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Cagrilintide is a novel long-acting amylin receptor agonist, which has shown a potent induction of weight loss. Interestingly, cagrilintide is a Dual Amylin and Calcitonin Receptor Agonist (DACRA) derived from an amylin backbone. Another class of long-acting DACRAs exists, namely the KBPs. These are salmon calcitonin-based and have shown preclinical potential; however, how and if they differentiate from amylin-derived molecules remain to be studied. Here, we compare cagrilintide to the DACRA KBP-336 with respect to receptor activation balance in vitro and using metabolic in vivo models. Peptide potencies were assessed using receptor-specific assays in vitro and in vivo. In vivo efficacies on body weight and glucose homeostasis were investigated head-to-head in high-fat diet (HFD) fed obese and T2D (ZDF) rat models. Both peptides activate the amylin and the calcitonin receptor in vitro and in vivo, with KBP-336 being more potent, and showing a CTR bias. KBP-336 and cagrilintide induced a potent and dose-dependent weight loss in HFD rats, with the highest dose of KBP-336 being superior to cagrilintide. In diabetic ZDF rats, DACRA treatment improved fasting blood glucose, HbA1c levels, and insulin action, with KBP-336 being superior to cagrilintide in improving glucose control. In summary, both KBP-336 and cagrilintide are DACRAs, however with KBP-336 being biased towards the CTR resulting in a different receptor activation balance. Interestingly, KBP-336 showed superior long-term efficacy on both weight loss and glucose control, supporting relevance of the receptor balance, and highlighting KBP-336 as a promising agent for the treatment of obesity and T2D.

Key Points Question What is the evidence for nonpharmacological interventions to treat persistent postconcussion symptoms? Findings Following a systematic review and meta-analysis of 19 randomized clinical trials comprising 2007 participants, using the Grading of Recommendations, Assessment, Development, and Evaluations method, weak recommendations for the following were assigned: systematic provision of early information and advice, use of graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, psychological treatment, and interdisciplinary rehabilitation. No studies were identified regarding oculomotor vision treatment, resulting in a consensus-based statement. Meaning Based on very low to low certainty of evidence or on consensus, individually tailored nonpharmacological treatment of persistent symptoms was recommended, both through specific disciplines and interdisciplinary rehabilitation., This systematic review and meta-analysis assesses the outcomes related to 7 nonpharmacological interventions for persistent postconcussion symptoms in adults and provides recommendations for clinical practice., Importance Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. Objective To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. Data Sources Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. Study Selection A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. Data Extraction and Synthesis Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Main Outcomes and Measures All outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). Results Eleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately identified and included. Evidence for the 7 interventions ranged from no evidence meeting the inclusion criteria to very low and low levels of evidence. Recommendations were weak for early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. No relevant evidence was identified for oculomotor vision treatment, so the panel provided a good clinical practice recommendation based on consensus. Conclusions and Relevance Based on very low to low certainty of evidence or based on consensus, the guideline panel found weak scientific support for commonly applied nonpharmacological interventions to treat PPCS. Results align with recommendations in international guidelines. Intensified research into all types of intervention for PPCS is needed.

Background: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. Methods:This paper describes the design and methodology behind the VIVIAD-trial. The aim of this study is to evaluate varoglutamstat in a state-of-the-art phase 2b, placebo-controlled, double-blind, randomized clinical trial on safety and tolerability, efficacy on cognition, brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. Results: to be expected early 2023Conclusion: This state of the art phase 2b study will yield important results for the field and the treatment of AD with a small molecule directed against pyroglutamate-A-beta.

To compare the effectiveness of a specialized, interdisciplinary rehabilitation (S-REHAB) with standard care (STAND) for people with persistent post-concussive symptoms (PPCS6 month).Randomized controlled trial.Eighty-nine adults.22-week programme combining individual and group-based neuropsychological treatment with exercise therapy and physiotherapeutic coaching (S-REHAB), and the usual treatment offered by the public municipality services (STAND).The Rivermead Postconcussion Symptoms Questionnaire (RPSQ) (primary), The Headache Impact Test (HIT-6), Major Depression Inventory (MDI), Multidimensional Fatigue Inventory (MFI-20) and The Short Form (36) Health Survey (SF-36); all collected at baseline, post-treatment, and at 6-month follow-up.The S-REHAB group showed a significant reduction in symptoms measured by RPSQ compared to the STAND immediately post-treatment (effect size [ES] = 0.28) and at follow-up (ES = 0.26). The S-REHAB groups also showed significant improvements regarding HIT-6 post-treatment (ES = 0.38) and at follow-up (ES = 0.68), MFI-20 - dimension 'mental fatigue' post-treatment (ES = 0.42), MFI-20 - dimension 'reduced activities' at follow-up (ES = 0.74) and SF-36 - dimension 'social functioning' post-treatment (ES = 0.31).The S-REHAB is more effective than the STAND in reducing the PPCS affecting physical, cognitive and emotional domains. This symptom reduction was associated with experienced improvement in social functioning, increased levels of activity, a decrease in mental fatigue and increased life satisfaction.

Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.

The calcite shields produced by unicellular marine algae demonstrate the remarkable crystal control that organisms can achieve through biomineralization. Emiliania huxleyi produces complex polysaccharides (“coccolith associated polysaccharides”, CAP) that regulate crystal morphology by preferentially attaching to calcite acute step edges, thus promoting growth of the specific crystal faces required for design of that species of coccolith. However, to control crystal growth, the alga must be able to control CAP behavior at the local scale, so its functionality can be switched on and off. Here, we show that the functionality of CAP from E. huxleyi depends directly on solution composition. We used atomic force microscopy (AFM) to investigate the behavior of calcite surfaces under varying pH, in the presence of CAP and cations chosen to test the role of ionic potential, that is, charge per unit radius (K+, Na+, Sr2+, Ca2+, Mg2+, Zn2+, and Eu3+ at 1 M charge concentration). Site-specific adsorption to calcite ...

Type I collagen is a fibrillar type collagen, and most likely the best investigated collagen. Type I collagen is the most abundant collagen and is the key structural composition of several tissues. It is expressed in almost all connective tissues and the predominant component of the interstitial membrane. Type I collagen mutations have documented important roles in a range of diseases, with particular focus on bone and connective tissue disease, in particular osteogenesis imperfecta and Ehlers–Danlos syndrome. Type I collagen is predominantly modified at the posttranslational level, with several crosslinks and other modifications. Several biomarkers of type I collagen have been developed, of both type I collagen degradation and formation, as surrogate makers of bone degradation and formation, respectively. Type I collagen formation is also associated with fibrosis, and fibrogenesis.

Biomineralisation can only be understood as an interplay between organic and mineral phases. With this objective, we conducted an investigation of coccoliths using atomic force microscopy (AFM), an ultra-high resolution technique that requires no surface coating and can be used in air or under solution at ambient conditions of temperature and pressure. The detailed morphology, crystal structure, organic scales and organic coating of the coccolith species Coccolithus pelagicus, Helicosphaera carteri and Oolithotus fragilis were investigated. The fine structure of coccoliths is very complex, with the calcite either being smooth, dominated by steps or tuberculate; organic cover can be either granular or fibrous. Behaviour of coccolith surfaces during dissolution is influenced both by mineral and organic material and different surface types show variable resistance to dissolution. The organic coating protects element faces against etching. Through atomic resolution AFM, it is possible to establish the crystallographic structure of the distal shields of C. pelagicus and O. fragilis. Though elements of both species are dominated by stable crystal faces, there are important differences between them, with the external edge of elements being parallel to a cleavage direction in C. pelagicus but parallel to the atomic rows in O. fragilis. Thus, there is evidence that the biomineralisation of each species, and also of select areas of coccoliths of the same species, is markedly different.

Chloride extraction and realkalization are nondestructive, electrochemical treatments to halt and prevent corrosion in chloride-contaminated and carbonated concrete, respectively. The process actually removes chloride ions from the contaminated concrete by the principle of ion migration while at the same time raising the pH of the carbonated concrete through electro-osmosis. Concrete to be treated is first tested to determine the level of chloride contamination. Then, after preparing the surface, a steel or titanium mesh electrode is attached to the structure. The electrode is embedded in a nontoxic biodegradable electrolytic media. Next, electric contacts are established between the attached electrode and the steel reinforcement bars (rebars) inside the concrete. When an electric field is applied, chloride ions migrate away from the rebars and towards the externally attached electrode, eventually ending up in the temporary electrolytic media, which is then discarded. Simultaneously, alkali ions migrate from the electrolyte into the concrete, raising its pH to the original levels. The passivating layer of the rebars is thus reestablished to protect them from corrosion.

A method of treating pig manure is described, such that the necessary storage volume is reduced to 25–30% of the original volume. The manure is separated into a water fraction with a low content of dry matter and nutrients, and into a slurry fraction which contains most of the dry matter and nutrients. The water fraction can be purified to appear like pure water with a desired nitrogen concentration. The separation is made by flocculation, a process whereby a flocculation agent collects the organic matter in the liquid manure into bigger particles, which causes them to sink. The experiments showed that it is pos- sible to flocculate the volatile solids in 14 d old pig manure. For this purpose, a dosing of 0·2% of the clay mineral bentonite was sufficient to obtain adequate sedimentation. The liquid fraction can be purified by ion exchange with clinoptillolite or glauconite. It is possible to reach as low a content of ammonia as is wanted with an appropriate processing time.

Structural elements form the backbone of a spacecraft. They provide the overall mechanical integrity of the spacecraft under launch and in-orbit loads. Furthermore, the structure ensures that the spacecraft configuration is maintained during all mission phases, ensuring the relative alignment of components like antennas, reflectors, sensors and optical instruments. In the latter cases, the potential loss of dimensional stability of the spacecraft structure can severely degrade the mission performances.

Harvested yields of sour cherry ( Prunus cerasus ) cultivar ‘Stevnsbaer’ clones grown in Denmark have been highly variable over the years, yet some propagated derived trees selected from within the two widely grown clones of ‘Stevnsbaer’ clone ‘Birgitte’ and clone ‘Viki’ have consistently produced higher yields. A number of these selections were evaluated for yield and genomic differences to investigate variation between and within the ‘Birgitte’ and ‘Viki’ clones. Variation in yield was mainly found at the clonal level. The clone ‘Viki’ was found to be the highest yielding with an average of 20 kg/tree compared to only 7.0 kg/tree from clone ‘Birgitte’. The selected trees derived from within clone ‘Birgitte’ had a significantly higher, average yield over 7 years compared to the original ‘Birgitte’, indicating that such within-clone selection may be a possible approach for selection of improved breeding material. However, no differences in allele profile were found between or within the clones, calling into question the extent of the available genetic diversity and indicating that the observed variance in yield may have to be explained by other genetic mechanisms, including epigenetic change.

Despite the harshness of the weather, the winter months on Spitsbergen provide good opportunities for auroral observing. December is usually the cloudiest month, but it also has many short-lived periods of post-cyclonic clearing of excellent clarity. January, however, is the most favourable month, with long periods of clear, dark skies due to the dominance of anticyclonic systems over the polar cap. February is also a very good month from the meteorological point of view, but observing opportunities are much more restricted by increasing twilight, especially in the latter half of the month. The most frequently observed types of aurora are patchy prenoon aurora, noontime or cusp aurora, discrete postnoon arcs, discrete polar-cap aurora, and substorm aurora. Diffuse polar-cap (polar glow) aurora and storm-type aurora are also seen occasionally but only at times of great geomagnetic disturbance.

BACKGROUND--Bacterial lipopolysaccharide (LPS) has been proposed to participate in the pathogenesis of pancreatic inflammatory disease. AIMS--This study investigated the role of endotoxaemia in the pathogenesis of pancreatic acinar cell injury. METHODS--Sixty eight male Spraque-Dawley rats were used in the study. Escherichia coli LPS (5 mg/kg) was injected into the peritoneal cavity of the rats. The concentration of pancreatic phospholipase A2 (PLA2) in plasma was measured and pancreatic tissue examined by histology, in situ detection of free DNA 3'-ends, and electrophoretic DNA analysis. RESULTS--The concentration of pancreatic PLA2 increased in plasma and the catalytic activity of PLA2 increased in pancreatic tissue after an LPS injection. Apoptosis in pancreatic acinar cells and fragmentation of DNA typical of apoptosis in pancreatic tissue was seen 24 hours after an LPS injection. Pancreatic acinar atrophy was seen 72 hours after the LPS injection. CONCLUSIONS--These data show that LPS causes release of pancreatic PLA2 into blood plasma, activation of PLA2 in pancreatic tissue, and apoptosis of acinar cells.

The alkaline elution assay has been employed to study the induction and repair kinetics of DNA damage in human lymphocytes after irradiation with biologically relevant doses of UVB (297 and 302 nm) or UVA (365 nm) radiation. At 365 nm, when the predominant lesions are single-strand breaks, the rate of lesion induction was 1.5 × 10−3 per 108 Da per kJ m−2. The number of breaks decayed with a half-life of about 50 min after a dose of 20 kJ m−2. In the UVB region, cyclobutyl pyrimidine dimers and 6-4 photoproducts are formed, both of which are repairable via the nucleotide excision repair pathway. By using repair inhibitors, the rate of induction of such lesions at 297 and 302 nm was found to be 0.07 per 108 Da per J m−2. Lesions were removed with a half-life of about 100 min. Mathematical modelling of the excision repair process revealed a time-dependent polymerization-ligation rate: after an initial lag phase the polymerization-ligation rate increased, reaching 50% of its maximum rate at 80–100 min after the start of repair incubation. This course of development might be due to a damage-associated regulation of DNA precursors synthesis.

The present study confirms that the auroras of the nightside oval population consist of two main types, namely storm and substorm aurora. Storm-type aurora, which is relatively infrequent, results from bombardment of the upper ionosphere by fast particle streams generated in the solar wind by cataclysmic solar events related to coronal mass ejections. The associated turbulent plasma that is injected into the magnetosphere produces great magnetic storms of world-wide dimensions that may last for days. In contrast, substorm aurora is a frequent (almost daily) occurrence that lasts for an hour or two around geomagnetic midnight. It is generated by the impulsive release of stored magnetospheric energy from the substorm onset region in the Earth's magnetotail and is associated with localised negative magnetic bays in the H (horizontal)-component of the Earth's magnetic field in the vicinity of the auroral oval.

Polar-glow aurora is a diffuse type of polar-cap event that follows bombardment of the auroral ionosphere with high-energy protons from ‘cosmic ray’ flares at times of great solar and geomagnetic activity. Observations of five polar glows are presented together with details of the circumstances surrounding their occurrence. The first three glows were associated with enhanced solar activity between 3 and 15 February 1986 and the fourth and fifth glows with enhanced solar activity between 3 December 1993 and 10 February 1994. Despite the fact that the flares associated with the latter solar outburst were much smaller than those associated with the former, both periods of solar activity showed equally marked geophysical, geomagnetic, and auroral activity.

Daytime (or dayside cleft) aurora is almost a permanent feature of the midday skies over Spitsbergen during the continuous darkness of the polar night It was observed in one or other of its characteristic forms around geomagnetic noon on 58 of 59 clear day sduring the wintersof 1987/1988, 1990/1991, and 1992/1993. The three types of day time aurora were studied by visual, colour photographic, and interference-filter techniques to confirm the precise nature of the observed emissions. Prenoon aurora, which is characterised by diffuse, patchy, green aurora at 557.7 nm, was observed on 42 occasions. It is generated by low-energy electrons of less than 300 eV coming through the entry layer of the dayside cleft. Noontime aurora, which consists largely of pure red emissions at 630.0/636.4 nm, was observed on 50 occasions. It is generated by high-flux, very low-energy electrons of 10–50 eV flowing directly from the solar wind through the polar cusp. Postnoon aurora, which is characterised by discrete, green auroral arcs at 557.7 nm, was also observed on 42 occasions. Like prenoon aurora, it is generated by low-energy electrons of less than 300 eV derived from the entry layer of the cleft Occasionally, some background or diffuse aurora is also observed, generated by high fluxes of low-energy proton precipitation and characterised by the hydrogen lines Hα and Hβ. On the one exceptional day on which daytime aurora was not observed, magnetic activity was exceptionally low.These ground-based observations complement satellite studies of analogous auroral events. In particular, the visual characteristics of the different types of daytime aurora may be explained in terms of the flux rates and energy profiles of the electrons that have been mapped in the different regions of the dayside cleft by satellite-borne detectors.

Setting A passive case-finding strategy as present in the DOTS strategy presupposes a patient's willingness to seek care. This requires awareness of tuberculosis (TB) symptoms and the diagnostic process, and positive attitudes towards access and probability of cure. Objective To measure parameters of health-seeking intention in Southern Angola and to inform the design of context-specific interventions to improve case detection. Design A survey in four communities based on the cough-to-cure pathway represented by five domains with either one or two proxy measures. These were assessed for association with appropriate health-seeking behaviour (visiting a medical institution or service). Results In total, 805 individuals were included in the study. Appropriate health-seeking behaviour was positively associated with knowing the disease (OR 3.1, 95%CI 1.4-6.8), knowing key symptoms (OR 1.4, 95%CI 1.0-1.9), perceived curability (OR 1.3, 95%CI 1.0-1.6), and the perception that TB services were free of charge (OR 1.9, 95%CI 1.4-2.7). Respondents who perceived a personal risk for TB were less likely to have an appropriate intended health-seeking behaviour (OR 0.7, 95%CI 0.5-0.9). Conclusion Knowledge about TB should include key symptoms, perceived curability and information on access to services when designing interventions to improve case detection. The study highlights the importance of advocacy, social mobilisation and communication strategies.

Spatial distribution of sediment nitrification rates and fluxes of ammonium and nitrate were measured in shelf sediments of the northern Bering and Chukchi seas. The sediments could be divided into three main areas depending on macrofaunal activity and input of organic nitrogen. Sediments underlying the highly productive Bering Shelf-Anadyr water (BSAS) were characterized by a high macrofaunal biomass and a high input of nitrogen-rich organic material. Tube-dwelling amphipods dominated in the sandy sediments of the northern Bering Sea, while bivalves dominated in the fine textured sediments of the Chukchi Sea. Sediments underlying the low productive Alaska Coastal Water (ACS) were characterized by low macrofaunal biomass and an input of lower quality organic material. Generally nitrification rates and nutrification potentials (NP) were highest in BSAS and lower in ACS. Nitrification rates of surface sediment, calculated from NP, accounted for 90% of the measured rates in ACS, but only 35–75% in BSAS. These data together with the distribution patterns of NP and pore water nitrate profiles implied, that most sediment nitrification was confined to the sediment surface in ACS and in BSAS bivalve sediments, while most sediment nitrification took place in the ventilated burrow walls of BSAS amphipod sediments. The NH 4 + efflux was five-fold greater from BSAS compared to ACS, whereas the estimated sediment net NH 4 + production was three-fold greater. The increase in NH 4 + efflux relative to net NH 4 + production could mostly be attributed to macrofaunal excretion. The NO 3 − flux between sediment and water column was correlated with NO 3 − concentrations in the bottom water. At concentrations higher than 10 μM NO 3 − , the flux was directed into the sediment and at lower concentrations out of the sediment. Spatial distribution of high bottom water NO 3 − concentrations correlated with high NH 4 + fluxes out of the sediment. This resulted in a lower net efflux of inorganic nitrogen from these sediments.

Track and field includes a number of high-intensity disciplines with many demanding practices and represents a motivational challenge for talented athletes aiming to make a successful transition to the senior elite level. Based on a holistic ecological approach, this study presents an analysis of a particular athletic talent development environment, the IFK Växjö track and field club, and examines key factors behind its successful history of creating top-level athletes. The research takes the form of a case study. Data were collected from multiple perspectives (in-depth interviews with administrators, coaches and athletes), from multiple situations (observation of training, competitions and meetings) and from the analysis of documents. The environment was characterized by a high degree of cohesion, by the organization of athletes and coaches into groups and teams, and by the important role given to elite athletes. A strong organizational culture, characterized by values of open co-operation, by a focus on performance process and by a whole-person approach, provided an important basis for the environment's success. The holistic ecological approach encourages practitioners to broaden their focus beyond the individual in their efforts to help talented junior athletes make a successful transition to the elite senior level.

Discrete auroral arcs frequently bridge the polar cap connecting the morning and evening sectors of the auroral oval along the line of the transpolar (electron) current. Very high-latitude stations that lie wholly within the oval during the earth's diurnal rotation pass under this bridge twice a day, giving morning and evening maxima. Stations at slightly lower latitudes on Spitsbergen lie within the oval in the evening but under, or even south of, the oval in the morning. From such stations the evening, but not the morning, maximum is readily observed. This study is primarily concerned with the orientation of discrete polar cap arcs in the evening skies over Spitsbergen. It shows that the geomagnetic alignment of these arcs is latitude-dependent between geomagnetic colatitudes 6 to 20°N. At the highest latitudes within this range, the arcs are in transpolar alignment, whereas at the lowest latitudes within the polar cap, they are oval-aligned. At intermediate latitudes, the arcs are observed in transitional phases between transpolar and ovalalignment. The solar alignment of discrete polar cap arcs is a function of corrected geomagnetic local time. In the early afternoon, solar alignment is poor but this gradually improves throughout the late afternoon until there is excellent alignment at the time of the evening maximum. Recent satellite studies of plasma convection in the polar ionosphere have helped to explain some of the visual characteristics of discrete polar cap aurora observed from Spitsbergen, particularly the irregular alignment of arcs in the region of the Harang discontinuity.

Spectrophotometric observations, at Spitsbergen, of all auroral emissions in the near-infra-red (n.i.r.) region (~7700–9000 A) during the last solar minimum period show significant differences in the temporal variations of the O2atm (1, 1) band compared with the relatively more prompt emissions such as the N21P and the N2+M (2, 0) bands as well as the OI line at 8446 A. Whereas the intensities of the nitrogen bands decrease by about a factor of 4–5 in an aurora lasting more than 1 h, the O2atm (1, 1) band intensity decreases by only a factor of 2, yet the temperatures characterizing the rotational distributions increase less for O2 than for N2 and N2+ bands. Such a higher than expected level of sluggishness in the spatial and temporal variations of the O2atm system indicates that the main source of O2(b1Σg+, v′) in auroras may be a charge transfer reaction between O2+ and NO suggested by Slanger (1986, Can. J. Phys. 64, 1657). The relatively higher intensity of the O2atm (1, 1) band compared with the other auroral features cannot be attributed to an upward shift in the emission altitude where collisional frequency has decreased, and hence quenching of O2(b1Σ+g, v′ = 1) is less severe. Instead, we suggest that O2(b1Σ+g, v′ > 1) collision with O(3P) producing O(1D), accounting for the higher than expected vibrational population of the O2atm (1, 1) band, and especially causing a dip in the population of the v′ = 2 state.

It is an honour and a great pleasure for us to present this special issue of the CEAS Space Journal devoted to the development of large deployable antennas and related technologies. Large deployable antennas for space applications have been under development worldwide for several decades, driven by both mission performance enhancement goals as well as mission enabling goals. Developments in ESA started already in the 80s with a 5-m metal-mesh reflector built by MBB/ERNO in Germany, continued later with a 10-m inflatable reflector built by Contraves in Switzerland and more recently a 12-m antenna built by Thales Alenia Space in Italy. However, for various reasons all these developments did not result in a final available European antenna reflector product. As a matter of fact, today there is no European antenna reflector product larger than 4 m aperture available, forcing European spacecraft developers to procure large reflectors from non-European sources. Three years ago, an ESA Working Group on large reflector antennas was set up with the mandate to define recommendations on how to proceed with new large reflector developments in Europe. Several spacecraft missions in need of antenna reflectors were identified, including well-established telecommunication markets such as fixed and broadcasting satellite services, mobile interactive/broadcast services, broadband services, but also new applications such as air traffic management and emergency communications. These missions cover the frequency spectrum up to Ka-band. Synergies with Earth Observation, Navigation and Scientific deep space missions were also identified. One of the main conclusions of the Working Group was that near-term effort should be devoted to the development of technologies for reflectors with scalability and/or modularity features to cover sizes above 4 m and up to 25 m for frequency bands ranging from P to Ka. It was understood that many of the technologies were in fact available or within reach, and the missing task of coordination and industrial implementation was considered achievable. In October 2012, the first Large Deployable Antenna Workshop took place at ESA/ESTEC, The Netherlands, with a significant participation from European industry and research organisations. During this workshop, several recent technology developments for large antenna reflectors were presented and discussed together with a new reflector deployment demonstration. The workshop addressed as well developments for inflight reconfigurability of space antennas using reflector reshaping that is finally becoming technically feasible after many years of trials. Reflect-arrays and lenses were also addressed, as well as radio frequency testing, especially relevant due to the challenges ahead of us for the development of test facilities required for large apertures. This special issue of the CEAS Space Journal is intended to present the key technologies addressed in this workshop. A second edition of the workshop is under preparation for 2014 with the objective to report on the major developments performed over the last 2 years. T. K. Henriksen (&) Structures and Mechanisms Division, ESA/ESTEC, Keplerlaan 1, 2201 AZ Noordwijk, ZH, The Netherlands e-mail: Torben.Henriksen@esa.int

During the past fifteen years significant efforts have been made at national and European level to improve the technologies needed for future space transportation systems. Innovative concepts, advanced materials and manufacturing processes become of paramount importance to meet the challenging requirements of reusable launchers. The studies performed in the past years have highlighted promising capabilities in advanced composite materials and processes, which offer superior performance to that of conventional metals due to their high specific strength, high toughness, lightweight and high wear resistance obtained through appropriate fibres orientation. This paper addresses an ESA internal study on reusable launch vehicle primary structures, and specifically aspects related to advanced composite materials performance in such vehicle application.

The authors discuss software interface concerns in radiation oncology from a human factors perspective. An example of a series of disastrous consequences resulting from a poorly developed and tested interface design of a computer controlled treatment machine is described. Treatment planning computers are discussed in terms of their increasing requirement to provide complex data to the user resulting in the possibility of confusing the output or overloading the user. Finally, the priority given to software-based human interfaces in other industries is compared to that found in radiation oncology equipment manufacturers. The authors argue that radiation oncology equipment manufacturers lag behind other industries in terms of their emphasis on the human interface. >

Dr Lesley Colvin (Senior Lecturer in Anaesthesia, Western General Hospital, Edinburgh) discussed the challenges of pain management in patients with a history of addiction. Similar to other chronic conditions, substance misuse often follows a relapsing course. Pain is a frequently associated comorbidity. Mortality rates are high but can be reduced by successful methadone maintenance programmes, although pain, anxiety and depression have a negative effect on outcomes. Dr Colvin described experience of the Lothian Pain and Dependency Clinic. General guidance on patient management is available through the British Pain Society Guidelines.

SummaryMeasurements of soluble and total oxalate, malate, anthocyanins, total sugars, dry matter as well as several petiole and leaf characters were taken for 71 genotypes of culinary rhubarbs (Rheum spp.). The organic acids were simultaneously analysed by ion moderated partitioning chromatography, an HPLC technique that employs multiple mechanisms for separation. Sample run time was reduced to 11 min by allowing overlapping chromatograms. The grand mean (range of genotype means) of water soluble oxalate was 3.13% (1.56–6.03%), of total oxalate 5.88% (3.21–9.17%), of malate 20.98% (12.16–29.24%) all of dry matter. The range of anthocyanins in the petiole juice was 0–154 mg/kg of fresh weight. Negative correlations were found between the anthocyanin content and some growth characteristics.

Services for elderly, mentally ill people have developed in response to changing needs in society. In 1990 most of the 650 beds allocated to elderly patients in psychiatric hospitals were occupied by long-term care patients. Outpatient programmes hardly existed. In 1995 about 400 beds were allocated to geriatric psychiatry. They were served by 40 physicians and 20 psychologists. Out-patients' clinics were established. Most of the in-patients were short-term admissions. Nowadays, departments of geriatric psychiatry define themselves as diagnostic and short-term units. About a third of the in-patients suffer from dementia, a third from depression, and a third from various other psychiatric disorders. The authors recommend that a special unit for geriatric psychiatry should be established in every county in Norway. Funds should be allocated for professorships at all universities.

A series of human factors evaluations were undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multidisciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation therapists, conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was performed initially to guide subsequent evaluations in the areas of workplace environment, system-user interfaces, procedures, training, and organizational practices. To further acquire an in-depth and up-to-date understanding of the practice of teletherapy in support of these evaluations, a systematic literature review was conducted. Factors that have a potential impact on the accuracy of treatment delivery were of primary concern. The present volume is the literature review. The volume starts with an overview of the multiphased nature of teletherapy, and then examines the requirement for precision, the increasing role of quality assurance, current conceptualizations of human error, and the role of system factors such as the workplace environment, user-system interfaces, procedures, training, and organizational practices.

As a treatment methodology, teletherapy selectively destroys cancerous and other tissue by exposure to an external beam of ionizing radiation. Sources of radiation are either a radioactive isotope, typically Cobalt-60 (Co-60), or a linear accelerator. Records maintained by the NRC have identified instances of teletherapy misadministration where the delivered radiation dose has differed from the radiation prescription (e.g., instances where fractions were delivered to the wrong patient, to the wrong body part, or were too great or too little with respect to the defined treatment volume). Both human error and machine malfunction have led to misadministrations. Effective and safe treatment requires a concern for precision and consistency of human-human and human-machine interactions throughout the course of therapy. The present study is the first part of a series of human factors evaluations for identifying the root causes that lead to human error in the teletherapy environment. The human factors evaluations included: (1) a function and task analysis of teletherapy activities, (2) an evaluation of the human-system interfaces, (3) an evaluation of procedures used by teletherapy staff, (4) an evaluation of the training and qualifications of treatment staff (excluding the oncologists), (5) an evaluation of organizational practices and policies, and (6) anmore » identification of problems and alternative approaches for NRC and industry attention. The present report addresses the function and task analysis of teletherapy activities and provides the foundation for the conduct of the subsequent evaluations. The report includes sections on background, methodology, a description of the function and task analysis, and use of the task analysis findings for the subsequent tasks. The function and task analysis data base also is included.« less

A series of human factors evaluations was undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multi-disciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. The principal sources of radiation are a radioactive isotope, typically cobalt60 (Co-60), or a linear accelerator device capable of producing very high energy x-ray and electron beams. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation technologists, conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of user-system interfaces, procedures, training and qualifications, and organizational policies and practices. The final phase of the project focused on identification of the most significant human factors problems with respect to safe and effective operation of the teletherapy system and an identification and assessment of alternative approaches for resolving the problems. This report presents the findings of this final phase.

A series of human factors evaluations were undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multidisciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation therapists, conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of system-user interfaces, procedures, training and qualifications, and organizational policies and practices. The present work focuses solely on training and qualifications of personnel (e.g., training received before and during employment), and the potential impact of organizational factors on the performance of teletherapy. Organizational factors include such topics as adequacy of staffing, performance evaluations, commonly occurring errors, implementation of quality assurance programs, and organizational climate.