A marine reservoir effect ΔR value for Kitandach, in Prince Rupert Harbour, British Columbia, Canada

Prince Rupert Harbour (PRH), on the north Pacific Coast of British Columbia, contains at least 157 shell middens, of which 66 are known villages, in an area of approximately 180 km. These sites span the last 9500 yr and in some cases are immense, exceeding 20,000 m surface area and several meters in depth. Recent archaeological research in PRH has become increasingly reliant on radiocarbon dates from marine shell for developing chronologies. However, this is problematic as the local marine reservoir effect (MRE) remains poorly understood in the region. To account for the MRE and to better date the Harbour’s sites, we propose a ΔR of 273 ± 38 for the PRH area, based on our work at the site of Kitandach (GbTo-34), a massive shell midden-village centrally located within the Harbour. We followed the multiple paired sample approach for samples from speci fic contexts and ensured contemporaneity within the groups of marine and terrestrial materials by statistically assessing for outliers using the χ2 test. Taking together, the results for this and previous studies, it appears the MRE was fairly constant over the past 5000 yr

Where's the harm? A social marketing approach to reframing 'problem' drinking cultures

Alcohol consumption is often linked to a broad range of social and health problems, yet alcohol also plays a fundamental role in social bonding between people. This paper considers the potential of social marketing to contribute to alcohol consumption reduction and reframe social norms that encourage 'problem' drinking. Based on qualitative research with a variety of Scottish drinkers, the paper emphasises how and why a better understanding of the culturally bound meanings of alcohol (e.g. social identity, self-concept) are of crucial importance to inform any social marketing approach to reframing excessive drinking

A Critical Review of Constraint-Induced Movement Therapy and Forced Use in Children With Hemiplegia

Hemiplegia is a physical impairment that can occur in childhood following head trauma, cerebral vascular accident or transient ischemic attack (stroke), brain tumor, or congenital or perinatal injury. One of the most disabling symptoms of hemiplegia is unilaterally impaired hand and arm function. Sensory and motor impairments in children with hemiplegia compromise movement efficiency. Such children often tend not to use the affected extremity, which may further exacerbate the impairments, resulting in a developmentally learned non-use of the involved upper extremity, termed ‘developmental disuse’. Recent studies suggest that children with hemiplegia benefit from intensive practice. Forced use and Constraint-lnduced Movement Therapy (CI therapy) are recent therapeutic interventions involving the restraint of the non-involved upper extremity and intensive practice with the involved upper extremity. These approaches were designed for adults with hemiplegia, and increasing evidence suggests that they are efficacious in this population. Recently, forced use and constraint-induced therapy have been applied to children with hemiplegia. In this review, we provide a brief description of forced use and CI therapy and their historical basis, provide a summary of studies of these interventions in children, and discuss a number of important theoretical considerations, as well as implications for postural control. We will show that whereas the studies to date suggest that both forced use and CI therapy appear to be promising for improving hand function in children with hemiplegia, the data are limited. Substantially more work must be performed before this approach can be advocated for general clinical use

Allosteric p97 inhibitors can overcome resistance to ATP-competitive p97 inhibitors for potential anti-cancer therapy

A major challenge of targeted cancer therapy is the selection for drug‐resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is a central regulator of protein homeostasis and a promising anti‐cancer target because of its vital role in cell growth and survival. One ATP‐competitive p97 inhibitor, CB‐5083, has entered clinical trials. Selective pressure on HCT116 cells treated with CB‐5083 identified 5 different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB‐5083 resistant p97 mutants, N660K and T688A, were also resistant to several other ATP‐competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS‐873 and UPCDC‐30245 were unaffected by these mutations. We also established a CB‐5083 resistant cell line that harbors a new p97 double mutation (D649A/T688A). While CB‐5083, NMS‐873, and UPCDC‐30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS‐873 and UPCDC‐30245 were 30‐fold more potent than CB‐5083 in inhibiting the CB‐5083 resistant D649A/T688A double mutant. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP‐competitive p97 inhibitors arises during anti‐cancer treatment

Biofilm-forming capability of highly virulent, multidrug-resistant Candida auris

The emerging multidrug-resistant yeast pathogen Candida auris has attracted considerable attention as a source of healthcare–associated infections. We report that this highly virulent yeast has the capacity to form antifungal resistant biofilms sensitive to the disinfectant chlorhexidine in vitro

Estimating marine reservoir effects in archaeological chronologies: Comparing ΔR calculations in Prince Rupert Harbour, British Columbia, Canada

The best method for quantifying the marine reservoir effect (MRE) using the global IntCal Marine13 calibration curve remains unresolved. Archaeologists frequently quantify uncertainty on MRE values as errors computed from single pairs of marineterrestrial radiocarbon ages, which we argue significantly overstates their accuracy and precision. Here, we review the assumptions, methods, and applications of estimating MRE via an estimate of the additional regional offset between the marine and terrestrial calibration curves (ΔR) for the Prince Rupert Harbour (PRH) region of British Columbia, Canada.We acknowledge the influence on ΔR of MRE variation as (1) a dynamic oceanographic process, (2) its variable expression in biochemical and geochemical pathways, and (3) compounding errors in sample selection, measurement, and calculation. We examine a large set of marine-terrestrial pairs (n = 63) from PRH to compare a common archaeological practice of estimating uncertainty from means that generate an uncertainty value of ±49 years with a revised, more appropriate estimate of error of ± 230 years. However, we argue that the use of multiple-pair samples estimates the PRH ΔR as 273 ± 38 years for the last 5,000 years. Calculations of error that do not consider these issues may generate more inaccurate age estimates with unjustifiable precision