Gebrukothuria profundus, a new genus and species of laetmogonid holothurian (Elasipodida, Laetmogonidae) from around the Crozet Plateau in the Southern Indian Ocean

A new genus and species of laetmogonid holothurian (Elasipodida, Laetmogonidae), collected from around the Crozet Plateau in the Southern Indian Ocean, is described. It differs from other members of the family in that the body wall lacks the wheel-shaped calcareous deposits completely. Instead only rods are present. The genus is also distinguished by the combination of other morphological characters lacking in other known genera: absence of circum-oral and ventrolateral papillae together with development of midventral tube feet. All other members of the family Laetmogonidae are known to have wheel-shaped deposits, therefore diagnosis of the family is refined

Using new and innovative technologies to assess clinical stage in early intervention youth mental health services: Evaluation study

Background: Globally there is increasing recognition that new strategies are required to reduce disability due to common mental health problems. As 75% of mental health and substance use disorders emerge during the teenage or early adulthood years, these strategies need to be readily accessible to young people. When considering how to provide such services at scale, new and innovative technologies show promise in augmenting traditional clinic-based services. Objective: The aim of this study was to test new and innovative technologies to assess clinical stage in early intervention youth mental health services using a prototypic online system known as the Mental Health eClinic (MHeC). Methods: The online assessment within the MHeC was compared directly against traditional clinician assessment within 2 Sydney-based youth-specific mental health services (headspace Camperdown and headspace Campbelltown). A total of 204 young people were recruited to the study. Eligible participants completed both face-to-face and online assessments, which were randomly allocated and counterbalanced at a 1-to-3 ratio. These assessments were (1) a traditional 45- to 60-minute headspace face-to-face assessment performed by a Youth Access Clinician and (2) an approximate 60-minute online assessment (including a self-report Web-based survey, immediate dashboard of results, and a video visit with a clinician). All assessments were completed within a 2-week timeframe from initial presentation. Results: Of the 72 participants who completed the study, 71% (51/72) were female and the mean age was 20.4 years (aged 16 to 25 years); 68% (49/72) of participants were recruited from headspace Camperdown and the remaining 32% (23/72) from headspace Campbelltown. Interrater agreement of participants’ stage, as determined after face-to-face assessment or online assessment, demonstrated fair agreement (kappa=.39, P\u3c.001) with concordance in 68% of cases (49/72). Among the discordant cases, those who were allocated to a higher stage by online raters were more likely to report a past history of mental health disorders (P=.001), previous suicide planning (P=.002), and current cannabis misuse (P=.03) compared to those allocated to a lower stage. Conclusions: The MHeC presents a new and innovative method for determining key clinical service parameters. It has the potential to be adapted to varied settings in which young people are connected with traditional clinical services and assist in providing the right care at the right tim

Nutrient stripping: the global disparity between food security and soil nutrient stocks

1. The Green Revolution successfully increased food production but in doing so created a legacy of inherently leaky and unsustainable agricultural systems. Central to this are the problems of excessive nutrient mining. If agriculture is to balance the needs of food security with the delivery of other ecosystem services, then current rates of soil nutrient stripping must be reduced and the use of synthetic fertilisers made more efficient. 2. We explore the global extent of the problem, with specific emphasis on the failure of macronutrient management (e.g. nitrogen, phosphorus) to deliver continued improvements in yield and the failure of agriculture to recognise the seriousness of micronutrient depletion (e.g. copper, zinc, selenium). 3. Nutrient removals associated with the relatively immature, nutrient-rich soils of the UK are contrasted with the mature, nutrient-poor soils of India gaining insight into the emerging issue of nutrient stripping and the long-term implications for human health and soil quality. Whilst nutrient deficiencies are rare in developed countries, micronutrient deficiencies are commonly increasing in less-developed countries. Increasing rates of micronutrient depletion are being inadvertently accomplished through increasing crop yield potential and nitrogen fertiliser applications. 4. Amongst other factors, the spatial disconnects caused by the segregation and industrialisation of livestock systems, between rural areas (where food is produced) and urban areas (where food is consumed and human waste treated) are identified as a major constraint to sustainable nutrient recycling. 5. Synthesis and applications. This study advocates that agricultural sustainability can only be accomplished using a whole-systems approach that thoroughly considers nutrient stocks, removals, exports and recycling. Society needs to socially and environmentally re-engineer agricultural systems at all scales. It is suggested that this will be best realised by national-scale initiatives. Failure to do so will lead to an inevitable and rapid decline in the delivery of provisioning services within agricultural systems

Genetic background modifies vulnerability to glaucoma related phenotypes in Lmx1b mutant mice

Variants in the LIM homeobox transcription factor 1-beta (LMX1B) gene predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. However, the effect of LMX1Bmutations varies widely between individuals. To better understand the mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed the Lmx1bV265D (also known as Lmx1bIcst ) allele onto the C57BL/6J (B6), 129/Sj (129), C3A/BLiA-Pde6b+ /J (C3H) and DBA/2J-Gpnmb+ (D2-G) mouse strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes in Lmx1bV265D/+ mutant mice. Mice of the B6 background were the most susceptible to developing abnormal IOP distribution, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands and corneal abnormalities) and glaucomatous nerve damage. By contrast, Lmx1bV265D mice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages and showed no detectable nerve damage. To identify genetic modifiers of susceptibility to Lmx1bV265D -induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulating Lmx1b-induced phenotypes, providing a panel of strains with different phenotypic severities and identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments

Effects of air pollution and the introduction of the London Low Emission Zone on the prevalence of respiratory and allergic symptoms in schoolchildren in East London: a sequential cross-sectional study

The adverse effects of traffic-related air pollution on children’s respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8–9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00–1.02), NO2 (1.03, 1.00–1.06), PM10 (1.16, 1.04–1.28) and PM2.5 (1.38, 1.08–1.78), all per μg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions

Validation of an algorithm using inpatient electronic health records to determine the presence and severity of cirrhosis in patients with hepatocellular carcinoma in England: an observational study.

OBJECTIVES:Outcomes in hepatocellular carcinoma (HCC) are determined by both cancer characteristics and liver disease severity. This study aims to validate the use of inpatient electronic health records to determine liver disease severity from treatment and procedure codes. DESIGN:Retrospective observational study. SETTING:Two National Health Service (NHS) cancer centres in England. PARTICIPANTS:339 patients with a new diagnosis of HCC between 2007 and 2016. MAIN OUTCOME:Using inpatient electronic health records, we have developed an optimised algorithm to identify cirrhosis and determine liver disease severity in a population with HCC. The diagnostic accuracy of the algorithm was optimised using clinical records from one NHS Trust and it was externally validated using anonymised data from another centre. RESULTS:The optimised algorithm has a positive predictive value (PPV) of 99% for identifying cirrhosis in the derivation cohort, with a sensitivity of 86% (95% CI 82% to 90%) and a specificity of 98% (95% CI 96% to 100%). The sensitivity for detecting advanced stage cirrhosis is 80% (95% CI 75% to 87%) and specificity is 98% (95% CI 96% to 100%), with a PPV of 89%. CONCLUSIONS:Our optimised algorithm, based on inpatient electronic health records, reliably identifies and stages cirrhosis in patients with HCC. This highlights the potential of routine health data in population studies to stratify patients with HCC according to liver disease severity

Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein

We recently described the Palate Lung Nasal Clone (PLUNC) family of proteins as an extended group of proteins expressed in the upper airways, nose and mouth. Little is known about these proteins, but they are secreted into the airway and nasal lining fluids and saliva where, due to their structural similarity with lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein, they may play a role in the innate immune defence. We now describe the generation and characterisation of novel affinity-purified antibodies to SPLUNC2, and use them to determine the expression of this, the major salivary gland PLUNC. Western blotting showed that the antibodies identified a number of distinct protein bands in saliva, whilst immunohistochemical analysis demonstrated protein expression in serous cells of the major salivary glands and in the ductal lumens as well as in cells of minor mucosal glands. Antibodies directed against distinct epitopes of the protein yielded different staining patterns in both minor and major salivary glands. Using RT-PCR of tissues from the oral cavity, coupled with EST analysis, we showed that the gene undergoes alternative splicing using two 5' non-coding exons, suggesting that the gene is regulated by alternative promoters. Comprehensive RACE analysis using salivary gland RNA as template failed to identify any additional exons. Analysis of saliva showed that SPLUNC2 is subject to N-glycosylation. Thus, our study shows that multiple SPLUNC2 isoforms are found in the oral cavity and suggest that these proteins may be differentially regulated in distinct tissues where they may function in the innate immune response

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen