The clinically extremely vulnerable to COVID: identification and changes in healthcare while self-isolating (shielding) during the coronavirus pandemic.

In March 2020, the government of Scotland identified people deemed clinically extremely vulnerable to COVID due to their pre-existing health conditions. These people were advised to strictly self-isolate (shield) at the start of the pandemic, except for necessary healthcare. We examined who was identified as clinically extremely vulnerable, how their healthcare changed during isolation, and whether this process exacerbated healthcare inequalities. We linked those on the shielding register in NHS Grampian, a health authority in Scotland, to healthcare records from 2015-2020. We described the source of identification, demographics, and clinical history of the cohort. We measured changes in out-patient, in-patient, and emergency healthcare during isolation in the shielding population and compared to the general non-shielding population. The register included 16,092 people (3% of the population), clinically vulnerable primarily due to a respiratory disease, immunosuppression, or cancer. Among them, 42% were not identified by national healthcare record screening but added ad hoc, with these additions including more children and fewer economically-deprived. During isolation, all forms of healthcare use decreased (25%-46%), with larger decreases in scheduled care than in emergency care. However, people shielding had better maintained scheduled care compared to the non-shielding general population: out-patient visits decreased 35% vs 49%; in-patient visits decreased 46% vs 81%. Notably, there was substantial variation in whose scheduled care was maintained during isolation: younger people and those with cancer had significantly higher visit rates, but there was no difference between sexes or socioeconomic levels. Healthcare changed dramatically for the clinically extremely vulnerable population during the pandemic. The increased reliance on emergency care while isolating indicates that continuity of care for existing conditions was not optimal. However, compared to the general population, there was success in maintaining scheduled care, particularly in young people and those with cancer. We suggest that integrating demographic and primary care data would improve identification of the clinically vulnerable and could aid prioritising their care

The clinically extremely vulnerable to COVID : Identification and changes in healthcare while self-isolating (shielding) during the coronavirus pandemic

Peer reviewe

Improving children and young people’s mental health services

Across the UK, the number of children and young people experiencing mental health problems is growing. Mental health services are expanding, but not fast enough to meet rising needs, leaving many children and young people with limited or no support. Too little is known about who receives care and crucially, who doesn’t. This briefing presents analysis from the Health Foundation’s Networked Data Lab (NDL) about children and young people’s mental health. The analysis from local teams across England, Scotland and Wales has highlighted three key areas for urgent investigation, to help ensure children and young people get the care they need. These are: rapid increases in mental health prescribing and support provided by GPs the prevalence of mental health problems among adolescent girls and young women stark socioeconomic inequalities across the UK. To inform national policy decisions and local service planning and delivery, the quality of data collection, analysis and the linkage of datasets across services and sectors need to be improved and used more effectively

The clinically extremely vulnerable to COVID: Identification and changes in healthcare while self-isolating (shielding) during the coronavirus pandemic.

Objective In March 2020, Scottish government identified people clinically extremely vulnerable to COVID due to pre-existing health conditions. These people were advised to strictly self-isolate (shield) at home. We examined who was identified as clinically extremely vulnerable, how their healthcare changed during isolation, and whether this process exacerbated healthcare inequalities. Approach We linked all individuals on the shielding register in NHS Grampian to their in-patient and out-patient healthcare records from 2015 through 2020. We analysed the method of patients’ identification as clinically extremely vulnerable (via an algorithmic NHS record scan or designated ad hoc by their care-providers). We measured out-patient, in-patient, and emergency healthcare attendances, and compared use rates between two 3-month periods before and during the first strict isolation period. We evaluated changes in care use between those shielding and the general non-shielding population, and differences between shielding sub-populations (by clinical reason for shielding, age, sex, and socio-economic deprivation). Results The shielding register included 16,092 people (3% of the population). 42% of people on the register were not identified by national healthcare record screening, including the majority of cancer and immunocompromised patients. People added to the register by their care-providers were more likely to be young and less economically-deprived. Shielders’ healthcare use decreased during isolation (rate compared to pre-isolation: 0.65 out-patient, 0.54 scheduled in-patient; 0.75 emergency in-patient; 0.71 A&E). However, people shielding had better maintained care than the non-shielding population (e.g. RR 2.9 for scheduled in-patient care). There were inequalities in whose scheduled care was maintained while shielding: younger people and those with cancer had significantly higher visit rates. However, there were no differences in care-preservation between men and women or between socioeconomic deprivation levels. Conclusions The reliance on emergency care while shielding indicates that, overall, continuity of care for existing conditions was not optimal. However, there was notable success in maintaining care for cancer. We suggest that integrating demographic and primary care data would improve identification of the clinically vulnerable and help equitably prioritise care

IEA EBC Annex 72: Assessing Life Cycle Related Environmental Impacts Caused by Buildings: Guidelines for design decision-makers:Energy in Buildings and Communities Technology Collaboration Programme

The purpose of this report is to provide support to the design decisions-makers during the design process. For each of the defined design step decision the important topics to consider were identified, the key stakeholders are declared and the purpose of LCA at the selected design step is defined. The report covers: The definition of the design steps, the definition of the tasks in each design step and an overview of the relevant milestones for performing LCA; An overview of the systematic building decomposition methods and the appropriate levels at each design step; An overview of the tools that can be used for LCA and a selection process for choosing the right LCA tool. A special emphasize is given to the topic of Building Information Modelling (BIM), how the BIM tools can facilitate the LCA assessment and what information should be implemented in the BIM model; Strategies on how to reduce the design-related uncertainties; An overview of the visualization of the LCA results and which are appropriate in the selected design steps

White matter hyperintensities in progranulin-associated frontotemporal dementia: A longitudinal GENFI study.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial

Phylogeny and Biogeography of the Carnivorous Plant Family Sarraceniaceae

The carnivorous plant family Sarraceniaceae comprises three genera of wetland-inhabiting pitcher plants: Darlingtonia in the northwestern United States, Sarracenia in eastern North America, and Heliamphora in northern South America. Hypotheses concerning the biogeographic history leading to this unusual disjunct distribution are controversial, in part because genus- and species-level phylogenies have not been clearly resolved. Here, we present a robust, species-rich phylogeny of Sarraceniaceae based on seven mitochondrial, nuclear, and plastid loci, which we use to illuminate this family's phylogenetic and biogeographic history. The family and genera are monophyletic: Darlingtonia is sister to a clade consisting of Heliamphora+Sarracenia. Within Sarracenia, two clades were strongly supported: one consisting of S. purpurea, its subspecies, and S. rosea; the other consisting of nine species endemic to the southeastern United States. Divergence time estimates revealed that stem group Sarraceniaceae likely originated in South America 44–53 million years ago (Mya) (highest posterior density [HPD] estimate = 47 Mya). By 25–44 (HPD = 35) Mya, crown-group Sarraceniaceae appears to have been widespread across North and South America, and Darlingtonia (western North America) had diverged from Heliamphora+Sarracenia (eastern North America+South America). This disjunction and apparent range contraction is consistent with late Eocene cooling and aridification, which may have severed the continuity of Sarraceniaceae across much of North America. Sarracenia and Heliamphora subsequently diverged in the late Oligocene, 14–32 (HPD = 23) Mya, perhaps when direct overland continuity between North and South America became reduced. Initial diversification of South American Heliamphora began at least 8 Mya, but diversification of Sarracenia was more recent (2–7, HPD = 4 Mya); the bulk of southeastern United States Sarracenia originated co-incident with Pleistocene glaciation, <3 Mya. Overall, these results suggest climatic change at different temporal and spatial scales in part shaped the distribution and diversity of this carnivorous plant clade

The antimicrobial effect of metal substrates on food pathogens.

