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Perioperative bleeding is a common complication in surgeries that increases morbidity, risk of mortality, and leads to increased socioeconomic costs. In this study we investigated a blood-derived autologous combined leukocyte, platelet, and fibrin patch as a new means of activating coagulation and maintaining hemostasis in a surgical setting. We evaluated the effects of an extract derived from the patch on the clotting of human blood in vitro, using thromboelastography (TEG). The autologous blood-derived patch activated hemostasis, seen as a reduced mean activation time compared to both non-activated controls, kaolin-activated samples, and fibrinogen/thrombin-patch-activated samples. The accelerated clotting was reproducible and did not compromise the quality or stability of the resulting blood clot. We also evaluated the patch in vivo in a porcine liver punch biopsy model. In this surgical model we saw 100% effective hemostasis and a significant reduction of the time-to-hemostasis, when compared to controls. These results were comparable to the hemostatic properties of a commercially available, xenogeneic fibrinogen/thrombin patch. Our findings suggest clinical potential for the autologous blood-derived patch as a hemostatic agent. Graphical Abstract

The diagnosis and treatment of head and neck cancer (HNC) can have substantial impact on swallowing function, nutritional balance, physical function and quality of life (QoL). Early initiated swallowing exercises are hypothesized to improve swallowing function in HNC patients. The aim was to investigate the effects of swallowing exercises and progressive resistance training (PRT) during radiotherapy on swallowing function, physical function and QoL in patients with pharynx-, larynx-, oral cavity cancer or unknown primary compared to usual care. In a multi-centre RCT participants were assigned to (a) twice-weekly PRT and daily swallowing exercises throughout treatment or (b) usual care. Outcomes were measured at end of treatment and 2, 6 and 12 months after. Primary outcome was penetration aspiration score (PAS). Data were analysed on an “intention-to-treat” basis by GEE logistic regression model, linear mixed effects model and cox regression. Of 371 invited HNC patients, 240 (65%) enrolled. Five participants were excluded. At 12 months follow-up, 59 (25%) participants were lost. Analyses showed significant effect on mouth opening, QoL, depression and anxiety at 12 months when comparing intervention to non-active controls. The trial found no effect on swallowing safety in HNC undergoing radiotherapy, but several positive effects were found on secondary outcomes when comparing to non-active controls. The intervention period may have been too short, and the real difference between groups is too small. Nevertheless, the need to identify long-lasting intervention to slow down or avoid functional deteriorations is ever more crucial as the surviving HNC population is growing.

Background: Despite the intriguing potential of physical exercise being able to preserve or even restore brain volume (grey matter volume in particular)—a tissue essential for both cognitive and physical function—no reviews have so far synthesized the existing knowledge from randomized controlled trials investigating exercise-induced changes of the brain’s grey matter volume in populations at risk of neurodegeneration. Our objective was to critically review the existing evidence regarding this topic. Methods: A systematic search was carried out in MEDLINE and EMBASE databases primo April 2020, to identify randomized controlled trials evaluating the effects of aerobic training, resistance training or concurrent training on brain grey volume changes (by MRI) in adult clinical or healthy elderly populations. Results: A total of 20 articles (from 19 RCTs) evaluating 3–12 months of aerobic, resistance, or concurrent training were identified and included, involving a total of 1662 participants (populations: healthy older adults, older adults with mild cognitive impairment or Alzheimer’s disease, adults with schizophrenia or multiple sclerosis or major depression). While few studies indicated a positive effect—although modest—of physical exercise on certain regions of brain grey matter volume, the majority of study findings were neutral (i.e., no effects/small effect sizes) and quite divergent across populations. Meta-analyses showed that different exercise modalities failed to elicit any substantial effects on whole brain grey volume and hippocampus volume, although with rather large confidence interval width (i.e., variability). Conclusion: Altogether, the current evidence on the effects of physical exercise on whole/regional grey matter brain volume appear sparse and inconclusive, and does not support that physical exercise is as potent as previously proposed when it comes to affecting brain grey matter volume.

Topological properties of materials are of fundamental as well as practical importance1,2. Of particular interest are unconventional superconductors that break time-reversal symmetry, for which the superconducting state is protected topologically and vortices can host Majorana fermions with potential use in quantum computing3,4. However, in striking contrast to the unconventional A phase of superfluid 3He where chiral symmetry was directly observed5, identification of broken time-reversal symmetry of the superconducting order parameter, a key component of chiral symmetry, has presented a challenge in bulk materials. The two leading candidates for bulk chiral superconductors are UPt3 (refs. 6–8) and Sr2RuO4 (ref. 9), although evidence for broken time-reversal symmetry comes largely from surface-sensitive measurements. A long-sought demonstration of broken time-reversal symmetry in bulk Sr2RuO4 is the observation of edge currents, which has so far not been successful10. The situation for UPt3 is not much better. Here, we use vortices to probe the superconducting state in ultraclean crystals of UPt3. Using small-angle neutron scattering, a strictly bulk probe, we demonstrate that the vortices possess an internal degree of freedom in one of its three superconducting phases, providing direct evidence for bulk broken time-reversal symmetry in this material. Small-angle neutron scattering measurements show that the vortices of the heavy-fermion compound UPt3 possess an internal degree of freedom in one of its three superconducting phases, implying the breaking of time-reversal symmetry in the bulk.

