Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Moral Distress Amongst American Physician Trainees Regarding Futile Treatments at the End of Life: A Qualitative Study.

BACKGROUND: Ethical challenges are common in end of life care; the uncertainty of prognosis and the ethically permissible boundaries of treatment create confusion and conflict about the balance between benefits and burdens experienced by patients. OBJECTIVE: We asked physician trainees in internal medicine how they reacted and responded to ethical challenges arising in the context of perceived futile treatments at the end of life and how these challenges contribute to moral distress. DESIGN: Semi-structured in-depth qualitative interviews. PARTICIPANTS: Twenty-two internal medicine residents and fellows across three American academic medical centers. APPROACH: This study uses systematic qualitative methods of data gathering, analysis and interpretation. KEY RESULTS: Physician trainees experienced significant moral distress when they felt obligated to provide treatments at or near the end of life that they believed to be futile. Some trainees developed detached and dehumanizing attitudes towards patients as a coping mechanism, which may contribute to a loss of empathy. Successful coping strategies included formal and informal conversations with colleagues and superiors about the emotional and ethical challenges of providing care at the end of life. CONCLUSIONS: Moral distress amongst physician trainees may occur when they feel obligated to provide treatments at the end of life that they believe to be futile or harmful.This study was funded by the Health Resources and Service Administration T32 HP10025-20 Training Grant, the Gates Cambridge Scholarship, Society of General Internal Medicine Founders Grant, and the Ho-Chiang Palliative Care Research Fellowship at the Johns Hopkins School of Medicine.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11606-015-3505-

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Pilates based core stability training in ambulant individuals with multiple sclerosis: protocol for a multi-centre randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.</p> <p>This study builds upon the pilot work undertaken in the case series study by implementing a powered randomised controlled study, with the aims of:</p> <p>1 Establishing the effectiveness of core stability training</p> <p>2 Comparing core stability training with standardised physiotherapy exercise</p> <p>3 Exploring underlying mechanisms of change associated with this intervention</p> <p>Methods</p> <p>This is a multi-centre, double blind, block randomised, controlled trial. Eligible participants will be recruited from 4 UK centres. Participants will be randomly allocated to one of three groups: Pilates based core stability training, standardised physiotherapy exercise or contract-relax relaxation sessions (placebo control). All will receive face to face training sessions over a 12 week period; together with a 15 minute daily home programme. All will be assessed by a blinded assessor before training, at the end of the 12 week programme and at 4 week follow-up. The primary outcome measure is the 10 metre timed walk. Secondary outcome measures are the MS walking Scale (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical Rating Scale to determine "Difficulty in carrying a drink when walking", and the Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound imaging of the abdominal muscles will be performed before and after intervention to assess changes in abdominal musculature at one of the four centres (Plymouth).</p> <p>Discussion</p> <p>This pragmatic trial will assess the effect of these exercise programmes on ambulatory people with MS. It may not be possible to extrapolate the conclusions to those who are non-ambulatory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01414725">NCT01414725</a></p

Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of down syndrome-related phenotypes

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish if this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder

H4 Histamine Receptors Mediate Cell Cycle Arrest in Growth Factor-Induced Murine and Human Hematopoietic Progenitor Cells

The most recently characterized H4 histamine receptor (H4R) is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs

Patterns of polymorphism and selection in the subgenomes of the allopolyploid Arabidopsis kamchatica

Genome duplication is widespread in wild and crop plants. However, little is known about genome-wide selection in polyploids due to the complexity of duplicated genomes. In polyploids, the patterns of purifying selection and adaptive substitutions may be affected by masking owing to duplicated genes or homeologs as well as effective population size. Here, we resequence 25 accessions of the allotetraploid Arabidopsis kamchatica, which is derived from the diploid species A. halleri and A. lyrata. We observe a reduction in purifying selection compared with the parental species. Interestingly, proportions of adaptive non-synonymous substitutions are significantly positive in contrast to most plant species. A recurrent pattern observed in both frequency and divergence–diversity neutrality tests is that the genome-wide distributions of both subgenomes are similar, but the correlation between homeologous pairs is low. This may increase the opportunity of different evolutionary trajectories such as in the HMA4 gene involved in heavy metal hyperaccumulation

Microstructural evolution and trace element mobility in Witwatersrand pyrite

Microstructural analysis of pyrite from a single sample of Witwatersrand conglomerate indicates a complex deformation history involving components of both plastic and brittle deformation. Internal deformation associated with dislocation creep is heterogeneously developed within grains, shows no systematic relationship to bulk rock strain or the location of grain boundaries and is interpreted to represent an episode of pyrite deformation that predates the incorporation of detrital pyrite grains into the Central Rand conglomerates. In contrast, brittle deformation, manifest by grain fragmentation that transects dislocation-related microstructures, is spatially related to grain contacts and is interpreted to represent post-depositional deformation of the Central Rand conglomerates. Analysis of the low-angle boundaries associated with the early dislocation creep phase of deformation indicates the operation of {100} slip systems. However, some orientation boundaries have geometrical characteristics that are not consistent with simple {100} deformation.These boundaries may represent the combination of multiple slip systems or the operation of the previously unrecognized {120} slip system. These boundaries are associated with order of magnitude enrichments in As, Ni and Co that indicate a deformation control on the remobilization of trace elements within pyrite and a potential slip system control on the effectiveness of fast-diffusion pathways. The results confirm the importance of grain-scale elemental remobilization within pyrite prior to their incorporation into the Witwatersrand gold-bearing conglomerates. Since the relationship between gold and pyrite is intimately related to the trace element geochemistry of pyrite, the results have implications for the application of minor element geochemistry to ore deposit formation, suggest a reason for heterogeneous conductivity and localized gold precipitation in natural pyrite and provide a framework for improving mineral processing

Loss of Metal Ions, Disulfide Reduction and Mutations Related to Familial ALS Promote Formation of Amyloid-Like Aggregates from Superoxide Dismutase

Mutations in the gene encoding Cu-Zn superoxide dismutase (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (FALS). Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1. Therefore, the formation of amyloid fibrils from human SOD1 was investigated. When agitated at acidic pH in the presence of low concentrations of guanidine or acetonitrile, metalated SOD1 formed fibrillar material which bound both thioflavin T and Congo red and had circular dichroism and infrared spectra characteristic of amyloid. While metalated SOD1 did not form amyloid-like aggregates at neutral pH, either removing metals from SOD1 with its intramolecular disulfide bond intact or reducing the intramolecular disulfide bond of metalated SOD1 was sufficient to promote formation of these aggregates. SOD1 formed amyloid-like aggregates both with and without intermolecular disulfide bonds, depending on the incubation conditions, and a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) formed amyloid-like aggregates at neutral pH under reducing conditions. ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Furthermore, the occurrence of amyloid-like aggregates per se does not depend on forming intermolecular disulfide bonds, and multiple forms of such aggregates can be produced from SOD1