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Background Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. Methods We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. Results A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] Conclusion Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

Root vegetables have unique techno-functional and nutritional properties however, their use in processed foods is limited to a few species, partially due to a lack of knowledge related to the impact of thermal treatments on the sensory properties. This study investigated the effect of steaming and boiling on the microstructure, mechanical properties, and sensory profile of three model root vegetables with distinct carbohydrate composition: Jerusalem artichoke (Helianthus tuberosus L.), parsnip (Pastinaca sativa), and beetroot (Beta vulgaris). Thermally treated Jerusalem artichoke and parsnip showed higher content of cell wall polysaccharides, particularly β-glucans (e.g. cellulose) and pectic components, compared to raw. Steaming produced more cell shrinkage and loss of cell-cell adhesion than boiling, leading to softer vegetables. Processed beetroot showed loss of cell turgor and drastic softening but not clear changes in overall carbohydrate content. The scores for several flavour and in-mouth attributes were higher for steamed vegetables compared to boiled. Our results give insights on the processability of root vegetables towards products with enhanced sensory and nutritional properties. The study was funded by Jordbruksverket 2018-2132.

Background Health literacy is increasingly recognized as an essential determinant for the health of the population. Liver patients report perceived stigma to be a considerable problem. Little is however known about liver health literacy in the general population and to what extent liver disease is considered stigmatizing in comparison with other chronic diseases. We aimed to explore these knowledge gaps. Methods We performed an exploratory e-survey in a statistically representative sample of 500 Swedes from the general population. A questionnaire developed for this purpose investigated awareness, attention, knowledge and attitudes towards liver health and compared some aspects with other common health problems. Findings Few worry (23%), think (28%), discuss with their doctor (31%) or hear about liver health in the news (19%). Few (18%) had a liver test in the last year and knew (23%) what is considered a normal liver test. More knew what is considered normal blood pressure (89%), blood sugar (74%) and BMI (73%). Few (22%) talk about liver health, mainly (50%) because abuse is presumed. Many (36%) believe that cirrhosis is only caused by alcohol, 31% that the liver produces urine and 21% that you can survive without a liver. Only mental illness (78%) and obesity (74%) were considered more stigmatizing than liver cirrhosis (61%). Interpretation The study confirms often held views that liver health receives less attention than many other health areas. Knowledge about liver health is generally poor, and liver cirrhosis carries significant social stigma. Improving public awareness and knowledge about liver health, and thereby ameliorating stigma, should be essential parts of policy objectives and action plans to improve liver health in Europe. Funding This research was supported by a general grant from the Bengt Ihre Foundation

Behavioral sensitization to amphetamine is a complex phenomenon that engages several neurotransmitter systems and brain regions. While dysregulated signaling in the mesolimbic dopamine system repeatedly has been linked to behavioral sensitization, later research has implicated dorsal striatal circuits and GABAergic neurotransmission in contributing to behavioral transformation elicited by amphetamine. The aim of this study was thus to determine if repeated amphetamine exposure followed by abstinence would alter inhibitory neurotransmission in dorsal striatal subregions. To this end, male Wistar rats received amphetamine (2.0 mg/kg) in an intermittent manner for a total of five days. Behavioral sensitization to amphetamine was measured in locomotor-activity boxes, while neuroadaptations were recorded in the dorsolateral (DLS) and dorsomedial striatum (DMS) using ex vivo electrophysiology at different timepoints of amphetamine abstinence (2 weeks, 4-5 weeks, 10-11 weeks). Data show that repeated drug-exposure produces behavioral sensitization to the locomotor-stimulatory properties of amphetamine, which sustains for at least ten weeks. Electrophysiological recordings demonstrated a long-lasting suppression of evoked population spikes in both striatal subregions. Furthermore, following ten weeks of abstinence, the responsiveness to a dopamine D2 receptor agonist was significantly impaired in brain slices from rats previously receiving amphetamine. However, neither the frequency nor the amplitude of spontaneous inhibitory currents was affected by treatment at any of the time points analyzed. In conclusion, passive administration of amphetamine initiates long-lasting neuroadaptations in brain regions associated with goal-directed behavior and habitual performance, but these transformations do not appear to be driven by changes in GABAergic neurotransmission.

AimsThe increased morbidity and mortality relating to the poor physical health of patients with severe mental illness has repeatedly been an area identified as requiring improvement. Despite this, no national minimum standard has been published around the minimum level of physical health equipment that should be available within an inpatient psychiatric setting.The aim of this project was to improve and standardise availability of physical health equipment across the five clinical areas within a medium secure inpatient forensic setting, thus enabling optimal and timely medical care and physical examination of patients to occur.MethodThis project used a combination of audit and quality improvement practices. An audit standard was created and current practice was established within the 5 clinical areas of a Medium Secure Forensic Unit. Improvements were made in a systematic and measured way and two audit cycles were completed.ResultAt baseline, the attainment of audit standard ranged from 14-76%. Clinical areas were sharing equipment and there was an inconsistency as to where and how equipment was being stored. Changes implemented included redistribution and reorganisation of equipment which increased attainment to between 48% - 86%. Following this further equipment was ordered and the equipment was separated into that which was required on a daily basis to conduct physical observations and more specialist specific examination equipment. Re-audit found attainment across the five clinical areas being between 90-100%.ConclusionMonitoring of physical health within psychiatric inpatient settings is a key area of patient care, and is frequently identified as requiring improvement. Without access to equipment to monitor and assess physical health, this becomes challenging and potentially poorly completed. By standardizing available equipment and furthermore through practical steps such as separating the equipment required on a daily basis and that used less frequently the retention of equipment improved. This enables delivery of high quality, timely and thorough monitoring and assessment of physical health to be achievable.

The environmental potential of reusing interior and building products (notably furniture, lighting, doors, windows, flooring and ceilings) has been calculated by a rather basic model based on life cycle approach. By making a calculation model available to housing and renovation companies in Sweden, a total of over 43000 items have been included in calculations as objects for reuse, stemming from about 130 renovation projects with a total waste saving of 800 tonnes of waste in the renovation stage. The first calculations of the corresponding avoided climate impact, from avoided waste management and avoided new product extraction and manufacturing, corresponds to around 1600 tonnes of CO2-equivalents. Translating this and other environmental aspects to monetary values with the EPS system, socio-economic savings is around 2.3 million Euro. Assuming the same composition of items for potential reuse from all renovation activities in Sweden and extrapolating to the total annual amount of building waste, the potential annual savings on the national scale is estimated to be 900000 tons of building waste and 1.3 million tons of CO2 equivalents, corresponding to around 7% of the total annual greenhouse gas emissions of the Swedish building sector. With the EPS evaluation, the total annual environmental benefit adds up to 600 million Euro. The calculation model is currently being refined to include a better coverage of logistics and refurbishment activities.

This paper presents a study of children’s ideas of the body’s internal structure. Children between four and 13 years (N = 170) individually produced drawings. During each drawing session the children explained their drawings to a facilitator and added written labels either by them- selves or, if they were too young to write, with the facilitator’s help. The results provide an updated comprehensive picture of children in differ- ent age groups and their views on the internal structure of the body. The type and numbers of organs drawn are similar to those documented in previous studies. However, in comparison to recent studies, the children drew more organs, the brain was indicated almost as often as the heart, and the Valentine heart was frequently used as a symbol. In contrast with previous research, children drew connections between organs. This result calls for caution regarding conclusions made from decontextua- lized questions. The importance of providing children with the opportu- nity to clarify their drawings is emphasised since it otherwise becomes a question of the researcher’s interpretation. The connections they draw, and explanations they give to their drawings, have interesting implica- tions for understanding children’s ideas, and hence both for teaching and learning and for science education research.

The prevalence, distribution, and location of dental caries were studied in complete and partial human dentitions dating from the Viking Age dating (900-1050 AD) excavated in Kopparsvik on island of Gotland, Sweden. 18 individuals and a total of 370 teeth were examined, using a strong light source and dental probe. Carious lesions were found in a large number of the individuals, 14 out of 18. The percentage of teeth affected by caries (11,9%) corresponds well with studied skull materials from the same period. The surface most susceptible to caries was the occlusal surface, whereas only a few proximal lesions and one single carious root surface was found. The tooth most commonly affected by caries was the mandibular first molar. The tooth most commonly missing ante-mortem was also the mandibular molar, and the tooth most commonly missing post mortem was the mandibular incisor. Other findings included apical infections, which were detected clinically in 3% of the teeth.

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) causing gait impairment, dementia and urinary incontinence among the elderly, is probably under-diagnosed and under-treated. Despite being known since the 1960s, there is still a lack of prospective, population-based studies on the prevalence of iNPH. Such studies are warranted to minimize selection bias and estimate the true prevalence of the disease.MethodsThe prevalence of iNPH was determined in a randomly selected sample of residents, aged 65 years and older, in the Swedish county of Jämtland. Out of 1,000 individuals invited to participate, 673 (67.3%) completed a questionnaire with seven questions on iNPH symptoms. A subgroup, with and without self-reported symptoms, participated in clinical and radiological evaluations and were diagnosed according to international guidelines. Measurement of cerebrospinal fluid opening pressure was not performed as it was considered too invasive.ResultsThose who reported at least two symptoms in the questionnaire (n = 117) and 51 randomly selected individuals with 0-1 symptom participated in further examinations. Out of them, 25 individuals received the diagnosis probable iNPH according to American-European guidelines (except for the criterion of CSF opening pressure) corresponding to a prevalence of 3.7%. The prevalence of iNPH was four times higher among those aged 80 years and older (8.9%) than among those aged 65-79 years (2.1%) (p ConclusionsIn this prospective, population-based study the prevalence of iNPH was 3.7% among individuals 65 years and older, and more common in the higher age group, 80 years and above. INPH should be increasingly recognized since it is a fairly common condition and an important cause of gait impairment and dementia among the elderly that can be effectively treated by shunt surgery.

DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.

This unique study combined the lab and full scales to investigate how the anaerobic digestion process of sewage sludge was affected by a temperature change within the lower mesophilic temperature range (32–37.5 °C). Both scientific methane potential experiments and dewaterability studies were made to be used in changes of the operational conditions for a full-scale wastewater treatment plant. The aim of this study was to reduce anaerobic digestions heat consumption by altering the operational mesophilic temperature in first lab-scale experiments and then in continuation to full-scale conditions. The results of the study suggest that it is possible to save approximately 13% in heat energy demand each year by reducing the temperature for anaerobic digestion by 2.5 °C. At the lab scale, the effect of temperature on biogas production was tested in a batch experiment by measuring the biochemical methane production. At 32 °C, the production of biogas decreased by 11% compared to that at 37.5 °C. No significant difference was observed between 37.5 °C and 34.5 °C. The effect of temperature on sludge dewaterability was tested by measuring the capillary suction time, and no difference was detected between various temperatures. To confirm these results, the temperature in two full-scale digesters was gradually adjusted from 37.5 °C to 35 °C. No change was observed in biogas production, process stability, or dewaterability. The amount of heat energy that can be saved for the full-scale digesters was calculated using a heat balance. This study shows that it is possible to reduce the heat demand for AD in real applications without compromising the biogas production and process stability.

Hypothesis Liquid can move by capillary action through interconnected porous materials, as in fabric or paper towels. Today mass transport is controlled by chemical modification. It is, however, possible to direct mass transport by geometrical modifications. It is here proposed that it is possible to tailor capillary flow speed in a model system of micro-channels by the angle, size and position of attached side channels. Experiments A flexible, rapid, and cost-effective method is used to produce micro-channels in gels. It involves 3D-printed moulds in which gels are cast. Open channels of micrometre size with several side channels on either one or two sides are produced with tilting angles of 10 – 170°. On a horizontal plane the meniscus of water driven by surface tension is tracked in the main channel. Findings The presence of side channels on one side slowed down the speed of the meniscus in the main channel least. Channels having side channels on both sides with tilting angles of up to 30° indicated tremendously slower flow, and the liquid exhibited a stick-slip motion. Broader side channels decreased the speed more than thinner ones, as suggested by the hypothesis. Inertial forces are suggested to be important in branched channel systems studied here.

Capillary action has been described by Lucas and Washburn and extensively studied experimentally in hard materials, but few studies have examined capillary action in soft materials such as hydrogels. In tissue engineering, cells or dispersions must be often distributed within a hydrogel via microporous paths. Capillary action is one way to disperse such substances. Here, we examine the dynamics of capillary action in a model system of straight capillaries in two hydrogels. The channels had a circular cross-section in the micrometer size range (180-630 ?m). The distance travelled over time was recorded and compared with the predictions of Lucas and Washburn. Besides water, we used a sucrose solution and a hydroxyethyl cellulose solution, both with viscosities slightly higher than that of water. The results showed that the distance travelled is proportional to the square root of time, , and that larger capillaries and lower viscosities result, as expected, in faster speeds. However, the absolute experimental values display large discrepancies from the predictions. We demonstrate that several possible reasons for these discrepancies can be ruled out and we describe a novel hypothesis for the cause of the retarded meniscus movement.

This study investigates primary school children’s (7-8 year-old, N = 25) ideas of mixing of marbles and of heat, expressed in small-group predict-observe-explain exercises, and drawings representing the children’s own analogies in a classroom setting. The children were typically found to predict that marbles of two different colours would mix when rocked back and forth on a board. This idea of mixing is slightly more advanced than previously reported in the literature. The children’s ideas of heat included reference to warm objects, their own bodies when exercising, and the process of one warm solid object heating another object in direct contact. In addition, through scaffolding, some of the children expressed a substance view of heat. Finally, the potential and challenges in probing children’s ideas through a combination of data collection techniques in a classroom setting are reflected upon. Key words: heat, mixing, children’s ideas, primary school, classroom setting.

Purpose– The purpose of this paper is to analyse how accounts of collaboration practice were made and used to construct accountability in the empirical context of coordination associations, a Swedish form of collaboration between four authorities in health and social care. They feature pooled budgets, joint leadership and joint reporting systems, intended to facilitate both collaboration and (shared) accountability.Design/methodology/approach– Empirical data were collected in field observations in local, regional and national settings. In addition, the study is based on analysis of local association documents such as evaluations and annual reports, and analysis of national agency reports.Findings– Accountability is constructed hierarchically with a narrow focus on performance, and horizontal (shared) accountability as well as outcomes are de-emphasised. Through this narrow construction of accountability the coordination associations are re-created as hierarchical and accountability is delegated rather than shared.Research limitations/implications– Features such as pooled budgets, joint leadership and joint reporting systems can support collaboration but do not necessarily translate into shared accountability if accountability is interpreted and constructed hierarchically.Practical implications– When practice conforms to what is counted and accounted for, using the hierarchical and narrow construction of accountability, the result may be that the associations become an additional authority. That would increase rather than decrease fragmentation in the field.Originality/value– This research derives from first-hand observations of actor-to-actor episodes complemented with the analysis of documents and reports. It provides critical analysis of the construction and evaluation of accounts and accountability related to practice and performance in collaboration. The main contribution is the finding that despite the conditions intended to facilitate inter-organisational collaboration and horizontal accountability, the hierarchical accountability persisted.

The slow dissociation of DNA threading intercalators makes them interesting as model compounds in the search for new DNA targeting drugs, as there appears to be a correlation between slow dissociation and biological activity. Thus, it would be of great value to understand the mechanisms controlling threading intercalation, and for this purpose we have investigated how the length of the bridging ligand of binuclear ruthenium threading intercalators affects their DNA binding properties. We have synthesised a new binuclear ruthenium threading intercalator with slower dissociation kinetics from ct-DNA than has ever been observed for any ruthenium complex with any type of DNA, a property that we attribute to the increased distance between the ruthenium centres of the new complex. By comparison with previously studied ruthenium complexes, we further conclude that elongation of the bridging ligand reduces the sensitivity of the threading interaction to DNA flexibility, resulting in a decreased AT selectivity for the new complex. We also find that the length of the bridging ligand affects the enantioselectivity with increasing preference for the ΔΔ enantiomer as the bridging ligand becomes longer.

The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.

X‐ray crystal structures of three Λ‐[Ru(L)2dppz]2+ complexes (dppz=dipyridophenazine; L=1,10‐phenanthroline (phen), 2,2′‐bipyridine (bpy)) bound to d((5BrC)GGC/GCCG) showed the compounds intercalated at a 5′‐CG‐3′ step. The compounds bind through canted intercalation, with the binding angle determined by the guanine NH2 group, in contrast to symmetrical intercalation previously observed at 5′‐TA‐3′ sites. This result suggests that canted intercalation is preferred at 5′‐CG‐3′ sites even though the site itself is symmetrical, and we hypothesise that symmetrical intercalation in a 5′‐CG‐3′ step could give rise to a longer luminescence lifetime than canted intercalation.

The bi-exponential emission decay of [Ru(L)(2)dppz](2+) (L = N,N'-diimine ligand) bound to DNA has been studied as a function of polynucleotide sequence, enantiomer, and nature of L (phenanthroline vs. bipyridine). The lifetimes (τ(i)) and pre-exponential factors (α(i)) depend on all three parameters. With [poly(dA-dT)](2), the variation of α(i) with [Nu]/[Ru] has little dependence on L for Λ-[Ru(L)(2)dppz](2+) but a substantial dependence for Δ-[Ru(L)(2)dppz](2+). With [poly(dG-dC)](2), by contrast, the Λ-enantiomer α(i) values depend strongly on the nature of L, whereas those of the Δ-enantiomer are relatively unaffected. DNA-bound linked dimers show similar photophysical behaviour. The lifetimes are identified with two geometries of minor-groove intercalated [Ru(L)(2) dppz](2+), resulting in differential water access to the phenazine nitrogen atoms. Interplay of cooperative and anti-cooperative binding resulting from complex-complex and complex-DNA interactions is responsible for the observed variations of α(i) with binding ratio. [Ru(phen)(2)dppz](2+) emission is quenched by guanosine in DMF, which may further rationalise the shorter lifetimes observed with guanine-rich DNA.

A newly developed gentle ion beam polishing technique was established for preparing of cross sections of dental implants feasible for high resolution scanning electron microscope investigation. This approach was applied to investigate the interfacial microstructure between newly formed bone and dental implants with modified surfaces extracted after in vivo test in adult miniature pigs. The results obtained so far reveal that it has become possible to analyze the bone coherence to implants besides measuring the bone coverage. The amount and density of the mineralized extra cellular matrix has found to be different in different sub-microscopic regions around the implant. From our observations, it can be seen that new bone grows from the existing bone and advances towards the implant surface by in growth mechanism. The images also reveal that new bone is formed directly at the implant surface; we propose a deposition mechanism to explain this. Eventually the in grown and the deposited bone connect to give a good anchorage of the implant. This achievement bears implication for understanding osseointegration at microscopic level.

This exploratory study in a classroom setting investigates first graders (age 78 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at making analogical comparisons between known objects provided by a researcher and that some of the children could come up with their own analogies for the abstract natural phenomena with which they interacted. The use of full-class and small-group settings, shared laboratory experiences of the phenomena and childrens drawings as different kinds of scaffolding was found to be helpful for the childrens analogical reasoning. As an implication for science education, self-generated analogies are put forward as a potential learning tool within a constructivist approach to education.

Threading intercalation is an unusual DNA binding mode that displays extremely slow dissociation kinetics, which is an important feature for cytotoxicity, making threading intercalating compounds interesting as model compounds in the search for new DNA binding drugs. This type of binding has for ruthenium complexes previously only been observed for complexes containing 11-substituted dipyridophenazine ligands. In this work we have synthesized and investigated the DNA binding properties of two new 10,13-diarylsubstituted dipyridophenazine ruthenium complexes, using spectroscopic techniques, and found that this substitution pattern provides a new strategy for development of drugs with slow dissociation kinetics. However, the nature of the aryl substituents largely affects the binding properties of the complexes as it was found that a dithienyl substituted complex exhibit slow dissociation kinetics characteristic for threading intercalation while its diphenyl substituted analogue seems to bind DNA by partial intercalation of one phenyl substituent resulting in faster dissociation.

The binuclear ruthenium complex [μ-bidppz(phen)(4)Ru(2)](4+) has been extensively studied since the discovery of its unusual threading intercalation interaction with DNA, a binding mode with extremely slow binding and dissociation kinetics. The complex has been shown to be selective towards long stretches of alternating AT base pairs, which makes it interesting, for example, as a model compound for anti-malaria drugs due to the high AT content of the genome of the malaria parasite P. falciparum. We have investigated the effect of bridging ligand structure on threading intercalation ability and found that length and rigidity as well as the size of the intercalated ring system are all factors that affect the rate and selectivity of the threading intercalation. In particular, we discovered a new DNA-threading compound, [μ-dppzip(phen)(4)Ru(2)](4+), which appears to be just at the border of being capable of threading intercalation and displays even greater selectivity for AT-DNA than the parent compound, [μ-bidppz(phen)(4)Ru(2)](4+).

The European Commission (EC) Directive on in vitro diagnostic medical devices requires—amongst other obligations—manufacturers to establish metrological traceability of values assigned to calibrators to available measurement procedures and/or available reference materials of a higher order. Manufacturers use different procedures to accomplish this task and to indicate uncertainties of assigned values. Medical laboratories may want to calculate the uncertainties of their results or accreditation bodies may require them to do so. For this purpose some practical approaches are presented and some examples discussed.

The National Institute of Clinical Excellence (NICE) released new fluid guidelines following data suggesting 20% of patients receiving fluids suffer adversely (2013). This quality improvement group assessed fluid prescribing in a tertiary teaching centre and introduced a new fluid- prescribing chart to align practice with NICE recommendations. Notes and corresponding fluid prescription charts were reviewed for evidence of (1) indication, (2) co-morbidities, and (3) further management as surrogate markers of safe prescribing in accordance with NICE. Overall, the data showed practice fell short and prompted a redesign of the Trust fluid prescription chart. Three different variations of the chart were issued consecutively using a PDSA method (plan, do, study, act) over a 6-month period. They all included indication, co-morbidities and further management plans as constant design features. Suggestions from interested parties were incorporated and an educational programme was implemented to promote awareness. Prior to our intervention, an indication for fluids was documented in 26% of notes, it took an average of 4.6 minutes to find co-morbidities, and further management plans were rarely documented. Following the new prescription chart, an indication was recorded in 72% of cases, co-morbidities noted on 63% of charts with 93.1% accuracy, and further management documented in 100% of cases. The new fluid prescription chart encourages prescribers to incorporate NICE recommendations when prescribing fluids. The new fluid prescription design has since been rolled out Trust wide.

Binuclear ruthenium complexes demonstrate slow dissociation upon binding to DNA, and they are considered as potential DNA-targeted therapeutic drugs. Quantitative investigations of their properties, such as binding affinity, binding mode and kinetics, require approaches beyond traditional experimental techniques. In particular, previous reports showed that the rotationally flexible binuclear ruthenium complex Δ,Δ-[µ-bipb(phen)4Ru2]4+ (Δ,Δ-Pi) strongly condenses DNA. However, the strong DNA condensation poses a challenge in bulk experiments such that even the DNA-ligand binding mode could not be resolved. We examined the kinetics of ΔΔ-Pi interactions with single λ-DNA molecule as a function of a constant applied force of 30 pN and ligand concentration of 5 nM using dual-beams optical tweezers. We find that Δ,Δ-Pi exhibits characteristics of threading intercalation into DNA base pairs. DNA elongation measurements, as monitored over tens of minutes, illustrate two distinct phases during association; rapid intercalation that is analogous to classic intercalation, followed by very slow intercalation that approaches equilibrium with a rate that is comparable to that observed for other threading intercalators. We investigated ΔΔ-Pi dissociation after reaching the equilibrium extension by rinsing the binding ligands from the surrounding solution, and observed that the DNA-ligand complex extension decreases to the DNA-only extension over a timescale longer than the association process. Interestingly, the dissociation measurements fit well to a single rate that is slower than the dissociation rate measured for the previously reported binuclear ruthenium complex Δ,Δ-[µ-bidppz-(phen)4Ru2]4+ (Δ,Δ-P), which is a threading intercalator. Further measurements of force-dependent intercalation thermodynamics and kinetics will allow us to fully quantitatively characterize the complex binding mechanism of this unusual intercalator.

Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.

PurposeA Swedish framework law has enabled integration between public agencies in vocational rehabilitation. With the support of this law, coordination associations can be formed to fund and organize joint activities. The purpose of this study is to describe and analyze how the law has been interpreted and translated into local coordination associations and how local institutional logics have developed to guide the organization of these associations.Design/methodology/approachData was collected through observations of meetings within two coordination associations and supplemented with documents. The material was analyzed by compilation and examination of data from field notes, whereupon the most important aspects were crystallized and framed with institutional organization theory.FindingsTwo different translations of the law were seen in the associations studied: the association as an independent actor, and as an arena for its member organizations. Two subsequent institutional logics have developed, influencing decisions on autonomy, objectives and rationality for initiating and organizing in the two associations and their activities. The institutional logics are circular, further enhancing the different translations creating different forms of integration.Research implications/limitationsBoth forms of integration are legitimate, but the different translations have created integration with different degrees of autonomy in relation to the member organizations. Only a long‐term analysis can show whether one form of integration is more functional than the other.Originality/valueThis article is based on an extensive material providing insights into a form of interorganizational integration which has been scarcely researched. The findings show how different translations can influence the integration of welfare services.

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors. Electronic supplementary material The online version of this article (doi:10.1007/s00775-012-0877-0) contains supplementary material, which is available to authorized users.

Introduction: Collaboration between welfare organizations is an important strategy for integrating different health and welfare services. This article reports a review of the international literature on vocational rehabilitation, focusing on different organizational models of collaboration as well as different barriers and facilitating factors. Methods: The review was based on an extensive search in scientific journals from 1995 to 2010, which generated more than 13 000 articles. The number of articles was reduced in different steps through a group procedure based on the abstracts. Finally, 205 articles were read in full text and 62 were included for content analysis. Results: Seven basic models of collaboration were identified in the literature. They had different degrees of complexity, intensity and formalization. They could also be combined in different ways. Several barriers and facilitators of collaboration were also identified. Most of these were related to factors as communication, trust and commitment.Conclusion: There is no optimal model of collaboration to be applied everywhere, but one model could be more appropriate than others in a certain context. More research is needed to compare different models and to see whether they are applicable also in other fields of collaboration inside or outside the welfare system.

Threading intercalation is an unusual DNA binding mode with significantly slower association and dissociation rates compared with classical intercalation. The latter has been shown to correlate well with cytotoxicity, and therefore, threading intercalating compounds are of great interest in the search for new DNA binding drugs. Thus, there is a need for better understanding of the mechanisms behind this type of binding. In this work, we have investigated the threading intercalation ability, of the four stereoisomers of the AT-specific binuclear ruthenium complex [mu-dppzip(phen)(4)Ru(2)](4+) using different spectroscopic techniques. This complex contains an unsymmetrical bridging ligand consisting of a dipyridophenazine and an imidazophenanthroline ring system, in which the photophysical properties of the Ru-dipyridophenazine complex moiety make it possible to distinguish the intercalating part from the nonintercalating part We have found that Delta geometry around the ruthenium on the intercalating dipyridophenazine moiety and Lambda geometry on the nonintercalating imidazophenanthroline moiety is the optimal configuration for threading intercalation Of this complex and that the chirality on the ruthenium of the nonintercalating half dominates the stereospecificity in the threaded state. This is the cause of the reversed enantioselectivity compared with the parent threading intercalating complex [mu-bidppz(phen)(4)Ru(2)](4+), in which the enantioselectivity is controlled by the chirality on the intercalating half. The differences in the interactions with DNA between the two, complexes are most likely due to the fact that [mu-dppzip(phen)(4)Ru(2)](4+) has a slightly shorter bridging ligand than the parent complex.