Archaeological Investigations at the Carmichael Inn Site: Testing a Model for Cultural Patterning of the Rural Nineteenth Century Inn in the Ridge and Valley of Tennessee

Cultural patterning in the archaeological context has been studied at a number of historic sites in the southeast United States. Patterns associated with ethnicity, socioeconomic level and type of activity have been investigated. This work proposed a cultural pattern associated with the rural nineteenth century inn in the Ridge and Valley of Tennessee. The research tested a model for such inn sites which might differentiate them from purely residential sites of the the same time period in the area. Archaeological investigations were conducted at the Carmichael Inn site in Loudon County, Tennessee. This site was formerly the location of a stagecoach stop and inn as well as a residence during the early to mid-nineteenth century. Data obtained was compared with that from other sites, both residential and inn sites, in the Ridge and Valley of Tennessee. The data from the Carmichael Inn site do not strongly support the proposed model. It is thought that the Carmichael Inn was not a formal establishment, but was operated on a more casual level, and that inn-related activities which occurred there did not impact the archaeological record in such a way as to significantly differentiate it from purely residential sites of the same time period, area and socioeconomic level

Benthic foraminifera and Neogene sea level changes in the Pelotas Basin, offshore south Brazil

The Neogene benthic foraminiferal ecostratigraphy of offshore Pelotas Basin has not yet been researched. The benthic foraminifera were examined in twenty-nine ditch cuttings samples from Well 1-SCS-3B, present water depth 200 m. These samples ranged from the Lower Miocene Catapsydrax dissimilis planktonic foraminiferal Zone to the Pliocene Globigerinoides trilobus fistulosus Zone. Only ditch cuttings were available, which allowed us to present just broad paleoenvironmental trends within the studied section. Benthic foraminifera indicate deposition mostly between outer neritic to upper bathyal paleodepths. A peak in uvigerinid relative abundance marks a possible flooding surface or condensed section with a high nutrient flux, low diversity (marked by the Shannon Function H), and sluggish circulation within the Globorotalia mayeri Zone. This peak is bracketed by high abundances of Cibicidoides, which indicate stronger current action than within the condensed section. Biostratigraphic hiatuses within these Cibicidoides-rich intervals are concluded not to indicate subaerial exposure, but to reflect current action sufficiently strong to induce either non-deposition or seafloor scouring. A second possible flooding surface occurs at the top of the section, indicated by a decline in Cibicidoides associated with upticks in Sphaeroidina and Bolivina and a dip in H. The top of this younger maximum flood was not encountered, probably occurring above the studied section. That the timing of these floods differs from those recorded elsewhere in the Pelotas Basin implies that they were tectonically induced, perhaps as distal effects associated with the interaction between the South American and Nazca tectonic plates. Future studies with better quality core samples will add detail to this picture; such studies can incorporate eustatic sea-level changes into the model presented

Closed-system marine burial diagenesis: isotopic data from the Austin Chalk and its components

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73692/1/j.1365-3091.1984.tb00892.x.pd

Increased traffic exposure and negative birth outcomes: a prospective cohort in Australia

Background: Pregnant women exposed to traffic pollution have an increased risk of negative birth outcomes. We aimed to investigate the size of this risk using a prospective cohort of 970 mothers and newborns in Logan, Queensland. ----- ----- Methods: We examined two measures of traffic: distance to nearest road and number of roads around the home. To examine the effect of distance we used the number of roads around the home in radii from 50 to 500 metres. We examined three road types: freeways, highways and main roads.----- ----- Results: There were no associations with distance to road. A greater number of freeways and main roads around the home were associated with a shorter gestation time. There were no negative impacts on birth weight, birth length or head circumference after adjusting for gestation. The negative effects on gestation were largely due to main roads within 400 metres of the home. For every 10 extra main roads within 400 metres of the home, gestation time was reduced by 1.1% (95% CI: -1.7, -0.5; p-value = 0.001).----- ----- Conclusions: Our results add weight to the association between exposure to traffic and reduced gestation time. This effect may be due to the chemical toxins in traffic pollutants, or because of disturbed sleep due to traffic noise

Extracellular Matrix Protein Tenascin C Increases Phagocytosis Mediated by CD47 Loss of Function in Glioblastoma.

Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of the brain tumor microenvironment (TME). CD47 has been shown to mediate immune evasion, as the CD47-SIRPα axis prevents phagocytosis of tumor cells by macrophages and other myeloid cells. In this study, we established CD47 homozygous deletion (CD47-/-) in human and mouse GBM cells and investigated the impact of eliminating the "don't eat me" signal on tumor growth and tumor-TME interactions. CD47 knockout (KO) did not significantly alter tumor cell proliferation in vitro but significantly increased phagocytosis of tumor cells by macrophages in cocultures. Compared with CD47 wild-type xenografts, orthotopic xenografts derived from CD47-/- tumor cells grew significantly slower with enhanced tumor cell phagocytosis and increased recruitment of M2-like tumor-associated microglia/macrophages (TAM). CD47 KO increased tumor-associated extracellular matrix protein tenascin C (TNC) in xenografts, which was further examined in vitro. CD47 loss of function upregulated TNC expression in tumor cells via a Notch pathway-mediated mechanism. Depletion of TNC in tumor cells enhanced the growth of CD47-/- xenografts in vivo and decreased the number of TAM. TNC knockdown also inhibited phagocytosis of CD47-/- tumor cells in cocultures. Furthermore, TNC stimulated release of proinflammatory factors including TNFα via a Toll-like receptor 4 and STAT3-dependent mechanism in human macrophage cells. These results reveal a vital role for TNC in immunomodulation in brain tumor biology and demonstrate the prominence of the TME extracellular matrix in affecting the antitumor function of brain innate immune cells. SIGNIFICANCE: These findings link TNC to CD47-driven phagocytosis and demonstrate that TNC affects the antitumor function of brain TAM, facilitating the development of novel innate immune system-based therapies for brain tumors

Measurement of low‐density lipoprotein cholesterol levels in primary and secondary prevention patients: Insights from the PALM registry

Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low-density lipoprotein cholesterol ( LDL -C) to identify untreated patients with LDL -C ≥190 mg/dL, assess lipid-lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL -C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL -C levels measured in the 2 years before enrollment. Patients without chart-documented LDL -C levels were more often women, nonwhite, uninsured, and non-college graduates (all P\u3c0.01). Patients without prior lipid testing were less likely to receive statin treatment (72.6% versus 76.0%; P=0.0034), a high-intensity statin (21.5% versus 24.3%; P=0.016), nonstatin lipid-lowering therapy (24.8% versus 27.3%; P=0.037), and had higher core laboratory LDL -C levels at enrollment (median 97 versus 92 mg/dL; P\u3c0.0001) than patients with prior LDL -C testing. Of 166 individuals with core laboratory LDL -C levels ≥190 mg/dL, 36.1% had no LDL -C measurement in the prior 2 years, and 57.2% were not on a statin at the time of enrollment. Conclusions In routine clinical practice, LDL -C testing is associated with higher-intensity lipid-lowering treatment and lower achieved LDL -C level

The economic case for investing in the prevention of mental health conditions in the UK

This report provides an overview of the economic case for the prevention of mental health conditions. To do this, we first estimated the societal costs of living with mental health conditions in the UK in 2019 and then reviewed what is known about the cost-effectiveness of wellevidenced actions to prevent these mental health conditions. To estimate costs, we used a prevalencebased costing approach. This measures the number of people living with mental health conditions over a specific short time period (usually one year) and estimates the average costs associated with these conditions over this time period. Our prevalencebased costing model makes use of data on prevalence from the 2019 Institute of Health Metrics and Evaluation Global Burden of Disease (GBD) study. The GBD study quantifies the impact of all health conditions, both infectious and non-communicable, including mental health conditions, as well as the impacts on injury, including intentional self-harm. As part of the study, the GBD systematically searches for and assesses mental health surveys around the globe. To allow for comparability in measurement, case definitions used by GBD predominantly adhered to international diagnostic criteria guidance, either the DSM-IV-TR, mainly used in the United States or the ICD-10 criteria used mainly elsewhere, as these are used by the majority of mental health surveys included in the GBD. The GBD study estimates are periodically updated, apply a common methodology, are subject to peer review, and are routinely used by the World Health Organization (WHO) when looking at the global impact of mental health conditions. Furthermore, GBD estimates are provided separately for all four nations of the UK, as well as at English Region level. These estimates are conservative, as the GBD does not include the impact of sub-diagnostic threshold mental health conditions, as well as risk factors such as undue stress which do not fit into diagnostic criteria, all of which will also have economic costs. We included 11 of 12 broad categories of mental disorder meeting diagnosable thresholds used in the GBD1. These were depressive disorders (major depressive disorder and dysthymia), anxiety disorders, bipolar affective disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder (ADHD), eating disorders (anorexia nervosa and bulimia nervosa), and a final category of other mental disorders (which mainly covers personality disorders). A detailed list of conditions is listed in Table A-2 in the appendix. We excluded the idiopathic intellectual disabilities category in the GBD. Neurological conditions such as dementia, as well as alcohol and substance use disorders, are not included. Although not all intentional self-harm is linked with a mental health condition, we also separately provide an estimate of the health and intangible costs associated with intentional self-harm, including suicide, reported in the GBD. All costs are calculated and reported in 2020 pounds sterling

The Economic Case for Investing in the Prevention of Mental Health Conditions in the UK

This report provides an overview of the economic case for the prevention of mental health conditions. To do this, we first estimated the societal costs of living with mental health conditions in the UK in 2019 and then reviewed what is known about the cost-effectiveness of wellevidenced actions to prevent these mental health conditions. To estimate costs, we used a prevalencebased costing approach. This measures the number of people living with mental health conditions over a specific short time period (usually one year) and estimates the average costs associated with these conditions over this time period. Our prevalencebased costing model makes use of data on prevalence from the 2019 Institute of Health Metrics and Evaluation Global Burden of Disease (GBD) study. The GBD study quantifies the impact of all health conditions, both infectious and non-communicable, including mental health conditions, as well as the impacts on injury, including intentional self-harm. As part of the study, the GBD systematically searches for and assesses mental health surveys around the globe. To allow for comparability in measurement, case definitions used by GBD predominantly adhered to international diagnostic criteria guidance, either the DSM-IV-TR, mainly used in the United States or the ICD-10 criteria used mainly elsewhere, as these are used by the majority of mental health surveys included in the GBD. The GBD study estimates are periodically updated, apply a common methodology, are subject to peer review, and are routinely used by the World Health Organization (WHO) when looking at the global impact of mental health conditions. Furthermore, GBD estimates are provided separately for all four nations of the UK, as well as at English Region level. These estimates are conservative, as the GBD does not include the impact of sub-diagnostic threshold mental health conditions, as well as risk factors such as undue stress which do not fit into diagnostic criteria, all of which will also have economic costs. We included 11 of 12 broad categories of mental disorder meeting diagnosable thresholds used in the GBD1. These were depressive disorders (major depressive disorder and dysthymia), anxiety disorders, bipolar affective disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder (ADHD), eating disorders (anorexia nervosa and bulimia nervosa), and a final category of other mental disorders (which mainly covers personality disorders). A detailed list of conditions is listed in Table A-2 in the appendix. We excluded the idiopathic intellectual disabilities category in the GBD. Neurological conditions such as dementia, as well as alcohol and substance use disorders, are not included. Although not all intentional self-harm is linked with a mental health condition, we also separately provide an estimate of the health and intangible costs associated with intentional self-harm, including suicide, reported in the GBD. All costs are calculated and reported in 2020 pounds sterling

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1 and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3 marked heterochromatin in a PWWP-independent mannerthat is facilitated by the protein’s N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome