Grassland vegetation from three conservation measures

accepted for publicationSemi-natural grassland habitats have declined significantly throughout Europe. To halt the decline, grassland conservation measures have been included in most European agri-environment schemes. This is the first study to compare the botanical composition of grassland habitats managed under the Irish Agri Environment Options Scheme (AEOS). Sixty fields on dry stock pastoral farms in receipt of agri-environment payments for grassland conservation were surveyed, with twenty fields being enrolled in each of the following AEOS options: Traditional Hay Meadow (THM), Species Rich Grassland (SRG) and Natura 2000 species rich grassland (Natura). The vegetation quality of sites enrolled in the Natura measure was higher than those enrolled in the THM and SRG measures. Natura sites had the greatest species richness with a mean > 40 species per site, which included approximately 17 species indicative of high botanical quality. Traditional Hay Meadow sites had the lowest species richness (mean 29 species per site) and were dominated by species associated with improved grassland. Some THM sites had good levels of botanical richness and were similar in composition to Natura sites, with some Natura sites having a lower vegetation quality, more similar to that of THM sites. Species Rich Grassland had a botanical richness that was intermediate between THM and Natura sites. A thorough assessment of the effectiveness of these measures was confounded by a lack of quantitative objectives for the target community composition to be attained. We discuss limitations and potential opportunities regarding the design, targeting, implementation and cost-effectiveness of these agri-environment measures.Teagasc Walsh Fellowship Programm

A comparison of grassland vegetation from three agri-environment conservation measures

peer-reviewedSemi-natural grassland habitats have declined significantly throughout Europe. To halt the decline, grassland conservation measures have been included in most European agri-environment schemes. This is the first study to compare the botanical composition of grassland habitats managed under the Irish Agri-Environment Options Scheme (AEOS). Sixty fields on drystock pastoral farms in receipt of agri-environment payments for grassland conservation were surveyed, with 20 fields being enrolled in each of the following AEOS options: Traditional Hay Meadow (THM), Species-Rich Grassland (SRG) and Natura 2000 species-rich grassland (Natura). The vegetation quality of sites enrolled in the Natura measure was higher than the quality of those enrolled in the THM and SRG measures. Natura sites had the greatest species richness, with a mean >40 species per site, which included approximately 17 species indicative of high botanical quality. Traditional Hay Meadows sites had the lowest species richness (mean: 29 species per site) and were dominated by species associated with improved grassland. Some THM sites had good levels of botanical richness and were similar in composition to Natura sites, with some Natura sites having lower vegetation quality, more similar to that of THM sites. Species-Rich Grassland had botanical richness that was intermediate between THM and Natura sites. A thorough assessment of the effectiveness of these measures was confounded by a lack of quantitative objectives for the target community composition to be attained. We discuss limitations and potential opportunities regarding the design, targeting, implementation and cost-effectiveness of these agri-environment measures

Effect of Training Phase on Physical and Physiological Parameters of Male Powerlifters

Longitudinal research on training and dietary practices of natural powerlifters is limited. This study investigated the effect of phases of training on physical and physiological parameters in male natural powerlifters. Nine participants completed testing at two time points: (i) preparatory phase (~3 months prior to a major competition) and (ii) competition phase (1–2 weeks from a major competition). No significant changes between training phases were found for muscle strength and power. A trend for significance was found for decreased muscle endurance of the lower body (−24.4%, p = 0.08). A significant increase in leg lean mass was found at the competition phase (2.3%, p = 0.04), although no changes for other body composition measures were observed. No change was observed for any health marker except a trend for increased urinary creatinine clearance at the competition phase (12.5%, p = 0.08). A significant reduction in training volume for the lower body (−75.0%, p = 0.04) and a trend for a decrease in total energy intake (−17.0%, p = 0.06) was observed during the competition phase. Despite modifications in training and dietary practices, it appears that muscle performance, body composition, and health status remain relatively stable between training phases in male natural powerlifters

Co-creation of a complex, multicomponent rehabilitation intervention and feasibility trial protocol for the PostUraL tachycardia Syndrome Exercise (PULSE) study

Background: There is a dearth of research to support the treatment of people with postural tachycardia syndrome (PoTS). Despite expert consensus suggesting exercise is recommended for this patient group, there are no randomised control trials examining this rigorously. The aim was to co-create a feasibility trial protocol and a rehabilitation intervention for people living with PoTS. // Methods: The intervention and feasibility trial design were co-created as part of the PostUraL tachycardia Syndrome Exercise (PULSE) study. We used the ‘three co’s framework’ of co-define, co-design and co-refine. Recruitment included key national charities and National Health Service Trusts treating people living with PoTS in the UK. Eighteen patient and public involvement members attended the co-define session, and 16 co-creators with a mix of expertise attended the subsequent co-design and co-refine sessions. Seven intervention practitioners were trained in the rehabilitation intervention, providing feedback for further co-refinement. // Results: The final co-created intervention comprises online physical activity, and lifestyle and behaviour change support sessions. It is based on functional movement activities using a patient-centred approach tailored to individual needs. Physical activity intensity is guided by individuals’ perception of effort rather than by objective measures. Recumbent bikes are provided for home use. Patients deemed randomisation to be acceptable because research in this area was considered important. // Conclusions: An innovative approach was used to co-create the PULSE intervention and feasibility trial protocol to meet the evidence-based and logistical needs of people living with PoTS, clinicians, service deliverers, third-sector organisations, academics and funders. This can be used as a successful example and template for future research internationally. People living with PoTS were recognised as experts and involved in every aspect of conceptualisation, design and refinement. This complex rehabilitation intervention is currently being tested in a randomised feasibility trial comparing the PULSE intervention with best-practice usual care for people living with PoTS. // Trial registration: ISRCTN45323485 was registered on April 7, 2020

Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK

Human-to-human transmission of Creutzfeldt–Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy (CAA), regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA

Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform

On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required.   For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance.  This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.</ns4:p

Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.

OBJECTIVE: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. DESIGN: Matched cohort study, emulating a comparative effectiveness trial. SETTING: Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant. PARTICIPANTS: 3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1. INTERVENTION: Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose. MAIN OUTCOME MEASURES: Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose. RESULTS: 1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras. CONCLUSIONS: This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance

Erratum to: Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains.

Mitochondria play a key role in common neurodegenerative diseases and contain their own genome: mtDNA. Common inherited polymorphic variants of mtDNA have been associated with several neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions. However, there are conflicting reports describing the role of rare inherited variants and somatic point mutations in neurodegenerative disorders, and recent evidence also implicates mtDNA levels. To address these issues we studied 1363 post mortem human brains with a histopathological diagnosis of Parkinson's disease (PD), Alzheimer's disease (AD), Frontotemporal dementia - Amyotrophic Lateral Sclerosis (FTD-ALS), Creutzfeldt Jacob disease (CJD), and healthy controls. We obtained high-depth whole mitochondrial genome sequences using off target reads from whole exome sequencing to determine the association of mtDNA variation with the development and progression of disease, and to better understand the development of mtDNA mutations and copy number in the aging brain. With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects. However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease. In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD. Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation