Post-depositional weathering of cave sediments in Berry Cave, Pulaski County, Missouri

Berry Cave is a vadose system, and is classified as a branchwork cave with superposed anastomotic mazes. The cave is situated in the non-glaciated karst region of Roubidoux Creek in Pulaski County, south-central Missouri. Two types of sediment deposits have been identified in the cave: an allogenic fine clay fill preserved in a stream cut canyon and an autogenic/allogenic loam comprising a debris flow. The surface soil above the cave is silt loam, and is the source for the sediments o f the debris flow in Berry Cave. Three episodes o f geomorphic development have been determined to be related to sediment deposition within Berry Cave. The first is the deposition of fine clay units in the cave. These units may have been deposited as slackwater deposits. Next is the erosion of the clay fill units resulting in the formation o f a stream cut canyon in the cave sediments, which was associated with the cave’s transition(s) from vadose flow to phreatic. Finally is the deposition of the debris flow sediments that is related to the present day vadose flow through the cave system. This model of cave sedimentation, though simplified, provides the best understanding of the timing and effects of post-depositional alterations of sediments in Berry Cave. Although the present literature suggests that the weathering o f cave sediments is limited or absent in many cave systems, it is important to recognize that weathering does occur to cave sediments. The sediments in Berry Cave were affected by post-depositional weathering processes throughout the geomorphic evolution of the cave system. These post depositional alterations include: enrichment, melanization, illuviation of clay minerals, iron translocation, and braunification, rubifaction, and ferrugination. The postdepositional processes that affected the clay fill sediments are presently inactive, because there is not sufficient water available to alter these sediments. Conversely the processes affecting the debris flow are active

Metabolic Reprogramming of Macrophages: GLUCOSE TRANSPORTER 1 (GLUT1)-MEDIATED GLUCOSE METABOLISM DRIVES A PROINFLAMMATORY PHENOTYPE

Glucose is a critical component in the proinflammatory response of macrophages (MΦs). However, the contribution of glucose transporters (GLUTs) and the mechanisms regulating subsequent glucose metabolism in the inflammatory response are not well understood. Because MΦs contribute to obesity-induced inflammation, it is important to understand how substrate metabolism may alter inflammatory function. We report that GLUT1 (SLC2A1) is the primary rate-limiting glucose transporter on proinflammatory-polarized MΦs. Furthermore, in high fat diet-fed rodents, MΦs in crown-like structures and inflammatory loci in adipose and liver, respectively, stain positively for GLUT1. We hypothesized that metabolic reprogramming via increased glucose availability could modulate the MΦ inflammatory response. To increase glucose uptake, we stably overexpressed the GLUT1 transporter in RAW264.7 MΦs (GLUT1-OE MΦs). Cellular bioenergetics analysis, metabolomics, and radiotracer studies demonstrated that GLUT1 overexpression resulted in elevated glucose uptake and metabolism, increased pentose phosphate pathway intermediates, with a complimentary reduction in cellular oxygen consumption rates. Gene expression and proteome profiling analysis revealed that GLUT1-OE MΦs demonstrated a hyperinflammatory state characterized by elevated secretion of inflammatory mediators and that this effect could be blunted by pharmacologic inhibition of glycolysis. Finally, reactive oxygen species production and evidence of oxidative stress were significantly enhanced in GLUT1-OE MΦs; antioxidant treatment blunted the expression of inflammatory mediators such as PAI-1 (plasminogen activator inhibitor 1), suggesting that glucose-mediated oxidative stress was driving the proinflammatory response. Our results indicate that increased utilization of glucose induced a ROS-driven proinflammatory phenotype in MΦs, which may play an integral role in the promotion of obesity-associated insulin resistance

The 2018 report of the Lancet Countdown on health and climate change: shaping the health of nations for centuries to come

The Lancet Countdown: tracking progress on health and climate change was established to provide an independent, global monitoring system dedicated to tracking the health dimensions of the impacts of, and the response to, climate change. The Lancet Countdown tracks 41 indicators across five domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; finance and economics; and public and political engagement. This report is the product of a collaboration of 27 leading academic institutions, the UN, and intergovernmental agencies from every continent. The report draws on world-class expertise from climate scientists, ecologists, mathematicians, geographers, engineers, energy, food, livestock, and transport experts, economists, social and political scientists, public health professionals, and. doctors. The Lancet Countdown’s work builds on decades of research in this field, and was first proposed in the 2015 Lancet Commission on health and climate change,1 which documented the human impacts of climate change and provided ten global recommendations to respond to this public health emergency and secure the public health benefits available (panel 1)

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes

The 2020 report of The Lancet Countdown on health and climate change: responding to converging crises

The Lancet Countdown is an international collaboration, established to provide an independent, global monitoring system dedicated to tracking the emerging health profile of the changing climate. The 2020 report presents 43 indicators across five sections: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. This report represents the findings and consensus of the 35 leading academic institutions and UN agencies that make up the Lancet Countdown, and draws on the expertise of climate scientists, geographers, and engineers; of energy, food, and transport experts; and of economists, social and political scientists, data scientists, public health professionals, and doctors

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

p75, but Not proNGF, Is Upregulated Following Status Epilepticus in Mice

ProNGF and p75 NTR are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75 NTR , sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that mature NGF, p75 NTR , and proBDNF were upregulated following SE, while proNGF was not altered, indicating potential mechanistic differences between rats and mice. ProBDNF was localized to mossy fibers and microglia following SE. p75 NTR was transiently induced primarily in axons and axon terminals following SE, as well as in neuron and astrocyte cell bodies. ProBDNF and p75 NTR increased independently of cell death and their localization was different depending on the severity of SE. We also examined the expression of proneurotrophin co-receptors, sortilin and sorCS2. Following severe SE, sorCS2, but not sortilin, was elevated in neurons and astrocytes. These data indicate that important differences exist between rat and mouse in the proneurotrophin response following SE. Moreover, the proBDNF and p75 NTR increase after seizures in the absence of significant cell death suggests that proneurotrophin signaling may play other roles following SE

Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guérin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis

Contextual design choices and partnerships for scaling early child development programmes

Translating the Nurturing Care Framework and unprecedented global policy support for early child development (ECD) into action requires evidence-informed guidance about how to implement ECD programmes at national and regional scale. We completed a literature review and participatory mixed-method evaluation of projects in Saving Brains®, Grand Challenges Canada® funded ECD portfolio across 23 low- and middle-income countries (LMIC). Using an adapted programme cycle, findings from evaluation related to partnerships and leadership, situational analyses, and design for scaling ECD were considered. 39 projects (5 'Transition to Scale' and 34 'Seed') were evaluated. 63% were delivered through health and 84% focused on Responsive Caregiving and Early Learning (RCEL). Multilevel partnerships, leadership and targeted situational analysis were crucial to design and adaptation. A theory of change approach to consider pathways to impact was useful for design, but practical situational analysis tools and local data to guide these processes were lacking. Several RCEL programmes, implemented within government services, had positive impacts on ECD outcomes and created more enabling caregiving environments. Engagement of informal and private sectors provided an alternative approach for reaching children where government services were sparse. Cost-effectiveness was infrequently measured. At small-scale RCEL interventions can be successfully adapted and implemented across diverse settings through processes which are responsive to situational analysis within a partnership model. Accelerating progress will require longitudinal evaluation of ECD interventions at much larger scale, including programmes targeting children with disabilities and humanitarian settings with further exploration of cost-effectiveness, critical content and human resources