Dolata Jacqueline , Nonguierma Elodie , Shediac-Rizkallah Mona , Sehgal Ashwini R. , Thornton J. Daryl
Published: January 2025

Background:

Academic-community research partnerships focusing on addressing the social determinants of health and reducing health disparities have grown substantially in the last three decades. Early-stage investigators (ESIs), however, are less likely to receive grant funding from organizations like the National Institutes of Health, and we know little about the facilitators and barriers they face on their career journeys or the best ways to support them and their community research partnerships. This study examines ESIs’ experiences with a program that funded and supported their community-partnered pilot health disparities research.

Methods:

Fourteen ESIs from five cohorts of pilot investigators participated in in-depth focus groups between April 2020 and February 2024. Two reviewers independently identified significant quotes and created codes. Thematic analysis was used to develop relevant themes.

Results:

The overarching theme was that the program was a launch pad for the ESIs’ research careers. Four distinct sub-themes contributing to the launch pad theme were: (1) ESI Growth & Adaptation; (2) Community and Support; (3) The Value of Collaboration and Partnership; (4) Need for Effective Mentorship. The results suggest the program offered ESIs and community partners substantial, unique support and resources, but challenges remained.

Conclusions:

Future programs helping ESIs who conduct community-engaged research to launch their research careers should consider implementing tailored support while offering strategies to eliminate or reduce institutional barriers, including strengthening mentoring.
Catching a CAPTCHA: the impact of variable input on the processing of emerging orthographic representations
Authors: Solaja Olga , Fernández-López María , Crepaldi Davide , Perea Manuel
Published: January 2025

Variability inherent to handwriting has been suggested to help establish more robust letter representations than other methods (e.g., typing). The present study tests whether encoding letter strings from a novel alphabet becomes more resistant to distortion when trained with variable input. Over 5 days, participants learned an 11-character artificial alphabet in a variable handwritten format involving reading, listening and handwriting practice. Another set of 11 artificial characters served as a visual control. Before and after the training, participants completed a masked priming same–different matching task with the novel alphabet letters. The key manipulation was in the primes: the identity/unrelated primes could be presented in a printed or distorted format. Results showed identity priming in both conditions, with a stronger effect for the printed primes. These effects increased post training for experimental and visual control scripts, indicating that exposure to variable input enhances distortion resistance even without explicit training. A second experiment assessed the transposed-letter effect – another marker of orthographic processing – in the novel scripts with an unprimed same–different matching task. Results showed that the transposed-letter effect occurred similarly before and after the training for both scripts. Therefore, letter shape variability when learning to read does not seem to boost orthographic processing.
FURTHER ARITHMETIC PROPERTIES OF OVERCUBIC PARTITION TRIPLES
Authors: SAIKIA MANJIL P. , SARMA ABHISHEK
Published: January 2025

We prove several new congruences for the overcubic partition triples function, using both elementary techniques and the theory of modular forms. These extend the recent list of such congruences given by Nayaka, Dharmendra and Kumar [‘Divisibility properties for overcubic partition triples’, Integers24 (2024), Article no. a80, 9 pages]. We also generalise overcubic partition triples to overcubic partition k-tuples and prove arithmetic properties for these partitions.
Were the Newdigate Earthquakes, Southern England, of 2018–2019 triggered by oil extraction?
Authors: Fox Matthew , Meredith Philip G.
Published: January 2025

The ability to attribute earthquakes to specific causes is challenging. The 2018–2019 earthquake swarm in Newdigate, Surrey, Southern England, generally coincides with local oil extraction at Horse Hill, located just 5–10 km away. Nevertheless, it remains debated whether these earthquakes were triggered by oil extraction or whether they were coincidental. Due to the onset of seismic activity before major oil extraction and the lack of a clear correlation between seismic activity and extraction volume, it has been suggested that the earthquakes may be coincidental. However, we show that time delays between fluid pressure changes and concomitant seismic activity are common in nature. Further, we develop a simple Bayesian Machine Learning time series model to test whether different units respond differently to oil extraction. We find that extraction from the Portland units at Horse Hill may produce earthquakes with a delay of a few days. In contrast, extraction from the Kimmeridge units may produce fewer earthquakes, but with a delay of tens of days. We also show that the occurrence of earthquakes before extraction might be related to surface works. This simple model reproduces the overall trend in seismicity. We are unable to rule out coincidental seismic activity, but our analysis suggests that these earthquakes maybe triggered by Horse Hill activity.
Ramsey numbers of hypergraphs with a given size
Authors: BRADAČ DOMAGOJ , FOX JACOB , SUDAKOV BENNY
Published: January 2025

The q-colour Ramsey number of a k-uniform hypergraph H is the minimum integer N such that any q-colouring of the complete k-uniform hypergraph on N vertices contains a monochromatic copy of H. The study of these numbers is one of the central topics in Combinatorics. In 1973, Erdős and Graham asked to maximise the Ramsey number of a graph as a function of the number of its edges. Motivated by this problem, we study the analogous question for hypergaphs. For fixed

$k \ge 3$

and

$q \ge 2$

we prove that the largest possible q-colour Ramsey number of a k-uniform hypergraph with m edges is at most

$\mathrm{tw}_k(O(\sqrt{m})),$

where tw denotes the tower function. We also present a construction showing that this bound is tight for

$q \ge 4$

. This resolves a problem by Conlon, Fox and Sudakov. They previously proved the upper bound for

$k \geq 4$

and the lower bound for

$k=3$

. Although in the graph case the tightness follows simply by considering a clique of appropriate size, for higher uniformities the construction is rather involved and is obtained by using paths in expander graphs.
Dyadic resilience after postpartum depression: The protective role of mother-infant respiratory sinus arrhythmia synchrony during play for maternal and child mental health across early childhood
Authors: Somers Jennifer A.
Published: January 2025

Coordination in mothers’ and their infants’ parasympathetic nervous system functioning (i.e., respiratory sinus arrhythmia [RSA] synchrony) specifically during playful interactions may promote resilience against exposure to postpartum depressive symptoms (PPD), for both members of the dyad. To test biobehavioral synchrony theory-derived hypotheses, we evaluated whether positive mother-infant RSA synchrony during play attenuated associations between maternal PPD symptoms and future child behavior problems and maternal depressive symptoms. 322 low-income, Mexican-origin mothers and their children participated in 5-min resting baseline and free play interaction tasks when children were 24 weeks of age; mothers reported on their PPD symptoms and on child behavior problems and maternal depressive symptoms at 12- and 36-months child age. Results of multilevel structural equation models demonstrated that, though the associations between maternal PPD symptoms and future child behavior problems and maternal depressive symptoms differed depending on levels of RSA synchrony during play and non-interactive tasks, the protective benefits of positive RSA synchrony on 12-month maternal depressive symptoms and 36-month child internalizing problems were specific to its assessment during a playful interaction. Results suggest that the dyadic coordination of physiological capacities during playful interactions is an active mechanism that promotes resilience to emotional distress for mothers and their children.
Periaortic fat thickness and cardiovascular risk factors in children with congenital adrenal hyperplasia
Authors: Akyürek Nesibe , Eklioğlu Beray Selver , Atabek Mehmet Emre , Alp Hayrullah , Gün Halil Ibrahim
Published: January 2025

Objective:

Children with congenital adrenal hyperplasia are considered to be at an elevated risk for cardiovascular morbidity and mortality. The objective of this study was to evaluate the association between periaortic fat thickness and the cardiometabolic profile in children diagnosed with congenital adrenal hyperplasia.

Method:

A total of 20 children and adolescents with congenital adrenal hyperplasia and 20 healthy control subjects were enrolled in the study. We investigated metabolic and anthropometric parameters, comparing these values to those of the control group. Periaortic fat thickness was assessed using an echocardiographic method that has not previously been applied to paediatric patients with congenital adrenal hyperplasia.

Results:

The subjects in the congenital adrenal hyperplasia group were significantly shorter than the control subjects (p = 0.021) and exhibited a higher body mass index (p = 0.044) and diastolic blood pressure (p = 0.046). No significant differences were observed between the congenital adrenal hyperplasia group and control subjects concerning age, weight, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. Additionally, dyslipidemia was identified in 5% (N = 1) of the congenital adrenal hyperplasia group. The mean fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, and fasting glucose-to-fasting insulin ratio were similar between the congenital adrenal hyperplasia group and the control subjects. However, 15% (n = 3) of the congenital adrenal hyperplasia group had insulin resistance. Two children with congenital adrenal hyperplasia (10%) were diagnosed with hypertension.

Periaortic fat thickness was significantly greater in the congenital adrenal hyperplasia group compared to the control group (p = 0.000), with measurements of 0.2039 ± 0.045 mm in the congenital adrenal hyperplasia group and 0.1304 ± 0.022 mm in the control group. In children with congenital adrenal hyperplasia, periaortic fat thickness exhibited a negative correlation with high-density lipoprotein cholesterol (r = −0.549, p = 0.034) and a positive correlation with the dose of hydrocortisone (r = 0.688, p = 0.001).

Conclusion:

Our results provide further evidence of subclinical cardiovascular disease in children with congenital adrenal hyperplasia. It is crucial to regularly assess cardiometabolic risk in children with congenital adrenal hyperplasia. The measurement of periaortic fat thickness in this population may serve as a valuable tool for identifying individuals at high risk for developing early atherosclerosis.
Evaluation of the Efficacy of Viloxazine ER in Children and Adolescents with ADHD Inattentive and Combined Presentations
Authors: Findling Robert L , Newcorn Jeffrey H. , Cutler Andrew J , Childress Ann , Qin Peibing , Koch Jennifer , Teter Christian , Earnest Jami , Rubin Jonathan
Published: January 2025

Introduction

Studies show stimulant medications are effective for different ADHD presentations (predominantly inattentive [IA], predominantly hyperactive-impulsive [HI] or combined [C]); however, few studies have evaluated nonstimulant efficacy in different ADHD presentations. Viloxazine ER [VLX ER] is a nonstimulant, FDA-approved medication for pediatric (≥6 yrs) and adult ADHD. This post-hoc analysis of 4 double-blind (DB), Phase 3, clinical trials (2 in adolescents [NCT03247517 and NCT03247556], 2 in children [NCT03247530 and NCT03247543]), evaluates VLX ER efficacy by ADHD presentation as derived from ADHD Rating Scale, 5th Edition (ADHD-RS-5) assessments at Baseline.

Methods

Children and adolescents with ADHD and an ADHD-RS-5 Total score ≥ 28 were eligible for enrollment. ADHD presentation was defined as a rating of ≥2 on at least 6 of 9 ADHD-RS-5 inattention items, or hyperactive-impulsive items or both. For each ADHD presentation, the change from Baseline (CFB) in ADHD-RS-5 Total score (primary outcome in each study) was assessed using mixed models for repeated measures (MMRM). Responder rate (secondary outcome), ≥50% reduction from baseline in ADHD-RS-5 Total score, was analyzed using generalized estimating equations (GEE).

Results

Of 1354 subjects [placebo N = 452, VLX ER N = 902], ADHD presentation was assigned as 288 (21.3%) [IA], 1010 (74.5%) [C], 40 (3.0%) [HI], 16 (1.2%) [none of these]. Due to the small sample size of [HI], only the [IA] and [C] results are presented. At Week 6 (pooled data endpoint), ADHD-RS-5 Total scores were significantly improved for VLX ER relative to placebo for both the [IA] and [C] ADHD presentations. LS mean (SE) treatment differences, p-values were: [IA] -3.1 (1.35), p = 0.0219, and [C] 5.8 (0.97), p < 0.0001. Responder rates were also significantly higher for VLX ER: 43.0% [IA] and 42.7% [C] relative to placebo 29.5% [IA] and 25.5 % [C] (p=.0311 and p<.0001).

Conclusions

Viloxazine ER significantly reduced ADHD symptoms in individuals meeting criteria for ADHD [IA] or [C] presentations at Baseline. Limitations include post-hoc methodology, smaller sample sizes of [IA] and [HI] groups, and the ADHD-RS-5 ≥ 28 eligibility requirement, that may favor enrollment of individuals with ADHD [C] over ADHD [IA] or [HI] presentations. Consistency of response during long-term use should be evaluated.

Funding

Supernus Pharmaceuticals, Inc.
Aripiprazole Once-Monthly for the Treatment of Adult Patients in the Earlier Stages of Bipolar I Disorder: A Post Hoc Analysis of Clinical Trial Data
Authors: Bell Lynum Karimah S. , Zhang Zhen , Castro Christine F. , Patel Mehul , Tohen Mauricio
Published: January 2025

Introduction

The efficacy and safety of aripiprazole once-monthly 400 mg (AOM 400) as maintenance monotherapy treatment for bipolar I disorder (BP-I) were demonstrated in a double-blind, placebo-controlled, 52-week randomized withdrawal trial (NCT01567527). This post hoc analysis of data from NCT01567527 evaluated the efficacy of AOM 400 in the earlier BP-I population.

Methods

Patients within the first quartile of the dataset according to age (18–32 years: AOM 400, n=36; placebo, n=34) or disease duration (≤4.6 years: AOM 400, n=33; placebo, n=34) were considered to be in the earlier stages of BP-I, and were included. The primary outcome was time from randomization to recurrence of any mood episode, defined as meeting any one of several predetermined criteria, including Young Mania Rating Scale (YMRS) total score ≥15 or clinical worsening.

Results

Time to recurrence of any mood episode was significantly delayed with AOM 400 versus placebo in patients aged 18–32 years (hazard ratio [HR]: 2.462 [95% confidence interval (CI): 1.092, 5.547]; p<0.05) and in patients with a disease duration ≤4.6 years (HR: 3.207 [95% CI: 1.346, 7.645]; p<0.01). Further analysis suggested that the benefit of AOM 400 versus placebo was driven by a significantly lower proportion of patients experiencing a YMRS total score ≥15 (18–32 years: 5.60% versus 44.10%, p<0.001; disease duration ≤4.6 years: 6.10% versus 41.20%, p<0.01) or clinical worsening (18–32 years: 8.30% versus 38.20%, p<0.01; disease duration ≤4.6 years: 6.10% versus 38.20%, p<0.01).

Conclusion

The efficacy of AOM 400 was demonstrated in the earlier BP-I population.

Study registration number: NCT01567527 (ClinicalTrials.gov)

The data in this poster were originally presented at Psych Congress, held on 6–10th September 2023 in Nashville, TN, USA.

Funding

Otsuka Pharmaceutical Development & Commercialization Inc. (Princeton, NJ, USA) and Lundbeck LLC (Deerfield, IL, USA).
Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm
Authors: Chepke Craig , Cutler Andrew J. , Floam Samantha , Parks Gregory , Rosenberg Russell
Published: January 2025

Craig Chepke, MD: Excel Psychiatric Associates, Huntersville, NC, and Atrium Health, Charlotte, NC; Andrew J. Cutler, MD: SUNY Upstate Medical University, and Neuroscience Education Institute, Syracuse, NY; Samantha Floam, DMD: Axsome Therapeutics, New York, NY; Gregory, Parks, PhD: Axsome Therapeutics, New York, NY; Russell Rosenberg, PhD: Neurotrials Research, Atlanta, GA

Introduction

Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor that has been shown to activate TAAR1, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150 mg/day) or obstructive sleep apnea (OSA) (37.5-150 mg/day).Effect size, number needed to treat (NNT) and number needed to harm (NNH) are statistical representations of efficacy and tolerability that clinicians may find helpful in guiding treatment decisions. This analysis characterized these statistical parameters from two registrational studies.

Methods

Post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or obstructive sleep apnea (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events.

Results

On the maintenance of wakefulness test (MWT), effect size compared to placebo (Cohen’s d) was 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg doses of solriamfetol in TONES 2 and 0.46, 0.89,1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg, respectively. On the Epworth sleepiness scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg doses in TONES 2, and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. NNT for patients achieving an ESS ≤10 was 7, 5, and 3 for 75mg, 150mg, and 300mg doses in TONES 2 and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. On the patient global impression of change (PGIc), NNT was 4, 3, and 3 for 75mg,150mg, and 300mg doses in TONES 2 and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg in TONES 3. Similar NNT were found for the clinician global impression of change (CGIc) as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in at least 5% of patients and greater than placebo were all >10, with the exception for headache in TONES 2 (NNH=6).

Conclusion

This post-hoc analysis demonstrates favorable effect size, NNT and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA.

Funding

Axsome Therapeutics
Real-World Antipsychotic and Vesicular Monoamine Transporter Type 2 Inhibitor Treatment Patterns in Patients Newly Diagnosed with Tardive Dyskinesia
Authors: Mychaskiw Marko , Casciano Julian , Dotiwala Zenobia , Chaijale Nayla , Finkbeiner Stacy
Published: January 2025

Introduction

Tardive dyskinesia (TD) is associated with antipsychotic (AP) use and management includes antipsychotic (AP) dose modification/discontinuation, often leaving underlying psychiatric conditions undertreated. Deutetrabenazine (DTBZ) is a vesicular monoamine transporter type 2 inhibitor (VMAT2i) approved to treat TD and Huntington disease– associated chorea. AP and VMAT2i treatment patterns post-TD diagnosis are unclear.

Methods

Patients aged ≥18 years, newly diagnosed with TD (July 2019– June 2022), with ≥1 AP and no VMAT2i claims pre-index were identified from the Symphony Health Solutions Integrated Dataverse (medical, hospital, and prescription claims across all US payer types). Patients were grouped into DTBZ (≥1 DTBZ claim within ≤6 months post-diagnosis) and non-VMAT2i groups, and further by stable DTBZ dose (for ≥60 days). The index date was the first DTBZ claim (DTBZ group) or the difference between TD diagnosis and first DTBZ claim (of the matched patient) added to TD diagnosis (non-VMAT2i group).

Results

Among 18,375 patients meeting inclusion criteria, 587 (3%) received DTBZ (292 stable-dose DTBZ), 676 (4%) received a different VMAT2i, and 17,112 (93%) had no VMAT2i claims. Among propensity score-matched patients with ≥1 AP claim pre- and post-index (326 DTBZ, 627 non-VMAT2i), pre-index mean AP proportions of days covered (PDCs) were similar between DTBZ (86%), stable-dose DTBZ (86%), and non-VMAT2i (83%) groups. Mean PDCs decreased post-index for DTBZ (86% to 85%) and non-VMAT2i (83% to 81%) groups, but increased for the stable-dose DTBZ group (86% to 88%). While these changes were small, post-index mean PDCs were significantly greater (versus non-VMAT2i) in the DTBZ (5% difference; P=.030) and stable-dose DTBZ (9%; P=.001) groups. Similar proportions of patients in the DTBZ (20%) and non-VMAT2i (20%) groups discontinued APs (ie, no AP claims within ≤6 months post-index). Proportions of patients with AP restarts (7%– 8%) and dose decreases (13%– 17%) were also similar between DTBZ, stable-dose DTBZ, and non-VMAT2i groups. Proportions of patients (16%– 18%) with AP dose increases were similar between DTBZ and non-VMAT2i groups, but significantly greater in the stable-dose DTBZ group (21%) vs non-VAMT2i (P=.02).

Conclusions

AP adherence was significantly, though not substantially, greater for DTBZ versus non-VMAT2i groups. These results suggest that DTBZ, when titrated to a stable/optimal dose, allows flexibility in treating underlying psychiatric conditions.

Funding

Teva Branded Pharmaceutical Products R&D, Inc.
Prevalence of Concomitant Medications Among Patients with Schizophrenia Prescribed Atypical Antipsychotics
Authors: Wang Yifei , Semwal Monika , Zeni Courtney , Dembek Carole
Published: January 2025

Introduction

Typical and atypical antipsychotics (AAPs) are the main treatment options among patients with schizophrenia. However, AAPs have been associated with several side effects and comorbid conditions. To manage side effects, often patients are prescribed concomitant medications to manage their condition, increasing polypharmacy. Though common in practice, the prevalence of concomitant medication use in patients with schizophrenia is not well established. This study evaluated the annual prevalence of concomitant medications among patients with schizophrenia who were prescribed AAPs.

Methods

This retrospective study was conducted using the PharMetrics database (01/2019 – 12/2021). Patients were included in the analyses if they had a diagnosis of schizophrenia, were continuously enrolled in pharmacy and medical claims for the full year and were prescribed AAPs. A sensitivity analysis was also conducted among patients who demonstrated ≥50% adherence to their prescribed AAPs (with a grace period of 30 days). For both the main and sensitivity analyses patient populations, the concomitant drugs prescribed were labeled at the drug class (GPI2) and generic drug level. Prevalence for drug class and each drug was calculated as a percentage of patients who were prescribed ≥1 of the agent among those who met the inclusion and exclusion criteria within the given year.

Results

For the year 2019, 2020 and 2021, 12,360; 13,242 and 14,780 patients met the inclusion and exclusion criteria, respectively. The mean age of the cohort ranged from 43.5 - 45.4 years. Patients were predominantly male and commercially insured. Antidepressants were the most prevalent concomitant medication prescribed (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). Other highly prevalent drug classes identified were - anticonvulsants (2019: 44.2%, 2020: 44.5%, 2021: 45.0%), antianxiety agents (2019: 36.3%, 2020: 37.6%, 2021: 38.9%), antihyperlipidemics (2019: 26.3%, 2020: 28.1%, 2021: 30.7%), antihypertensives (2019: 25.7%, 2020: 27.2%, 2021: 28.1%), antiparkinson agents (2019: 61.2%, 2020: 61.2%, 2021: 62.0%), anticholinergics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%) and analgesics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). At the individual drug level, benzotropine mesylate (2019: 19.5%, 2020: 18.7%, 2021: 18.8%), atorvastatin (2019: 14.5%, 2020: 16.7%, 2021: 18.4%), lorazepam (2019: 14.1%, 2020: 14.7%, 2021: 14.3%), gabapentin (2019: 13.7%, 2020: 13.9%, 2021: 14.8%), and metformin (2019: 13.2%, 2020: 13.7%, 2021: 15.4%) were the most prevalent prescribed concomitant medications. There was no difference when similar analyses were conducted in the adherent patient population.

Conclusions

These results indicate a high prevalence of concomitant antidepressants, antihyperlipidemics, antihypertensives and anticholinergics among patients with schizophrenia who are prescribed AAPs.

Funding

Sumitomo Pharma America Inc.
Clinical Characteristics of a Commercial Pharmacogenetic Testing Population
Authors: Dowd Daniel , Amato Russell , Williams Gabriela , Krause David S
Published: January 2025

Pharmacogenetic testing is becoming more common, especially to provide guidance for psychiatric medications. Over 17 psychotropic medications currently have a Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline. Several clinical trials have described PGx testing in specific patient populations, but various exclusion criteria create cohorts that may not represent real-world populations. Given the overall undefined characteristics of a real-world population utilizing commercial PGx testing, the clinical presentation of 15,198 patients that used a commercial PGx laboratory (Genomind) from October 15, 2018 through April 11, 2023 was assessed. These 15,198 patients include those whose provider conducted a clinical consultation with a Genomind psychopharmacologist, regardless of ICD diagnosis on the requisition form. Data were extracted from de-identified consult notes entered by the psychopharmacologist. Consultants made a total symptom severity assessment based on CGI-S (Clinician Global Impression Severity) criteria. Most patients were described as mildly (15%), moderately (59%), or markedly ill (21%). The most common presenting symptoms identified in the cohort were “Anxious” (61.6%), “Depressed” (61.1%), “Inattentive” (37.8%) and “Hyperactive” (11.4%). The most common co-occurring symptoms in patients with a depressive presentation were “Anxious” (68.1%), “Inattentive” (16.0%), “Manic/Hypomanic” (11.1%), “Insomnia” (9.8%) and “Irritable/Angry” (7.4%). The most common co-occurring symptoms in patients presenting with anxiety were “Depressed” (67.6%), “Inattentive” (20.9%), “Panic” (11.5%), “Worry/Rumination” (11.2%) and “Hyperactive” (11.1%). This analysis suggests that PGx testing is commonly being utilized in patients with symptoms of anxiety, mood lability and inattentiveness. Future PGx research should prioritize the selection of patients with these symptoms to generate evidence that matches the real-world users of commercial PGx services.

Funding

Genomind, Inc.
Utilization of Psychiatric Pharmacogenomic Testing by Primary Care Physicians and Advanced Practice Providers: Confidence and Implementation Barriers
Authors: Griggs Ryan B. , Albers Renee E. , Maheshwari Priya , Kartikeyan Ramya , Kasten Chelsea R. , Bahra Sukhbir , Lubarda Jovana , Guevara Natalie , Parikh Sagar V. , Johnson Holly L.
Published: January 2025

Introduction

Pharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Sentiment and barriers may limit PGx testing. Here we compare confidence in utilizing PGx testing and barriers to implementation by type of provider and treatment condition as identified in a survey.

Methods

Healthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.

Results

Of 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], 32% of NPs/PAs and 29% of MDs/DOs had used PGx testing for mental health conditions. The major barriers to adopt PGx testing were similar for mental health and primary care conditions yet differed by provider type. NPs/PAs (72-77%) were more concerned with patient cost than MDs/DOs (46-55%), whereas MDs/DOs were more concerned with evidence of clinical utility (54-59%) than NPs/PAs (40-42%). In respondents who use PGx testing, MDs/DOs reported slightly more confidence utilizing PGx than NPs/PAs. For both groups, confidence in using PGx for mental health conditions was somewhat greater than for non-mental health conditions.

Conclusions

These data illuminate the implementation barriers and confidence levels of clinicians utilizing PGx testing. Increasing awareness around patient cost and evidence of clinical utility for PGx testing may improve utilization.

Funding

Myriad Genetics, Inc.
Reforming ESG: a European and Global South perspective
Authors: Borghesi Simone , Costantini Valeria , D'Amato Alessio , Dibattista Ilaria , Koundouri Phoebe , Li Qinci , Mazzarano Matteo , Sterner Thomas , Tiwari Mira Manini , Vis Peter , Xepapadeas Anastasios
Published: January 2025

The EU's non-financial reporting (NFR) regulations have significant impacts on Global South stakeholders, firms that must report, actors lower in the value chain, and organisations seeking investment from NFR-compliant firms or institutions. This paper sets forth six proposals to improve the global equity and sustainability implications of the EU's NFR from a Global South perspective. The proposals involve (1) developing regulation cooperatively with the Global South; (2) streamlining reporting to enable the regulations to have real effects and limit incorrect accounting; (3) digitalising reporting through accessible technologies for greater accountability and lower administrative burdens; (4) mandating scope 3 emissions accounting and incentivising related investment; (5) anchoring financial institutions' role in ethical investment and bridging Northern and Southern actors; and (6) strengthening citizen data and sustainability literacy to close the circle of incentives, implementation, and impact.
Unraveling the enigma: decomposing China’s output and productivity growth in the new era—insights from listed companies
Authors: Huang Minjie , Zhao Shunan , Xie Mengjun
Published: January 2025

Building upon recent developments in production function identification and decomposition methods, this paper investigates the sources of output and productivity growth among China’s listed manufacturing companies from 2000 to 2022. While previous studies on China’s manufacturing have predominantly focused on the period preceding 2007, our study extends the analysis to a broader timeframe and divide it into four sub-periods to accommodate diverse economic conditions and varying growth rates. We provide new insights into the Chinese economy during a period marked by gradual economic transformation. Specifically, we first decompose industry output growth into factor deepening and firm productivity progress within each sub-period. To account for heterogeneity across firms in terms of production technology and sources of growth, we employ a nonparametric production function and decompose firm output growth at both the mean and different quantiles of the output distribution. We find that increased materials usage and productivity growth are primary growth drivers. However, the contribution of productivity experiences a significant decline, particularly in recent years and among median-sized and large firms. Furthermore, we examine China’s industry aggregate productivity growth and its origins among state-invested, foreign-invested, and domestic private firms. Our findings suggest that reforms among state firms are the largest contributor to industry productivity growth before the 2008 financial crisis, whereas productivity progress of domestic private firms emerges as the sole significant driver in recent years. Additionally, there is no evidence of improvements in output reallocation efficiency within China’s manufacturing sector throughout our sample period.
NONLINEAR MODULATION OF RANDOM WAVE SPECTRA FOR SURFACE-GRAVITY WAVES WITH LINEAR SHEAR CURRENTS
Authors: MUKHERJEE SUMAN , HALDER SOURAV , DHAR A. K.
Published: January 2025

We first derive Alber’s equation for the Wigner distribution function using the fourth-order nonlinear Schrödinger equation, and on the basis of this equation we next analyse the stability of the narrowband approximation of the Joint North Sea Wave Project spectrum. Therefore, one interesting result of this study concerns the effect of modulational instability obtained from the fourth-order nonlinear Schrödinger equation. The analysis is restricted to one horizontal direction, parallel to the direction of wave motion, to take advantage of potential flow theory. We find that shear currents considerably modify the instability behaviours of weakly nonlinear waves. The key point of this study is that the present fourth-order analysis shows considerable deviations in the modulational instability properties from the third-order analysis and reduces the growth rate of instability. Moreover, we present here a connection between the random and deterministic properties of a random wavetrain for vanishing spectrum bandwidth.
The pseudo-kindness of wartime lawbreakers
Authors: Hayashi Nobuo
Published: January 2025

It is sometimes said that cruel yet short wars are better for humanity than restrained yet lengthy ones. The idea finds sympathy among Francis Lieber and his Prussian contemporaries, as well as some modern writers who back selective non-compliance with international humanitarian law (IHL) on act-utilitarian grounds. This article refutes three underlying claims and reaffirms that IHL progressively narrows room for crude interest-balancing by its duty-bearers. First, it is claimed that toughening wars quickens them, whereas moderating wars prolongs them. This empirical claim overlooks how actions of the party resorting to brutality – the “brutalizer”, for short – interact with the intention of its adversary. Although the brutalizer clearly controls the amount of violence that it chooses to inflict on its opponent, it does not control the opponent's will to resist and, consequently, the length of the war it fights. History abounds with instances where adding cruelty has stiffened the enemy's resolve rather than accelerating surrender. Second, it is claimed that ruthless but swift wars lessen net inhumanity. On this act-utilitarian view, it is normatively superior to hasten wars through barbarity than to lengthen them through moderation; it is therefore the brutalizer's responsibility to toughen fighting and the brutalized party's responsibility to refrain from resisting the brutalizer. Problematically, the brutalizer usurps authority by imposing its own utilitarian considerations upon the brutalized party. Moreover, the brutalizer blames its disobliging adversary for the extra bloodshed to which it resorts in the name of maximum utility. Third, it is claimed that IHL does or should permit non-conformity when non-conformity stands a reasonable chance of increasing net humanity. This position is inconsistent with IHL's functions, however. IHL does aim to reduce net wartime harm, but it would be a mistake to assume that utilitarian ends necessarily justify, let alone require, utilitarian means. When IHL enacts unqualified rules, it predetermines their conformity or non-conformity through processes that are distinctly not act-utilitarian. Nowhere in these processes do lesser-evil justifications naturally belong.
Stream Discharge Determinations Using Slug Additions and Specific Conductance
Authors: McCleskey R. Blaine , Runkel Robert L. , Murphy Sheila F. , Roth David A.
Published: January 2025

Stream discharge is often determined by wading the stream and measuring the point velocity at fixed widths and depths. However, there are conditions when wading measurements are not safe or the measurements are poor because of high turbulence, rocky streambeds, non‐standard velocity distributions, shallow or sheet flow, aquatic plants, or inaccessibility due to ice. Under these conditions, it is often preferable to determine discharge using salt slug addition and downstream measurement of salt concentration with time. A new method for determining stream discharge using specific conductance as a surrogate for salt concentrations is presented. The method adapts an approach that accurately calculates the specific conductance by utilizing ionic molal conductivities to determine the concentration of salt. The method was applied at four mountainous stream sites where a total of twenty‐nine slug‐additions were performed. The discharge determined from the new method was compared to four alternative methods including discharge from continuous injection, slug addition with discrete sample calibration, wading measurements with velocity measurement, and a stream gage. The discharge ranged from 21.5 to 778 L/s and the median difference between the new method and the traditional methods was −0.01%. Additionally, the p‐value (0.75) determined from a paired t‐test indicates that there is no significant difference between the discharge determined from the new and alternative discharge methods. The primary advantage of the new method is that it obviates the need to collect and analyze discrete samples to accurately quantify the specific conductance‐salt surrogate relationship, allowing for rapid, low‐cost determination of discharge.
Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome
Authors: Mondéjar-Parreño Gema , Moreno-Manuel Ana I. , Ruiz-Robles Juan Manuel , Jalife José
Published: January 2025

A well-balanced ion channel trafficking machinery is paramount for the normal electromechanical function of the heart. Ion channel variants and many drugs can alter the cardiac action potential and lead to arrhythmias by interfering with mechanisms like ion channel synthesis, trafficking, gating, permeation, and recycling. A case in point is the Long QT syndrome (LQTS), a highly arrhythmogenic disease characterized by an abnormally prolonged QT interval on ECG produced by variants and drugs that interfere with the action potential. Disruption of ion channel trafficking is one of the main sources of LQTS. We review some molecular pathways and mechanisms involved in cardiac ion channel trafficking. We highlight the importance of channelosomes and other macromolecular complexes in helping to maintain normal cardiac electrical function, and the defects that prolong the QT interval as a consequence of variants or the effect of drugs. We examine the concept of “interactome mapping” and illustrate by example the multiple protein–protein interactions an ion channel may undergo throughout its lifetime. We also comment on how mapping the interactomes of the different cardiac ion channels may help advance research into LQTS and other cardiac diseases. Finally, we discuss how using human induced pluripotent stem cell technology to model ion channel trafficking and its defects may help accelerate drug discovery toward preventing life-threatening arrhythmias. Advancements in understanding ion channel trafficking and channelosome complexities are needed to find novel therapeutic targets, predict drug interactions, and enhance the overall management and treatment of LQTS patients.
Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
Authors: Abdel Wadood Noran , Hollenhorst Monika I. , Elhawy Mohamed Ibrahem , Zhao Na , Englisch Clara , Evers Saskia B. , Sabachvili Mahana , Maxeiner Stephan , Wyatt Amanda , Herr Christian , Burkhart Ann-Kathrin , Krause Elmar , Yildiz Daniela , Beckmann Anja , Kusumakshi Soumya , Riethmacher Dieter , Bischoff Markus , Iden Sandra , Becker Sören L. , Canning Brendan J. , Flockerzi Veit , Gudermann Thomas , Chubanov Vladimir , Bals Robert , Meier Carola , Boehm Ulrich , Krasteva-Christ Gabriela
Published: January 2025

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels. Taste signaling through the Trpm5 channel is essential for bacterial tuft cell activation and ATP release. We demonstrate that activated tuft cells recruit dendritic cells to the trachea and lung. ATP released by tuft cells initiates dendritic cell activation, phagocytosis and migration. Tuft cell stimulation also involves an adaptive immune response through recruitment of IL-17A secreting T helper cells. Collectively, the results provide a molecular framework defining tuft cell dependent regulation of both innate and adaptive immune responses in the airways to combat bacterial infection.