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Intraparenchymal convection enhanced delivery of AAV in sheep to treat Mucopolysaccharidosis IIIC
Get PDFBackground Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9.
Methods Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread.
Results Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere.
Conclusions Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC
“Got milk alternatives?” Understanding key factors determining U.S. consumers’ willingness to pay for plant-based milk alternatives
Get PDFMilk is an important dairy product in U.S. food retail. Lifestyle changes toward climate-conscious consumption, animal welfare, and food safety concerns have increased the popularity of plant-based milk alternatives. This study is focused on such beverages and provides insights and best practice recommendations for marketing managers in the U.S. food retail sector. An online survey was distributed to explore factors explaining the intentions of U.S. consumers to purchase and pay a premium for plant-based milk alternatives. Food curiosity and food price inflation were identified as relevant for both willingness to buy and willingness to pay a price premium. In addition, animal welfare concerns and the green and clean product image of plant-based alternatives were relevant to the willingness to pay a premium for plant-based milk
House prices, airport location proximity, air traffic volume and the COVID-19 effect
Get PDFAlthough house prices and airports are influenced by distinct factors that shape their evolutions, they are also intrinsically connected through the natural and built environment. Standard theory suggests that air-traffic noise and proximity to key economic hubs such as airports are of prime importance to house prices and the housing market. This study contributes to understanding the link between the housing market, airport location proximity and air traffic. The research investigates this association across four key urban areas within New Zealand proximal to an international airport: Auckland, Wellington, Christchurch and Queenstown. Applying a generalized least squares (GLS) regression approach, the analysis reveals that house prices, air-traffic activity and proximity to airports within New Zealand demonstrate a statistically significant effect, and that air traffic volume has a positive effect on house prices. Moreover, the findings reveal a ‘U’-shape relationship between distance to the airport and house prices, suggesting that airport noise and pollution adversely affect house prices, with this effect diminishing with distance, indicating that economic influences and employment may also serve as a positive externality
Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis
Get PDFNeuronal ceroid lipofuscinoses (Batten disease) are a group of inherited lysosomal storage disorders characterized by progressive neurodegeneration leading to motor and cognitive dysfunction, seizure activity and blindness. The disease can be caused by mutations in 1 of 13 ceroid lipofuscinosis neuronal (CLN) genes. Naturally occurring sheep models of the CLN5 and CLN6 neuronal ceroid lipofuscinoses recapitulate the clinical disease progression and post-mortem pathology of the human disease. We used longitudinal MRI to assess global and regional brain volume changes in CLN5 and CLN6 affected sheep compared to age-matched controls over 18 months. In both models, grey matter volume progressively decreased over time, while cerebrospinal fluid volume increased in affected sheep compared with controls. Total grey matter volume showed a strong positive correlation with clinical scores, while cerebrospinal fluid volume was negatively correlated with clinical scores. Cortical regions in affected animals showed significant atrophy at baseline (5 months of age) and progressively declined over the disease course. Subcortical regions were relatively spared with the exception of the caudate nucleus in CLN5 affected animals that degenerated rapidly at end-stage disease. Our results, which indicate selective vulnerability and provide a timeline of degeneration of specific brain regions in two sheep models of neuronal ceroid lipofuscinoses, will provide a clinically relevant benchmark for assessing therapeutic efficacy in subsequent trials of gene therapy for CLN5 and CLN6 disease
Investigating the effects of anthropogenic stressors on lake biota using sedimentary DNA
No full text1. Analyses of sedimentary DNA (DNA) have increased exponentially over the last decade and hold great potential to study the effects of anthropogenic stressors on lake biota over time.
2. Herein, we synthesise the literature that has applied a DNA approach to track historical changes in lake biodiversity in response to anthropogenic impacts, with an emphasis on the past 200 years.
3. We identified the following research themes that are of particular relevance: (1) eutrophication and climate change as key drivers of limnetic communities; (2) increasing homogenisation of limnetic communities across large spatial scales; and (3) the dynamics and effects of invasive species as traced in lake sediment archives.
4. Altogether, this review highlights the potential of sedDNA to draw a more comprehensive picture of the response of lake biota to anthropogenic stressors, opening up new avenues in the field of paleoecology by unrevealing a hidden historical biodiversity, building new paleo-indicators, and reflecting either taxonomic or functional attributes.
5. Broadly, sedDNA analyses provide new perspectives that can inform ecosystem management, conservation, and restoration by offering an approach to measure ecological integrity and vulnerability, as well as ecosystem functioning
Kysten nu: perspektiver på baggrund af 19 kommuners arbejde med kystbyer og stigende havvand
No full textOpen source rapport baseret på netværksaktiviteten ´Rejsehold´i regi af indsatsen ´Byerne og det stigende havvand´som er støttet af Realdania.
I perioden 2018-2022 har Realdania og Kystdirektoratet indgået partnerskab om projektet Byerne og det stigende havvand. I alt 19 kommuner har modtaget støtte fra partnerskabet til udvikling af pilotprojekter, der relaterer sig til kystbyers tilpasning til oversvømmelser fra havet. Pilotprojekterne ligger i såvel store kommuner og bye som København, Aalborg og Randers, mellemstore byer som Svendborg, Skive og Nykøbing Falster, samt mindre byer som Taarbæk, Strøby Egede og Juelsminde. Sideløbende er der kørt et netværks- og forskningsspor, som haft til formål at bygge bro mellem forskning og praksis, og som samtidig har bidraget til, at forskerne har kunne høste erfaringer på tværs af kommunerne fra deres arbejde med kystbyer og klimaforandringer. Det er der kommet en tværgående opsamlingsrapport ud af.
Rapporten ’Man vil jo gerne en by – indsigter fra 19 pilotkommuners arbejde med udvikling af kystbyer i lyset af det stigende havvand’ formidler de tværgående emner, der fylder i de kommunale forvaltninger, når det gælder tilpasning til oversvømmelser fra havet. Der er fire hovedkonklusioner i rapporten. For det første, at der i kommunerne er fokus på beskyttelse, hvilket sker på bekostning af imødekommelse og især tilbageføring og friholdelse af bebyggelse som løsningsmuligheder i forhold til oversvømmelser fra havet. For det andet er der fokus på stormflod, mens de meget langsigtede, permanente og løbende stigninger i havniveauet ikke for alvor tages med i overvejelserne om byens udvikling og tilpasning til klimaforandringerne. For det tredje er der i de fleste kommuner konsensus om, at de lavtliggende kystområder, herunder særligt havneområderne, er vigtige byudviklingsarealer. Og endelig for det fjerde, viser undersøgelsen, at de danske kommuner er meget forskellige steder rent modningsmæssigt i deres arbejde med udvikling af kystbyer i lyset af det stigende havvand.
Konsekvenserne af dette er, at det er svært for kommunerne at tænke langsigtet og dynamisk i planlægningen af kystbyerne. Samtidig har det den konsekvens, at byudviklingen på havnefronterne og i de andre lavtliggende kystområder fortsætter relativt ukritisk i store såvel som små danske byer. Klimatilpasningsindsatsen bliver reduceret til en diskussion om stormflodskoter og et valg mellem forskellige beskyttelsesteknologier, mens muligheden for at ’løfte blikket’ og tage en mere grundlæggende diskussion om byernes relation til havet på kort, mellemlangt og lang sigt til en vis grad forpasses.
Partnerskabet mellem Miljøministeriet og Realdania og kommunernes arbejdet med pilotprojekter har bidraget til en udvikling af videnniveauet i kommunerne. Det er tydeligt, at der sker en modning og nuancering af problemstillingen over tid, men samtidig viser undersøgelsen, at kommunernes indhentning f viden generelt sker ret sporadisk. Danmarks samlede kompetence på kystområdet kan derfor hjælpes på vej af en mere systematisk vidensopbygning på tværs af kommuner og på tværs af landets geografi
Investigating bacterial 3-hydroxy fatty acids as new indicators of past air temperature in lake sediments from New Zealand
No full textSedimentary lipid biomarkers are important indicators to reconstruct past air and water temperatures in lakes, particularly for paleoreconstructions beyond monitored periods. Currently, glycerol dialkyl glycerol tetraethers (GDGTs) are widely used as temperature proxies in these settings, but uncertainties remain around biological sources and non-thermal impacts (e.g. pH, redox and relative contributions of in situ production and terrestrial supply). An alternate novel terrestrial biomarker proxy for temperature reconstructions has been developed based on the relative distributions of 3-hydroxy-fatty acids (3-OH-FAs), sourced from the outer membrane of Gram-negative bacteria. Preliminary studies in contemporary soils, stalagmites and lake sediments correlating bacterial 3-OH-FA compositions to air temperature and pH have shown promising results. However, their performance under discrete physical and chemical conditions remains largely unexplored. In this study, we have analysed 3-OH-FA distributions in surface sediments of 143 lakes across New Zealand. The lakes span a large diversity of lake and catchment sizes, water depths, geographic locations (latitude and altitude), productivity and trophic level, catchment vegetation and land-use. We have also studied the community composition and diversity of Gram-negative bacteria in the surface sediments of the studied lakes. 3-OH-FAs were detected in the sediments of all lakes and generally showed a correlation with monitored air temperatures. The strongest correlation was shown in a sub-set of remote lakes along an altitudinal transect with limited human impact where the ratio of anteiso to normal C17 3-OH-FAs (RAN17 index) and iso to normal C17 homologues (RIN17 index) correlate with mean annual air temperature (MAAT) with R2 of 0.73 and 0.64, respectively. In contrast, the RIN13 index, which was previously proposed for lake sediments, showed no correlation with MAAT. For the whole dataset comprising all studied lakes, only the RAN17 index correlates with MAAT with R2 of 0.46. Therefore, 3-OH-FAs have great potential as new indicators applicable to the reconstruction of past air temperatures from sediments of New Zealand’s lakes
COVID-19 and physical activity among older Japanese: Unequal outcomes across the pandemic highlight a problematic life stage
No full textIntroduction: The COVID-19 pandemic has affected the health and everyday behaviors of individuals and communities across the globe. Major life disruptions have also been experienced across Japan, yet few studies have examined behavioral variations among older cohorts in this super-aged society.
Objectives: The aim of the study was to investigate physical activity behavior changes among representative samples of middle-aged (45-64 years) and older adults (>65 years) in Tokyo across two time points, before and during the COVID-19 pandemic.
Methods: Repeated online surveys were conducted with quota samples of 800 older residents of Tokyo in 2019 and 2021 using valid and reliable measures of general health, physical activity, walking, and sitting behavior, including a Japanese-language translation of the International Physical Activity Questionnaire (IPAQ).
Results: Differential outcomes were identified between age and gender cohorts in relation to reported general health, physical activity, and walking behavior across the pandemic. Older adults were found to be significantly more active and report better health compared to those in middle age. Middle-aged women reported particularly low levels of activity in relation to both middle-aged men and older-adult respondents.
Conclusion: The results suggest that older adults in Tokyo were comparatively resilient and active in the face of the pandemic when compared with their middle-aged counterparts. Middle-aged women appeared to be particularly constrained in terms of their physical activity behavior, which may be related to unequal and gendered life responsibilities. The results have implications for healthy transitions to retirement and the promotion of resilience among aging cohorts
Effects of smartphone social applications on elderly people’s quality of life
No full textAs people age, maintaining and improving their Quality of Life becomes increasingly important. To understand the impact of smartphone technology and communications applications on Quality of Life, a quasi-experimental study was conducted with elderly people living in Shiraz-Iran. The study population included all the registered senior in public health centers in Shiraz, Fars, Iran during 2018 and 2019. Overall, 119 elderly people participated in the study. The study randomly categorized participants into intervention (59 participants with mean age 66.19±2.73) and control (60 participants with mean age 66.67±3.00) groups. They were asked to answer the validated Persian version of the Control, Autonomy, Self-realisation, Pleasure scale (CASP-19) scale questionnaire for Quality of Life assessment. A significant mean difference was observed by the paired t-test between pre-and post-test (t= -8.61, p<0.00), post-and follow-up-test (t= -2.24, p=0.02), and pre-test and follow-up test (t= -8.42, p<0.00) in the intervention group. The results of paired t-test for the control group showed no significant mean difference between pre-test and post-test (t= 1.35, p=0.18), post-test and follow-up test (t= 0.38, p=0.70) and pre-test and follow-up test (t= 1.94, p=0.06) for Quality of Life. The rationale for this study, along with the educational training associated with it, was to help families, and the aging field practitioners to understand the importance of modern communication technology teaching to promote a greater Life Quality in the community of the elderl
Practicing together: designing with consent, towards a new theoretical approach to the professional-led participatory design of urban space : A thesis submitted in partial fulfilment of the requirements for the Degree of Doctor of Philosophy at Lincoln University
Get PDFLocal participation is now a mainstream practice within Landscape Architecture and Urban Design. The literature review considers ‘participation’ as the primary lens for democratising design practice and examines how it has enabled and limited participatory design practice - pinpointing the need for further theorisation at the intersection of design professionals and local people. This study addresses this intersection by developing an interpretative model that draws on interdisciplinary concepts of informed consent. A grounded, more-than-human empirical study interprets two case studies, Aro Park in Wellington, Aotearoa New Zealand and Grønne Park, Superkilen in Copenhagen, Denmark. The substantive findings are presented in the form of seven episodes that follow how participatory design enables and limits the formation of informed consent. In addition, this analysis both develops and applies the theoretical model, leading to a Framework of Informed Consent. Three key synthetic insights examine why the interrelationships between design professionals, local people and the sites led to the disruption of the participatory design process and designed landscape. Theoretical, methodological, and substantive conclusions are drawn detailing opportunities for future research and practice