N, P and K budgets for crop rotations on nine organic farms in the UK

On organic farms, where the importation of materials to build/maintain soil fertility is restricted, it is important that a balance between inputs and outputs of nutrients is achieved to ensure both short-term productivity and long-term sustainability. This paper considers different approaches to nutrient budgeting on organic farms and evaluates the sources of bias in the measurements and/or estimates of the nutrient inputs and outputs. The paper collates 88 nutrient budgets compiled at the farm scale in 9 temperate countries. All the nitrogen (N) budgets showed an N surplus (average 83.2 kg N ha-1 year-1). The efficiency of N use, defined as outputs/inputs, was highest (0.9) and lowest (0.2) in arable and beef systems respectively. The phosphorus (P) and potassium (K) budgets showed both surpluses and deficits (average 3.6 kg P ha-1 year-1, 14.2 kg K ha-1 year-1) with horticultural systems showing large surpluses resulting from purchased manure. The estimation of N fixation and quantities of nutrients in purchased manures may introduce significant errors in nutrient budgets. Overall, the data illustrate the diversity of management systems in place on organic farms, and suggest that used together with soil analysis, nutrient budgets are a useful tool for improving the long-term sustainability of organic systems

Adaptation of Left Ventricular Twist Mechanics in Exercise-Trained Children Is Only Evident after the Adolescent Growth Spurt.

The extent of structural cardiac remodeling in response to endurance training is maturity dependent. In adults, this structural adaptation is often associated with the adaptation of left ventricular (LV) twist mechanics. For example, an increase in LV twist often follows an expansion in end-diastolic volume, whereas a reduction in twist may follow a thickening of the LV walls. While structural cardiac remodeling has been shown to be more prominent post-peak height velocity (PHV), it remains to be determined how this maturation-dependent structural remodeling influences LV twist. Therefore, we aimed to (1) compare LV twist mechanics between trained and untrained children pre- and post-PHV and (2) investigate how LV structural variables relate to LV twist mechanics pre- and post-PHV. Left ventricular function and morphology were assessed (echocardiography) in endurance-trained and untrained boys (n = 38 and n = 28, respectively) and girls (n = 39 and n = 34, respectively). Participants were categorized as either pre- or post-PHV using maturity offset to estimate somatic maturation. Pre-PHV, there were no differences in LV twist or torsion between trained and untrained boys (twist: P = .630; torsion: P = .382) or girls (twist: P = .502; torsion: P = .316), and LV twist mechanics were not related with any LV structural variables (P > .05). Post-PHV, LV twist was lower in trained versus untrained boys (P = .004), with torsion lower in trained groups, irrespective of sex (boys: P < .001; girls: P = .017). Moreover, LV torsion was inversely related to LV mass (boys: r = -0.55, P = .001; girls: r = -0.46, P = .003) and end-diastolic volume (boys: r = -0.64, P < .001; girls: r = -0.36, P = .025) in both sexes. A difference in LV twist mechanics between endurance-trained and untrained cohorts is only apparent post-PHV, where structural and functional remodeling were related

Relative Equilibria in the Four-Vortex Problem with Two Pairs of Equal Vorticities

We examine in detail the relative equilibria in the four-vortex problem where two pairs of vortices have equal strength, that is, \Gamma_1 = \Gamma_2 = 1 and \Gamma_3 = \Gamma_4 = m where m is a nonzero real parameter. One main result is that for m > 0, the convex configurations all contain a line of symmetry, forming a rhombus or an isosceles trapezoid. The rhombus solutions exist for all m but the isosceles trapezoid case exists only when m is positive. In fact, there exist asymmetric convex configurations when m < 0. In contrast to the Newtonian four-body problem with two equal pairs of masses, where the symmetry of all convex central configurations is unproven, the equations in the vortex case are easier to handle, allowing for a complete classification of all solutions. Precise counts on the number and type of solutions (equivalence classes) for different values of m, as well as a description of some of the bifurcations that occur, are provided. Our techniques involve a combination of analysis and modern and computational algebraic geometry

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. Results We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society