Can remote testing for chronic kidney disease improve outcomes without widening existing health inequalities? A collaborative quality improvement project in primary care.

BACKGROUND: In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups. AIM: To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups. METHOD: 13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test. RESULTS: Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing. DISCUSSION: Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening.

'Palaeoshellomics' reveals the use of freshwater mother-of-pearl in prehistory.

The extensive use of mollusc shell as a versatile raw material is testament to its importance in prehistoric times. The consistent choice of certain species for different purposes, including the making of ornaments, is a direct representation of how humans viewed and exploited their environment. The necessary taxonomic information, however, is often impossible to obtain from objects that are small, heavily worked or degraded. Here we propose a novel biogeochemical approach to track the biological origin of prehistoric mollusc shell. We conducted an in-depth study of archaeological ornaments using microstructural, geochemical and biomolecular analyses, including 'palaeoshellomics', the first application of palaeoproteomics to mollusc shells (and indeed to any invertebrate calcified tissue). We reveal the consistent use of locally-sourced freshwater mother-of-pearl for the standardized manufacture of 'double-buttons'. This craft is found throughout Europe between 4200-3800 BCE, highlighting the ornament-makers' profound knowledge of the biogeosphere and the existence of cross-cultural traditions.

Identification of the earliest collagen- and plant-based coatings from Neolithic artefacts (Nahal Hemar cave, Israel).

Mortuary practices in human evolution record cognitive, social changes and technological innovations. The Neolithic Revolution in the Levant was a watershed in this domain that has long fascinated the archaeological community. Plaster modelled skulls are well known at Jericho and several other Neolithic sites, and in Nahal Hemar cave (Israel, ca. 8200 -7300 cal. BC) excavations yielded six unique human skulls covered with a black organic coating applied in a net pattern evoking a headdress. This small cave was used as storage for paraphernalia in the semi-arid area of the Judean desert and the dry conditions preserved other artefacts such as baskets coated with a similar dark substance. While previous analysis had revealed the presence of amino acids consistent with a collagen signature, in the present report, specific biomarkers were characterised using combined proteomic and lipid approaches. Basket samples yielded collagen and blood proteins of bovine origin (Bos genus) and a large sequence coverage of a plant protein charybdin (Charybdis genus). The skull residue samples were dominated by benzoate and cinnamate derivatives and triterpenes consistent with a styrax-type resin (Styrax officinalis), thus providing the earliest known evidence of an odoriferous plant resin used in combination with an animal product.

New chronology for Ksâr 'Akil (Lebanon) supports Levantine route of modern human dispersal into Europe.

Modern human dispersal into Europe is thought to have occurred with the start of the Upper Paleolithic around 50,000-40,000 y ago. The Levantine corridor hypothesis suggests that modern humans from Africa spread into Europe via the Levant. Ksâr 'Akil (Lebanon), with its deeply stratified Initial (IUP) and Early (EUP) Upper Paleolithic sequence containing modern human remains, has played an important part in the debate. The latest chronology for the site, based on AMS radiocarbon dates of shell ornaments, suggests that the appearance of the Levantine IUP is later than the start of the first Upper Paleolithic in Europe, thus questioning the Levantine corridor hypothesis. Here we report a series of AMS radiocarbon dates on the marine gastropod Phorcus turbinatus associated with modern human remains and IUP and EUP stone tools from Ksâr 'Akil. Our results, supported by an evaluation of individual sample integrity, place the EUP layer containing the skeleton known as "Egbert" between 43,200 and 42,900 cal B.P. and the IUP-associated modern human maxilla known as "Ethelruda" before ∼ 45,900 cal B.P. This chronology is in line with those of other Levantine IUP and EUP sites and demonstrates that the presence of modern humans associated with Upper Paleolithic toolkits in the Levant predates all modern human fossils from Europe. The age of the IUP-associated Ethelruda fossil is significant for the spread of modern humans carrying the IUP into Europe and suggests a rapid initial colonization of Europe by our species.

A functional variant in the core promoter of the CD95 cell death receptor gene predicts prognosis in acute promyelocytic leukemia.

Up to 15% of acute promyelocytic leukemia (APL) patients fail to achieve or maintain remission. We investigated a common G > A polymorphism at position -1377 (rs2234767) in the core promoter of the CD95 cell death receptor gene in 708 subjects with acute myeloid leukemia, including 231 patients with APL. Compared with the GG genotype, carrier status for the -1377A variant was associated with a significantly worse prognosis in APL patients. Carriers were more likely to fail remission induction (odds ratio = 4.22; 95% confidence interval, 1.41-12.6, P = .01), were more likely to die during the first 8 weeks of remission induction therapy (hazard ratio = 7.26; 95% confidence interval, 2.39-22.9, P = .0005), and had a significantly worse 5-year overall survival (odds ratio = 2.14; 95% confidence interval, 1.10-4.15, P = .03). The -1377A variant destroys a binding site for the SP1 transcriptional regulator and is associated with lower transcriptional activity of the CD95 promoter. Identifying patients at high risk of life-threatening events, such as remission induction failure, is a high priority in APL, especially because such events represent a major cause of death despite the introduction of differentiation therapy.

Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution.

For decades, cytogenetic studies have demonstrated that somatically acquired structural rearrangements of the genome are a common feature of most classes of human cancer. However, the characteristics of these rearrangements at sequence-level resolution have thus far been subject to very limited description. One process that is dependent upon somatic genome rearrangement is gene amplification, a mechanism often exploited by cancer cells to increase copy number and hence expression of dominantly acting cancer genes. The mechanisms underlying gene amplification are complex but must involve chromosome breakage and rejoining. We sequenced 133 different genomic rearrangements identified within four cancer amplicons involving the frequently amplified cancer genes MYC, MYCN, and ERBB2. The observed architectures of rearrangement were diverse and highly distinctive, with evidence for sister chromatid breakage-fusion-bridge cycles, formation and reinsertion of double minutes, and the presence of bizarre clusters of small genomic fragments. There were characteristic features of sequences at the breakage-fusion junctions, indicating roles for nonhomologous end joining and homologous recombination-mediated repair mechanisms together with nontemplated DNA synthesis. Evidence was also found for sequence-dependent variation in susceptibility of the genome to somatic rearrangement. The results therefore provide insights into the DNA breakage and repair processes operative in somatic genome rearrangement and illustrate how the evolutionary histories of individual cancers can be reconstructed from large-scale cancer genome sequencing.

Exercise and sleep.

This paper reviews the literature on the association between exercise and sleep. The epidemiological and experimental evidence for whether or not acute and chronic exercise promote sleep is discussed, as well as moderating factors and agendas for future directions of study. The expectation that exercise will benefit sleep can partly be attributed to traditional hypotheses that sleep serves energy conservation, body restoration or thermoregulatory functions, all of which have guided much of the research in this field. Exercise is a complex activity that can be beneficial to general well-being but may also stress the body. Differences in the exercise protocols studied (e.g. aerobic or anaerobic, intensity, duration) and interactions between individual characteristics (e.g. fitness, age and gender) cloud the current experimental evidence supporting a sleep-enhancing effect of exercise. In addition, the tendency to study changes in small groups of good sleepers may also underestimate the efficacy of exercise for promoting sleep. Athough only moderate effect sizes have been noted, meta-analytical techniques have shown that exercise increased total sleep time and delayed REM sleep onset (10 min), increased slow-wave sleep (SWS) and reduced REM sleep (2-5 min). The sleep-promoting efficacy of exercise in normal and clinical populations has yet to be established empirically.