bluuebunny/crossref_metadata_2025 huggingface dataset:
Stratigraphic paleobiology
Authors: Holland Steven M. , Patzkowsky Mark E. , Loughney Katharine M.
Published: March 2024

Stratigraphic paleobiology uses a modern understanding of the construction of the stratigraphic record—from beds to depositional sequences to sedimentary basins—to interpret patterns and guide sampling strategies in the fossil record. Over the past 25 years, its principles have been established primarily through forward numerical modeling, originally in shallow-marine systems and more recently in nonmarine systems. Predictions of these models have been tested through outcrop-scale and basin-scale field studies, which have also revealed new insights. At multi-basin and global scales, understanding the joint development of the biotic and sedimentary records has come largely from macrostratigraphy, the analysis of gap-bound packages of sedimentary rock. Here, we present recent advances in six major areas of stratigraphic paleobiology, including critical tests in the Po Plain of Italy, mass extinctions and recoveries, contrasts of shallow-marine and nonmarine systems, the interrelationships of habitats and stratigraphic architecture, large-scale stratigraphic architecture, and the assembly of regional ecosystems. We highlight the potential for future research that applies stratigraphic paleobiological concepts to studies of climate change, geochemistry, phylogenetics, and the large-scale structure of the fossil record. We conclude with the need for more stratigraphic thinking in paleobiology.
The Remaking of South African Administrative Law
Authors: Hoexter Cora , Penfold Glenn
Published: March 2024

This article explores the remaking of administrative law review in South Africa since the introduction of constitutional democracy in 1994. It characterizes the construction of the constitutional and legislative framework, as well as the courts’ interpretation of that framework, as the first phase of the remaking. The second phase encompasses the courts’ recognition of a constitutional principle of legality based on the rule of law, and their swift development of the content of this principle. This judicial creativity has resulted in an elaborate avenue to review, parallel to the Promotion of Administrative Justice Act 3 of 2000, and has caused problems of rivalry and avoidance. The article identifies and discusses some of the more significant implications of each of these phases of reconstruction. It also proposes corrective measures likely to advance the coherence and effectiveness of judicial review and discourage the adoption of a doctrine of non-justiciability.
Modelling a thrust imparted by a highly ionized magnetic nozzle rf plasma thruster
Authors: Takahashi Kazunori
Published: March 2024

Influence of the local-ionization-induced neutral depletion on the thrust imparted by the magnetic nozzle plasma thruster is discussed by simply considering reduction of the neutral density due to the ionization in the thruster model combining the global source model and the one-dimensional magnetic nozzle model. When increasing the rf power, it is shown that the increase rate of the plasma density is reduced, while the electron temperature continues to increase due to a decrease in the neutral density. Since the major components of the thrust are originated from the electron pressures in the source and in the magnetic nozzle, the increase in the electron temperature contributes to the increase in the thrust in addition to the gradual density increase by the rf power. The model qualitatively predicts the reduction of the thruster efficiency by the neutral depletion for the high-power condition, compared with the constant neutral density model.
Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index
Authors: Keeler Johanna Louise , Bahnsen Klaas , Wronski Marie-Louis , Bernardoni Fabio , Tam Friederike , Arold Dominic , King Joseph A. , Kolb Theresa , Poitz David M. , Roessner Veit , Treasure Janet , Himmerich Hubertus , Ehrlich Stefan
Published: March 2024

Background

Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity.

Methods

Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable.

Results

Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI).

Conclusions

These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.
What socio-cultural, emotional and relational factors shape older people's experiences of death and dying in residential aged care? A scoping review
Authors: van Toorn Georgia , Kirby Emma , Hamilton Myra , MacArtney John
Published: March 2024

Research internationally has revealed a range of medical and health-related issues that shape care at the end of life for people living in residential aged care facilities (RACFs), their families and the staff who care for them. Yet, less is known about the lived experiences of residents, and the broader socio-cultural, emotional and relational factors that shape experiences of dying within such settings. In this article, we present findings from a scoping review designed to establish what is known about the lived experience of residents nearing the end of life. In doing so, we identify research gaps and move towards an agenda for future research. Five electronic databases were used to identify empirical research articles investigating end-of-life experiences from the perspective of older people living in RACFs, from which we selected 22 papers for thematic analysis. Our analysis highlighted three key themes: connections and closeness; place and the end of life; and temporality, care and the anticipation of dying. A majority of the articles (15) highlighted the importance of social connectedness with staff, co-residents and family in enabling people to die with dignity and a sense of belonging in residential settings. The physical layout and living arrangements in RACFs were found to affect the ways in which residents relate within the space, especially during and after the death of a resident. Anticipatory fears of dying were oriented towards the context of illness and care, and its management within the RACF, rather than death itself. Our analysis highlights considerable evidence that ‘good deaths’ are embedded in experiences of socio-emotional wellbeing, connectedness and relationality. However, much of the extant research analysed is exploratory, pointing to the need for further social scientific study of the social and cultural embeddedness of end-of-life experiences with residential aged care.
A NONPARAMETRIC TEST OF HETEROGENEITY IN CONDITIONAL QUANTILE TREATMENT EFFECTS
Authors: Cai Zongwu , Fang Ying , Lin Ming , Tang Shengfang
Published: March 2024

This paper proposes a nonparametric test to assess whether there exist heterogeneous quantile treatment effects (QTEs) of an intervention on the outcome of interest across different sub-populations defined by covariates of interest. Specifically, a consistent test statistic based on the Cramér–von Mises type criterion is developed to test if the treatment has a constant quantile effect for all sub-populations defined by covariates of interest. Under some regularity conditions, the asymptotic behaviors of the proposed test statistic are investigated under both the null and alternative hypotheses. Furthermore, a nonparametric Bootstrap procedure is suggested to approximate the finite-sample null distribution of the proposed test; then, the asymptotic validity of the proposed Bootstrap test is theoretically justified. Through Monte Carlo simulations, we demonstrate the power properties of the test in finite samples. Finally, the proposed testing approach is applied to investigate whether there exists heterogeneity for the QTE of maternal smoking during pregnancy on infant birth weight across different age groups of mothers.
[bɪt] by [bɪʔ]: Variation in T-glottaling in Scottish Standard English
Authors: Li Zeyu , Gut Ulrike
Published: March 2024

The present study investigates internal and external constraints conditioning variable T-glottaling, the realization of the voiceless alveolar stop /t/ as a glottal stop [ʔ], in supraregional Scottish Standard English. Drawing on phonemically annotated speech data from the Scottish component of the International Corpus of English, a total of 12,162 /t/ tokens produced by 138 speakers were extracted from eight formal speaking categories in the corpus and analyzed auditorily. The results showed that about 28% of the analyzed /t/ tokens were produced as glottal stops, with significant inter- and intra-speaker variability. The realization of T-glottaling is subject to both linguistic (phonetic context and word type) and social factors (age, gender, and speech style). Moreover, patterns of various types of T-glottaling differ from each other and constitute distinctive processes of ongoing sound change in Scotland.
Report of the target end-states for defined benefit pension schemes working party
Authors: Aponte A. , Caleechurn D. , Jones N. , Kola J. , Littlewood R. , Mikulskis D. , Wesbroom K. , Yiasoumi C. A.
Published: March 2024

Running off the £2 trillion of UK corporate sector defined benefit liabilities in an efficient and effective fashion is the biggest challenge facing the UK pensions industry. As more and more defined benefit pension schemes start maturing, the trustees running those schemes need to consider what their target end-state will be and the associated journey plan. However, too few trustee boards have well-articulated and robust plans. Determining the target end-state requires a grasp of various disciplines and an ability to work collaboratively with different professional advisers. This paper sets out issues trustees, employers and their advisers can consider when addressing whether their target end state should be low- dependency, buyout or transfer to a superfund. Member outcomes analysis is introduced as a central tool through which to differentiate alternative target end-states. A five-step methodology is set out for deriving an optimal target end-state for a scheme. Also considered are the specific factors impacting stressed schemes, which highlights the importance to trustee boards when considering their Plan B should their employer or scheme ever become stressed. The paper ends with specific recommendations for the actuarial profession and The Pensions Regulator to take forward.
Is this advertisement designed to appeal to you? Adolescents’ views about Instagram advertisements promoting ultra-processed products
Authors: Ares Gastón , Antúnez Lucía , Alcaire Florencia , Natero Virginia , Otterbring Tobias
Published: March 2024

Objective:

Examine the key elements that characterise social media advertisements targeted at adolescents by asking adolescents which features of Instagram ads promoting ultra-processed products make them designed to appeal to adolescents.

Design:

Instagram ads promoting ultra-processed products and brands were selected from a database in which ads had been classified regarding whether they were primarily targeted at adolescents from an adult perspective. Adolescents completed a sorting task in small groups and were requested to reach a consensus through discussions and sticky notes regarding whether sixty ads were designed to appeal to them. The sorting task was analysed using content analysis based on inductive coding.

Setting:

One private secondary school and two after-school clubs.

Participants:

Convenience sample of 105 Uruguayan adolescents aged 11–17 years.

Results:

Ten categories were identified regarding the reasons for sorting ads as (not) designed to appeal to adolescents: product type, graphic design, explicit references to age groups, language, activities or themes, memes, celebrities, characters, promotions and novelty. Product type emerged as a key element, with adolescents perceiving ads as designed to appeal to them simply because they promoted specific products.

Conclusions:

This research contributes to the validation of criteria defined in previous studies and can be used for the development of tools to monitor the prevalence and power of adolescent-targeted digital marketing. However, the importance attributed to type of product suggests that regulations should not exclusively focus on exposure to digital marketing specifically targeted at adolescents but also on exposure to marketing in general.
Social support among chronically ill adolescent and young adult patients using a hospital-based online health community as part of a palliative care program: A qualitative study
Authors: LeBeau Kelsea , Raponi Jayne-Marie , Walker Drew , Swygert Anna , Marchi Emily
Published: March 2024

Objectives

Chronically ill adolescent and young adult (AYA) patients experience barriers to accessing psychosocial support/palliative care, increasing their risk for negative psychosocial outcomes. Online health communities (OHCs) have been recommended for AYAs as part of palliative care support programs; however, we lack research investigating palliative care programs targeting AYAs’ psychosocial support needs that are delivered virtually and able to engage with patients both during and beyond inpatient admissions. Streetlight is a palliative care program designed for chronically ill AYAs. Developed as a complementary component that extends beyond the hospital setting, Streetlight Gaming and Online Team (SGOT) is an OHC aimed at facilitating social support to influence psychosocial outcomes. We investigated the existence and enactment of social support among chronically ill AYAs using SGOT and compared this to existing online social support categories to determine which support types are present within SGOT.

Methods

This was a qualitative phenomenological study. We performed deductive thematic analysis based on existing online social support categories. Nine semi-structured interviews were conducted with SGOT participants.

Results

Social companionship/belonging, esteem/emotional, and informational support were most prevalent within SGOT. Thirteen subthemes emerged representing how social support impacted AYAs’ psychosocial wellbeing. Notably, coping with/managing illness, sense of community and normalcy, recommendations and advice, and shared interests unrelated to illnesses were subthemes that resonated with AYAs and added value to their experiences.

Significance of results

SGOT is an impactful OHC used to meet AYAs’ social support needs. What makes SGOT especially unique is its virtual delivery, wherein AYAs can conveniently maintain beneficial relationships with other chronically ill same-aged peers. AYAs need spaces where they can feel normal and access continuous support, both within and beyond inpatient admissions. This study enhances our understanding of online AYA psychosocial support programs. Findings can be used by healthcare professionals to implement similar palliative care and psychosocial support programs.
The association of prognostic awareness with quality of life, spiritual well-being, psychological distress, and pain severity in patients with advanced cancer: Results from the APPROACH Study in Indonesia
Authors: Putranto Rudi , Shatri Hamzah , Irawan Cosphiadi , Gondhowiardjo Soehartati , Finkelstein Eric , Malhotra Chetna , Ozdemir Semra , Teo Irene , Yang Grace Meijuan
Published: March 2024

Background and objectives

Advanced cancer patients’ understanding of their illness is key for making informed treatment decisions. Despite the known importance of patients’ awareness of their disease prognosis, it is debatable whether this awareness is positively, negatively, or not associated with clinical and psychological outcomes among patients with advanced cancer. This paper aims to determine the prevalence of and factors associated with prognostic awareness and its association with quality of life (QoL), spiritual well-being, pain control, and psychological distress in patients with advanced cancer in Indonesia.

Methods

This cross-sectional questionnaire-based survey was part of a multicountry study titled “Asian Patient Perspectives Regarding Oncology Awareness, Care and Health (APPROACH).” Patients were asked what they knew about their cancer and treatment. QoL and spiritual well-being were measured using the Functional Assessment of Cancer Therapy – General (FACT-G) and Functional Assessment of Chronic Illness Therapy – Spiritual Well-being (FACIT-Sp) questionnaire. Psychological distress experienced by patients was recorded via the Hospital Anxiety and Depression Scale. Pain severity was also assessed. Data from 160 patients were analyzed using descriptive statistics and multivariable regression models.

Results

Of the 160 patients who participated, 55 (34.4%) were unaware of their cancer stage. Those who were aware of their stage of cancer were younger than those who were not aware (45.7 years vs 50.4 years, p = .015). There was no significant difference in spiritual well-being and other domains of QoL between those who were aware and those who were not aware of their advanced cancer stage. There was also no significant difference in anxiety depression or pain severity, even after adjustment for demographic and clinical characteristics.

Significant of results

Given the high prevalence of patients who wrongly thought their cancer was curable, more could be done to improve disease and prognostic understanding among patients with advanced cancer in Indonesia. Those who were aware of their advanced cancer stage did not have a poorer QoL, nor did they have more anxiety or depression than those who were unaware. This finding suggests that concerns about the negative impact of prognostic disclosure may be unfounded.
Identification of photothermo-insensitive with climate-smart early-maturing chickpea genotypes
Authors: S. Gurumurthy , B. C. Mamatha , P. S. Basu , K. Rudresh , T. Basavaraja , Bheemanahalli Raju , Pal Madan , Jha Prakash , K. R. Soren , J. M. Nidagundi , K. Sammi Reddy , J. Rane
Published: March 2024

Chickpea is a cool season, photothermal-sensitive crop, that is adversely affected by high temperatures (>35°C) and whose flowering is promoted by long-day conditions (>12 h). This prevents horizontal crop spread under a variety of agro-climatic conditions and the development of insensitive genotypes that perform well in all seasons. Therefore, a study was conducted to identify genotypes that are mature early, insensitive to photoperiod, high temperature and tolerant to drought stress. A set of 74 genotypes was evaluated under rainfed conditions in Kharif 2021 (off-season) to select eight promising early-maturing genotypes with high-yielding capacity. Then further investigations were conducted in five different seasons Late Kharif 2021, rabi 2021, summer 2022, early Kharif 2022 and Kharif 2022 to identify the genotypes with photothermo-insensitivity among the selected eight genotypes. With the exception of rabi 2021, each of these seasons were distinct from the chickpea's typical growing season. Among these eight, the stable genotypes which are performed better in all the seasons, especially in summer were considered, such as IPC 06-11, MNK-1, JG-14 and ICE 15654-A as a photothermo-insensitive, were able to flower and set pods with higher seed yield and, resulting in early maturity in a temperature range of 41.4/9.3°C with photoperiods of 13.1/10.9 h to reach in all seasons throughout the year. The heritability was more than 60%. Hence, these genotypes can be used as donor aids in the development of early maturing, drought stress tolerant and photothermo-insensitive chickpea.
Rapid Changes in Strength and Direction of Earth's Magnetic Field Over the Past 100,000 Years
Authors: Constable Catherine G. , Davies Christopher J.
Published: March 2024

Previous studies of rapid geomagnetic changes have highlighted the most extreme changes in direction and field strength found in paleomagnetic field models over the past 100 ky. Here we study distributions of rates of change in both time and space. Field models based on direct observations provide the most accurate values for rates of change, but their short duration precludes a complete description of field behavior. Broader representation is provided by time‐varying paleofield models, here including GGF100k, GGFSS70, LSMOD.2, CALS10k.2, HFM.OL1.A1, pfm9k.2, and SHAWQ‐iron age although variability across models and lack of temporal and spatial resolution of fine scale variations make direct comparisons difficult. For the paleofield we define rapid changes as exceeding the peak overall value of 0.4° yr−1 for directional changes and 150 nT yr−1 for intensities as established by the gufm1 model spanning 1590–1990 CE. We find that rapid directional changes are associated with low field strength and can spread across all latitudes during such episodes. Distributions of directional rates of change exhibit high skewness for models that include excursions. Rates of change in field intensity exceeding 150 nT yr−1 arise in brief intervals during the Holocene particularly associated with the strong field Levantine Iron Age Anomaly. Around the Laschamp excursion there are also rare localized occurrences of rapid intensity change. Limitations in current models make it difficult to define absolute rates for past changes, but we see that rapid changes are essential field characteristics not observed in the modern field that should nevertheless be regarded as an essential for Earth‐like dynamo simulations.
Robust Imaging of Fault Slip Rates in the Walker Lane and Western Great Basin From GPS Data Using a Multi‐Block Model Approach
Authors: Hammond William C. , Kreemer Corné , Blewitt Geoffrey
Published: March 2024

The Walker Lane (WL) in the western Great Basin (GB) is an active plate boundary system accommodating 10%–20% of the relative tectonic motion between the Pacific and North American plates. Its neotectonic framework is structurally complex, having hundreds of faults with various strikes, rakes, and crustal blocks with vertical axis rotation. Faults slip rates are key parameters needed to quantify seismic hazard in such tectonically active plate boundaries but modeling them in complex areas like the WL and GB is challenging. We present a new modeling strategy for estimating fault slip rates in complex zones of active crustal deformation using data from GPS networks. The technique does not rely on prior estimates of slip rates from geologic studies, and only uses data on the surface trace location, dip, and rake. The iterative framework generates large numbers of block models algorithmically from the fault database to obtain many estimates of slip rates for each fault. This reduces bias from subjective choices about how discontinuous faults connect and interact to accommodate strain. Each model iteration differs slightly in block boundary configuration, but all models honor geodetic and fault data, regularization, and are kinematically self‐consistent. The approach provides several advantages over bespoke models, including insensitivity to outlier data, realistic uncertainties, explicit mapping of off‐fault deformation, and slip rates that are more objective and independent of geologic slip rates. Comparisons to the U.S. National Seismic Hazard Model indicate that ∼80% of our geodetic slip rates agree with their geologic slip rates to within uncertainties.
The Ancient Lithospheric Parameters of Impact Basins on the Far Side of the Moon Based on the Mantle and Mare Basalt Load Model
Authors: Zhang Wensong , Deng Qingyun , Ye Mao , Hao Weifeng , Chen Yihao , Zheng Yingjun , Zhong Zhen , Yan Jianguo , Sun Xuemei , Li Fei
Published: March 2024

Research on the lithospheric elastic thickness (Te) of lunar mascon basins can provide a deeper understanding of heterogeneous thermal activity. In this study, we focused on four basins (Moscoviense, Freundlich‐Sharonov, Hertzsprung, and Apollo) located on the far side of the Moon. These basins exhibit a significant variation in admittance and correlation spectra, making it challenging to develop precise fitted models. Based on the global lunar crustal thickness model and mare basalt thickness, we developed a mantle and mare basalt load model to estimate the Te. This small Te (10.1 km) suggests a double impact process or extreme thermal activity caused by volcanism during the formation of the Moscoviense. For the typical highland basins, that is, Freundlich‐Sharonov and Hertzsprung, the Te (∼20 km) corresponds to a minimum heat flux of 34 mW m−2. Considering the additional energy introduced by the impact, this heat flux can be considered as the upper limit for the heat flux of the highland itself during the formation of a mascon basin. For the Apollo basin within the South Pole‐Aitken (SPA) terrane, the Te is 30.7 km. The crust beneath the SPA region is thinned, allowing a greater contribution of stiffer mantle material to the lithosphere, perhaps explaining the higher effective Te. Furthermore, the disparity between the highland and SPA terranes can give rise to their distinct basin formation processes. Impact basins formed within the SPA terrane may have experienced a faster cooling process compared to those formed on the highland terrane following the impact event, leading to a higher Te.
Call to Action: Screening and Addressing Caregiver Mental Health Needs Within All Pediatric Medical Subspecialty Settings as Standard of Care
Authors: Salley Christina G. , Bakula Dana M. , Driscoll Colleen F. Bechtel , Flanagan-Priore Catherine , Kapke Theresa L. , Moore Rachel M. , Parris Kendra R. , Sharkey Christina M.
Published: March 2024

Objective:

The objective of this topical review is to provide a rationale for the development of standards of care to address the mental health needs of caregivers of youth with chronic and acute conditions.

Method:

In this topical review, we describe the relationship between pediatric medical conditions and caregiver mental health, the state of available screening and intervention options, standards of care in medicine, existing caregiver mental health standards in pediatric subspecialty populations, and exemplar caregiver mental health programs that were developed in response to standards. Finally, we will describe our rationale for this standard of care, provide a call to action, and describe anticipated challenges in developing and implementing such standards. The content of this topical review was guided by expert knowledge, literature review, and communication with members of the American Psychological Association Division 54 through listserv communication. This review did not involve human subjects research and thus did not require Institutional Review Board approval, informed consent, or assent.

Results:

Standards of Care to address caregiver mental health in pediatrics is one approach to reduce gaps between caregivers’ needs and access to treatment. Standards that address caregiver mental health exist for a subset of pediatric medical subspecialty populations but are nonexistent across most pediatric populations.

Conclusions:

Multidisciplinary collaboration, with broad stakeholder input, could result in the writing of Standards of Care to lead to program development that addresses mental health for caregivers of children with a range of chronic and acute conditions.

Implications for Impact Statement

This topical review calls attention to the gap between what is known about the mental healthcare needs of caregivers of children with chronic and acute conditions and the implementation of assessments and interventions to address these needs. The development of standards of care is one way to bridge this gap and could lead to the development of universally implemented caregiver mental health supports in pediatric healthcare settings.
Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities
Authors: Bettadapura Sahana , Dowling Katherine , Jablon Kelli , Al-Humadi Ahmed W. , le Roux Carel W.
Published: March 2024

Background

Glucagon-like peptide-1 (GLP-1) analogs are approved for the treatment of obesity in adults and adolescents. Reports have emerged that the weight loss effect of these medications may be related to changes in food preferences and ingestive behaviors following the treatment. Understanding the mechanisms which impact ingestive behavior could expand opportunities to develop more refined and personalized treatment options for obesity.

Methods

Recent studies investigating the relationship between GLP-1 analogs and ingestive behaviors were retrieved from PubMed using the search terms: “obesity,” “food preference,” “taste,” “ingestive behavior,” “weight loss medication,” “anti-obesity medication,” “GLP-1 analog,” “tirzepatide,” “liraglutide,” “semaglutide.” Measurement tools were studied to compare variables used to assess food intake behavior. The main outcomes from each study were analyzed to evaluate the current standing and future directions of appetitive, ingestive, and consummatory behaviors and their association with GLP-1 analogs.

Results

Thus far, studies have primarily explored the weight loss phase and report decreased short-term appetite and food intake upon treatment. However, research during the weight maintenance phase and objective measurements of food intake are notably sparse. Additionally, verbal reports have been primarily used to examine food intake, which can be susceptible to subjectivity.

Conclusions

Elucidating the relationship between GLP-1 analogs and ingestive behavior could reveal additional parameters which contribute to their anti-obesity effects. To better understand these mechanisms, it is imperative to consider objective measurements of food intake in future studies. Several measurement tools have been adapted to measure variables of food behavior in humans, and each must be carefully considered with their strengths and limitations to develop optimal investigations.
Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial
Authors: Papakostas George I. , Trivedi Madhukar H. , Shelton Richard C. , Iosifescu Dan V. , Thase Michael E. , Jha Manish K. , Mathew Sanjay J. , DeBattista Charles , Dokucu Mehmet E. , Brawman-Mintzer Olga , Currier Glenn W. , McCall William Vaughn , Modirrousta Mandana , Macaluso Matthew , Bystritsky Alexander , Rodriguez Fidel Vila , Nelson Erik B. , Yeung Albert S. , Feeney Anna , MacGregor Leslie C. , Carmody Thomas , Fava Maurizio
Published: March 2024

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = −17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = −14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = −13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = −37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = −42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = −34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.

Trial registration: ClinicalTrials.gov, NCT02977299
Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway
Authors: de Nys Rebekah , Gardner Alison , van Eyk Clare , Mincheva-Tasheva Stefka , Thomas Paul , Bhattacharjee Rudrarup , Jolly Lachlan , Martinez-Garay Isabel , Fox Ian W. J. , Kamath Karthik Shantharam , Kumar Raman , Gecz Jozef
Published: March 2024

Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes a protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into the molecular role of PCDH19 in the brain, we investigated the PCDH19 interactome in the developing mouse hippocampus and cortex. Combined with a meta-analysis of all reported PCDH19 interacting proteins, our results show that PCDH19 interacts with proteins involved in actin, microtubule, and gene regulation. We report CAPZA1, αN-catenin and, importantly, β-catenin as novel PCDH19 interacting proteins. Furthermore, we show that PCDH19 is a regulator of β-catenin transcriptional activity, and that this pathway is disrupted in CE individuals. Overall, our results support the involvement of PCDH19 in the cytoskeletal network and point to signalling pathways where PCDH19 plays critical roles.
PAK3 activation promotes the tangential to radial migration switch of cortical interneurons by increasing leading process dynamics and disrupting cell polarity
Authors: Viou Lucie , Atkins Melody , Rousseau Véronique , Launay Pierre , Masson Justine , Pace Clarisse , Murakami Fujio , Barnier Jean-Vianney , Métin Christine
Published: March 2024

Mutations of PAK3, a p21-activated kinase, are associated in humans with cognitive deficits suggestive of defective cortical circuits and with frequent brain structural abnormalities. Most human variants no longer exhibit kinase activity. Since GABAergic interneurons express PAK3 as they migrate within the cortex, we here examined the role of PAK3 kinase activity in the regulation of cortical interneuron migration. During the embryonic development, cortical interneurons migrate a long distance tangentially and then re-orient radially to settle in the cortical plate, where they contribute to cortical circuits. We showed that interneurons expressing a constitutively kinase active PAK3 variant (PAK3-ca) extended shorter leading processes and exhibited unstable polarity. In the upper cortical layers, they entered the cortical plate and extended radially oriented processes. In the deep cortical layers, they exhibited erratic non-processive migration movements and accumulated in the deep pathway. Pharmacological inhibition of PAK3 kinase inhibited the radial migration switch of interneurons to the cortical plate and reduced their accumulation in the deep cortical layers. Interneurons expressing a kinase dead PAK3 variant (PAK3-kd) developed branched leading processes, maintained the same polarity during migration and exhibited processive and tangentially oriented movements in the cortex. These results reveal that PAK3 kinase activity, by promoting leading process shortening and cell polarity changes, inhibits the tangential processive migration of interneurons and favors their radial re- orientation and targeting to the cortical plate. They suggest that patients expressing PAK3 variants with impaired kinase activity likely present alterations in the cortical targeting of their GABAergic interneurons.
Spatiotemporal dynamics of hippocampal-cortical networks underlying the unique phenomenological properties of trauma-related intrusive memories
Authors: Clancy Kevin J. , Devignes Quentin , Ren Boyu , Pollmann Yara , Nielsen Sienna R. , Howell Kristin , Kumar Poornima , Belleau Emily L. , Rosso Isabelle M.
Published: March 2024

Trauma-related intrusive memories (TR-IMs) possess unique phenomenological properties that contribute to adverse post-traumatic outcomes, positioning them as critical intervention targets. However, transdiagnostic treatments for TR-IMs are scarce, as their underlying mechanisms have been investigated separate from their unique phenomenological properties. Extant models of more general episodic memory highlight dynamic hippocampal-cortical interactions that vary along the anterior-posterior axis of the hippocampus (HPC) to support different cognitive-affective and sensory-perceptual features of memory. Extending this work into the unique properties of TR-IMs, we conducted a study of eighty-four trauma-exposed adults who completed daily ecological momentary assessments of TR-IM properties followed by resting-state functional magnetic resonance imaging (rs-fMRI). Spatiotemporal dynamics of anterior and posterior hippocampal (a/pHPC)-cortical networks were assessed using co-activation pattern analysis to investigate their associations with different properties of TR-IMs. Emotional intensity of TR-IMs was inversely associated with the frequency and persistence of an aHPC-default mode network co-activation pattern. Conversely, sensory features of TR-IMs were associated with more frequent co-activation of the HPC with sensory cortices and the ventral attention network, and the reliving of TR-IMs in the “here-and-now” was associated with more persistent co-activation of the pHPC and the visual cortex. Notably, no associations were found between HPC-cortical network dynamics and conventional symptom measures, including TR-IM frequency or retrospective recall, underscoring the utility of ecological assessments of memory properties in identifying their neural substrates. These findings provide novel insights into the neural correlates of the unique features of TR-IMs that are critical for the development of individualized, transdiagnostic treatments for this pervasive, difficult-to-treat symptom.
Association between patent ductus arteriosus flow and home oxygen therapy in extremely preterm infants
Authors: Termerova Jana , Kubena Ales A. , Liska Karel , Tomek Viktor , Plavka Richard
Published: March 2024

Background

Central blood flow measurements include the estimation of right and left ventricular output (RVO, LVO), superior vena cava (SVC) flow, and calculated patent ductus arteriosus (PDA) flow. We aimed to provide an overview of the maturation patterns of these values and the relationship between PDA flow and the need for home oxygen therapy.

Methods

This prospective single-center study was conducted in infants born at <26 weeks of gestation. We performed echocardiographic measurements five times during their life (from the 4th post-natal day to the 36th postmenstrual week).

Results

Sixty patients with a mean birth weight of 680 (590, 760) g were included. Postnatal development of LVO and PDA flow peaked at the end of the second postnatal week (427 and 66 mL/kg/min, respectively). The RVO increased between days 4 and 7–8. The SVCF was most stable. The development curves of PDA flow differed between the groups with (n = 28; 47%) and without home oxygen therapy.

Conclusion

We present the central blood flow values and their postnatal development in infants <26 weeks of gestation. This study demonstrates the association between PDA flow and the future need for home oxygen therapy.

Impact

This study enriches our knowledge of the long-term development of central blood flow parameters and derived patent ductus arteriosus (PDA) flow in extremely preterm infants (<26 weeks).

While pulmonary resistance decreased, PDA flow continued to increase from day 4 to the end of the second week of life. Similarly, left ventricular output increased as a marker of preload. The superior vena cava flow remained stable.

The observed association between PDA flow and an unfavorable respiratory outcome is important for future studies focusing on the prevention of chronic lung disease.
Association between resting-state connectivity patterns in the defensive system network and treatment response in spider phobia—a replication approach
Authors: Leehr Elisabeth J. , Seeger Fabian R. , Böhnlein Joscha , Gathmann Bettina , Straube Thomas , Roesmann Kati , Junghöfer Markus , Schwarzmeier Hanna , Siminski Niklas , Herrmann Martin J. , Langhammer Till , Goltermann Janik , Grotegerd Dominik , Meinert Susanne , Winter Nils R. , Dannlowski Udo , Lueken Ulrike
Published: March 2024

Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n = 79 patients with spider phobia (discovery sample) and n = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.
TREM2 deficiency impairs the energy metabolism of Schwann cells and exacerbates peripheral neurological deficits
Authors: Zhang Nannan , Ji Qingjie , Chen Yunfeng , Wen Xiwu , Shan Fangzhen
Published: March 2024

Triggering receptor expressed on myeloid cells-2 (TREM2) has been implicated in susceptibility to neurodegenerative disease. Schwann cells (SCs), the predominant glial cell type in the peripheral nervous system (PNS), play a crucial role in myelination, providing trophic support for neurons and nerve regeneration. However, the function of TREM2 in SCs has not been fully elucidated. Here, we found that TREM2 is expressed in SCs but not in neurons in the PNS. TREM2 deficiency leads to disruption of glycolytic flux and oxidative metabolism in SCs, impairing cell proliferation. The energy crisis caused by TREM2 deficiency triggers mitochondrial damage and autophagy by activating AMPK and impairing PI3K-AKT-mTOR signaling. Combined metabolomic analysis demonstrated that energic substrates and energy metabolic pathways were significantly impaired in TREM2-deficient SCs. Moreover, TREM2 deficiency impairs energy metabolism and axonal growth in sciatic nerve, accompanied by exacerbation of neurological deficits and suppression of nerve regeneration in a mouse model of acute motor axonal neuropathy. These results indicate that TREM2 is a critical regulator of energy metabolism in SCs and exerts neuroprotective effects on peripheral neuropathy.
Comparison of intraocular pressure profiles during the water drinking test and the modified diurnal tension curve
Authors: Yap Timothy E. , Gao Yuan , Ahmad Hanif , Susanna Fernanda , Susanna Remo , Normando Eduardo M. , Bloom Philip A. , Cordeiro Maria Francesca
Published: March 2024

Objectives

To compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry.

Methods

Open-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water. Blood pressure, heart rate, pupillometry measurements, and optical coherence tomography (AS-OCT) were also recorded.

Results

Forty-two subjects’ right eyes were included. 48% were using topical glaucoma medication. Mean baseline IOP was 14.9 ± 4.52 mmHg, with mean visual field mean deviation (±SD) −5.05 ± 5.45 dB. Strong association was found between maximum IOP during mDTC and WDT (r = 0.90, 95% CI 0.82–0.95 p < 0.0001) with agreement (mDTC-WDT) bias −0.82 mmHg, 95% LoA −1.46 to −0.18. During the WDT, mean systolic blood pressure (±SD) increased from 140.0 ± 20.0 to 153.3 ± 24.0 mmHg (p < 0.0001), mean heart rate ( ± SD) reduced from 69.5 ± 11.3 bpm to 63.6 ± 10.0 bpm (p < 0.0001), and temporal iridocorneal angle increased from 29.2 ± 6.0° to 29.6 ± 5.2° (p = 0.04).

Conclusion

This study presents repeated, observer-masked IOP data showing strong correlation between maximum IOP during mDTC and WDT using multimodal tonometry. This supports WDT as a meaningful alternative to mDTC when investigating diurnal IOP characteristics in clinic, with reduced time requirements and associated costs.