The development of surfaces as antimicrobial materials is important to the food industry. This study investigated the antimicrobial potential of a range of metal coated surfaces including silver, titanium, copper, iron, molybdenum, zinc and silicon (control) against Staphylococcus aureus, Escherichia coli and Listeria monocytogenes. The leaching potential of the metals were measured by inductively coupled plasma-atomic adsorption spectroscopy and were compared to the antibacterial activity of the metals using a nitroblue tetrazolium assay and an adapted BS ISO 22196:2011 standard. Leaching into solution from the coatings alone was not related to the antimicrobial activity of the coatings. Copper and zinc showed the greatest propensity to leach from the coatings; silver, titanium, iron and molybdenum leached at lower rates and silicon showed no leaching. Copper demonstrated the greatest antimicrobial potential followed by silver and zinc. Titanium displayed the least antimicrobial potential, however using the standard method in humid conditions resulted in increased growth of Listeria. This study provides evidence of the efficacy of copper and silver as effective antimicrobial metal surface coatings, however use of titanium under humid conditions suggest that surfaces for use in the food industry needs to be given careful consideration before application

Altered plasma protein profiles in genetic FTD – a GENFI study

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. Methods: Blood samples from 693 participants in the GENetic Frontotemporal Dementia Initiative study were analysed using a multiplexed antibody array targeting 158 proteins. Results: We found 13 elevated proteins in symptomatic mutation carriers, when comparing plasma levels from people diagnosed with genetic FTD to healthy non-mutation controls and 10 proteins that were elevated compared to presymptomatic mutation carriers. Conclusion: We identified plasma proteins with altered levels in symptomatic mutation carriers compared to non-carrier controls as well as to presymptomatic mutation carriers. Further investigations are needed to elucidate their potential as fluid biomarkers of the disease process.Open access funding provided by Karolinska Institute. C.G. received funding from EU Joint Programme—Neurodegenerative Disease Research -Prefrontals Vetenskapsrådet Dnr 529–2014-7504, Vetenskapsrådet 2015–02926, Vetenskapsrådet 2018–02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation, Dementia Foundation and Region Stockholm ALF-project. PN received funding from KTH Center for Applied Precision Medicine (KCAP) funded by the Erling-Persson Family Foundation, the Swedish FTD Inititative-Schörling Foundation and Åhlén foundation. D.G. received support from the EU Joint Programme—Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. E.F. has received funding from a Canadian Institute of Health Research grant #327387. F.M. received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease. J.B.R. has received funding from the Welcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215–20014). J.C.V.S. was supported by the Dioraphte Foundation grant 09–02-03–00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056–13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield Project. J.D.R. is supported by the Bluefield Project and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and a Miriam Marks Brain Research UK Senior Fellowship. M.M. has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. M.O. has received funding from Germany’s Federal Ministry of Education and Research (BMBF). R.S-V. is supported by Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2) and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). R.V. has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. This work was also supported by the EU Joint Programme—Neurodegenerative Disease Research GENFI-PROX grant [2019–02248; to J.D.R., M.O., B.B., C.G., J.C.V.S. and M.S.info:eu-repo/semantics/publishedVersio

Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. Methods: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Results: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. Conclusions: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.This study was supported in the Netherlands by Memorabel grants from Deltaplan Dementie (ZonMw and Alzheimer Nederland; grant numbers 733050813, 733050103, 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), and the European Joint Programme—Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1) and the JPND GENFI-PROX grant (2019-02248); JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); ASE supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK; IJS is supported by the Alzheimer’s Association; JBR is supported by the Wellcome Trust (103838); in Spain by the Fundació Marató de TV3 (20143810 to RSV); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and by grant 779357 “Solve-RD” from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529–2014-7504, Swedish Research Council (VR) 2015–02926, Swedish Research Council (VR) 2018–02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral Funding, and StratNeuro. HZ is a Wallenberg Scholar.info:eu-repo/semantics/publishedVersio