The Hartley site (FaNp-19) and the use of sandhill environments in the late precontact period

The Hartley site (FaNp-19) is a Late Precontact Period multicomponent habitation and bison kill and processing site located on the periphery of a sand dune environment surrounded by grasslands. The Hartley site, located within the Saskatoon city limits, was originally identified by Ken Cronk and members of the Saskatoon Archaeological Society in the 1950’s. Subsequent excavations by Millenium Consulting Ltd., the University of Saskatchewan, Western Heritage Services Inc., and Stantec Consulting Ltd. have all added to the database of knowledge pertaining to this site. Radiometric dates and the recovery of artifacts characteristic of the Avonlea Horizon, the Old Women’s Phase, and the Mortlach Phase have demonstrated that this region was a popular place for occupation and bison procurement during the Late Precontact Period. A detailed analysis of the faunal remains recovered from the area known as the Wooded Hollow has demonstrated that this assemblage differs significantly from the remains recovered from the previously researched Brushy Depression. It appears that bison were being heavily harvested and that the use of secondary faunal sources was extremely limited. Determination of seasonality is based on cluster and discriminant function analysis of carpal, tarsal, longbone and phalange data. The resulting herd structure of almost equal numbers of males and females suggests an occupation during the rut, or the fall months. Some immature elements and non-bison remains suggest occupation may have occurred in the spring. It is therefore possible that this region was utilized over a period of time for the purposes of procuring animals from the spring to the fall months. The complete lack of foetal bone in this region suggests that, unlike in the Brushy Depression, the Wooded Hollow was not occupied during the winter months. Taphonomic factors were considered in performing a complete faunal analysis of this thesis. Non-human agents and associated processes suggest that the assemblage was buried quickly after the site was vacated. The extremely fragmented nature of the assemblage, however, suggests that humans had a greater effect on the assemblage than the non-human agents. Based on breakage patterns it is determined that these remains were being processed for the purposes of both marrow and grease extraction. Application of a site determination model also suggests that it is likely that both kill and processing activities occurred in this area. Location of the Hartley site within a dune environment is linked to the activities that occurred at this site. A review of ethnographic accounts of bison pounding and surrounding activities has revealed that availability of ecological resources such as wood and necessary topographic features characteristic of dune environments were essential to the success of bison procurement. Although it has been suggested that settlement of these regions is also linked to the variety and stability of resources in ‘ecotones’, or areas of resource overlap, between grassland and sandhill environments, a review of several faunal assemblages from various similar Northern Plains assemblages reveals that bison was by far the dominant species exploited. Variety in terms of faunal resources may not have been a factor at all. It is therefore suggested in this thesis that settlement on the periphery of sandhill environments is linked to the presence of bison in the surrounding grassland region, as well as to the stability of the resources in wetland areas supported by high water tables in the dune environments. Also known as ‘ecological islands’ these regions may have been more stable in terms of essential resources such as wood and other botanical resources, in addition to providing areas of shelter during the colder winter months. It is concluded that settlement and large scale bison procurement activities in several sandhill environments on the Northern Plains is tightly linked to availability of bison, the availability of wood, a conducive topographic setting, and the stability of resources in these ‘ecological islands’

Sensitive HPV detection in oropharyngeal cancers.

BACKGROUND: Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples. METHODS: We compared PGMY09/11, MY09/11 and GP5+/6+ primers sets in PCRs of 34 clinically diagnosed samples of genital warts, cervical brushings (with associated histological diagnosis) and vulval biopsies. All negative samples were subsequently tested using the previously reported PGMY/GP PCR method and amplicons directly sequenced for confirmation and typing. An optimised PCR protocol was then compared to a line blot assay for detection of HPV in 15 oropharyngeal cancer samples. RESULTS: PGMY09/11 primers detected HPV presence in more cervical brushing (100%) and genital wart (92.9%) samples compared to MY09/11 (90% and 64.3%) and GP5+/6+ (80% and 64.3%) primer sets, respectively. From vulval biopsies, HPV detection rates were: MY09/11 (63.6%), GP5+/6+ (54.5%) and PGMY09/11 (54.5%). PGMY/GP nested PCR demonstrated that HPV was present, and direct sequencing confirmed genotypes. This nested PCR protocol showed detection of HPV in 10/15 (66.7%) of oropharyngeal cancer samples. CONCLUSIONS: PGMY09/11 primers are the preferred primer set among these three for primary PCR screening with different clinical samples. MY09/11 and GP5+/6+ may be used (particularly for cervical samples) but demonstrate lower detection rates. A nested PCR approach (i.e. a PGMY-GP system) may be required to confirm negativity or to detect low levels of HPV, undetectable using current primary PCR methods, as demonstrated using oropharyngeal cancer samples.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Analyses of human papillomavirus genotypes and viral loads in anogenital warts.

International audienceCondylomata acuminata (genital warts) are the most common sexually transmitted viral diseases. These lesions are caused by infection with mucosal human papillomaviruses (HPVs). However there is limited information on HPV strain distribution involved in the molecular pathogenesis of these lesions. To address this the strain prevalence and the frequency of multiple HPV infections in wart tissue were examined in samples from 31 patients attending a wart clinic. These lesions were bisected and subjected to parallel DNA and mRNA extractions. HPV-type prevalence and incidence of multiple infections were determined by the Roche Linear Array assay. qPCR compared HPV6, 11 16 and 18 viral loads and RT-qPCR measured HPV 6 and 11 E6 genomic expression levels. 71% of these samples were infected with multiple HPVs. Only 1 sample was negative for HPV6 or 11 DNA. 48% of samples were positive for a high risk (oncogenic) HPV. These results show that multiple infections in tissue are frequent and the subsequent analysis of HPV6 and 11 E6 DNA viral loads suggested that other HPVs could be causing lesions. Further analysis of HPV6/11 E6 mRNA levels showed that there was no discernable relationship between HPV6 E6 DNA viral load and relative HPV 6 or 11 E6 mRNA levels thereby questioning the relevance of viral load to lesion causality

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

Abstract Background Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. Methods In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. Results The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. Conclusion The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and simplification of the regulatory requirements for clinical research in Europe.</p