A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology

Global patterns in endemicity and vulnerability of soil fungi

Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms

Validity of carbohydrate deficient transferrin and other markers as diagnostic aids in the detection of alcohol related seizures

OBJECTIVE—The role of alcohol misuse in the genesis of seizures is probably often undetected. The aim was to investigate the utility of carbohydrate deficient transferrin (CDT) compared with other biomarkers and clinical examination in the diagnosis of alcohol related seizures.
METHODS—The study included consecutively 158 seizure patients—83 men and 75 women—with mean age 45 (16-79) years. Seizures related to alcohol use were identified by a score ⩾8 in the alcohol use disorders identification test (AUDIT positive). AUDIT was applied as the gold standard to which sensitivity and specificity of the various markers were related. Blood samples were obtained from 150 patients on admission and analysed for ethanol, liver enzymes, and CDT, using AXIS Biochemicals' %CDT-TIA kit.
RESULTS—53 patients (34%) were AUDIT positive. Using the commonly applied decision value for %CDT of 5.0%, a sensitivity of 41% and a specificity of 84% were obtained. Analysis of receiver operator characteristics (ROC) curves disclosed an optimal cut off value for %CDT of 5.4%, which yielded a sensitivity of 39% and a specificity of 88%. At a specificity of 80%, the sensitivity was 43% for %CDT and 26% for GGT. The %CDT sensitivity was markedly higher for men than for women. Compared with GGT, ASAT, ALAT, and ASAT/ALAT ratio, CDT was the best single biomarker for alcohol related seizures. However, even in the subgroup of withdrawal seizures, the sensitivity level barely exceeded 50%. Clinicians scored alcohol as the main cause of the seizure in only 19 cases (12%). In 38 (24%) cases, clinicians suspected that alcohol had a role (sensitivity of 62% at a specificity of 89%). Their ability to identify AUDIT positive patients was better than that of any biomarker, but many cases were missed. Agreement of clinicians' scores to CDT was only fair (κ=0.28). CDT concentrations were significantly increased among alcohol abstaining patients on enzyme-inducing antiepileptic drugs. Six out of 16 patients with false positive CDT results were exposed to such drugs.
CONCLUSIONS—CDT is not recommended as a stand alone marker for alcohol related seizures, but may provide a useful contribution to the overall diagnostic investigation of seizures. Confirmatory studies are needed as to the apparent vulnerability of CDT to antiepileptic drugs.


Digital twins: A critical discussion on their potential for supporting policy‐making and planning in urban logistics

Poor logistics efficiency, due to low load factors caused by high demand fragmentation, will have relevant negative consequences for cities in terms of pollution, congestion and overall city liveability. Policy‐makers should equip themselves with appropriate tools to perform reliable, comprehensive and timely analyses of urban logistics scenarios, also considering upcoming (i) technological changes, (ii) business model evolutions and (iii) spatial‐temporal changes these innovations will produce. This paper discusses the Digital Twin (DT) concept, illustrating the role it might play and clarifying how to properly conceive it with respect to urban freight transport policy‐making and planning. The main message is that without a sound theory and knowledge with respect to the relationships linking contextual reality and choice/behaviour, it is not possible to make sense of what happens in the real world. Therefore, the joint use of behavioural and simulation models should characterise a DT within a Living Lab approach so to stimulate effective, wellinformed and participated planning processes, but also to forecast both behaviour and reactions to structural changes and policy measures implementations

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Data from: DNA from soil mirrors plant taxonomic and growth form diversity

Ecosystems across the globe are threatened by climate change and human activities. New rapid survey approaches for monitoring biodiversity would greatly advance assessment and understanding of these threats. Taking advantage of next-generation DNA sequencing, we tested an approach we call metabarcoding: high-throughput and simultaneous taxa identification based on a very short (usually less than 100 base pairs) but informative DNA fragment. Short DNA fragments allow the use of degraded DNA from environmental samples. All analyses included amplification using plant-specific versatile primers, sequencing and estimation of taxonomic diversity. We tested in three steps whether degraded DNA from dead material in soil has the potential of efficiently assessing biodiversity in different biomes. First, soil DNA from eight boreal plant communities located in two different vegetation types (meadow and heath) was amplified. Plant diversity detected from boreal soil was highly consistent with plant functional and structural diversity estimated from conventional above-ground surveys. Second, we assessed DNA persistence using samples from formerly cultivated soils in temperate environments. We found that number of crop DNA sequences retrieved strongly varied with years since last cultivation, and crop sequences were absent from nearby, uncultivated plots. Third, we assessed the universal applicability of DNA metabarcoding using soil samples from tropical environments: a large proportion of species and families from the study site was efficiently recovered. The results open unprecedented opportunities for large-scale DNA-based biodiversity studies across a range of taxonomic groups using standardized metabarcoding approaches