Mexican Muralists and Frida Kahlo

“Mexican Muralists and Frida KahloLatin American Studie

Comparison of high-resolution climate reanalysis datasets for hydro-climatic impact studies

Continuous high-quality meteorological information is needed to describe and understand extreme hydro-climatic events, such as droughts and floods. Information of highest quality relying on observations is often only available on a national level and for few meteorological variables. As an alternative, large-scale climate reanalysis datasets blending model simulations with observations are often used. However, their performance can be biased due to coarse spatial resolution, model uncertainty, and data assimilation biases. Previous studies on the performance of reanalysis datasets either focused on the global scale, on single variables, or on few aspects of the hydro-climate. Therefore, we here conduct a comprehensive spatio-temporal evaluation of different precipitation, temperature and snowfall metrics for four state-of-the-art reanalysis datasets (ERA5, ERA5-Land, CERRA-Land, and CHELSA-v2.1) over complex terrain. We consider climatologies of mean and extreme climate metrics, daily to inter-annual variability, as well as the consistency in long term trends. Further, we compare the representation of extreme events, namely the intensity and severity of the 2003 and 2018 droughts, as well as the 1999 and 2005 floods in Switzerland. The datasets generally show a satisfactory performance for most of these characteristics, exceptions being the representation of snowfall (solid precipitation) and the number of wet days in ERA5 and ERA5-Land. Our results show clear differences in the representation of precipitation among datasets and a substantial improvement of the representation of precipitation in CERRA-Land compared to the other datasets. In contrast to precipitation, temperature is more comparable among datasets, with CERRA-Land and CHELSA showing smaller biases yet a clear increase of bias with elevation. All datasets are able to identify the 2003 and 2018 drought events, however, ERA5, ERA5-Land, and CHELSA overestimate their intensity and severity, while CERRA-Land underestimates it. The 1999 and 2005 floods are overall well represented by all datasets, with CERRA-Land showing the best agreement with observations and the other datasets overestimating the spatial extent of the events. We conclude that overall, CERRA-Land is the most reliable dataset and suitable for a broad range of analyses, particularly for regions where snow processes are relevant and for applications where the representation of daily to inter-annual precipitation variability is important

Smartphone accessibility: Understanding the lived experience of users with cervical spinal cord injuries

Purpose: To explore accessibility challenges encountered by smartphone users with cervical spinal cord injuries (C1-C8).To investigate the suitability of current technology and make recommendations to help future technology meet user needs. Methods: The study uses a mixed-method approach combining an inductive thematic analysis of nine semi-structured interviews with a quantitative analysis of thirty-nine questionnaires. Results: The analysis generated four themes: ’the drive for independence and self-efficacy’; ’trying to make it work’; ’getting the right technology for me’; ’using the phone as and when I want to’. These themes highlighted how unresolved access issues and situational barriers limited independence and created unwanted privacy compromises for effective communication. There was a lack of information or support on available smartphone accessibility features and assistive technology (AT). Smartphone AT was regarded as overpriced, poorly designed and lacking the voices of people with disabilities. Conclusions: The smartphone’s potential to improve quality of life, participation, and well-being is limited by accessibility challenges hindering independent and private smartphone use. Future design work should focus on improving accessibility, investigating reasons for AT’s poor quality and high cost, and removing barriers to end-user inclusion. To enhance user awareness of available technology, stakeholders should build and maintain an open platform to act as an information source for peer and professional support on assistive technology

Stercobilin: A Putative Link between Autism and Gastrointestinal Distress?

Despite the increasing prevalence for its diagnosis in children, there are no clinical biomarkers of autism spectrum disorders (ASD). Herein a research journey is described that began by seeking evidence for the opioid excess theory of autism using mass spectrometry methods to screen human urine specimens and has evolved into the discovery of promising murine fecal biomarkers for ASD. Our results are consistent with an emerging body of evidence that shows that intestinal microflora from ASD subjects can be distinguished from controls, suggesting that metabolite differences due to the action of intestinal microbes may provide a means to identify ASD biomarkers

Rising Prevalence of Mild Chronic Gastritis in Children: A Single Center Experience

OBJECTIVES AND METHODS: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea. RESULTS: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%; CONCLUSIONS: There has been a significant rise in the prevalence of mild chronic gastritis or non-specific gastritis over the last decade in our population

What adolescents living with long-term conditions say about being involved in decision-making about their healthcare: A systematic review and narrative synthesis of preferences and experiences

Objective To understand the preferences and experiences of adolescents (age 10–19) with long-term conditions (LTCs) towards involvement in discussions and decisions regarding management of their condition. Methods A systematic review and narrative synthesis of mixed-methods, quantitative and qualitative and research was performed. Six databases were searched from inception to March 2017. The quality of the articles was assessed, and relevant data were extracted and coded thematically. Results The search yielded 27 articles which met the inclusion criteria. Decision-making involvement preferences and experiences were reported from the adolescents’ perspectives. Adolescents often report that they do not have any choice of treatment options. Variability in preferences and experiences were found within and between individuals. Mismatches between preferences and experiences are common, and often with negative emotional consequences. Discussion Adolescent preferences for involvement in the decision-making process are situational and individualistic. Healthcare professionals can encourage involvement by ensuring that adolescents are informed of treatment options, and aware of the value of their contribution. Future research should explore adolescent perceived barriers and facilitators to SDM. Practical implications Interventions are needed to effectively train HCPs in the delivery of shared decision-making, and to support the participation of adolescents with LTCs in shared decision-making

"I'd like to have more of a say because it's my body?: Adolescents' perceptions around barriers and facilitators to shared decision-making

PURPOSE: Adolescents living with long-term conditions (LTCs) often feel as though they are left out of discussions and decisions with healthcare professionals, which can give them the impression that their views are not important. Research around decision-making during clinical encounters often fails to represent adolescents' perspectives. This study explores adolescents' perceptions and experiences, focusing on identifying the perceived barriers to, and facilitators for, their involvement in shared decision-making (SDM). METHODS: Nineteen adolescents (aged 13-19 years) with LTCs were recruited from endocrinology, rheumatology, neurology, and nephrology clinics. Participatory qualitative interviews were conducted using life grids and pie charts, and transcripts were analyzed thematically. RESULTS: Four overarching themes and nine sub-themes were identified which describe barriers and facilitators around SDM. Adolescents need to feel, as though their involvement is supported by parents and healthcare professionals, that their contribution to the decision-making process is important and will yield a positive outcome. Adolescents often feel it is their right to be involved in decisions that affect them but also feel as though the adults' contributions to the decisions are considered more valuable. Adolescents need to feel capable of being involved, in terms of being able to understand and process information about the available options and ask appropriate questions. CONCLUSIONS: This work highlights a number of ways SDM can be facilitated between healthcare practitioners and adolescents with LTCs. Identifying the needs of adolescents with LTCs is necessary for optimizing the SDM process and to support them during healthcare consultation

An immortalised mesenchymal stem cell line maintains mechano-responsive behaviour and can be used as a reporter of substrate stiffness

The mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment to lineage. However, current tools for characterizing substrates’ mechanical properties, such as atomic force microscopy (AFM), often do not fully recapitulate the length and time scales over which cells ‘feel’ substrates. Here, we show that an immortalised, clonal line of human mesenchymal stem cells (MSCs) maintains the responsiveness to substrate mechanics observed in primary cells, and can be used as a reporter of stiffness. MSCs were cultured on soft and stiff polyacrylamide hydrogels. In both primary and immortalised MSCs, stiffer substrates promoted increased cell spreading, expression of lamin-A/C and translocation of mechano-sensitive proteins YAP1 and MKL1 to the nucleus. Stiffness was also found to regulate transcriptional markers of lineage. A GFP-YAP/RFP-H2B reporter construct was designed and virally delivered to the immortalised MSCs for in situ detection of substrate stiffness. MSCs with stable expression of the reporter showed GFP-YAP to be colocalised with nuclear RFP-H2B on stiff substrates, enabling development of a cellular reporter of substrate stiffness. This will facilitate mechanical characterisation of new materials developed for applications in tissue engineering and regenerative medicine

Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARSCoV- 2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery

Mechanotransductive feedback control of endothelial cell motility and vascular morphogenesis

Vascular morphogenesis requires persistent endothelial cell motility that is responsive to diverse and dynamic mechanical stimuli. Here, we interrogated the mechanotransductive feedback dynamics that govern endothelial cell motility and vascular morphogenesis. We show that the transcriptional regulators, YAP and TAZ, are activated by mechanical cues to transcriptionally limit cytoskeletal and focal adhesion maturation, forming a conserved mechanotransductive feedback loop that mediates human endothelial cell motility in vitro and zebrafish intersegmental vessel (ISV) morphogenesis in vivo. This feedback loop closes in 4 hours, achieving cytoskeletal equilibrium in 8 hours. Feedback loop inhibition arrested endothelial cell migration in vitro and ISV morphogenesis in vivo. Inhibitor washout at 3 hrs, prior to feedback loop closure, restored vessel growth, but washout at 8 hours, longer than the feedback timescale, did not, establishing lower and upper bounds for feedback kinetics in vivo. Mechanistically, YAP and TAZ induced transcriptional suppression of myosin II activity to maintain dynamic cytoskeletal equilibria. Together, these data establish the mechanoresponsive dynamics of a transcriptional feedback loop necessary for persistent endothelial cell migration and vascular morphogenesis