Contextual Studies of the Middle Archaic Component at Cave Spring in Middle Tennessee

Research in 1980 and 1981 at the Cave Spring site, located on the Duck River in the Nashville Basin of Middle Tennessee, revealed a buried paleosol in a Holocene terrace which contained charcoal, river gravel and chipped stone artifacts. Radiocarbon dates from this buried stratum range from 6500 to 7300 years before present. Evaluating the potential of this buried deposit for yielding behaviorally significant information depended upon learning (1) whether the cultural materials were undisturbed or were redeposited by the river, (2) whether one or several periods of deposition or occupation were represented, and (3) whether material from one or more than one cultural group was included in the deposit. Gravel from the excavation was studied and compared to control samples from a nearby gravel bar and from a Pleistocene terrace. A significantly higher percentage of reddened and broken gravel occurred with the artifacts than in the control situations. This information, in conjunction with a gravel concentration exposed during excavation, suggests that the gravel had been culturally introduced for use in stone boiling or as hearth stones. Refitting analysis was conducted using chipped stone artifacts and debris to determine if the highly leptokurtic vertical distribution of artifacts resulted from disturbance processes or sequent occupations. Reconstructed flake sequences and conjoined artifact fragments documented that vertical post depositional movement of these buried materials had occurred. Pieces from the same refitted set had dispersed as much as 40 cm vertically through silty clay during the past 7,000 years. Horizontal movement of pieces and systematic size sorting, as would result from stream action, had not occurred. The problem of how many cultural groups were responsible for the archaeological remains was confronted using the Cave Spring projectile point-knife sample. Given the perspective of systematic chipped stone reduction, the concept of multistage types is developed. The Eva biface reduction system is proposed with the Eva multistage type encompassing a variety of morphological and functional states which reflect expectable variation in the reduction or uselife sequences of particular artifacts within the overall system. The variability observed in the Cave Spring projectile point-knife sample, including specimens traditionally classified as Morrow Mountain points, can be attributed to a single biface reduction system and we need not infer the activities of two distinct cultural groups in accounting for the observed variability. The Morrow Mountain type in the southern Appalachian region apparently represents a biface reduction system distinct from that in the Middle Tennessee region commonly denoted as the Eva-Morrow Mountain cluster. This conclusion has significant ramifications for the assignment of assemblages to specific archaeological taxonomic units, and for making appropriate assemblage comparisons. It is not tenable to refer variability in the archaeological record directly to cultural variability. The situational nature of behaviors which operated to create the archaeological record must also be considered

On Renormalization Group Flows in Four Dimensions

We discuss some general aspects of renormalization group flows in four dimensions. Every such flow can be reinterpreted in terms of a spontaneously broken conformal symmetry. We analyze in detail the consequences of trace anomalies for the effective action of the Nambu-Goldstone boson of broken conformal symmetry. While the c-anomaly is algebraically trivial, the a-anomaly is "non-Abelian," and leads to a positive-definite universal contribution to the S-matrix of 2->2 dilaton scattering. Unitarity of the S-matrix results in a monotonically decreasing function that interpolates between the Euler anomalies in the ultraviolet and the infrared, thereby establishing the a-theorem.Comment: 24 pages, 4 figures. v2: references added and minor correction

Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GR

Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry

Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.Peer reviewe

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease