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Borehole temperature depth profiles are commonly used to infer time variations in the ground surface temperature on centennial time scales. We compare different procedures to obtain a regional ground surface temperature history (GSTH) from an ensemble of borehole temperature depth profiles. We address in particular the question of selecting profiles that are not contaminated by non climatic surface perturbations and we compare the joint inversion of all the profiles with the average of individual inversions. Very few profiles of the Canadian data set meet the selection criteria (e.g. only 13 out of 73 profiles in Manitoba and Saskatchewan were retained). We show that the resolution and the stability of the inversion of selected profiles are much improved over those for a complete data set. When profiles have been selected, the average GSTH of individual inversions and the GSTH of the joint inversion are almost identical. This is not observed when the entire data set is inverted: the average of individual inversions is different from the joint inversion. We also show that the joint inversion of very noisy data sets does not improve the resolution but, on the contrary, causes strong instabilities in the inversion. When the profiles that are affected by noise can not be eliminated, averaging of the individual inversions yields the most stable result, but with very poor resolution.

In phagocytes, cytoskeletal and membrane remodeling is finely regulated at the phagocytic cup. Various smaFll G proteins, including those of the Arf family, control these dynamic processes. Human neutrophils express AGAP2, an Arf GTPase activating protein (ArfGAP) that regulates endosomal trafficking and focal adhesion remodeling. We first examined the impact of AGAP2 on phagocytosis in CHO cells stably expressing the FcγRIIA receptor (CHO-IIA). In unstimulated CHO-IIA cells, AGAP2 only partially co-localized with cytoskeletal elements and intracellular compartments. In CHO-IIA cells, AGAP2 transiently accumulated at actin-rich phagocytic cups and increased Fcγ receptor-mediated phagocytosis. Enhanced phagocytosis was not dependent on the N-terminal GTP-binding protein-like (GLD) domain of AGAP2. AGAP2 deleted of its GTPase-activating protein (GAP) domain was not recruited to phagocytic cups and did not enhance the engulfment of IgG-opsonized beads. However, the GAP-deficient [R618K]AGAP2 transiently localized at the phagocytic cups and enhanced phagocytosis. In PLB-985 cells differentiated towards a neutrophil-like phenotype, silencing of AGAP2 reduced phagocytosis of opsonized zymosan. In human neutrophils, opsonized zymosan or monosodium urate crystals induced AGAP2 phosphorylation. The data indicate that particulate agonists induce AGAP2 phosphorylation in neutrophils. This study highlights the role of AGAP2 and its GAP domain but not GAP activity in FcγR-dependent uptake of opsonized particles.

Perfluorohexane sulfonate (PFHxS) is a ubiquitous perfluoroalkyl substance known for its environmental persistence and potential toxicity. This study investigated PFHxS's impact on zebrafish embryos, focusing on sensorimotor behavior, circadian rhythm disruption, and underlying molecular mechanisms. Under 24 hr dark incubations, PFHxS exposure induced concentration-dependent hyperactivity within larval photomotor response, characterized by the distinctive "O-bend" response, strong light-phase hyperactive movement and seizure-like movements. It appears that PFHxS-treated embryos cannot sense light cues in a normal manner. Similar hyperactivity was seen for acoustic startle response assay, suggesting that the response is not merely visual, but sensorimotor. LC-MS studies confirmed detectable uptake of PFHxS into embryos. We then conducted mRNA-sequencing across multiple time points (48 and 120 hpf) and concentrations (0.00025, 0.0025 and 25 µM). Data at the 25 µM (2-120 hpf) exposure showed disrupted pathways associated with DNA and cell cycle. Interestingly, data at 0.00025 µM - an environmentally relevant concentration- at 48 hpf showed disruption of MAPK and other signaling pathways. Immunohistochemistry of eyes showed reduced retinal stem cell proliferation, consistent with observed DNA replication pathway disruptions. To assess if these impacts were driven by circadian rhythm development, we manipulated light/dark cycles during PFHxS incubation; this manipulation altered behavioral patterns, implicating circadian rhythm modulation as a target of PFHxS. Since circadian rhythm is modulated by the pineal gland, we ablated the gland using metronidazole; this ablation partially rescued hyperactivity, indicating the gland's role in driving the phenotype. Collectively, these findings underscore proclivity of PFHxS to cause neurodevelopmental toxicity, necessitating further mechanistic exploration and environmental health assessments.

The term 'mental health crisis' is a widely used concept in clinical practice and research, appearing prominently in mental health literature across healthcare and social science disciplines. Within these contexts, the term is frequently either left undefined or defined rather narrowly, confined to clinical observations or guidelines targeted at healthcare providers and negating the multifaceted nature of crisis as described by those with lived experience. Therefore, the aim of this paper is to explore the characteristics of and provide a conceptual definition for the concept of 'mental health crisis'. Rodgers' method of evolutionary concept analysis was employed and 34 articles, ranging from 1994 to 2021 and a variety of disciplines, were analysed. The results highlighted the contrast between clinically oriented surrogate terms and related concepts and those used by individuals with lived crisis experience. Antecedents of crisis included underlying vulnerabilities, relational dysfunction, collapse of life structure and struggles with activities of daily living. The concept's attributes encompassed the temporality of crisis, signs and symptoms of crisis, functional decline and crisis in family and caregivers. Finally, the consequences comprised looking inward for help, looking outward for help, and opportunities and dangers. This concept analysis serves as a foundational step in understanding 'mental health crisis' and its various dimensions, facilitating more nuanced discussions and interventions in the realm of mental healthcare., (© 2024 The Author(s). International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

It is well documented that early sensory loss typically alters brain morphology in the areas associated with the lost sense. However, much less is known about the impact of early sensory loss on the remainder of the sensory regions. Therefore, we investigated whether congenitally blind (CB) individuals show brain alterations in the olfactory system by comparing cortical morphology and olfactory bulb (OB) volume between 16 congenitally blind individuals and 16 sighted matched controls. Our results showed that not only CB blind individuals exhibited smaller OB but also alterations of cortical density in some higher olfactory processing centres, but unchanged cortical thickness. Our current findings suggest that a lifelong absence of visual input leads to morphological alterations in olfactory processing areas., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Although often considered a nondominant sense for spatial perception, chemosensory perception can be used to localize the source of an event and potentially help us navigate through our environment. Would blind people who lack the dominant spatial sense-vision-develop enhanced spatial chemosensation or suffer from the lack of visual calibration on spatial chemosensory perception? To investigate this question, we tested odorant localization abilities across nostrils in blind people compared to sighted controls and if the time of vision loss onset modulates those abilities. We observed that congenitally blind individuals (10 subjects) outperformed sighted (20 subjects) and late-blind subjects (10 subjects) in a birhinal localization task using mixed olfactory-trigeminal stimuli. This advantage in congenitally blind people was selective to olfactory localization but not observed for odorant detection or identification. We, therefore, showed that congenital blindness but not blindness acquired late in life is linked to enhanced localization of chemosensory stimuli across nostrils, most probably of the trigeminal component. In addition to previous studies highlighting enhanced localization abilities in auditory and tactile modalities, our current results extend such enhanced abilities to chemosensory localization., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alpha (8-12 Hz) and beta (13-30 Hz) oscillations are believed to be involved in motor control. Their modulation with transcranial alternating current stimulation (tACS) has been shown to alter motor behavior and cortical excitability. The aim of the present study was to determine whether tACS applied bilaterally over sensorimotor cortex at 10 Hz and 20 Hz modulates interhemispheric interactions and corticospinal excitability. Thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind protocol. Sham and active tACS (10 Hz, 20 Hz, 1 mA) were applied for 20 min over bilateral sensorimotor areas. The physiological effects of tACS on corticospinal excitability and interhemispheric inhibition were assessed with transcranial magnetic stimulation. Physiological mirror movements were assessed to measure the overflow of motor activity to the contralateral M1 during voluntary muscle contraction. Bilateral 10 Hz tACS reduced corticospinal excitability. There was no significant effect of tACS on physiological mirror movements and interhemispheric inhibition. Ten Hz tACS was associated with response patterns consistent with corticospinal inhibition in 57% of participants. The present results indicate that application of tACS at the alpha frequency can induce aftereffects in sensorimotor cortex of healthy individuals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Recognition memory for concrete, nameable pictures is typically faster and more accurate than for abstract pictures. A dual-coding account for these findings suggests that concrete pictures are processed into verbal and image codes, whereas abstract pictures are encoded in image codes only. Recognition memory relies on two successive and distinct processes, namely familiarity and recollection. Whether these two processes are similarly or differently affected by stimulus concreteness remains unknown. This study examined the effect of picture concreteness on visual recognition memory processes using event-related potentials (ERPs). In a sample of children involved in a longitudinal study, participants (N=96; mean age=11.3years) were assessed on a continuous visual recognition memory task in which half the pictures were easily nameable, everyday concrete objects, and the other half were three-dimensional abstract, sculpture-like objects. Behavioral performance and ERP correlates of familiarity and recollection (respectively, the FN400 and P600 repetition effects) were measured. Behavioral results indicated faster and more accurate identification of concrete pictures as "new" or "old" (i.e., previously displayed) compared to abstract pictures. ERPs were characterized by a larger repetition effect, on the P600 amplitude, for concrete than for abstract images, suggesting a graded recollection process dependent on the type of material to be recollected. Topographic differences were observed within the FN400 latency interval, especially over anterior-inferior electrodes, with the repetition effect more pronounced and localized over the left hemisphere for concrete stimuli, potentially reflecting different neural processes underlying early processing of verbal/semantic and visual material in memory., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: This paper aims to identify the main scientific literature on patient involvement in the education of health professionals., Methods: A literature review with keywords ''patient partner' OR 'service user' AND 'education'' in the CINAHL database identified 26 articles related to the involvement of patient partners in the training and education of health professionals., Results: The presence of patient partners is positively assessed. Teachers would be able to humanize and to nuance theoretical concepts by presenting people living with a mental health problem. Students have new skills, change their attitude positively by being more aware of the factors of stigmatization in mental health and their perspective on the patient would broaden by taking in consideration the health in its entirety. Finally, patient partners, by their unveiling, would feel the therapeutic effects, a sense of pride to be recognized as peers and would exercise a civic contribution by participating in the training of health professionals. However, the literature does not allow these assertions to be evidence-based., Conclusion: Some challenges remain for genuine involvement of patients beginning with their integration at every levels of development in training and education programs and a better balance between scientific knowledge and experiential knowledge.