Children with congenital heart defects (CHDs) have increased risk of cognitive disabilities for reasons not fully understood. Previous studies have indicated signs of disrupted fetal brain growth from mid-gestation measured with ultrasound and magnetic resonance imaging (MRI) and infants with CHDs have decreased brain volumes at birth. We measured the total and regional brain volumes of infants with and without CHDs using MRI to investigate, if certain areas of the brain are at particular risk of disrupted growth. MRI brain volumetry analyses were performed on 20 infants; 10 with- (postmenstrual age 39–54 weeks, mean 44 weeks + 5 days) and 10 without CHDs (postmenstrual age 39–52 weeks, mean 43 weeks + 5 days). In six infants with- and eight infants without CHDs grey and white matter were also differentiated. Infants with CHDs had smaller brains (48 ml smaller; 95% CI, 6.1–90; p = 0.03), cerebrums (37.8 ml smaller; 95% CI, 0.8–74.8; p = 0.04), and cerebral grey matter (25.8 ml smaller; 95% CI, 3.5–48; p = 0.03) than infants without CHD. Brain volume differences observed within weeks after birth in children with CHDs confirm that the brain impact, which increase the risk of cognitive disabilities, may begin during pregnancy.

Background The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. Methods Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. Results Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer’s disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. Conclusions Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer’s disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

Improving outcomes for patients undergoing transitions of care has become an international priority. A key ingredient of effective care transitions is compassionate care provided by healthcare providers with a good understanding of patients’ post-discharge needs. Enhancing empathy in future physicians is a critical task of medical education best promoted by experiential methods of training that allow for student interaction with patients across care settings. Our curriculum aimed at promoting understanding of the risks associated with care transitions, clinical empathy, and positive attitudes towards patient safety in transitions. The curriculum was delivered to 140 fourth year medical students during their required 4-week inpatient medicine clerkship, using a multimodal approach that combined didactic, experiential, and web-based study. This paper describes a qualitative evaluation of students’ responses to their experiences while monitoring the transition of their patients across care settings. Findings reflect development of empathetic insight among students, as well as increased ability to identify and address post-discharge needs of at-risk patients. Of the 140 students who participated in the curriculum, 64 students identified three potential areas of lapses during the transition of their patients from the inpatient to the outpatient setting within the following categories: (1) system-related issues, (2) provider-related issues, (3) patient-related issues. Curricular methods that provide direct patient exposure along with reflection will be helpful in promoting empathy and positive attitudes towards best practices in care transitions.

Corrosive wear of cylinder liners in large two-stroke marine diesel engines that burn heavy fuel oil containing sulfur is coupled to the formation of gaseous sulfur trioxide (SO3) and subsequent combined condensation of sulfuric acid (H2SO4) and water (H2O) vapor. The present work seeks to address how fuel sulfur content, charge air humidity and liner temperature variations affects the deposition of water and sulfuric acid at low load operation. A phenomenological engine model is applied to simulate the formation of cylinder/bulk gas combustion products and dew points comply with H2O–H2SO4 vapor liquid equilibrium. By assuming homogenous cylinder gas mixtures condensation is modeled using a convective heat and mass transfer analogy combined with realistic liner temperature profiles. Condensation of water is significantly altered by the liner temperature and charge air humidity while sulfuric acid condensation (the order is a few mg per cylinder every cycle) is proportional to the fuel sulfur content. Condensation takes place primarily in the upper part of the cylinder liner where a reduction of the surface temperature or saturated charge air provides that the deposited acid can be highly diluted with water.

