Relationships between nitrogen cycling microbial community abundance and composition reveal the indirect effect of soil pH on oak decline

Tree decline is a global concern and the primary cause is often unknown. Complex interactions between fluctuations in nitrogen (N) and acidifying compounds have been proposed as factors causing nutrient imbalances and decreasing stress tolerance of oak trees. Microorganisms are crucial in regulating soil N available to plants, yet little is known about the relationships between soil N-cycling and tree health. Here, we combined high-throughput sequencing and qPCR analysis of key nitrification and denitrification genes with soil chemical analyses to characterise ammonia-oxidising bacteria (AOB), archaea (AOA) and denitrifying communities in soils associated with symptomatic (declining) and asymptomatic (apparently healthy) oak trees (Quercus robur and Q. petraea) in the United Kingdom. Asymptomatic trees were associated with a higher abundance of AOB that is driven positively by soil pH. No relationship was found between AOA abundance and tree health. However, AOA abundance was driven by lower concentrations of NH4+, further supporting the idea of AOA favouring lower soil NH4+ concentrations. Denitrifier abundance was influenced primarily by soil C:N ratio, and correlations with AOB regardless of tree health. These findings indicate that amelioration of soil acidification by balancing C:N may affect AOB abundance driving N transformations, reducing stress on declining oak trees

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies

Background: Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor-outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct-level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. Methods: Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A-levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. Results: Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. Conclusions: Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, ‘dark matter’ and ‘dark energy’ are posited to balance various theoretical equations, so medical student selection must also have its ‘dark variance’, whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills

How many steps/day are enough? for adults

Physical activity guidelines from around the world are typically expressed in terms of frequency, duration, and intensity parameters. Objective monitoring using pedometers and accelerometers offers a new opportunity to measure and communicate physical activity in terms of steps/day. Various step-based versions or translations of physical activity guidelines are emerging, reflecting public interest in such guidance. However, there appears to be a wide discrepancy in the exact values that are being communicated. It makes sense that step-based recommendations should be harmonious with existing evidence-based public health guidelines that recognize that "some physical activity is better than none" while maintaining a focus on time spent in moderate-to-vigorous physical activity (MVPA). Thus, the purpose of this review was to update our existing knowledge of "How many steps/day are enough?", and to inform step-based recommendations consistent with current physical activity guidelines. Normative data indicate that healthy adults typically take between 4,000 and 18,000 steps/day, and that 10,000 steps/day is reasonable for this population, although there are notable "low active populations." Interventions demonstrate incremental increases on the order of 2,000-2,500 steps/day. The results of seven different controlled studies demonstrate that there is a strong relationship between cadence and intensity. Further, despite some inter-individual variation, 100 steps/minute represents a reasonable floor value indicative of moderate intensity walking. Multiplying this cadence by 30 minutes (i.e., typical of a daily recommendation) produces a minimum of 3,000 steps that is best used as a heuristic (i.e., guiding) value, but these steps must be taken over and above habitual activity levels to be a true expression of free-living steps/day that also includes recommendations for minimal amounts of time in MVPA. Computed steps/day translations of time in MVPA that also include estimates of habitual activity levels equate to 7,100 to 11,000 steps/day. A direct estimate of minimal amounts of MVPA accumulated in the course of objectively monitored free-living behaviour is 7,000-8,000 steps/day. A scale that spans a wide range of incremental increases in steps/day and is congruent with public health recognition that "some physical activity is better than none," yet still incorporates step-based translations of recommended amounts of time in MVPA may be useful in research and practice. The full range of users (researchers to practitioners to the general public) of objective monitoring instruments that provide step-based outputs require good reference data and evidence-based recommendations to be able to design effective health messages congruent with public health physical activity guidelines, guide behaviour change, and ultimately measure, track, and interpret steps/day

Perivascular spaces in the brain:anatomy, physiology and pathology

Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance

The 894G>T variant in the endothelial nitric oxide synthase gene and spina bifida risk

The 894G>T single nucleotide polymorphism (SNP) in the endothelial NOS (NOS3) gene, has recently been associated with embryonic spina bifida risk. In this study, a possible association between the NOS3 894G>T SNP and spina bifida risk in both mothers and children in a Dutch population was examined using both a case-control design and a transmission disequilibrium test (TDT). Possible interactions between the NOS3 894G>T SNP and the MTHFR 677C>T SNP, elevated plasma homocysteine, and decreased plasma folate concentrations were also studied. The NOS3 894TT genotype did not increase spina bifida risk in mothers or children (OR 1.50, 95%CI 0.71–3.19 and OR 1.78, 95%CI 0.75–4.25, respectively). The TDT demonstrated no preferential transmission of the NOS3 894T allele (Χ2 = 0.06, P = 0.81). In combination with the MTHFR 677TT genotype or elevated plasma homocysteine concentrations, the NOS3 894GT/TT genotype increased maternal spina bifida risk (OR 4.52, 95%CI 1.55–13.22 and OR 3.38, 95%CI 1.46–7.84, respectively). In our study population, the NOS3 894GT/TT genotype might be a risk factor for having a spina bifida affected child in mothers who already have an impaired homocysteine metabolism

Can flash glucose monitoring improve glucose management for Aboriginal and Torres Strait Islander peoples with type 2 diabetes? A protocol for a randomised controlled trial

Background: Aboriginal and Torres Strait Islander peoples are disproportionately impacted by type 2 diabetes. Continuous glucose monitoring (CGM) technology (such as Abbott Freestyle Libre 2, previously referred to as Flash Glucose Monitoring) offers real-time glucose monitoring that is convenient and easy to use compared to self-monitoring of blood glucose (SMBG). However, this technology’s use is neither widespread nor subsidised for Aboriginal and Torres Strait Islander peoples with type 2 diabetes. Building on existing collaborations with a national network of Aboriginal and Torres Strait Islander communities, this randomised controlled trial aims to assess the effect of CGM compared to SMBG on (i) haemoglobin A1c (HbA1c), (ii) achieving blood glucose targets, (iii) reducing hypoglycaemic episodes and (iv) cost-effective healthcare in an Aboriginal and Torres Strait Islander people health setting. Methods: This is a non-masked, parallel-group, two-arm, individually randomised, controlled trial (ACTRN12621000753853). Aboriginal and Torres Strait Islander adults with type 2 diabetes on injectable therapy and HbA1c ≥ 7.5% (n = 350) will be randomised (1:1) to CGM or SMBG for 6 months. The primary outcome is change in HbA1c level from baseline to 6 months. Secondary outcomes include (i) CGM-derived metrics, (ii) frequency of hypoglycaemic episodes, (iii) health-related quality of life and (iv) incremental cost per quality-adjusted life year gained associated with the CGM compared to SMBG. Clinical trial sites include Aboriginal Community Controlled Organisations, Aboriginal Medical Services, primary care centres and tertiary hospitals across urban, rural, regional and remote Australia. Discussion: The trial will assess the effect of CGM compared to SMBG on HbA1c for Aboriginal and Torres Strait Islander people with type 2 diabetes in Australia. This trial could have long-term benefits in improving diabetes management and providing evidence for funding of CGM in this population. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12621000753853. Registered on 15th June 2021

High resolution ancient sedimentary DNA shows that alpine plant diversity is associated with human land use and climate change.

The European Alps are highly rich in species, but their future may be threatened by ongoing changes in human land use and climate. Here, we reconstructed vegetation, temperature, human impact and livestock over the past ~12,000 years from Lake Sulsseewli, based on sedimentary ancient plant and mammal DNA, pollen, spores, chironomids, and microcharcoal. We assembled a highly-complete local DNA reference library (PhyloAlps, 3923 plant taxa), and used this to obtain an exceptionally rich sedaDNA record of 366 plant taxa. Vegetation mainly responded to climate during the early Holocene, while human activity had an additional influence on vegetation from 6 ka onwards. Land-use shifted from episodic grazing during the Neolithic and Bronze Age to agropastoralism in the Middle Ages. Associated human deforestation allowed the coexistence of plant species typically found at different elevational belts, leading to levels of plant richness that characterise the current high diversity of this region. Our findings indicate a positive association between low intensity agropastoral activities and precipitation with the maintenance of the unique subalpine and alpine plant diversity of the European Alps