Geospatial modelling of the glacial archaeological potential of the Pennine Alps

Les humains fréquentent les environnements froids et englacés depuis des milliers d'années, comme passage permettant de relier deux régions ou dans le but d’en exploiter les ressources. Dans certaines zones de haute montagne et situées sous les hautes latitudes, la fonte et le retrait des glaciers, des névés et du pergélisol, liés à des changements climatiques récents, a ainsi permis la découverte, souvent accidentelle, d’artéfacts et de restes archéologiques. Ces découvertes ont éveillé l’intérêt des archéologues pour ces régions englacées et ont ainsi contribué au développement de l’archéologie glaciaire. Le but des recherches dans ce domaine étant de collecter et de conserver ces objets uniques, fraîchement libérés des glaces, avant qu’ils ne disparaissent pour toujours. Les Alpes pennines désignent la région comprise entre le canton du Valais en Suisse et les provinces d'Aoste et du Piémont en Italie. En raison de l’étendue des masses glaciaires et de sa longue histoire culturelle qui a débuté au mésolithique (12'000-9'000 années BP), cette région représente un grand intérêt pour l'archéologie glaciaire. Les cols de hautes altitudes situés à la frontière entre la Suisse et l'Italie ont servi de routes commerciales, ainsi que de voie de migration depuis des milliers d'années. Des objets archéologiques, mis à jour par le retrait glaciaire sur les cols et dans leurs environs, apportent des indices quant à leur utilisation historique et préhistorique. Or, ces artéfacts, étant fréquemment de composition organique (comme le bois ou les pièces de vêtements), se décomposent rapidement au contact de l'air. Il y a par conséquent une urgence de les collecter avant qu'ils ne se dégradent. Toutefois, ces sites potentiels sont souvent situés à une altitude élevée et donc inaccessibles, ce qui rend difficile toute prospection systématique et représente donc un défi pour les archéologues. Pour répondre à ce défi, et dans le but d’identifier les zones de fort potentiel archéologique dans les Alpes pennines, cette thèse de doctorat se base sur les analyses géospatiales. Ces dernières ont la particularité de permettre l’intégration à la fois des informations géographiques, historiques et archéologiques. L’outil développé, basé sur des systèmes d'information géographique (SIG, ou GIS en anglais) et des méthodes d’étude glaciologiques, a pour ambition, à terme, de permettre de localiser, de collecter et finalement de conserver ces artéfacts archéologiques uniques libérés des glaces. Une approche intégrative utilisant différentes méthodes géospatiales a été développée. Elle inclut deux types d’analyses spatiales, l’analyse du trajet optimal, et l’analyse de localisation, ainsi que des modélisations du retrait glaciaire. Cette approche permet d’identifier les zones archéologiques les plus intéressantes et de proposer des zones de prospection de quelques kilomètres carrés chacune. Trente et un cols d’intérêt pour l’archéologie glaciaire ont notamment été identifiés dans les Alpes pennines. Lors d'une prospection, un objet datant de l'âge du Bronze a été découvert dans une des zones définies, jusqu'à là inconnue aux archéologues et historiens. Ainsi, la méthodologie développée dans cette recherche fournit un outil d’aide à la décision aux archéologues, afin qu’ils puissent cibler et mener des campagnes de prospection sur les secteurs les plus prometteurs

Combining glaciological and archaeological methods for gauging glacial archaeological potential

Recent climate changes have led to an increase in the exposure of archaeological remains in frozen environments due to the melting of glaciers and ice patches, and the thawing of permafrost. In some cases, the discovery of glacial archaeological findings has occurred due to chance. In order to avoid the risk of losing exceptional, often organic, cultural remains due to decomposition, systematic and predictive methods should be employed to locate areas of high glacial archaeological potential. Here, we merged archaeological and glaciological methods to create a new type of archaeological prediction model in the field of glacial archaeology. Locational analysis and glaciological modelling were used to highlight current and future areas of archaeological potential in the Pennine Alps, located between Switzerland and Italy. Future glacier area was calculated in 10 year increments until 2100. By 2090, 93% of glacier area is expected to have disappeared. The results from the final model, GlaciArch, provide new insights into future glacial archaeological prospection in the Pennine Alps by narrowing down a study region of 4500 km2 into several manageable square kilometre sites

Arterial stiffness and wave reflection 1 year after a pregnancy complicated by hypertension.

Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular disease (CVD) later in life. The authors investigated the association of HDP with blood pressure (BP) and arterial stiffness 1-year postpartum. Seventy-four participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined using applanation tonometry to measure BP, carotid-femoral pulse wave velocity (cfPWV), and augmentation index (AIx). On average, women with HDP had a 9 mm higher systolic BP (

Identification of dfrA14 in two distinct plasmids conferring trimethoprim resistance in Actinobacillus pleuropneumoniae

OBJECTIVES: The objective of this study was to determine the distribution and genetic basis of trimethoprim resistance in Actinobacillus pleuropneumoniae isolates from pigs in England. METHODS: Clinical isolates collected between 1998 and 2011 were tested for resistance to trimethoprim and sulphonamide. The genetic basis of trimethoprim resistance was determined by shotgun WGS analysis and the subsequent isolation and sequencing of plasmids. RESULTS: A total of 16 (out of 106) A. pleuropneumoniae isolates were resistant to both trimethoprim (MIC >32 mg/L) and sulfisoxazole (MIC ≥256 mg/L), and a further 32 were resistant only to sulfisoxazole (MIC ≥256 mg/L). Genome sequence data for the trimethoprim-resistant isolates revealed the presence of the dfrA14 dihydrofolate reductase gene. The distribution of plasmid sequences in multiple contigs suggested the presence of two distinct dfrA14-containing plasmids in different isolates, which was confirmed by plasmid isolation and sequencing. Both plasmids encoded mobilization genes, the sulphonamide resistance gene sul2, as well as dfrA14 inserted into strA, a streptomycin-resistance-associated gene, although the gene order differed between the two plasmids. One of the plasmids further encoded the strB streptomycin-resistance-associated gene. CONCLUSIONS: This is the first description of mobilizable plasmids conferring trimethoprim resistance in A. pleuropneumoniae and, to our knowledge, the first report of dfrA14 in any member of the Pasteurellaceae. The identification of dfrA14 conferring trimethoprim resistance in A. pleuropneumoniae isolates will facilitate PCR screens for resistance to this important antimicrobial

Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS.

OBJECTIVE: To evaluate urinary neurotrophin receptor p75 extracellular domain (p75(ECD)) levels as disease progression and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). METHODS: The population in this study comprised 45 healthy controls and 54 people with ALS, 31 of whom were sampled longitudinally. Urinary p75(ECD) was measured using an enzyme-linked immunoassay and validation included intra-assay and inter-assay coefficients of variation, effect of circadian rhythm, and stability over time at room temperature, 4°C, and repeated freeze-thaw cycles. Longitudinal changes in urinary p75(ECD) were examined by mixed model analysis, and the prognostic value of baseline p75(ECD) was explored by survival analysis. RESULTS: Confirming our previous findings, p75(ECD) was higher in patients with ALS (5.6 ± 2.2 ng/mg creatinine) compared to controls (3.6 ± 1.4 ng/mg creatinine, p < 0.0001). Assay reproducibility was high, with p75(ECD) showing stability across repeated freeze-thaw cycles, at room temperature and 4°C for 2 days, and no diurnal variation. Urinary p75(ECD) correlated with the revised ALS Functional Rating Scale at first evaluation (r = -0.44, p = 0.008) and across all study visits (r = -0.36, p < 0.0001). p75(ECD) also increased as disease progressed at an average rate of 0.19 ng/mg creatinine per month (p < 0.0001). In multivariate prognostic analysis, bulbar onset (hazard ratio [HR] 3.0, p = 0.0035), rate of disease progression from onset to baseline (HR 4.4, p < 0.0001), and baseline p75(ECD) (HR 1.3, p = 0.0004) were predictors of survival. CONCLUSIONS: The assay for urinary p75(ECD) is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75(ECD) provides prognostic information and is currently the only biological fluid-based biomarker of disease progression

Genetic influences on response to novel objects and dimensions of personality in Papio baboons

Behavioral variation within and between populations and species of the genus Papio has been studied extensively, but little is known about the genetic causes of individual- or population-level differences. This study investigates the influence of genetic variation on personality (sometimes referred to as temperament) in baboons and identifies a candidate gene partially responsible for the variation in that phenotype. To accomplish these goals, we examined individual variation in response to both novel objects and an apparent novel social partner (using a mirror test) among pedigreed baboons (n = 578) from the Southwest National Primate Research Center. We investigated the frequency and duration of individual behaviors in response to novel objects and used multivariate factor analysis to identify trait-like dimensions of personality. Exploratory factor analysis identified two distinct dimensions of personality within this population. Factor 1 accounts for 46.8 % of the variance within the behavioral matrix, and consists primarily of behaviors related to the boldness of the subject. Factor 2 accounts for 18.8 % of the variation, and contains several anxiety like behaviors. Several specific behaviors, and the two personality factors, were significantly heritable, with the factors showing higher heritability than most individual behaviors. Subsequent analyses show that the behavioral reactions observed in the test protocol are associated with animals\u27 social behavior observed later in their home social groups. Finally we used linkage analysis to map quantitative trait loci for the measured phenotypes. Single nucleotide polymorphisms in a positional candidate gene (SNAP25) are associated with variation in one of the personality factors, and CSF levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. This study documents heritable variation in personality among baboons and suggests that sequence variation in SNAP25 may influence differences in behavior and neurochemistry in these nonhuman primates

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain\u27s functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of temporally evolving neural dynamics as they relate to cerebral hemodynamics for bridging with human studies. In order to adequately study the underlying mechanisms of RT-induced cognitive dysfunction, the development of clinically mimetic RT protocols in animal models is needed. To address these challenges, we developed a fractionated whole-brain RT protocol (3Gy/day for 10 days) and applied longitudinal wide field optical imaging (WFOI) of neural and hemodynamic brain activity at 1, 2, and 3 months post RT. At each time point, mice were subject to repeated behavioral testing across a variety of sensorimotor and cognitive domains. Disruptions in cortical neuronal and hemodynamic activity observed 1 month post RT were significantly worsened by 3 months. While broad changes were observed in functional brain organization post RT, brain regions most impacted by RT occurred within those overlapping with the mouse default mode network and other association areas similar to prior reports in human subjects. Further, significant cognitive deficits were observed following tests of novel object investigation and responses to auditory and contextual cues after fear conditioning. Our results fill a much-needed gap in understanding the effects of whole-brain RT on systems level brain organization and how RT affects neuronal versus hemodynamic signaling in the cortex. Having established a clinically-relevant injury model, future studies can examine therapeutic interventions designed to reduce neuroinflammation-based injury following RT. Given the overlap of sequelae that occur following RT with and without chemotherapy, these tools can also be easily incorporated to examine chemotherapy-related cognitive impairment