In Situ Contaminated Sediments Project – Work Package 1A Report

Project aims Defra is seeking to understand the magnitude of risks (e.g. to aquatic ecology and human health) or impacts (e.g. on the way that water bodies are managed) posed by contaminated sediment in England, as part of its work towards meeting its environmental objectives. In the context of this project, in-situ contaminated sediment is defined as: Chemically contaminated sediment within the water column, bed, banks and floodplain of a surface water body that has been transported alongside the normal sediment load and deposited by fluvial or coastal processes. This project considers the risk posed by non-agricultural diffuse pollution sources in England that result in the contamination of in-situ sediments (for example, contamination from toxic metals, hydrocarbons and surfactants). The scope encompasses both freshwater and marine sediments in England and extends to one nautical mile off-shore (the seaward limit of coastal waters under the Water Framework Directive (WFD) in England). Previous national strategies, including the 2007 Defra UK Strategy for Managing Contaminated Marine Sediments (CDMS), focussed on characterising the risks associated with contaminated sediments in the marine environment. However, while extensive research has been carried out in many locations (including as part of WFD implementation studies) and for particular sources of contamination (e.g. historical metal mining; Environment Agency, 2008) there has not been a comprehensive overview of sediment contamination on a national scale. This project seeks to build on the existing evidence base, drawing together information on the freshwater environment to complement that already gathered for marine waters. This project’s overall aim is to provide a sound evidence base on the contamination of in-situ sediments, which can underpin the development of tools and methods that will help Defra, the Environment Agency and other bodies engaged in regulation and protection of water quality

At what age do normal weight Canadian children become overweight adults? Differences according to sex and metric

Background: The prevalence of overweight and obesity doubles between adolescence and young adulthood. However, the exact age, and appropriate metric to use, to identify when overweight develops is still debated. Aim: To examine the age of onset of overweight by sex and four metrics: body mass index (BMI), fat mass (%FM), waist circumference (WC) and waist-to-height ratio (WHtR). Methods: Between 1991 and 2017, serial measures of body composition, were taken on 237 (108 males) individuals (aged 8 to 40 years of age). Hierarchical random effects models were used to develop growth curves. Curves were compared to BMI, %FM and WC overweight age and sex-specific cut-points. Results: In males the BMI growth curve crossed the cut-point at 22.0 years compared to 23.5 and 26.5 years for WHtR and %FM respectively; WC cut-off were not reached until 36 years. In females the BMI growth curve, crossed the overweight cut-point at 21.5 years compared to 14.2 years for %FM and at 21.9 and 27.5 years for WC and WHtR respectively. Conclusions: Overweight onset occurs during young adulthood with the exception of WC in males. BMI in males and %FM in females were the metric identifying overweight the earliest

Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

IMPORTANCE: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations. These patients include those in whom the pathognomonic features of axonal spheroids and pigmented microglia have been found. Achieving a genetic diagnosis in these patients is important to our understanding of this disorder. OBJECTIVE: To genetically characterize a group of patients with typical features of ALSP who do not carry CSF1R mutations. DESIGN, SETTING, AND PARTICIPANTS: In this case series study, 5 patients from 4 families were identified with clinical, radiologic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequencing. Data were collected between May 2014 and September 2015 and analyzed between September 2015 and February 2016. MAIN OUTCOMES AND MEASURES: Focused exome sequencing was used to identify candidate variants. Family studies, long-range polymerase chain reaction with cloning, and complementary DNA sequencing were used to confirm pathogenicity. RESULTS: Of these 5 patients, 4 were men (80%); mean age at onset of ALSP was 29 years (range, 15-44 years). Biallelic mutations in the alanyl-transfer (t)RNA synthetase 2 (AARS2) gene were found in all 5 patients. Frameshifting and splice site mutations were common, found in 4 of 5 patients, and sequencing of complementary DNA from affected patients confirmed that the variants were loss of function. All patients presented in adulthood with prominent cognitive, neuropsychiatric, and upper motor neuron signs. Magnetic resonance imaging in all patients demonstrated a symmetric leukoencephalopathy with punctate regions of restricted diffusion, typical of ALSP. In 1 patient, brain biopsy demonstrated axonal spheroids and pigmented microglia, which are the pathognomonic signs of ALSP. CONCLUSIONS AND RELEVANCE: This work indicates that mutations in the tRNA synthetase AARS2 gene cause a recessive form of ALSP. The CSF1R and AARS2 proteins have different cellular functions but overlap in a final common pathway of neurodegeneration. This work points to novel targets for research and will lead to improved diagnostic rates in patients with adult-onset leukoencephalopathy

The prevalence of injection-site reactions with disease-modifying therapies and their effect on adherence in patients with multiple sclerosis: an observational study

<p>Abstract</p> <p>Background</p> <p>Interferon beta (IFNβ) and glatiramer acetate (GA) are administered by subcutaneous (SC) or intramuscular (IM) injection. Patients with multiple sclerosis (MS) often report injection-site reactions (ISRs) as a reason for noncompliance or switching therapies. The aim of this study was to compare the proportion of patients on different formulations of IFNβ or GA who experienced ISRs and who switched or discontinued therapy because of ISRs.</p> <p>Methods</p> <p>The Swiss MS Skin Project was an observational multicenter study. Patients with MS or clinically isolated syndrome who were on the same therapy for at least 2 years were enrolled. A skin examination was conducted at the first study visit and 1 year later.</p> <p>Results</p> <p>The 412 patients enrolled were on 1 of 4 disease-modifying therapies for at least 2 years: IM IFNβ-1a (n = 82), SC IFNβ-1b (n = 123), SC IFNβ-1a (n = 184), or SC GA (n = 23). At first evaluation, ISRs were reported by fewer patients on IM IFNβ-1a (13.4%) than on SC IFNβ-1b (57.7%; <it>P </it>< 0.0001), SC IFNβ-1a (67.9%; <it>P </it>< 0.0001), or SC GA (30.4%; <it>P </it>= not significant [NS]). No patient on IM IFNβ-1a missed a dose in the previous 4 weeks because of ISRs, compared with 5.7% of patients on SC IFNβ-1b (<it>P </it>= 0.044), 7.1% of patients on SC IFNβ-1a (<it>P </it>= 0.011), and 4.3% of patients on SC GA (<it>P </it>= NS). Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy. Similar patterns were observed at 1 year.</p> <p>Conclusions</p> <p>Patients on IM IFNβ-1a had fewer ISRs and were less likely to switch therapies than patients on other therapies. This study may have implications in selecting initial therapy or, for patients considering switching or discontinuing therapy because of ISRs, selecting an alternative option.</p

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Brokering Gender Empowerment in Energy Access in the Global South

How do energy professionals in the Global South facilitate the brokerage of gender equity and empowerment in energy access? Energy sector professionals, including planners and members of non-governmental organisations (NGOs), are crucial development actors in off-grid contexts. They operate at the intersection between grassroots-level energy access in off-grid household and community buildings and overarching policy frameworks. However, despite their central role, the relationship between their professional practices and gender empowerment in energy access has received little attention. This paper investigates ‘energy brokers’ across Ghana, India, Nigeria and Pakistan based on interviews (n = 86). Subsequent thematic analysis explores these energy brokers’ overarching understandings of gender equity and empowerment, their agency, and brokering practices for energy access (including in relation to emerging energy technologies). Analysis shows ‘differentiated brokerage’ in that energy professionals from the NGOs and the delivery sectors are often better positioned to broker gender equity and women’s empowerment in energy access. However, linkages between equitable access and empowerment need to be better understood, especially at the ‘top’ and go beyond women’s economic productivity. Women’s participation across supply chains of emerging energy-access technology, in energy governance and as energy brokers needs strengthening. Practice relevance Energy professionals occupy an important ‘middle’ position and can help to create changes to overcome gender bias in access to energy. They facilitate the brokerage (understandings, agency and practices) of gender equity and empowerment in energy access in off-grid contexts, including household and community buildings. The evidence from this study shows the performance of energy professionals is critical in facilitating women’s empowerment in energy access. Key recommendations are: (1) energy professionals at the top need to recognise differentiated brokerage across the grassroots–policy spectrum to better identify and equip key actors; (2) energy brokers need to move beyond gender neutrality and economic participation acting on the breadth of women’s empowerment, including psychological dimensions; and (3) women’s participation across energy system transitions needs to be strengthened, with regard to energy supply chains, energy governance and as energy brokers

PAPSS2‐related brachyolmia : clinical and radiological phenotype in 18 new cases

Brachyolmia is a skeletal dysplasia characterized by short spine‐short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short‐spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over‐faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi‐parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under‐recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester