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High quality radiation therapy requires highly accurate and precise dose delivery. MR-guided radiotherapy (MRgRT), integrating an MRI scanner with a linear accelerator, offers excellent quality images in the treatment room without subjecting patient to ionizing radiation. MRgRT therefore provides a powerful tool for intrafraction motion management. This paper summarizes different sources of intrafraction motion for different disease sites and describes the MR imaging techniques available to visualize and quantify intrafraction motion. It provides an overview of MR guided motion management strategies and of the current technical capabilities of the commercially available MRgRT systems. It describes how these motion management capabilities are currently being used in clinical studies, protocols and provides a future outlook. [ABSTRACT FROM AUTHOR]

Poor preoperative sleep quality and impaired sleep continuity may heighten acute postoperative pain intensity and increase analgesic consumption, with negative implications for recovery, mental and physical health. The main objective of the current review was to investigate the relationship between preoperative sleep disturbance and acute postoperative pain control. Four electronic databases were systematically searched from inception to December 2023. Two reviewers screened articles, extracted data, and assessed risk of bias for each included study. The search identified 26 prospective cohort studies and 3 retrospective cohort studies (16104 participants). Of the 29 included studies, 23 focused on preoperative insomnia symptoms, and three studies each focused on preoperative objective sleep continuity or sleep-disordered breathing. Meta-analysis, based on five studies with 1226 participants, showed that clinically significant preoperative insomnia symptoms were associated with moderate to severe pain intensity on the first postoperative day (odds ratio 2.69 (95 % confidence interval 2.03–3.57), p < 0.0001). Qualitative analysis showed relatively robust associations between preoperative insomnia symptoms, impaired sleep continuity and poorer acute, as well as subacute, postoperative pain control. Findings related to obstructive sleep apnea syndrome were mixed. Given that insomnia is a potentially modifiable risk factor, interventions targeting sleep prior to surgery may improve postoperative pain control. [ABSTRACT FROM AUTHOR]

Background: Asthma is common, resulting in 53 million emergency department (ED) visits annually. Little is known about variation in cost and quality of ED asthma care.Study Objective: We sought to describe variation in costs and 7-day ED revisit rates for asthma care across EDs. Our primary objective was to test for an association between ED costs and the likelihood of a 7-day revisit for another asthma exacerbation.Methods: We used the 2014 Florida State Emergency Department Database to perform an observational study of ED visits by patients ≥18 years old with a primary diagnosis of asthma that were discharged home. We compared patient and hospital characteristics of index ED discharges with and without 7-day revisits, then tested the association between ED revisits and index ED costs. Multilevel regression was performed to account for hospital-level clustering.Results: In 2014, there were 54,060 adult ED visits for asthma resulting in discharge, and 1667 (3%) were associated with an asthma-related ED revisit within 7 days. Median cost for an episode of ED asthma care was $597 with an interquartile range of $371-980. After adjusting for both patient and hospital characteristics, lack of insurance was associated with higher odds of revisit (OR 1.42, 95% CI 1.18-1.71), while private insurance, female gender, and older age were associated with lower odds of revisit. Hospital costs were not associated with ED revisits (OR = 1.00; 95% CI 1.00-1.00).Conclusion: Hospital costs associated with ED asthma visits vary but are not associated with odds of ED revisit. [ABSTRACT FROM AUTHOR]

Addition of nitrogen (N) to forest soil may alter wood decay rates and fungal community structure and richness. In a northern Sweden Pinus sylvestris L. forest, two levels of ammonium nitrate were applied annually from 1971 to 2008. In 2007 we initiated an investigation into wood decay (assessed through mass loss) and fungal responses using stakes of trembling aspen (Populus tremuloides Michx.) and loblolly pine (Pinus taeda L.) wood installed at different soil depths in plots where zero (N0), low (34 kg; N1), or high (68 kg; N2) levels of N were applied. Stakes were located either horizontally on the surface of the organic horizon, at the interface between the mineral and organic horizons, or vertically in the mineral soil. For litter and mineral soil, fertilizer treatment was not significant for any soil chemical or physical property. Overall, pine and aspen wood stake mass loss was less than 35 % three years after deployment. Notably, the N1 treatment had the most pronounced effect on wood decay, and significantly accelerated aspen decomposition at the organic horizon surface in the second and third years. Analysis of fungal DNA extracted from the wood stakes revealed fluctuations in fungal richness and community composition depending upon stake location and duration since deployment. Fungal richness was notably higher in surface aspen stakes under N0 and N1 treatments and in surface pine stakes under N0 in the second year, though richness generally decreased with time as stake decay increased. Fungal community composition also varied by stake location and time since deployment. These results indicate that prolonged N addition can affect fungal richness, which may in turn affect wood decomposition rates. Further research is needed to clarify the nature and persistence of long-term soil N-addition effects on organic matter decomposition and soil microbial communities. • Fungi and wood decay • Long-term N fertilization increased fungal richness on aspen wood stakes. • Pine wood stakes had the highest fungal richness under no N fertilization. • Wood decay was highest under the moderate N fertilization treatment. [ABSTRACT FROM AUTHOR]

Ecological restoration is a key part of the global solution to help repair damaged ecosystems and moderate climate change. However, there are enormous challenges to contemporary restoration. Solutions that integrate western science and traditional ecological knowledge offer great opportunities to overcome these challenges. Partnerships with Indigenous Ranger programs can assist with solutions to some of the age-old restoration challenges. Managing and caring for a living and dynamic Country is at the heart of wellbeing for all Indigenous Peoples. The act of participating in restoration activities On Country assists with connecting to Country, healing people and Country. We describe the development of a successful partnership between western science and Indigenous traditional knowledge via a collaborative Malgana Aboriginal Corporation Ranger program that included On Country workshop-based knowledge sharing in north-west Western Australia, with a focus on seagrass restoration. Field-based restoration workshops helped people reconnect with Country through two-way knowledge sharing. Additional benefits of the partnership included education and preservation of Malgana language, educating western scientists and general public about Malgana culture, and adapting and field trialling seagrass restoration methods for Gathaagudu. Restoration can be successfully implemented through partnerships that share western science and traditional ecological knowledge. • Ecological restoration is a key global solution to help moderate climate change and conserve biodiversity. • Partnerships between western scientists and Aboriginal Traditional Custodians can lead to improved restoration outcomes. • Field-based restoration-focused workshops helped people reconnect with Country through two-way knowledge sharing. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics.Methods: A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed.Results: Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only.Discussion: There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE. [ABSTRACT FROM AUTHOR]

The dorsal intercarpal ligament (DICL) is crucial for carpal stability and is frequently associated with injuries to other carpal ligaments, notably the scapholunate and lunotriquetral interosseous ligaments. Although isolated DICL injuries are uncommon, they can manifest as ligament avulsions, bony avulsions, or attenuations from chronic injury. Surgical repair of isolated DICL tears may be necessary when conservative management fails. We have previously described the first isolated DICL avulsion from the scaphoid dorsal ridge, suggesting an arthroscopic repair via the radiocarpal joint. This article details a repair technique through the midcarpal joint. [Display omitted] [ABSTRACT FROM AUTHOR]

Connective tissue serves a role beyond mere spatial filling. Furthermore, there is increasing evidence that connective tissue plays an important role in the pathogenesis of conditions such as carpal tunnel syndrome (CTS). According to our hypothesis, the median nerve (MN) is surrounded by a system of connective tissue distal to the pronator teres and extending up to, and including, the carpal tunnel. To visualize the connective tissue surrounding the median nerve, we dissected the forearms of 15 body donors from pronator teres to the carpal tunnel, created plastination slices stained with Periodic Acid-Schiff (PAS), and injected ink into the seen spaces. We verified our findings with a segmentational analysis of radiological data of 10 healthy individuals. We macroscopically describe the median nerve´s system of connective tissue (MC) distal to the pronator teres and up to and including the carpal tunnel. This system creates, connects, and separates spaces. At least from the pronator teres to the carpal tunnel it also creates subspaces from proximal to distal. For the MC, we established a mean cross-sectional area of 153.1 mm2 (SD=37.15) in the carpal tunnel. The median nerve consistently resides at the center of this MC, which further connects to flexor muscles of the forearm, and to the radius bone. In the carpal tunnel, the MC creates subspaces inside. There, it also acts as the outermost internal layer enveloping flexor tendons, and the MN. The term MC does not negate but orders the existence of other "connectives", like subsynovial connective tissue, endo-, epi- or perineuria, epimysia, periostea, or peritendinea, to a hierarchy related to the median nerve. Diseases of the MN are common. Knowing the anatomy of the MC and how it relates to MN function may help clinicians recognize and understand conditions like CTS. [ABSTRACT FROM AUTHOR]

IgE causes anaphylaxis in type I hypersensitivity diseases by activating degranulation of effector cells such as mast cells and basophils. The mechanisms that control IgE activity and prevent anaphylaxis under normal conditions are still enigmatic. We aimed to unravel how anti-IgE autoantibodies are induced and we aimed to understand their role in regulating serum IgE level and allergic anaphylaxis. We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analyzed the effect of those antibodies on serum kinetics and their in vitro and in vivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera. Immunization of mice with IgE-immune complexes induced glycan-specific anti-IgE autoantibodies. The anti-IgE autoantibodies prevented effector cell sensitization, reduced total IgE serum levels, protected mice from passive and active IgE sensitization, and resulted in cross-protection against different allergens. Furthermore, glycan-specific anti-IgE autoantibodies were present in sera from subjects with allergy and subjects without allergy. In conclusion, this study provided the first evidence that in the murine model, the serum level and anaphylactic activity of IgE may be downregulated by glycan-specific IgG anti-IgE autoantibodies. [ABSTRACT FROM AUTHOR]

Stakeholder participation in healthcare curriculum design is an important aspect of higher education with stakeholders including students, staff members, clinical partners, healthcare organisations, patients and members of the public. Significantly, student co-creation, of the curriculum, has become increasingly important. Yet there is limited research which addresses how to engage this group in design processes. This paper represents the first phase of a three stage action research spiral whereby the authors evaluated the use of a novel tool for curriculum design processes, anonymised crowdsourcing. This initial phase was open to all students enrolled on an undergraduate diagnostic radiography programme in the UK. To confirm the reliability of the crowdsource design an established eight point crowdsourcing verification tool was applied. Twenty-three unique ideas were generated by participants, 40 comments made and 173 votes cast. Inductive analysis of the comments generated five themes. These included: the role of technology enhanced learning; simulation activities; patient focused curriculum; mental wealth (resilience) authentic assessment approaches. An evaluation of those who had and had not engaged highlighted areas of improvement for the administration of the second and third iterations which will include a wider pool of participants. This study from a single programme offers lessons for others wishing to adopt and develop this approach elsewhere. Several ideas elicited by the crowdsource have been considered by the curriculum design team and will be implemented in the 2020 curriculum thus demonstrating the impact on local education practice of this research approach. [ABSTRACT FROM AUTHOR]

Adiabatic blanking of advanced high-strength steels with initial flow stresses above 1300 MPa is investigated. The blanked edge exhibits a unique S-shape. Localisation and properties of shear bands are analysed in shear-compression tests. A shear-compression stress state before separation leads to blanked edges without fracture zone, burr, or roll-over. Numerical modelling predicts the characteristic shape of the blanked edge satisfactorily. Physics-based models reveal that the strain rate sensitivity of the workpiece material is the key parameter affecting the width and the surface hardness of the shear band. Stress triaxiality and strain rate sensitivity determine the minimum size of radii in complex parts blanked without failure. [ABSTRACT FROM AUTHOR]

• Quantitative estimation of beta + emitters production rates with the GEANT4 simulation toolkit at 55, 65, 120 and 220 MeV. • Comparison of the 55 MeV simulated production rates to data from Dendooven et al. • Comparison of the simulated β + activity profiles to those extracted from experimental data. • Study of 12N which, from the work of Dendooven et al., is known to be the main isotope for in-beam PET. The purpose of this work is to evaluate the precision with which the GEANT4 toolkit simulates the production of β + emitters relevant for in-beam and real-time PET in proton therapy. An important evolution in proton therapy is the implementation of in-beam and real-time verification of the range of protons by measuring the correlation between the activity of β + and dose deposition. For that purpose, it is important that the simulation of the various β + emitters be sufficiently realistic, in particular for the 12N short-lived emitter that is required for efficient in-beam and real-time monitoring. The GEANT4 toolkit was used to simulate positron emitter production for a proton beam of 55 MeV in a cubic PMMA target and results are compared to experimental data. The three β + emitters with the highest production rates in the experimental data (11C, 15O and 12N) are also those with the highest production rate in the simulation. Production rates differ by 8 % to 174 %. For the 12N isotope, the β + spatial distribution in the simulation shows major deviations from the data. The effect of the long range (of the order of 20 mm) of the β + originating from 12N is also shown and discussed. At first order, the GEANT4 simulation of the β + activity presents significant deviations from the data. The need for precise cross-section measurements versus energy below 30 MeV is of first priority in order to evaluate the feasibility of in-beam and real-time PET. [ABSTRACT FROM AUTHOR]

Mercury and selenium were measured for first time in the endangered species whale shark (Rhyncodon typus) from two areas of the Gulf of California, Bahía Los Angeles (BLA) and Bahía La Paz (LAP) using dermal biopsies of seventy specimens. Additionally, nineteen zooplankton samples from LAP were analysed. Concentrations (ng/g, wet weight (ww)) in biopsies of BLA ranged from 1 to 40 for Hg and 100 to 680 for Se; while in LAP varied from 1 to 9 for Hg and 11 to 850 for Se. A positive correlation was found for Hg in BLA males biopsies with length. Hg and Se concentrations in the zooplankton from LAP were 1.6 ± 1.8 and 770 ± 930 ng/g, respectively. Hg biomagnification factor ranged from 0.8 to 5.3 in sharks. A molar excess of Se over Hg was found in the biopsies and the zooplankton. Unlabelled Image • Hg and Se were determined in 70 biopsies of whale shark from the Gulf of California. • A molar excess of Se over Hg was found in the biopsies and the zooplankton. • Hg showed a negative correlation with total length in males from Bahía Los Ángeles. • Probably Hg biomagnification factor in whale shark is >1.0. [ABSTRACT FROM AUTHOR]

Cat allergy in human subjects is usually caused by the major cat allergen Fel d 1 and is found in approximately 10% of the Western population. Currently, there is no efficient and safe therapy for cat allergy available. Allergic patients usually try to avoid cats or treat their allergy symptoms. We developed a new strategy to treat Fel d 1–induced allergy in human subjects by immunizing cats against their own major allergen, Fel d 1. A conjugate vaccine consisting of recombinant Fel d 1 and a virus-like particle derived from the cucumber mosaic virus containing the tetanus toxin–derived universal T-cell epitope tt830-843 (CuMV TT) was used to immunize cats. A first tolerability and immunogenicity study, including a boost injection, was conducted by using the Fel-CuMV TT vaccine alone or in combination with an adjuvant. The vaccine was well tolerated and had no overt toxic effect. All cats induced a strong and sustained specific IgG antibody response. The induced anti–Fel d 1 antibodies were of high affinity and exhibited a strong neutralization ability tested both in vitro and in vivo. A reduction in the endogenous allergen level and a reduced allergenicity of tear samples, were observed. Vaccination of cats with Fel-CuMV TT induces neutralizing antibodies and might result in reduced symptoms of allergic cat owners. Both human subjects and animals could profit from this treatment because allergic cat owners would reduce their risk of developing chronic diseases, such as asthma, and become more tolerant of their cats, which therefore could stay in the households and not need to be relinquished to animal shelters. [ABSTRACT FROM AUTHOR]

Robust, regular and integrated evidence on the environment and its relationship with the economy and human well-being is needed to deliver effective environmental policy. This paper highlights the role the United Nations System of Environmental-Economic Accounting Ecosystem Accounting (SEEA EA) can play in delivering this 'policy-ready' evidence. We demonstrate this using forest ecosystems as a policy theme of high international concern, via structured reviews of evidence needs for two case studies: the EU Green Deal; and, Liberia's forest policy framework. The EU Green Deal case study highlights evidence gaps in a proposed regulation on environmental-economic accounting that are policy relevant and could be met using the SEEA EA. These gaps concern old growth forest extent, carbon storage, biodiversity, water regulation and erosion control ecosystem services. The Liberia case study highlights evidence needs for policy concerning the extent of natural forests important for biodiversity and ecosystem services of timber provisioning, global climate regulation and non-wood forest products, which could be met by the SEEA EA. Starting from these policy perspectives is critical to establishing evidence needs that the SEEA EA should be compiled to meet. This address concerns that the compilation of SEEA EA accounts has often been an exercise in best organising available data, rather than a demand driven exercise in response to policy evidence needs. We argue that addressing clear policy needs is essential for the SEEA EA to deliver on its potential to mainstream the many benefits from natural, as well as managed forests, into development planning. • Illustrates possibilities and advantages of using environmental-economic accounting to deliver 'policy-ready' evidence. • Presents a structured approach for linking environmental-economic accounting to policy evidence needs. • EU Green Deal case study highlighting evidence gaps for forest policy in proposed environmental-economic accounts. • Liberia case study highlighting evidence needs for national forest policy environmental-economic accounts can meet. [ABSTRACT FROM AUTHOR]

Sex-bias in gene expression is a widespread mechanism for controlling the development of phenotypes that differ between males and females. Most studies on sex-bias in gene expression have focused on species that exhibit traditional sex-roles (male-male competition and female parental care). By contrast the Syngnathid fishes (sea horses, pipefish, and sea dragons) are a group of organisms where many species exhibit male brooding and sex-role reversal (female-female competition for mates and paternal parental care), and little is known about how patterns of sex-bias in gene expression vary in species with sex-role reversal. Here we utilize RNA-seq technology to investigate patterns of sex-bias in gene expression in the brain tissue of the Gulf Pipefish ( Syngnathus scovelli ) a species that exhibits sex-role reversal. Gene expression analysis identified 73 sex-biased genes, 26 genes upregulated in females and 47 genes upregulated in males. Gene ontology analysis found 52 terms enriched for the sex-biased genes in a wide range of pathways suggesting that multiple functions and processes differ between the sexes. We focused on two areas of interest: sex steroids/hormones and circadian rhythms, both of which exhibited sex-bias in gene expression, and are known to influence sexual development in other species. Lastly, the work presented herein contributes to a growing body of genome data available for the Syngnathids, increasing our knowledge on patterns of gene expression in these unusual fishes. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) is rapidly becoming an alternative to surgery for the treatment of early-stage non-small cell lung cancer patients. Lung SBRT is administered in a hypo-fractionated, conformal manner, delivering high doses to the target. To avoid normal-tissue toxicity, it is crucial to limit the exposure of nearby healthy organs-at-risk (OAR). Current image-guided radiotherapy strategies for lung SBRT are mostly based on X-ray imaging modalities. Although still in its infancy, magnetic resonance imaging (MRI) guidance for lung SBRT is not exposure-limited and MRI promises to improve crucial soft-tissue contrast. Looking beyond anatomical imaging, functional MRI is expected to inform treatment decisions and adaptations in the future. This review summarises and discusses how MRI could be advantageous to the different links of the radiotherapy treatment chain for lung SBRT: diagnosis and staging, tumour and OAR delineation, treatment planning, and inter- or intrafractional motion management. Special emphasis is placed on a new generation of hybrid MRI treatment devices and their potential for real-time adaptive radiotherapy. [ABSTRACT FROM AUTHOR]

Biosphere reserves, designated under UNESCO’s Man and the Biosphere (MAB) Programme, are now regarded as key mechanisms to achieve global imperatives such as the Sustainable Development Goals. The concept of biosphere reserves has evolved significantly from the 1970s to include a larger number of functions and zones, as well as the inclusion of stakeholders in governance, as codified in the 1996 Statutory Framework for the World Network of Biosphere Reserves. Its implementation has led to the re-territorialisation of 66 biosphere reserves, as they have been extended beyond the protected areas that form their ‘core areas’. One example is Wester Ross in northwest Scotland. This region has been nationally recognised for its high biodiversity and landscape values since the late 1940s, and a small biosphere reserve was established in 1976. In the current decade, as required by the MAB Programme, this biosphere reserve was extended to over 100 times its original area through a participatory process which is described in detail. Following re-territorialisation, this biosphere reserve, like others, both represents opportunities and faces challenges. These are discussed with regard to four requirements: effective communication, stakeholder engagement, participatory governance, and funding. [ABSTRACT FROM AUTHOR]

Background Body contouring surgery after massive weight loss remains a fast growing field due to the rising number of postbariatric surgery patients, and it can improve patients’ quality of life substantially. Patient expectations in these procedures are very high, but only little is known as to whether these procedures have a long lasting influence on body image, patient satisfaction, and quality of life. Setting University hospital, Austria. Methods We evaluated 40 consecutive female patients who underwent a lower body lift between 2009 and 2013. Patients took part in a prospective pre- and postoperative questionnaire survey inquiring about their psychological and physical wellbeing. The mean postoperative follow up interval was 61±14 months. We used 2 validated (Body Image Questionnaire and Body Appraisal Inventory) and one self-designed questionnaires (body lift follow-up questionnaire). The postoperative response rate in January 2016 was 72.5%. Results Lower body lift significantly reduced dismissive body ratings and increased long-term feelings of attractiveness and self-esteem, and significantly reduced discomfort associated with excess skin. Patients reported feeling happier, more attractive, and more self-confident. The procedure enhanced their physical wellbeing, even years after surgery. Conclusion Lower body lift satisfied patients’ expectations and improved long-term quality of life. Therefore, it is an essential component in the treatment of patients who have experienced massive weight loss. [ABSTRACT FROM AUTHOR]

A number of distinct methodologies are available for determining the oxygen isotope composition of minerals and rocks, these include laser-assisted fluorination, secondary ion mass spectrometry (SIMS) and UV laser ablation. In this review we focus on laser-assisted fluorination, which currently achieves the highest levels of precision available for oxygen isotope analysis. In particular, we examine how results using this method have furthered our understanding of early-formed differentiated meteorites. Due to its rapid reaction times and low blank levels, laser-assisted fluorination has now largely superseded the conventional externally-heated Ni “bomb” technique for bulk analysis. Unlike UV laser ablation and SIMS analysis, laser-assisted fluorination is not capable of focused spot analysis. While laser fluorination is now a mature technology, further analytical improvements are possible via refinements to the construction of sample chambers, clean-up lines and the use of ultra-high resolution mass spectrometers. High-precision oxygen isotope analysis has proved to be a particularly powerful technique for investigating the formation and evolution of early-formed differentiated asteroids and has provided unique insights into the interrelationships between various groups of achondrites. A clear example of this is seen in samples that lie close to the terrestrial fractionation line (TFL). Based on the data from conventional oxygen isotope analysis, it was suggested that the main-group pallasites, the howardite eucrite diogenite suite (HEDs) and mesosiderites could all be derived from a single common parent body. However, high precision analysis demonstrates that main-group pallasites have a Δ 17 O composition that is fully resolvable from that of the HEDs and mesosiderites, indicating the involvement of at least two parent bodies. The range of Δ 17 O values exhibited by an achondrite group provides a useful means of assessing the extent to which their parent body underwent melting and isotopic homogenization. Oxygen isotope analysis can also highlight relationships between ungrouped achondrites and the more well-populated groups. A clear example of this is the proposed link between the evolved GRA 06128/9 meteorites and the brachinites. The evidence from oxygen isotopes, in conjunction with that from other techniques, indicates that we have samples from approximately 110 asteroidal parent bodies (∼60 irons, ∼35 achondrites and stony-iron, and  ∼15 chondrites) in our global meteorite collection. However, compared to the likely size of the original protoplanetary asteroid population, this is an extremely low value. In addition, almost all of the differentiated samples (achondrites, stony-iron and irons) are derived from parent bodies that were highly disrupted early in their evolution. High-precision oxygen isotope analysis of achondrites provides some important insights into the origin of mass-independent variation in the early Solar System. In particular, the evidence from various primitive achondrite groups indicates that both the slope 1 (Y&R) and CCAM lines are of primordial significance. Δ 17 O differences between water ice and silicate-rich solids were probably the initial source of the slope 1 anomaly. These phases most likely acquired their isotopic composition as a result of UV photo-dissociation of CO that took place either in the early solar nebula or precursor giant molecular cloud. Such small-scale isotopic heterogeneities were propagated into larger-sized bodies, such as asteroids and planets, as a result of early Solar System processes, including dehydration, aqueous alteration, melting and collisional interactions. There is increasing evidence that chondritic parent bodies accreted relatively late compared to achondritic asteroids. This may account for the fact that apart from a few notable exceptions’ such as the aubrite-enstatite chondrite association, known chondrite groups could not have been the parents to the main achondrite groups. [ABSTRACT FROM AUTHOR]

As climate change and population growth, among other factors, put pressure on traditional water supplies, alternative sources of water are increasingly being used to supplement demand, particularly for non-potable applications. Stormwater from urban catchments can be harvested and treated to supply irrigation demands of public green spaces such as parks, reserves and sporting grounds. Operation of such systems often requires several pumping stages between multiple storage ponds, which can result in a significant amount of energy use and also increases the complexity of the operations. In many water supply systems, demand rates and patterns are determined by when consumers choose to use water and how much they use, thus the demands constrain the system operation. For irrigation of public green spaces, however, the operators can prescribe when water should be used at each demand point, and thus the demand pattern is a choice rather than a constraint. This paper discusses how harvested stormwater systems with multiple pumping stages can simulated as multiple ‘sub-systems’ in order to better understand the hydraulics and better formulate the corresponding optimization problem. A case study site from Australia that utilizes harvested stormwater for non-potable irrigation demands is used to demonstrate the simulation approach. Simulating the case study in smaller ‘sub-systems’ has highlighted the need for better pump and tank sizing for the system, and has then informed the optimization problem formulation. [ABSTRACT FROM AUTHOR]

The optimization of pump operations has been widely studied, as it can decrease operational and maintenance costs and can reduce greenhouse gas emissions caused by the energy consumption from fossil fueled electricity sources. However, only the optimization of pump scheduling (where pumps are controlled based on times) and the optimization of simple controls (where pumps are controlled based on one condition only, e.g. the level of one tank) were previously able to be used in the EPANET2 toolkit. This paper uses a modified version of the hydraulic solver EPANET2 that enables rule-based controls (i.e. controls based on more than one condition) to be automatically changed by an optimization algorithm. This modification is particularly useful in cases where the pump operations need to be decided based on multiple conditions: typical examples are the cases where the pumps are controlled according to the water levels of multiple tanks or when both tank levels and time of day are taken into account to reduce the pumping in the peak tariff period. The new toolkit, called ETTAR (EPANET2 Toolkit to Alter Rules), is applied to a large case study, where different types of pump operations will be tested. Results show that the optimization of rule-based controls can decrease operational costs while guaranteeing robust pump controls. [ABSTRACT FROM AUTHOR]

Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since some of the clinical trials proceeded without a study in large animals. No animal studies or clinical trials completely restored IVD structure. However, results suggest cause for optimism. In light of the fact that patients primarily seek medical care for back pain, attenuating local inflammation should be a priority in benchmarks for success. Clinicians generally agree that short-term back pain should be treated conservatively. When interventions are considered, the ideal therapy should also be minimally invasive and concurrent with other procedures such as discography or discectomy. Restoration of tissue structure and preservation of spinal motion are desirable. [ABSTRACT FROM AUTHOR]

Summary Background Long-chain polyunsaturated fatty acids (LCPUFA), particularly n-3 LCPUFA, play a central role in neuronal growth and the development of the human brain. Fish is the main dietary source of n-3 LCPUFA. To assess the relation between fish consumption, estimated dietary n-3 LCPUFA intake and cognition and behaviour in childhood in a multi-centre European sample. Methods Children from 2 European studies, CHOP and NUHEAL, were assessed at 8 and 7.5 years of age, respectively. Different outcomes of neuropsychological development (assessed with the standardized NUTRIMENTHE Neuropsychological Battery (NNB) consisting of 15 subtests) were related with outcomes from a food-frequency questionnaire (FFQ) focussing on the consumption of fish. Results A total of 584 children completed the FFQ and the neuropsychological tests. We found no associations with calculated DHA or EPA intakes for any of the neuropsychological domains. Children who consumed 2 fish meals per week including one of fatty fish, showed no substantive differences in the cognitive domains from the children who did not. However negative associations with fatty fish consumption were found for social problems (p = 0.019), attention problems (p = 0.012), rule-breaking problems (p = 0.019) and aggressive behaviour problems (p = 0.032). No association was observed with internalizing problems. Higher levels of externalizing problems (p = 0.018) and total problems (p = 0.018) were associated with eating less fatty fish. Conclusions Children who consumed 2 fish meals per week including one of fatty fish were less likely to show emotional and behavioural problems than those who did not. [ABSTRACT FROM AUTHOR]

Introduction Tumoral calcinosis (TC) is a rare disorder defined by hyperphosphatemia and ectopic calcifications in various locations. The most common form of TC is associated with disorders such as renal insufficiency, hyperparathyroidism, or hypervitaminosis D. The primary (hereditary) TC is caused by inactivating mutations in either the fibroblast growth factor 23 ( FGF23) , the GalNAc transferase 3 ( GALNT3) or the KLOTHO ( KL) gene. Presentation of case We report here a case of secondary TC in end-stage renal disease. The patient was on regular hemodialysis and presented with severe painful soft-tissue calcifications around her left hip and shoulder that had been increasing over the last two years. Initially, she was treated with dietary phosphate restriction and phosphate binders. Because of high phosphate blood levels, which were not yet managed with dialysis and medical therapy, a subtotal parathyroidectomy (sP) was performed. This approach demonstrated significant response. Three months after surgery a rapid regression of the tumors was observed. Disscusion Regardless of the etiology, the two types of TC do not differ in their radiologic or histopathologic presentations but need to be diagnosed correctly to initiate targeted and effective treatment. Considering the primary TC, primary treatment is early and complete surgical excision. In case of secondary TC surgical excision of the tumoral masses should be avoid because of extensive complications. These patients benefit from sP. Conclusion After initial conservative therapy chronic kidney disease patients with TC might benefit from sP to avoid prolonged suffering and potential mutilations. [ABSTRACT FROM AUTHOR]

Sleep and pain are critical homeostatic systems that interact in a bidirectional manner. Complaints of sleep disturbance are ubiquitous among patients with chronic pain disorders, and conversely, patients with persistent insomnia symptoms commonly report suffering from chronic pain. Sleep deprivation paradigms demonstrate that partial or complete sleep loss induce hyperalgesia, possibly due to shared mechanistic pathways including neuroanatomic and molecular substrates. Further, chronic pain conditions and sleep disturbances are intertwined through comorbidities, which together cause detrimental psychological and physical consequences. This critical review examines 29 polysomnography studies to evaluate whether nonmalignant chronic pain patients, as compared to controls, show differences in objective measures of sleep continuity and sleep architecture. Whereas these controlled studies did not reveal a consistent pattern of objective sleep disturbances, alterations of sleep continuity were commonly reported. Alterations of sleep architecture such as increases in light sleep or decreases in slow-wave sleep were less commonly reported and findings were mixed and also inconsistent. Methodological flaws were identified, which complicated interpretation and limited conclusions; hence, recommendations for future research are suggested. Knowledge of abnormalities in the sleep process has implications for understanding the pathophysiology of chronic pain conditions, which might also direct the development of novel intervention strategies. [ABSTRACT FROM AUTHOR]

Background Chronic hepatitis C is a major cause of liver-associated mortality caused by decompensated cirrhosis and hepatocellular carcinoma. With the approval of sofosbuvir, therapeutic efficacy has markedly increased. Early changes in non-invasive biomarkers of liver fibrosis under effective antiviral therapy are widely unknown. Aim To evaluate early changes of fibrosis markers determined by enhanced liver fibrosis (ELF) scores and liver stiffness measurement (FibroScan ® ) in patients treated with sofosbuvir. Methods A total of 32 hepatitis C patients treated prospectively with sofosbuvir were included. The ELF-panel and FibroScan measurements were performed at baseline, week 4, end-of-treatment and 12 weeks thereafter. Results Antiviral therapy resulted in a biochemical and virological response within 4 weeks. Sustained virological response rate at 12-week follow-up (SVR12) was 93.8%; there was a significantly decrease from baseline to 12-week post-treatment follow-up in ELF (10.00 vs. 9.37; p = 0.007) and FibroScan (8.0 vs. 6.8 kPa; p = 0.016) measurements, indicating improvement of the dynamics of liver fibrosis. Conclusion We observed a rapid decrease in non-invasive fibrosis markers measured by ELF-scores and FibroScan in hepatitis C-infected patients receiving sofosbuvir treatment. These initial results need to be histologically confirmed by liver biopsy in the future. [ABSTRACT FROM AUTHOR]

Background & Aims Cancer therapies are being developed based on our ability to direct T cells against tumor antigens. Glypican-3 (GPC3) is expressed by 75% of all hepatocellular carcinomas (HCC), but not in healthy liver tissue or other organs. We aimed to generate T cells with GPC3-specific receptors that recognize HCC and used them to eliminate GPC3-expressing xenograft tumors grown from human HCC cells in mice. Methods We used mass spectrometry to obtain a comprehensive peptidome from GPC3-expressing hepatoma cells after immune-affinity purification of human leukocyte antigen (HLA)-A2 and bioinformatics to identify immunodominant peptides. To circumvent GPC3 tolerance resulting from fetal expression, dendritic cells from HLA-A2−negative donors were cotransfected with GPC3 and HLA-A2 RNA to stimulate and expand antigen-specific T cells. Results Peptide GPC3 367 was identified as a predominant peptide on HLA-A2. We used A2-GPC3 367 multimers to detect, select for, and clone GPC3-specific T cells. These clones bound the A2-GPC3 367 multimer and secreted interferon-γ when cultured with GPC3 367 , but not with control peptide-loaded cells. By genomic sequencing of these T-cell clones, we identified a gene encoding a dominant T-cell receptor. The gene was cloned and the sequence was codon optimized and expressed from a retroviral vector. Primary CD8 + T cells that expressed the transgenic T-cell receptor specifically bound GPC3 367 on HLA-A2. These T cells killed GPC3-expressing hepatoma cells in culture and slowed growth of HCC xenograft tumors in mice. Conclusions We identified a GPC3 367 -specific T-cell receptor. Expression of this receptor by T cells allows them to recognize and kill GPC3-positive hepatoma cells. This finding could be used to advance development of adoptive T-cell therapy for HCC. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the potential of the partial plastination technique in minimizing material slippage and to discuss the effects on the tensile properties of thin dense connective tissue. The ends of twelve iliotibial tract samples were primed with polyurethane resin and covered by plastic plates to provide sufficient grip between the clamps. The central part of the samples remained in an anatomically unfixed condition. Strain data of twelve partially plastinated samples and ten samples in a completely anatomically unfixed state were obtained using uniaxial crosshead displacement and an optical image tracking technique. Testing of agreement between the strain data revealed ongoing but markedly reduced material slippage in partially plastinated samples compared to the unfixed samples. The mean measurement error introduced by material slippage was up to 18.0% in partially plastinated samples. These findings might complement existing data on measurement errors during material testing and highlight the importance of individual quantitative evaluation of errors that come along with self-made clamping techniques. [ABSTRACT FROM AUTHOR]

The number of transnational governance mechanisms specifically relating to mountains is limited. Using the three axes of the framework developed by Balsiger and VanDeveer (2012) – agency, substance, and territoriality – this paper reviews progress in this domain and looks forward. It introduces themes for transnational governance of mountains in the context of the Rio conferences of 1992 and 2012 and then presents progress with regard to governance arrangements in different regions of the world, first, for biodiversity and related issues and, second, for sustainable (mountain) development. As well as state actors, many nonstate actors are involved in these arrangements; these actors are discussed. The paper concludes with conclusions regarding transnational governance in mountain areas to date and identifies future actions in the realms of monitoring, research and policy. [ABSTRACT FROM AUTHOR]

Post ligature cardiac syndrome (PLCS) is a serious complication of surgical closure of the ductus arteriosus (DA) of preterm infants. Incidence of PLCS after percutaneous closure is poorly studied. The aim of this study was to compare the incidence of PLCS between percutaneous and surgical DA closure techniques. Mortality, major and minor post-procedural complications, and risk factors for PLCS had also been explored. We conducted a retrospective study including premature infants weighing less than 2000 g who had surgical (surgical group) or percutaneous (KT group) closure of the DA at Nantes University Hospital and Tours University Hospital between 2009 and 2021. Seventy-six children were included in the KT group and 78 in the surgery group. No cases of PLCS were diagnosed in the KT group versus 10 in the surgery group (0% vs. 13%, P < 0.01). Pre-discharge mortality was lower in the KT group (3% vs. 18%, P < 0.01). The rate of major complications also tended to be lower (5% vs. 15%, P = 0.07). Surgery (100% vs. 47%, P < 0.01), lower birth term (25 ± 1 vs. 26 ± 2 weeks, P < 0.05) and need for amines before closure procedure (90% vs. 26%, P < 0.001) were significantly associated with PLCS. Finally, PLCS significantly increased pre-discharge mortality (40% vs. 8%, P < 0.01). With no cases of PLCS and a reduction in all-cause mortality before discharge, our results suggest that percutaneous closure of the DA of preterm infants would be preferred to surgical closure. This technique must still be improved and widely diffused. [ABSTRACT FROM AUTHOR]

The article describes the effect of input material structure on the structure development during the subsequent processing by mini-thixoforming technology. Two different initial states were prepared from X210Cr12 tool steel for the experiment. The first semi-product was used in the soft-annealed state with ferritic-carbidic microstructure and coarse primary chromium carbides. Ferritic grain size 13,7 μm and the hardness was 210 HV30. The second state was prepared by high temperature annealing at 1200 °C for 1 hour. The microstructure then consisted of austenite and carbides. The grain size was in the range of cca 37 to 50 μm, hardness was 300 HV30. Treatment consisted of heating to a semi-solid state at the temperature 1265 °C in 9 s. That was followed by direct cooling to room temperature in 2 s. The grain size and distribution of eutectic in the volume of the processed material were selected as the attributes for microstructure evaluation after mini-thixoforming. The structure after processing in a semi-solid state consists of polyhedral austenite with a grain size of 43-59 μm, compared to the initial range 37-50 μm. This compares to the soft annealed state when, after semi-solid processing, the grain size was only 10 to 13 microns. [ABSTRACT FROM AUTHOR]

Abstract: The ocean regulates the global climate, provides humans with natural resources such as food, materials, important substances, and energy, and is essential for international trade and recreational and cultural activities. Together with human development and economic growth, free access to, and availability of, ocean resources and services have exerted strong pressure on marine systems, ranging from overfishing, increasing resource extraction, and alteration of coastal zones to various types of thoughtless pollution. Both economic theory and many case studies suggest that there is no “tragedy of the commons” but a “tragedy of open access”. With high likeliness, structures of open access are non-sustainable. International cooperation and effective governance are required to protect the marine environment and promote the sustainable use of marine resources in such a way that due account can be taken of the environmental values of current generations and the needs of future generations. For this purpose, developing and agreeing on one Sustainable Development Goal (SDG) specifically for the Ocean and Coasts could prove to be an essential element. The new SDGs will build upon the Millennium Development Goals (MDGs) and replace them by 2015. Ensuring environmental sustainability in a general sense is one of the eight MDGs but the ocean is not explicitly addressed. Furthermore, the creation of a comprehensive underlying set of ocean sustainability targets and effective indicators developed within a global Future Ocean Spatial Planning (FOSP) process would help in assessing the current status of marine systems, diagnosing ongoing trends, and providing information for inclusive, forward-looking, and sustainable ocean governance. [Copyright &y& Elsevier]

Despite recent progress in the study of the German Baltic Small-Scale Fishery (SSF), there is still a lack of relevant data and quantitative assessments of the SSF sector's key characteristics (e.g. fleet, catch). Moreover, little insight exists on the impacts of past environmental and management changes on the German Baltic SSF. Using a spatial database developed specifically for the German Baltic SSF sector, we assess the sector's key structural and operational characteristics (vessel numbers, gears, landings and target species) to review its development during the period between 2000-09. We link exhibited trends with changes that took place in the wider Baltic Sea region in fisheries' resource abundance and management, in order to provide insights in the sector's adaptation potential to past changes. Results suggest that the SSF was affected by changes in the abundance and allocation of fishing opportunities (TACs) of major target species (herring and cod) and technical measures for fishing gear. There is also evidence to suggest that the SSF was affected by measures directed to the activity of the Large-Scale Fishery (LSF). We argue that such an approach can provide new insights on the impacts of future management changes or incidents of environmental variability on the SSF sector and is crucial in order to effectively integrate SSFs within policy. [ABSTRACT FROM AUTHOR]

Retrofitting a new crown to an existing dental device is challenging. The continued evolution of computer-aided design and computer-aided manufacturing (CAD/CAM) significantly simplifies the process. This article demonstrates retrofitting a gold crown to an existing sleep apnea device. [Copyright &y& Elsevier]

Abstract: This paper explores how participants in community landownership initiatives in Scotland experience this emergent form of communal tenure and governance, set within their own narratives of sustainability. The research i) captures individual and collective as well as convergent and divergent narratives of community landownership and management; ii) explores the sustainability credentials of this form of tenure from a theoretical perspective; and iii) assesses key barriers and opportunities for progressing sustainability in a community land context. Four in-depth case studies from the Scottish Highlands and Islands, incorporating 77 semi-structured interviews within a purposive sample of participants, inform four narratives of community landownership. First, rebuilding community capacity. Second, redefining participatory governance and partnership working. Third, building a framework for economic development; and finally reconfiguring community-natural resource relationships. The findings reveal community landownership acts as a powerful catalyst and positive agent for reconstructing rural development set within locally prescribed narratives of sustainability. Thus, community landownership is linked with a re-construction of sustainability, with an emphasis on subsidiarity and legitimate governance processes set within strong conflict management and leadership attributes to maximize long-term success. [Copyright &y& Elsevier]

Abstract: In this paper a particularization of forging process is presented, studying the deformation of a ring specimen. Plastic forming is performed by means of the Upper Bound Theorem and the model of Triangular Rigid Blocks to calculate the minimal charge needed to deform the part. The establishing the part to deform an annular geometry is determined by the so-called Ring Compression Test under its canonical configuration, that allows assimilating to a plane strain process. A new perspective to calculate the neutral plane (radius at which the workpiece material flows in opposite directions) is proposed, a basic element in the solution of the problem. [Copyright &y& Elsevier]

Abstract: We have previously reported that spectrin increases dramatically in amount and is assembled into the cytoskeleton in differentiating keratinocytes both in vitro and in vivo (Zhao et al., PLoS ONE 6 (12) (2011) e28267). We demonstrate here that extracellular calcium (Ca2+) enhances differentiation of keratinocytes and that this is associated with increased spectrin expression and formation of a spectrin-based cytoskeleton. While Retinoic acid (RA) also enhanced keratinocyte differentiation, it abrogated the spectrin-based cytoskeleton in keratinocytes. Furthermore, RA substantially inhibited expression of both Src and PI3K-p85α and consequently the amounts of specific phosphorylation of both of these proteins. RA also enhanced AKT expression and dramatically induced phosphorylation of AKT(Thr308), accompanied by phosphorylation of both PKCδ(Thr505) and β-adducin(Ser662) and upregulated cyclin D2 and down-regulated cyclin B1. On the other hand, Ca2+ overcame the inhibitory effects of RA on expression of Src, PI3K-p85α and cyclin B1 by maintaining high levels of phosphorylation of both Src(Tyr527) and PI3K-p85α and preventing phosphorylation of AKT(Thr308), PKCδ(Thr505) and β-adducin(Ser662). These data highlight the importance of Ca2+ in both spectrin expression and the organizational integrity of the spectrin-based cytoskeleton in differentiating keratinocytes and assist in elucidating the signalling pathways involved. [Copyright &y& Elsevier]

Highlights: [•] Importance of the size and structure of antigens for B cell responses. [•] Impact of different pathogen associated molecular patterns and their receptors. [•] The trafficking of antigens to secondary lymphoid organs and cellular targeting. [Copyright &y& Elsevier]

Background: Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer. Methods: For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed. Results: Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor’s histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD. Conclusion: Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Preclinical data suggested all-trans retinoic acid (tretinoin) as a potential antiviral agent against chronic hepatitis C infection. Aims: To assess efficacy, safety, and tolerability of tretinoin in combination with peg-interferon and ribavirin in genotype-1 infected patients with prior non-response. Method: We performed an open-label multicentre clinical trial. Patients were randomised to either receive additional tretinoin (45mg/m2/day) for 12 weeks (arm A), or peg-interferon and ribavirin alone (arm B). Primary endpoint was the slope of the third phase of viral decline (Mδ) as determined in an established kinetic model known to correlate with treatment outcome. Secondary endpoints were additional kinetic parameters, viral response rates, safety, and tolerability. Results: 27 patients in arm A and 30 patients in arm B were treated per protocol until week 12. Viral kinetic parameters did not differ. Rates of early virological response (>2log10 drop at week 12) were similar (10/27 versus 11/30 patients). In arm A, patients experienced a higher rate and intensity of adverse events, most commonly skin and mucosal dryness, and headache. Conclusion: Addition of tretinoin was safe and acceptably well tolerated. However, it did not influence viral kinetics and thus cannot be further considered as a treatment option. [Copyright &y& Elsevier]

Background: Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response. Objective: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma. Methods: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734). Results: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma “well controlled” (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration. Conclusion: Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids. [Copyright &y& Elsevier]

Abstract: This paper presents and assesses a participatory research process that employed the Delphi technique to co-produce a sustainability assessment toolkit for upland estate management in Scotland. Upland areas in Scotland have a distinct pattern of ownership, with much of the land divided into ‘estates’ that are owned predominantly by a range of private individuals and organisations, as well as public agencies and non-governmental and community organisations. Management objectives and land uses are wide-ranging and attract the interest of many different stakeholders. As a result, translating sustainability principles for generic, practical application in this context is a complex challenge that has not yet been addressed in an inclusive and participatory manner. In response, a reflective research approach engaged an anonymous, mixed group of academic and non-academic stakeholders over a four-stage, interactive Delphi process which lasted 18 months. The process produced a toolkit within which five principles for sustainable upland estate management and 12 corresponding ‘actions’ were translated into operational practice. The toolkit provided a sustainability framework for estate owners, managers and other stakeholders to assess progress towards delivering a series of practical actions on individual estates. The paper explores the implications of this toolkit for upland estate management in Scotland and reflects on the benefits and wider application of this type of research approach. [Copyright &y& Elsevier]

Abstract: Cerebral palsy is a non-progressive disorder of movement, posture and coordination arising from a lesion or dysfunction of the developing brain which may develop pre, peri or post-natally and is not due to a progressive or degenerative brain disease. It is the most common cause of physical disability in children, occurring in approximately 2.5 per 1000 live births in the UK. Orthopaedic management is in a multi-disciplinary context and includes single-event multilevel surgery (SEMLS), spinal surgery, botulinus toxin injections and serial casting. [Copyright &y& Elsevier]