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School bullying has been researched extensively, yet research on student bullying at university is still in the early stages and lacks valid measurement instruments. This paper outlines three studies conducted to develop a new scale to measure victimisation and perpetration at university (ultimately focusing on victimisation). Wider bullying literature from the school context and the workplace was consulted alongside an initial qualitative study exploring students’ perceptions of university bullying. For Study One, an exploratory factor analysis on data from a sample of UK university students (N=243) resulted in a reliable scale with four factors: (1) psychological victimisation, (2) physical act/trace victimisation, (3) social victimisation, and (4) direct verbal victimisation. After modification, Study Two tested the altered structure of the scale on a new sample of UK university students (N=304), finding two alternative two- and three-factor models. Study Three tested the competing models from the first two studies using confirmatory factor analysis (N=441), finding the four-factor structure to be the best model out of the three, but with the scale requiring further work. Although none of the fit indices’ statistics were ideal, this is the first attempt to design a higher education bullying scale based on a multi-phase approach, which shows potential as a useful tool for measuring victimisation following further research.

This article extends upon research about the politics of work and the digital mundane. It does this via an ethnographic study I undertook at a digital detox retreat located in North America. At this particular digital detox retreat, participants were invited to relinquish use of their digital devices, discussion of their professions and use of their 'real names' for a four-day period. I consider the pertinence of why a detox from the 'digital' and from 'work' were bound with one another and how the centrality that was accorded to 'work' at this retreat was tied in with a cultural framework of the digital mundane. I tie themes iterated in 'digital detox' literature with epistemological concerns, highlighting how the signifier of the 'digital' allows for an obscuring of high-tech politics and agendas.

Microbial overproduction of aromatic chemicals has gained considerable industrial interest and various metabolic engineering approaches have been employed in recent years to address the associated challenges. So far, most studies have used sugars (mostly glucose) or glycerol as the primary carbon source. In this study, we used ethylene glycol (EG) as the main carbon substrate. EG could be obtained from the degradation of plastic and cellulosic wastes. As a proof of concept,Escherichia coliwas engineered to transform EG into L-tyrosine, a valuable aromatic amino acid. Under the best fermentation condition, the strain produced 2 g/L L-tyrosine from 10 g/L EG at approximately 50% of the theoretical yield, outperforming glucose (the most common sugar feedstock) in the same experimental conditions. To prove the concept that EG can be converted into different aromatic chemicals,E. coliwas further engineered with a similar approach to synthesize other valuable aromatic chemicals, L-phenylalanine andp-coumaric acid. Finally, waste polyethylene terephthalate (PET) bottles were degraded using acid hydrolysis and the resulting monomer EG was transformed into L-tyrosine using the engineeredE. coli, yielding a comparable titer to that obtained using commercial EG. The strains developed in this study should be valuable to the community for producing valuable aromatics from EG.

Summary Background Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries. Methods In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs. Pooled relative risks were calculated for associations between ACEs and harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular disease, stroke, and respiratory disease. Country-level ACE prevalence was calculated using available data. Country-level population attributable fractions (PAFs) due to ACEs were generated and applied to 2019 estimates of disability-adjusted life-years. Financial costs (US$ in 2019) were estimated using an adapted human capital approach. Findings In most countries, interpersonal violence had the largest PAFs due to ACEs (range 14·7–53·5%), followed by harmful alcohol use (15·7–45·0%), illicit drug use (15·2–44·9%), and anxiety (13·9%–44·8%). Harmful alcohol use, smoking, and cancer had the highest ACE-attributable costs in many countries. Total ACE-attributable costs ranged from $0·1 billion (Montenegro) to $129·4 billion (Germany) and were equivalent to between 1·1% (Sweden and Turkey) and 6·0% (Ukraine) of nations' gross domestic products. Interpretation Availability of ACE data varies widely between countries and country-level estimates cannot be directly compared. However, findings suggest ACEs are associated with major health and financial costs across European countries. The cost of not investing to prevent ACEs must be recognised, particularly as countries look to recover from the COVID-19 pandemic, which interrupted services and education, and potentially increased risk factors for ACEs. Funding WHO Regional Office for Europe.

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

Background: There is increased emphasis on the national reporting of Routine Outcome Measures (ROMS) as a way of improving Child and Adolescent Mental Health Services (CAMHS). This data needs to be viewed in context so that reasons for outcome completion rates are understood and monitored over time. Method: We undertook an in-depth prospective audit of consecutive referrals accepted into the Bath and North East Somerset, Swindon and Wiltshire (BSW) CAMHS service from November 2017 to January 2018 ( n = 1074) and April to September 2019 ( n = 1172). Results: Across both audits 90% of those offered an appointment were seen with three quarters completing baseline ROMS. One in three were not seen again with around 30% still being open to the service at the end of each audit. Of those closed to the service, paired ROMS were obtained for 46% to 60% of cases. There were few changes in referral problems or complexity factors over time. Conclusion: Understanding the referral journey and the reasons for attrition will help to put nationally collected data in context and can inform and monitor service transformation over time.

Background Despite the importance of routinely assessing the outcomes of everyday practice, few studies have reported outcome metrics for child and adolescent mental health services (CAMHS). Aims Our aim is to investigate reliable change and recovery rates for treatment as usual, provided by one community CAMHS over two time periods. Method We prospectively audited accepted consecutive referrals from November 2017 to January 2018, and April to September 2019. Cases with paired outcomes were identified, and reliable change and recovery rates were calculated. Results Baseline outcome data were obtained for 672 (78.2%) and 744 (77.5%) young people in 2018 and 2019, respectively. Of eligible participants, 174 (59.2%) and 155 (45.7%) completed at least one follow-up outcome measure in 2018 and 2019, respectively. Pre- and post-test scores on the Revised Child Anxiety and Depression Scale (RCADS) and Strengths and Difficulties Questionnaire (SDQ) showed a reduction in symptoms. Total RCADS scores showed 21–25% of participants reliably improved, with 44–49% showing reliable improvement on one or more subscale. On the SDQ, 11 (15.5%) and 19 (25.3%) participants reported reliable improvement on at least one subscale in 2018 and 2019, respectively. Reliable recovery rates ranged from 48 to 51% for youth-completed and 40 to 42% for parent-completed RCADS. Conclusions Half of young people receiving treatment as usual from CAMHS reliably improved on at least one routine outcome measure subscale, improvement rates comparable with adult psychological therapies services. Our findings indicate that reliable change and recovery on subscale rather than total scores may be a better indication of outcomes.

This paper describes the key basic elements required for a successful multi-parametric MRI data acquisition in awake children with autism. The procedure was designed by taking into account methodological challenges arising from the acquisition of Resting State fMRI (RS fMRI) data, and factors such as cost, time, and staff availability. The ultimate aim was to prepare an imaging preparation protocol with high transferability to the whole autism spectrum, adaptable for use in a multi-site research with multiple time points. As part of a randomized pharmaco-intervention study, 31 children aged 4-10 years with Neurofibromatosis 1 and autism underwent MR imaging at baseline and end of intervention. The protocol consisted of tailored habituation instructions including gradual exposure to scanner noise, a social stories booklet, positive incentive strategies, and Play Therapy support. Success rate for initial acquisition was 71% for GABA+ MR spectroscopy at either location, 87% for perfusion, and 67% for diffusion assessment, and 71% for RS fMRI. Qualitative data indicated that 84% parents found the habituation protocol helpful. LAY SUMMARY: Here we describe a protocol for brain Magnetic Resonance Imaging (MRI) tailored for children with ASD to help reduce stress and avoid sedation during scanning. This procedure can make advanced medical imaging more accessible and promote a better MRI experience for families of children with ASD.

Purpose To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep) derived from DCE MRI were compared before and after treatment. Results Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI. Published under a CC BY 4.0 license.

Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

This article presents findings from the Housing and Ageing programme conducted in 2018 that investigated how the housing sector can effectively plan for an ageing population. The project took a transdisciplinary approach to focus on new, critical insights into the process of decision making concerning housing and ageing across Scotland, England and Wales. A ‘Serious Game’ methodology was developed that explored over 200 policy maker, practitioner and service user perspectives. This was used as a framework to capture priorities, decisions, negotiations and processes that indicate how a ‘sense of place’ and ‘place belonging’ can influence the development of suitable housing for older people. Key housing provision challenges identified were tackling inequality, preserving autonomy, in(ter)dependence, empowerment and accessibility. Such challenges need consideration when strategically planning for the future. The findings recommend placing housing at the heart of service integration to support the co-production of decisions that emphasise the importance of working together across boundaries within social policy, service and stakeholder groups. A place-based approach can support the perception that we are all stakeholders in ageing.

Gold nanoparticles (AuNPs) functionalized with polyethylene glycol (PEG) and peptide ligands are promising drug delivery vectors for use in cancer therapy. However, to control the interaction of the ligands with blood proteins and specific cell receptors, more needs to be known about the arrangement and properties of these grafted ligands. This issue is examined here principally with atomic force microscopy (AFM) for ligands grafted to both gold films and gold nanoparticles. Macro-level sessile drop measurements on the films indicate that, in dilute solutions, the PEG and peptide ligands exhibit similar affinity to the gold surface. However, at the nano-level, AFM experiments show differences in the morphology and cohesion of the adsorbed ligand films. Differences in tip/surface adhesion are also measured, indicative of variations of hydrophilicity for the top surface of these ligand films. Analysis of force-separation curves suggests a low packing density of PEG ligands. AFM investigations of functionalized AuNPs shows that the ligands improve dispersion and modify the tip/surface adhesion behaviour on the nanoparticles. However, AFM images of as-synthesised citric-capped and functionalized AuNPs gave similar nanoparticle diameters. Analysis of the AFM tip tapping on the AuNPs suggests that Tapping-AFM is not suitable for detection of low packing density ligands.

The radiosensitising efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein we have developed a AuNP preparation, stress-tested to provide effective protection from salt and serum mediated agglomeration. Furthermore, the core AuNP is co-functionalised with two biologically derived peptides designed to enhance endocytosis and promote endosomal escape, thus maximising intracellular AuNP surface area. In summary, these investigations demonstrate restored AuNP internalisation using the co-functionalised preparation that generated significant radiosensitisation, in both in vitro and in vivo models, at clinically viable treatment concentrations. Furthermore, we have identified an underpinning biological mechanism in the inherent radical scavenging capacity that could be used to predict radiosensitising efficacy.

Changing climate is affecting life all over the world. The loggerhead turtle (Caretta caretta) is one of the most vulnerable turtle species to climate change, particularly with regard to sex determination being affected by high temperatures in most nesting areas, such as the Cuban archipelago. As yet, species information is scarce for the Cuban archipelago as a whole. This study provides information about loggerheads in order to determine the possible effects of climate change on this species, especially in Guanahacabibes. We monitored 10 beaches along the southernmost coast of the Guanahacabibes Peninsula for 18 yrs (1998–2015), from May to September of each year, to determine nesting activity and density. Females were measured and tagged and the remigration interval was determined. Temporal variation was reflected in apparent peaks in reproductive activity on a biennial cycle. We found intraseasonal variation with the highest nesting activity in June, with a 15% increase in nesting activity in ...

Background Failure of drugs to cross the blood brain barrier (BBB) can be a major reason for treatment failure for patients with brain tumors. For most patients who don't respond to treatment, it is not known whether this is due to inadequate drug concentrations in the tumor, or due to drug resistance. Preliminary data suggest that low-dose radiotherapy may disrupt the BBB, and could facilitate increased drug delivery into brain tumors. Afatinib is a potent, irreversible inhibitor of EGFR / HER2 / HER4 and takes approximately 8 days to achieve steady-state concentrations in cancer patients. Aims CamBMT1 has been designed to investigate the delivery of afatinib into brain metastases and whether this might be enhanced by low dose-radiotherapy. Patient Population Key eligibility criteria Patients with operable brain metastases from breast or lung primaries for whom neurosurgical resection would be standard of care, as determined by the local multi-disciplinary team. ECOG PS 0, 1 or 2. Trial design After a phase 1b safety run- in, the phase 2 part of the trial randomises patients (n=60) into 3 pre-operative arms: Arm 1afatinib alone for 11 days, then neurosurgery on day 12Arm 2afatinib for 11 days plus a single 2 Gy fraction on day 10, then neurosurgery on day 12Arm 3afatinib for 11 days plus a single 4 Gy fraction on day 10, then neurosurgery on day 12 Primary endpoint: to compare steady-state afatinib concentration in resected brain metastases, following afatinib administered alone, or in combination with radiotherapy (2 Gy or 4 Gy). Afatinib concentrations are measured in the resected brain metastases and in plasma. Secondary endpoints: safety of afatinib administration in combination with radiotherapy; and multi-sequence MRI (optional) to detect changes in perfusion, vascular density, blood-brain-barrier permeability and interstitial pressure. Exploratory endpoints: molecular profiling of resected brain metastases, for comparison with paired primary lung and breast cancers; the establishment and study of patient-derived xenografts. Statistical methods With 20 patients randomised in each of 3 arms in the phase 2 part of CamBMT1, the trial has a power of 84% at a significance level of 20% (one-sided) to detect an increase in afatinib concentrations with targeted radiotherapy, measured as a Cohen's D (standardised mean difference) ≥0.5. Accrual By the end of q2 2016, phase 1b had nearly completed enrolment. The randomised phase 2 part of CamBMT1 is due to open by q4 2016 at additional Experimental Cancer Medicine Centres. Acknowledgments CamBMT1 is funded by Cancer Research UK, the Brain Tumour Charity and Boehringer-Ingelheim. Citation Format: Baird RD, Ramenatte N, Watts C, Jonson A, Jones L, Biggs H, Harrison E, Oberg I, Bullen G, Williams M, Qian W, Gilbert F, Jodrell D, Caldas C, Karabatsou K, Dunn L, Jena R, Whitfield G, Chalmers A, Jefferies S, Price S. Cambridge brain mets trial 1 (CamBMT1): A proof-of-principle phase 1b / randomised phase 2 study of afatinib penetration into brain metastases for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-01.

To create clinically useful gold nanoparticle (AuNP) based cancer therapeutics it is necessary to co-functionalize the AuNP surface with a range of moieties; e.g. Polyethylene Glycol (PEG), peptides and drugs. AuNPs can be functionalized by creating either a mixed monolayer by attaching all the moieties directly to the surface using thiol chemistry, or by binding groups to the surface by means of a bifunctional polyethylene glycol (PEG) linker. The linker methodology has the potential to enhance bioavailability and the amount of functional agent that can be attached. While there is a large body of published work using both surface arrangements independently, the impact of attachment methodology on stability, non-specific protein adsorption and cellular uptake is not well understood, with no published studies directly comparing the two most frequently employed approaches. This paper compares the two methodologies by synthesizing and characterizing PEG and Receptor Mediated Endocytosis (RME) peptide co-functionalized AuNPs prepared using both the mixed monolayer and linker approaches. Successful attachment of both PEG and RME peptide using the two methods was confirmed using Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy and gel electrophoresis. It was observed that while the 'as synthesized' citrate capped AuNPs agglomerated under physiological salt conditions, all the mixed monolayer and PEG linker capped samples remained stable at 1M NaCl, and were stable in PBS over extended periods. While it was noted that both functionalization methods inhibited non-specific protein attachment, the mixed monolayer samples did show some changes in gel electrophoresis migration profile after incubation with fetal calf serum. PEG renders the AuNP stable in-vivo however, studies with MDA-MB-231 and MCF 10A cell lines indicated that functionalization with PEG, blocks cellular uptake. It was observed that co-functionalization with RME peptide using both the mixed monolayer and PEG linker methods greatly enhanced cellular internalization compared to PEG capped AuNPs.

Marine turtles are challenging species to protect because they occur over large geographic scales. Tagging individual turtles at nesting beaches and foraging areas, and the resulting mark-recapture data sets have gradually enabled us to understand marine turtle migratory behaviour and dispersal. Within the Caribbean region, several turtle tagging projects have led to longer-term evaluations and assessments of connectivity. Thus, marine turtle mark-recapture data is important for developing conservation strategies at regional-scale. In this study, we analyse turtle tagging data from the Gulf of Venezuela to determine regional (Caribbean and Atlantic geographic level) and local (within the Gulf of Venezuela) links. To achieve this, we retrieved, compiled, and analysed multiple databases with records of marine turtles that were tagged and then recaptured in the Gulf of Venezuela. Sixty-six tag return records were evaluated, 43 from animals initially tagged outside of the Gulf of Venezuela and then recaptured inside, plus 23 records retrieved from turtles that were tagged and recaptured within the Gulf of Venezuela. We found evidence of connectivity between 12 different locations where initial tagging events occurred, eight from other feeding areas and four from nesting beaches. We described four different movement patterns for 23 turtles tagged and re-captured within the Gulf of Venezuela. Most of the recapture records we obtained occurred after the turtles were known, or presumed, to have been killed by local fishers. Hence, knowing patterns of dispersal and connectivity are crucial to improving local and regional conservation and threat mitigation.

We report herein on the synthesis of mixed monolayer gold nanoparticles (AuNPs) capped with both polyethylene glycol (PEG) and one of three peptides. Either a receptor-mediated endocytosis peptide, an endosomal escape pathway (H5WYG) peptide or the Nrp-1 targeting RGD peptide (CRGDK) labeled with FITC. All three peptides have a thiol containing cysteine residue which can be used to bind the peptides to the AuNPs. In order to investigate the influence of pH on peptide attachment, PEGylated AuNPs were centrifuged, the supernatant removed, and the nanoparticles were then re-suspended in a range of pH buffer solutions above, below and at the respective isoelectric points of the peptides before co-functionalization. Peptide attachment was investigated using dynamic light scattering, Ultra-violet visible spectroscopy (UV/Vis), FTIR and photo luminescence spectroscopy. UV/Vis analysis coupled with protein assay results and photoluminescence of the FITC tagged RGD peptide concluded that a pH of ∼8 optimized the cysteine binding and stability, irrespective of the peptide used.

While many migratory marine organisms converge at breeding areas, identifying for- aging strategies away from these reproductive sites can be challenging. Adult female green tur- tles Chelonia mydas regularly migrate thousands of kilometers between nesting and foraging areas, making it difficult to identify foraging habitats that support nesting populations and to understand their feeding strategies. In this study, we use stable isotope analysis to investigate the trophic ecology and spatial distribution of foraging green turtles in the Greater Caribbean. Fur- ther, we explore the possibility that adult green turtles, originally considered to be herbivores, may, like their counterparts in the Pacific Ocean, display carnivorous feeding strategies. The wide range of carbon and nitrogen isotope values in bulk epidermis observed in the nesting population at Tortuguero, Costa Rica, could indicate that these turtles feed over several trophic levels. Iso- topic niches — or the range of δ 13 C and δ 15 N values, which can be used as a proxy for ecological niche — varied among the 5 green turtle foraging aggregations sampled. Similarly, the isotopic composition of the primary producer Thalassia testudinum also varied substantially with geo- graphic location. However, compound-specific stable isotope analysis of amino acids (AA-CSIA) indicated that individuals in the nesting population with different bulk δ 15 N values feed at the same trophic position. The combined results suggest that spatial differences in the isotopic com- position of seagrass at the base of the food web, rather than differences in turtle foraging strategy, contribute to the isotopic variation in the nesting population. This study improves understanding of the foraging ecology of a highly dispersed and migratory species.

To create a clinically relevant gold nanoparticle (AuNP) treatment, the surface must be functionalized with multiple ligands such as drugs, antifouling agents and targeting moieties. However, attaching several ligands of differing chemistries and lengths, while ensuring they all retain their biological functionality remains a challenge. This review compares the two most widely employed methods of surface co-functionalization, namely mixed monolayers and hetero-bifunctional linkers. While there are numerous in vitro studies successfully utilizing both surface arrangements, there is little consensus regarding their relative merits. Animal and preclinical studies have demonstrated the effectiveness of mixed monolayer functionalization and while some promising in vitro results have been reported for PEG linker capped AuNPs, any potential benefits of the approach are not yet fully understood.

Management of the critically endangered hawksbill turtle in the Wider Caribbean (WC) has been hampered by knowledge gaps regarding stock structure. We carried out a comprehensive stock structure re-assessment of 11 WC hawksbill rookeries using longer mtDNA sequences, larger sample sizes (N = 647), and additional rookeries compared to previous surveys. Additional variation detected by 740 bp sequences between populations allowed us to differentiate populations such as Barbados-Windward and Guadeloupe (F (st) = 0.683, P < 0.05) that appeared genetically indistinguishable based on shorter 380 bp sequences. POWSIM analysis showed that longer sequences improved power to detect population structure and that when N < 30, increasing the variation detected was as effective in increasing power as increasing sample size. Geographic patterns of genetic variation suggest a model of periodic long-distance colonization coupled with region-wide dispersal and subsequent secondary contact within the WC. Mismatch analysis results for individual clades suggest a general population expansion in the WC following a historic bottleneck about 100 000-300 000 years ago. We estimated an effective female population size (N (ef)) of 6000-9000 for the WC, similar to the current estimated numbers of breeding females, highlighting the importance of these regional rookeries to maintaining genetic diversity in hawksbills. Our results provide a basis for standardizing future work to 740 bp sequence reads and establish a more complete baseline for determining stock boundaries in this migratory marine species. Finally, our findings illustrate the value of maintaining an archive of specimens for re-analysis as new markers become available.

Leatherback turtle (Dermochelys coriacea) nesting activity was monitored, individual movements via flipper tag recoveries and satellite telemetry were determined, and illegal egg collection was quantified at Tortuguero, Costa Rica from 1995 to 2006. Annual nest deposition was estimated at 199–1,623 nests per year; a Bayesian regression model suggests that leatherback nesting decreased by 67.8% between 1995 and 2006. Tag recaptures from fisheries bycatch and strandings have been reported from Cuba, Nicaragua, and the United States. Two leatherbacks were followed with satellite telemetry; 1 swam to Cuba and 1 moved into the northwest Atlantic Ocean. Minimum rates for illegal egg collection from 2000 to 2005 were estimated at 13.0%–21.5%.

Satellite transmitters were deployed on three green turtles, Chelonia mydas, and two hawksbill turtles, Eretmochelys imbricata, nesting in the Lesser Antilles islands, Caribbean, between 2005 and 2007 to obtain preliminary information about the inter-nesting, migratory and foraging habitats in the region. Despite the extremely small dataset, both year-round residents and migrants were identified; specifically, (1) two green turtles used local shallow coastal sites within 50 km of the nesting beach during all of their inter-nesting periods and then settled at these sites on completion of their breeding seasons, (2) one hawksbill turtle travelled 200 km westward before reversing direction and settling within 50 km of the original nesting beach and (3) one green and one hawksbill turtle initially nested at the proximate site, before permanently relocating to an alternative nesting site over 190 km distant. A lack of nesting beach fidelity was supported by flipper tag datasets for the region. Tagging datasets from 2002 to 2012 supported that some green and hawksbill individuals exhibit low fidelity to nesting beaches, whereas other females exhibited a high degree of fidelity (26 turtles tagged, 40.0 km maximum distance recorded from original nesting beach). Individual turtles nesting on St Eustatius and St Maarten appear to exhibit behavioural plasticity in their inter-nesting behaviour and post-nesting migration routes in the eastern Caribbean. The tracking and tagging data combined indicate that some of the green and hawksbill females that nest in the Lesser Antilles islands are year-round residents, whilst others may nest and forage at alternative sites. Thus, continued year-round protection of these islands and implementation of protection programmes in nearby islands could contribute towards safeguarding the green and hawksbill populations of the region.

During 1955–2003, flipper tags were attached to 46,983 green turtles and ten turtles were fitted with satellite transmitters at Tortuguero, Costa Rica. Eight satellite-tracked turtles stayed within 135 km of the beach and probably returned to nest after release. The internesting area is more extensive than previously documented. Post-nesting migration routes of satellite-tracked turtles varied. Seven turtles swam close to the coast and three turtles swam through oceanic waters before moving toward nearshore areas. Sea surface height anomaly maps indicate that oceanic movements were consistent with the southwestern Caribbean gyre. Circling and semi-circling turtles could have been disoriented but submergence and surface times suggest they may have been feeding in Sargassum sp. concentrations. Rapid post-nesting migrations (mean 2.2 km hr−1) ended on benthic feeding grounds in shallow waters (

Mission Rabies have developed an app both assisting the monitoring and direction of field vaccination teams, and recording project findings to enable research. WVS is building on this for use in varied projects from emergency disaster response to wildlife poaching and reducing traffic accidents involving donkeys.

The number and pattern of neuroblasts that initially segregate from the neuroectoderm in the early Drosophila embryo is identical in thoracic and abdominal segments. However, during late embryogenesis differences in the numbers of neuroblasts and in the extent of neuroblast proliferation arise between these regions. We show that the homeotic genes Ultrabithorax and abdominal-A regulate these late differences, and that misexpression of either gene in thoracic neuroblasts after segregation is sufficient to induce abdominal behaviour. However, in wild type embryos we only detect abdominal-A and Ultrabithorax proteins in early neuroblasts. Furthermore, transplantation experiments reveal that segment-specific behaviour is determined prior to neuroblast segregation. Thus, the segment-specific differences in neuroblast behaviour seem to be determined in the early embryo, mediated through the expression of homeotic genes in early neuroblasts, and executed in later programmes controlling neuroblast numbers and proliferation.

WVS is a UK charity that provides sustainable veterinary resources to assist animal charities, and works to help animals in need throughout the world.

Background Mammalian Delta-like 1 (Dlk-1) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch in vivo. Unlike mammals, Drosophila have a single Notch receptor allowing a simple in vivo assay for mammalian Dlk1 function. Results Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by Notch mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative Dlk1 isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target. Conclusion Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.

Purpose Open government data and access to public sector information is commonplace, yet little attention has focussed on the essential roles and responsibilities in practice of the information and records management professionals, who enable public authorities to deliver open data to citizens. This paper aims to consider the perspectives of open government and information practitioners in England on the procedural and policy implications of open data across local public authorities. Design/methodology/approach Using four case studies from different parts of the public sector in England (local government, higher education, National Health Service and hospital trust), the research involved master’s level students in the data collection and analysis, alongside academics, thus enhancing the learning experience of students. Findings There was little consistency in the location of responsibility for open government data policy, the range of job roles involved or the organisational structures, policy and guidance in place to deliver this function. While this may reflect the organisational differences and professional concerns, it makes it difficult to share best practice. Central government policy encourages public bodies to make their data available for re-use. However, local practice is very variable and perhaps understandably responds more to local organisational strategic and resource priorities. The research found a lack of common metadata standards for open data, different choices about which data to open, problems of data redundancy, inconsistency and data integrity and a wide variety of views on the corporate and public benefits of open data. Research limitations/implications The research is limited to England and to non-national public bodies and only draws data from a small number of case studies. Originality/value The research contributes to the debate about emerging issues around the complexities of open government data and its public benefits, contributing to the discussions around technology-enabled approaches to citizen engagement and governance. It offers new insights into the interaction between open data and public policy objectives, drawing on the experience of local public sectors in England.

Pressure to reduce maintenance costs in power utilities has resulted in growing interest in prognostic monitoring systems. Accurate prediction of the occurrence of faults and failures would result not only in improved system maintenance schedules but also in improved availability and system efficiency. The desire for such a system has driven research into the emerging field of prognostics for complex systems. At the same time there is a general move towards implementing high fidelity simulators of complex systems especially within the power generation field, with the nuclear power industry taking the lead. Whilst the simulators mainly function in a training capacity, the high fidelity of the simulations can also allow representative data to be gathered. Using simulators in this way enables systems and components to be damaged, run to failure and reset all without cost or danger to personnel as well as allowing fault scenarios to be run faster than real time. Consequently, this allows failure data to be gathered which is normally otherwise unavailable or limited, enabling analysis and research of fault progression in critical and high value systems. This paper presents a case study of utilising a high fidelity industrial Combined Cycle Gas Turbine (CCGT) simulator to generate fault data, and shows how this can be employed to build a prognostic system. Advantages and disadvantages of this approach are discussed.