A Steroid-Conjugated Contrast Agent for Magnetic Resonance Imaging of Cell Signaling

We have synthesized the first steroid hormone−MR contrast agent conjugate designed to track the cell signaling process upon binding to a gene switch system. The derivative has a high relaxivity and when tested in vitro is active as a progesterone antagonist (RU-486). By combining a transcriptional system and a noninvasive imaging technology, such as MRI, it would be a powerful tool to research the cell signaling pathway in vivo

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

BackgroundTo characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful.MethodsAssessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic.ResultsThe cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p < 0.001, 2-sample t test). Colic cries outranked pain cries by measures of acoustic intensity, including energy, length of voiced periods, and fundamental frequency/pitch, while fussy and hungry cries showed reduced intensity measures compared to pain and colic.ConclusionsAcoustic features of cries are consistent across a diverse infant population and can be utilized as objective markers of pain, hunger, and fussiness. The ChatterBaby algorithm detected significant acoustic similarities between colic and painful cries, suggesting that they may share a neuronal pathway

What is the impact of structural and cultural factors and interventions within educational settings on promoting positive mental health and preventing poor mental health: a systematic review

Mental health (MH) difficulties are on the increase among children and young people (CYP). Evidence has shown that educational settings contain both risk and protective factors for MH. This review investigated which structural and cultural factors and interventions within educational settings promote positive MH and prevent poor MH in 4-18 year olds. Searches were conducted in PsychINFO, Embase, ERIC, ASSIA and British Education Index, and reference lists from key studies and relevant systematic reviews were hand-searched. Intervention, cohort, and qualitative studies were included. Of the 62 included papers, 36 examined cultural factors (30 social/relational and six value-related) while 12 studies examined structural factors (eight organisational and four physical) and 14 studies examined multiple factors. There was strong evidence for the impact of positive classroom management techniques, access to physical activity, and peer mentoring on student MH. Studies examining the impact of positive school culture, teacher training in MH and parent involvement in school MH activities also found predominantly positive results for student MH, albeit the evidence was of lower quality or from a low number of studies. Few studies explicitly examined the impact of interventions on MH inequalities; those that did indicated limited if any reduction to inequalities. A very small number of studies suggested that interventions targeting those at risk of poor MH due to socioeconomic factors could successfully improve wellbeing and reduce depression, anxiety and behavioural problems. Studies exploring the effect of management and leadership strategies within schools, policies, and aspects of the physical environment other than green space were scarce or absent in the literature. This review highlights the need to consider the ways in which educational settings are organised, the culture that is created and the physical space in order to improve the MH of CYP

An ontology-based modelling system (OBMS) for representing behaviour change theories applied to 76 theories

Background: To efficiently search, compare, test and integrate behaviour change theories, they need to be specified in a way that is clear, consistent and computable. An ontology-based modelling system (OBMS) has previously been shown to be able to represent five commonly used theories in this way. We aimed to assess whether the OBMS could be applied more widely and to create a database of behaviour change theories, their constructs and propositions. Methods: We labelled the constructs within 71 theories and used the OBMS to represent the relationships between the constructs. Diagrams of each theory were sent to authors or experts for feedback and amendment. The 71 finalised diagrams plus the five previously generated diagrams were used to create a searchable database of 76 theories in the form of construct-relationship-construct triples. We conducted a set of illustrative analyses to characterise theories in the database. Results: All 71 theories could be satisfactorily represented using this system. In total, 35 (49%) were finalised with no or very minor amendment. The remaining 36 (51%) were finalised after changes to the constructs (seven theories), relationships between constructs (15 theories) or both (14 theories) following author/expert feedback. The mean number of constructs per theory was 20 (min. = 6, max. = 72), with the mean number of triples per theory 31 (min. = 7, max. = 89). Fourteen distinct relationship types were used, of which the most commonly used was 'influences', followed by 'part of'. Conclusions: The OBMS can represent a wide array of behavioural theories in a precise, computable format. This system should provide a basis for better integration and synthesis of theories than has hitherto been possible.info:eu-repo/semantics/publishedVersio

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of big data (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA\u27s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Comparing Genetic Variation among Latin American Immigrants: Implications for Forensic Casework in the Arizona- and Texas-México Borderlands

The humanitarian crisis on the United States-México border is a long standing and evolving crisis in which nearly 8,000 deaths have been reported in the last two decades. These deaths are largely distributed across the Arizona-México and Texas-México border regions where demographic trends for immigrants attempting to cross into the U.S. have shifted dramatically. The demographic change and volume of immigrants seeking shelter in the U.S. presents new challenges for the forensic practitioners entrusted with the identification of individuals who lose their lives during the final segment of their journey. Within this Border context, the present study investigates how genetic variation inferred from forensically significant microsatellites can provide valuable information on regions of origin for unidentified remains on the group level. To explore how we can mobilize these genetic data to inform identification strategies, we conduct a comparative genetic analysis of identified and unidentified immigrant cases from the Arizona- and Texas-México contexts, as well as 27 other Latin American groups. Allele frequencies were utilized to calculate FST, and relationships were visually depicted in a multidimensional scaling plot. A Spearman correlation coefficient analysis assessed the strength and significance of population relationships and an agglomerative clustering analysis assessed population clusters. Results indicate that Arizona-México immigrants have the strongest relationship (\u3e80%) with groups from El Salvador, Guatemala, México, and an indigenous group from Southern México. Texas-México immigrants have the strongest relationships (\u3e80%) with groups from Belize, Colombia, Costa Rica, El Salvador, Guatemala, Honduras, and Nicaragua. These findings agree with, and are discussed in comparison to, previously reported demographic trends, population genetics research, and population history analyses. We emphasize the utility and necessity of coupling genetic variation research with a nuanced anthropological perspective for identification processes in the U.S-México border context

Annual and seasonal variability in high latitude dust deposition, West Greenland

High latitude regions (≥ 50°N and ≥ 40°S) are thought to contribute substantially to contemporary global dust emissions which can influence biogeochemical cycling as well as geomorphic, cryospheric and atmospheric processes. However, there are few measurements of the emission or deposition of dust derived from these areas that extend beyond a single event or season. This article reports the deposition of locally-derived dust to an ice-free area of West Greenland over 2 years from 23 traps distributed across five sampling sites. Local dust sources include glacial outwash plains, glacially-derived delta deposits and the reworking of loessic soils. Annual dust deposition is estimated at 37.3 to 93.9 g m−2 for 2017–2018 and 9.74 to 28.4 g m−2 in 2018–2019. This annual variation is driven by high deposition rates observed in spring 2017 of 0.48 g m−2 d−1 compared to the range of 0.03 to 0.07 g m−2 d−1 during the rest of the monitoring period. The high deposition rates in spring 2017 were due to warmer than average conditions and high meltwater sediment supply that delivered large quantities of sediment to local outwash plains in 2016. For other seasons, dust deposition was lower over both autumn–winter periods (0.03 g m−2 d−1) than during the spring and summer (0.04–0.07 g m−2 d−1). When sediment availability is limited, dust deposition increases with increasing temperature and wind speed. Secondary data from dust-related weather type/observation codes and visibility records were found to be inconsistent with measured dust deposition during the period of study. One possible reason for this is the complex nature of the terrain between the observation and sample sites. The dust deposition rates measured here and the infidelity of the observed dust with secondary data sources reveal the importance of direct quantification of dust processes to accurately constrain the dust cycle at high latitudes

Early experience with targeted therapy as a first-line adjuvant treatment for pediatric low-grade glioma.

OBJECTIVE: Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG. Here, the authors reviewed their institutional experience with using a personalized medicine approach to patients with newly diagnosed pLGGs. METHODS: All pediatric patients at the authors\u27 institution who had been treated with dabrafenib or trametinib for pLGG without first receiving conventional chemotherapy or radiation were retrospectively reviewed. Demographic, clinical, and radiological data were collected. RESULTS: Eight patients underwent targeted therapy as a first-line treatment for pLGG. Five patients had a BRAF alteration (1 with a BRAFV600E mutation, 4 with a KIAA1549:BRAF fusion), and 3 patients had an NF1 mutation. One of the 8 patients was initially treated with dabrafenib, and trametinib was added later. Seven patients were initially treated with trametinib; of these, 2 later transitioned to dual therapy, whereas 5 continued with trametinib monotherapy. Six patients (75%) demonstrated a partial response to therapy during their treatment course, whereas stable disease was identified in the remaining 2 patients (25%). One patient experienced mild disease progression after completing a course of trametinib monotherapy, but ultimately stabilized after a period of close observation. Another patient experienced tumor progression while on dabrafenib, but subsequently responded to dual therapy with dabrafenib and trametinib. The most common adverse reactions to targeted therapy were cutaneous toxicity (100%) and diarrhea (50%). CONCLUSIONS: Targeted therapies have the potential to become a standard treatment option for pLGG due to their favorable toxicity profile and oral route of administration. This case series provides preliminary evidence that targeted therapies can induce an early disease response as a first-line adjuvant treatment; however, large-scale studies are required to assess long-term durability and safety

What is the impact of structural and cultural factors and interventions within educational settings on promoting positive mental health and preventing poor mental health: a systematic review.

Mental health (MH) difficulties are on the increase among children and young people (CYP). Evidence has shown that educational settings contain both risk and protective factors for MH. This review investigated which structural and cultural factors and interventions within educational settings promote positive MH and prevent poor MH in 4-18 year olds. Searches were conducted in PsychINFO, Embase, ERIC, ASSIA and British Education Index, and reference lists from key studies and relevant systematic reviews were hand-searched. Intervention, cohort, and qualitative studies were included. Of the 62 included papers, 36 examined cultural factors (30 social/relational and six value-related) while 12 studies examined structural factors (eight organisational and four physical) and 14 studies examined multiple factors. There was strong evidence for the impact of positive classroom management techniques, access to physical activity, and peer mentoring on student MH. Studies examining the impact of positive school culture, teacher training in MH and parent involvement in school MH activities also found predominantly positive results for student MH, albeit the evidence was of lower quality or from a low number of studies. Few studies explicitly examined the impact of interventions on MH inequalities; those that did indicated limited if any reduction to inequalities. A very small number of studies suggested that interventions targeting those at risk of poor MH due to socioeconomic factors could successfully improve wellbeing and reduce depression, anxiety and behavioural problems. Studies exploring the effect of management and leadership strategies within schools, policies, and aspects of the physical environment other than green space were scarce or absent in the literature. This review highlights the need to consider the ways in which educational settings are organised, the culture that is created and the physical space in order to improve the MH of CYP