Should historic sites protection be targeted at the most famous? Evidence from a contingent valuation in Scotland

We used a contingent valuation survey of a random sample of the general public living in Scotland to estimate how willingness to pay (WTP) for the conservation of historic sites (such as castles and stone circles) varies with how well-known these sites are and whether people have visited them. Each respondent was asked to state a maximum WTP in terms of higher income taxes for the conservation of two sites, one of which was “famous” and one of which was less well-known. The hypothetical scenario involved payment to avoid future damage to each site. When observable differences in respondent characteristics are controlled for, we found no significant differences in mean WTP across sites. However, a significant effect was found for respondent familiarity with each site (in terms of recognising it on a photograph), with sites which respondents were more familiar with attracting higher WTP values. Distance effects on WTP were mixed: significant effects of distance of the site from respondents’ homes were only found for the less well-known sites, but not for famous sites. The main conclusions of the study were that (i) the Scottish general public are willing to pay for the conservation of historic sites and that (ii) such values exist as much for less well-known sites as for famous sites. This implies that public funds should not be allocated solely to conservation of the best-known sites

Prolonged Survival and Phenotypic Correction of Akp2−/− Hypophosphatasia Mice by Lentiviral Gene Therapy

Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNALP) isozyme. The clinical severity of HPP varies widely, with symptoms including rickets and osteomalacia. TNALP knockout (Akp2−/−) mice phenotypically mimic the severe infantile form of HPP; that is, TNALP-deficient mice are born with a normal appearance but die by 20 days of age owing to growth failure, hypomineralization, and epileptic seizures. In this study, a lentiviral vector expressing a bone-targeted form of TNALP was injected into the jugular vein of newborn Akp2−/− mice. We found that alkaline phosphatase activity in the plasma of treated Akp2−/− mice increased and remained at high levels throughout the life of the animals. The treated Akp2−/− mice survived for more than 10 months and demonstrated normal physical activity and a healthy appearance. Epileptic seizures were completely inhibited in the treated Akp2−/− mice, and X-ray examination of the skeleton showed that mineralization was significantly improved by the gene therapy. These results show that severe infantile HPP in TNALP knockout mice can be treated with a single injection of lentiviral vector during the neonatal period. © 2011 American Society for Bone and Mineral Research

Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial.

BACKGROUND: Our previous phase 2, open-label study of 11 infants and young children with life-threatening perinatal or infantile hypophosphatasia showed 1 year safety and efficacy of asfotase alfa, an enzyme replacement therapy. We aimed to report the long-term outcomes over approximately 7 years of treatment. METHODS: We did a prespecified, end of study, 7 year follow-up of our single-arm, open-label, phase 2 trial in which children aged 3 years or younger with life-threatening perinatal or infantile hypophosphatasia were recruited from ten hospitals (six in the USA, two in the UK, one in Canada, and one in the United Arab Emirates). Patients received asfotase alfa (1 mg/kg three times per week subcutaneously, adjusted to 3 mg/kg three times per week if required) for up to 7 years (primary treatment period plus extension phase) or until the product became commercially available; dosage adjustments were made at each visit according to changes in the patient's weight. The primary objectives of this extension study were to assess the long-term tolerability of asfotase alfa, defined as the number of patients with one or more treatment-emergent adverse events, and skeletal manifestations associated with hypophosphatasia, evaluated using the Radiographic Global Impression of Change (RGI-C) scale (-3 indicating severe worsening, and +3 complete or near-complete healing). Respiratory support, growth, and cognitive and motor functions were also evaluated. All efficacy and safety analyses were done in all patients who received any asfotase alfa (full-analysis population). This study and extension phase are registered with ClinicalTrials.gov, number NCT01205152, and EudraCT, number 2009-009369-32. FINDINGS: 11 participants were recruited between Oct 6, 2008, and Dec 4, 2009. Ten patients completed a 6 month treatment period and entered the extension phase; nine received asfotase alfa for at least 6 years and completed the study, with four being treated for more than 7 years. Skeletal healing was sustained over 7 years of treatment; all evaluable patients had RGI-C scores of at least +2 at year 6 (n=9; median score +2·0 [range 2·0-3·0]) and year 7 (n=7; median score +2·3 [2·0-3·0]). No patient who completed the study required respiratory support after year 4. Weight Z scores improved to within normal range from year 3 to study end; length or height Z scores improved but remained below normal. Age-equivalent scores on gross motor, fine motor, and cognitive subscales of the Bayley Scales of Infant and Toddler Development also improved. All 11 patients had at least one treatment-emergent adverse event. The most common adverse events were pyrexia (eight [73%] of 11 patients), upper respiratory tract infection (eight [73%]), craniosynostosis (seven [64%]), and pneumonia (seven [64%]). Serious adverse events related to asfotase alfa occurred in three (27%) patients (severe chronic hepatitis; moderate immediate post-injection reaction; and severe craniosynostosis with severe conductive deafness). INTERPRETATION: Patients with perinatal or infantile hypophosphatasia treated with asfotase alfa for up to 7 years showed early, sustained improvements in skeletal mineralisation. Respiratory function, growth, and cognitive and motor function also improved, and asfotase alfa was generally well tolerated. FUNDING: Alexion Pharmaceuticals, Inc

The relationship between regional medical campus enrollment and rates of matching to family medicine residency

Background: The Michael G. DeGroote School of Medicine expanded its medical education across three campus sites (Hamilton, Niagara Regional and Waterloo Regional) in 2007. Ensuring the efficacy and equivalency of the quality of training are important accreditation considerations in distributed medical education.  In addition, given the social accountability mission implicit to distributed medical education, the proportion of learners at each campus that match to family medicine residency programs upon graduation is of particular interest. Methods: By way of between campus comparisons of Canadian Residency Matching Service (CaRMS) match rates, this study investigates the family medicine match proportion of medical students from McMaster’s three medical education campuses. These analyses are further supported by between campus comparisons of Personal Progress Index (PPI), Objective Structured Clinical Examination (OSCE), Medical Council of Canada Qualifying Examination-Part 1 (MCCQE1) performances that offer insight into the equivalency and efficacy of the educational outcomes at each campus. Results: The Niagara Regional Campus (NRC) demonstrated a significantly greater proportion of students matched to family medicine. With respect to education equivalency, the proportion of students’ PPI scores that were more than two SD below the mean was comparable across campuses.  OSCE analysis yielded less than 2% differences across campuses with no differences in the last year of training.  The MCCQE1 pass rates were not statistically significant between campuses and there were no differences in CaRMS match rates. With respect to education efficacy, there were no differences among the three campuses’ pass rates on the MCCQE1 and CaRMS match rates with the national rates. Conclusions: Students in all campuses received equivalent educational experiences and were efficacious when compared to national metrics, while residency matches to family medicine were greater in the NRC. The reasons for this difference may be a factor of resident and leadership role-models as well as the local hospital and community environment

3D Printing of Food for People with Swallowing Difficulties

Dysphagia affects many people worldwide. Modifying foods to standard consistencies, and manual design and assembly of foods for the daily requirements of people with dysphagia is challenging. People with dysphagia may develop a dislike for pureed foods due to the unattractiveness of the appearance of the foods, the lack of variety in daily meals, and the diluted taste of meals. Three-dimensional (3D) food printing is emerging as a method for making foods for people with special mealtime needs. Very few efforts have been made to apply 3D food printing to improving the lives of people with special mealtime needs such as those with dysphagia. This paper presents the design and 3D printing of visually appetizing pureed foods for people with dysphagia with high consistency and repeatability. A tuna fish involving pureed tuna (protein), pureed pumpkin (fruit), and pureed beetroot (vegetable) is designed and then 3D printed. The steps involved in the design of tuna fish, preparation of purees, and printing of tuna fish are described. The obtained results are presented, and the findings of this research work are discussed

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical setting, and the clinician's professional judgment

The role of children in their HIV-positive parents’ management of antiretroviral therapy in Uganda

Adjustment to life on antiretroviral therapy (ART) and living with HIV as a long-term chronic condition, pose significant medical, social and economic challenges. We investigated children’s role in supporting HIV-positive parents to self-manage life on ART. Between 2010 and 2012, we conducted a qualitative study using semi-structured interviews with 38 HIV-positive parents who had been on ART for over a year. They were randomly selected from people accessing ART from three delivery sites in Wakiso district, Uganda. Data were analysed thematically. Participants reported children between the ages of 1 and 47 years providing support. Children were a source of happiness, self-worth, encouragement, and comfort. Both younger and older children supported parents’ adherence to treatment through reminding them to take the drugs and honour clinic appointments. Older children provided money to buy medication, food and shelter. Parents reported that the encouragement they received after they disclosed to their children enhanced their survival. After HIV disclosure to their children many of their fears about the future were allayed. Thinking about their children’s future brought hope. However, looking after younger children while on ART could be burdensome since some parents could not work to their full capacity due to reduced physical health. Children are an important resource in their parents’ adjustment to living with HIV while taking ART. There is a need for children to be supported by appropriate policy and other social and health development structures

The serum proteome of Atlantic salmon, Salmo salar, during pancreas disease (PD) following infection with salmonid alphavirus subtype 3 (SAV3)

Salmonid alphavirus is the aetological agent of pancreas disease (PD) in marine Atlantic salmon, Salmo salar, and rainbow trout, Oncorhynchus mykiss, with most outbreaks in Norway caused by SAV subtype 3 (SAV3). This atypical alphavirus is transmitted horizontally causing a significant economic impact on the aquaculture industry. This histopathological and proteomic study, using an established cohabitational experimental model, investigated the correlation between tissue damage during PD and a number of serum proteins associated with these pathologies in Atlantic salmon. The proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting. A number of humoral components of immunity which may act as biomarkers of the disease were also identified. For example, creatine kinase, enolase and malate dehydrogenase serum concentrations were shown to correlate with pathology during PD. In contrast, hemopexin, transferrin, and apolipoprotein, amongst others, altered during later stages of the disease and did not correlate with tissue pathologies. This approach has given new insight into not only PD but also fish disease as a whole, by characterisation of the protein response to infection, through pathological processes to tissue recovery. Biological significance: Salmonid alphavirus causes pancreas disease (PD) in Atlantic salmon, Salmo salar, and has a major economic impact on the aquaculture industry. A proteomic investigation of the change to the serum proteome during PD has been made with an established experimental model of the disease. Serum proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting with 72 protein spots being shown to alter significantly over the 12 week period of the infection. The concentrations of certain proteins in serum such as creatine kinase, enolase and malate dehydrogenase were shown to correlate with tissue pathology while other proteins such as hemopexin, transferrin, and apolipoprotein, altered in concentration during later stages of the disease and did not correlate with tissue pathologies. The protein response to infection may be used to monitor disease progression and enhance understanding of the pathology of PD

The Local, the ‘Indigenous’ and the Limits of Rethinking Peacebuilding

© 2021 Informa UK Limited, trading as Taylor & Francis Group. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1080/17502977.2021.1882755Recent critical perspectives on peacebuilding have sought to shed light on experiences so far marginalized by mainstream approaches. In particular, critics have pushed peacebuilding towards radically different ways of thinking about governance, conflict and peace, by engaging with narratives, experiences and knowledge coming from societies perceived as not invested in modernity or liberalism, such as Indigenous communities. Whilst this may force theory to confront questions of human-centrism, colonial erasure, and structural violence, turning to Indigeneity without questioning the impact of liberal peace ‘thinking', might further elicit marginalization and appropriation, and simply ‘save’ liberal peacebuilding through the back door.Peer reviewe