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

Atherosclerotic calcification is related to a higher risk of dementia and cognitive decline

Background: Longitudinal data on the role of atherosclerosis in different vessel beds in the etiology of cognitive impairmen

Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits

Two significant barriers have limited the development of effective treatment of Alzheimer's disease. First, for many cases the aetiology is unknown and likely multi-factorial. Among these factors, hypercholesterolemia is a known risk predictor and has been linked to the formation of β-amyloid plaques, a pathological hallmark this disease. Second, standardized diagnostic tools are unable to definitively diagnose this disease prior to death; hence new diagnostic tools are urgently needed. Magnetic resonance imaging (MRI) using high field-strength scanners has shown promise for direct visualization of β-amyloid plaques, allowing in vivo longitudinal tracking of disease progression in mouse models. Here, we present a new rabbit model for studying the relationship between cholesterol and Alzheimer's disease development and new tools for direct visualization of β-amyloid plaques using clinical field-strength MRI. New Zealand white rabbits were fed either a low-level (0.125–0.25% w/w) cholesterol diet (n = 5) or normal chow (n = 4) for 27 months. High-resolution (66 × 66 × 100 µm3; scan time = 96 min) ex vivo MRI of brains was performed using a 3-Tesla (T) MR scanner interfaced with customized gradient and radiofrequency coils. β-Amyloid-42 immunostaining and Prussian blue iron staining were performed on brain sections and MR and histological images were manually registered. MRI revealed distinct signal voids throughout the brains of cholesterol-fed rabbits, whereas minimal voids were seen in control rabbit brains. These voids corresponded directly to small clusters of extracellular β-amyloid-positive plaques, which were consistently identified as iron-loaded (the presumed source of MR contrast). Plaques were typically located in the hippocampus, parahippocampal gyrus, striatum, hypothalamus and thalamus. Quantitative analysis of the number of histologically positive β-amyloid plaques (P < 0.0001) and MR-positive signal voids (P < 0.05) found in cholesterol-fed and control rabbit brains corroborated our qualitative observations. In conclusion, long-term, low-level cholesterol feeding was sufficient to promote the formation of extracellular β-amyloid plaque formation in rabbits, supporting the integral role of cholesterol in the aetiology of Alzheimer's disease. We also present the first evidence that MRI is capable of detecting iron-associated β-amyloid plaques in a rabbit model of Alzheimer's disease and have advanced the sensitivity of MRI for plaque detection to a new level, allowing clinical field-strength scanners to be employed. We believe extension of these technologies to an in vivo setting in rabbits is feasible and that our results support future work exploring the role of MRI as a leading imaging tool for this debilitating and life-threatening disease

Ethnicity coding in a regional cancer registry and in Hospital Episode Statistics

BACKGROUND: The collection of ethnicity information as part of cancer datasets is important for planning services and ensuring equal access, and for epidemiological studies. However, ethnicity has generally not been well recorded in cancer registries in the UK. The aim of this study was to determine the completeness of ethnicity coding in the Thames Cancer Registry (TCR) database and within the Hospital Episode Statistics (HES) data as held by the London Health Observatory, and to investigate factors associated with ethnicity being recorded. METHODS: Records for 111821 hospital admissions of London residents with a malignant cancer as a primary diagnosis between April 2002 and March 2003 and records for 25581 London residents diagnosed with cancer in 2002 were examined. Data on sex, age, cancer network of residence, deprivation, proportion of non-whites in the local authority population, and site of cancer were available. The proportion of patients in each group with a valid ethnicity code was calculated. In the TCR data proportions were also calculated adjusted for all other variables. RESULTS: Ethnicity was recorded for 90661 (81.1%) of the hospital admissions in the HES data and 5796 (22.7%) patients on the TCR database. Patients resident in areas with a higher proportion of non-white residents and the most deprived populations were more likely to have an ethnic code on the TCR database, though this pattern was not seen in the HES data. Adjustment did not materially affect the association between deprivation and ethnicity being recorded in the TCR data. CONCLUSION: There was a large difference in completeness of ethnicity between the data sources. In order to improve the level of recording in TCR data there needs to be better recording of ethnicity in sources TCR data collection staff have access to, or use of information from other sources e.g. electronic data feeds from hospitals or pathology laboratories, or HES data itself supplied directly to TCR. Efforts to collect ethnicity data should be encouraged in all healthcare settings. Future research should explore where the difficulties collecting ethnicity information lie, whether with patients, healthcare professionals or the recording procedure, and how such problems can be overcome

Investigating the Relationships Between Hypothalamic Volume and Measures of Circadian Rhythm and Habitual Sleep in Premanifest Huntington’s Disease

Objective: Pathological changes within the hypothalamus have been proposed to mediate circadian rhythm and habitual sleep disturbances in individuals with Huntington’s disease (HD). However, investigations examining the relationships between hypothalamic volume and circadian rhythm and habitual sleep in individuals with HD are sparse. This study aimed to comprehensively evaluate the relationships between hypothalamic pathology and circadian rhythm and habitual sleep disturbances in individuals with premanifest HD. Methods: Thirty-two individuals with premanifest HD and twenty-nine healthy age- and gender-matched controls participated in this dual-site, cross-sectional study. Magnetic resonance imaging scans were performed to evaluate hypothalamic volume. Circadian rhythm and habitual sleep were assessed via measurement of morning and evening cortisol and melatonin levels, wrist-worn actigraphy, the Consensus Sleep Diary and sleep questionnaires. Information on mood, physical activity levels and body composition were also collected. Results: Compared to healthy controls, individuals with premanifest HD displayed significantly reduced grey matter volume in the hypothalamus, decreased habitual sleep efficiency and increased awakenings; however, no alterations in morning cortisol or evening melatonin release were noted in individuals with premanifest HD. While differences in the associations between hypothalamic volume and cortisol and melatonin output existed in individuals with premanifest HD compared to healthy controls, no consistent associations were observed between hypothalamic volume and circadian rhythm or habitual sleep outcomes. Conclusion: While significant differences in associations between hypothalamic volume and cortisol and melatonin existed between individuals with premanifest HD and healthy controls, no differences in circadian markers were observed between the groups. This suggests that circadian regulation is maintained despite hypothalamic pathology, perhaps via neural compensation. Longitudinal studies are required to further understand the relationships between the hypothalamus and circadian rhythm and habitual sleep disturbances in HD as the disease course lengthens

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 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

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

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