Background This paper reports on the process of involving former and current cancer patients and carers as co-researchers in a Danish mixed methods research project on patient empowerment of cancer patients in follow up (The Empowerment study 2015–2019). User-Involvement in health care research is a relatively new practice in Denmark and the Empowerment project was one of the first to systematically involve patients and carers in its research design, conduct and reporting. The paper has two aims: first, it provides a detailed account of the process of involving co-researchers in the Empowerment project and second, it presents findings from a workshop held with academic researchers and co-researchers on the project to discuss their experiences and recommendations for user-involvement in the Danish context. Methods The Empowerment project adopted a consultative and collaborative approach to user involvement and co-researchers were involved from the early stages and all through the project. Users gave feedback on the proposal, helped develop project documents and research tools, acted as peer interviewers in qualitative interviews, participated in data analysis and development of questionnaires, and co-authored journal articles. The workshop held with the academic researchers and co-researchers consisted of two parallel focus groups and a joint group discussion, following an interactive and informal format to facilitate discussion and exchange of ideas. Findings The focus group resulted in eleven recommendations for the further development of user-involvement in Denmark. Key issues encountered were the general lack of guidelines on user-involvement in the Danish context and the need for more organisational support. Particular issues, such as payment, recruitment and training, need to be carefully considered within individual projects and within the national context in which projects are carried out. Conclusion The paper adds to the current very limited knowledge base on user-involvement in the Danish context and provides a set of early recommendations for the further development of the practice in Danish Health Research. User-involvement needs to be developed with consideration to the local context, but common challenges also emphasise the usefulness of cross-country comparisons and knowledge exchange. Electronic supplementary material The online version of this article (10.1186/s40900-018-0105-3) contains supplementary material, which is available to authorized users.

All abstracts from the NIHR INVOLVE Conference 2017. Poster 27 - P27 Discovering the role of public co-applicant on a National Institute for Health Research (NIHR) Programme grant Research Involvement and Engagement 2017, 3(Suppl 1):P27

The Wadden Sea along the North Sea coasts of Denmark, Germany, and the Netherlands is the largest unbroken system of intertidal sand and mud flats in the world. Its habitats are highly productive and harbour high standing stocks and densities of benthic species, well adapted to the demanding environmental conditions. Therefore, the Wadden Sea is one of the most important areas for migratory birds in the world and thus protected by national and international legislation, which amongst others requires extensive monitoring. Due to the inaccessibility of major areas of the Wadden Sea, a classification approach based on optical and radar remote sensing has been developed to support environmental monitoring programmes. In this study, the general classification framework as well as two specific monitoring cases, mussel beds and seagrass meadows, are presented. The classification of mussel beds profits highly from inclusion of radar data due to their rough surface and achieves agreements of up to 79 % with areal data from the regular monitoring programme. Classification of seagrass meadows reaches even higher agreements with monitoring data (up to 100 %) and furthermore captures seagrass densities as low as 10 %. The main classification results are information on area and location of individual habitats. These are needed to fulfil environmental legislation requirements. One of the major advantages of this approach is the large areal coverage with individual satellite images, allowing simultaneous assessment of both accessible and inaccessible areas and thus providing a more complete overall picture.

Here we review recent small-angle scattering studies of the vortex lattice in a range of type-II superconductors carried out by our group. Emphasis is placed on providing examples of the kind of information which can be obtained by such measurements, focusing in particular on studies of the vortex lattice structure and form factor in LuNi2B2C, TmNi2B2C, CeCoIn5 and Ba(Fe0.93Co0.07)2As2.

In acute ischemic stroke, critical hypoperfusion is a frequent cause of hypoxic tissue injury: As cerebral blood flow (CBF) falls below the ischemic threshold of 20 mL/100 mL/min, neurological symptoms develop and hypoxic tissue injury evolves within minutes or hours unless the oxygen supply is restored. But is ischemia the only hemodynamic source of hypoxic tissue injury? Reanalyses of the equations we traditionally use to describe the relation between CBF and tissue oxygenation suggest that capillary flow patterns are crucial for the efficient extraction of oxygen: without close capillary flow control, “functional shunts” tend to form and some of the blood’s oxygen content in effect becomes inaccessible to tissue. This phenomenon raises several questions: Are there in fact two hemodynamic causes of tissue hypoxia: Limited blood supply (ischemia) and limited oxygen extraction due to capillary dysfunction? If so, how do we distinguish the two, experimentally and in patients? Do flow-metabolism coupling mechanisms adjust CBF to optimize tissue oxygenation when capillary dysfunction impairs oxygen extraction downstream? Cardiovascular risk factors such as age, hypertension, diabetes, hypercholesterolemia, and smoking increase the risk of both stroke and dementia. The capillary dysfunction phenomenon therefore forces us to consider whether changes in capillary morphology or blood rheology may play a role in the etiology of some stroke subtypes and in Alzheimer’s disease. Here, we discuss whether certain disease characteristics suggest capillary dysfunction rather than primary flow-limiting vascular pathology and how capillary dysfunction may be imaged and managed.

The aim of the present study was to compare the bioavailability of calcium from calcium carbonate and milk and to investigate if 1,200 IU of cholecalciferol a day increased intestinal absorption of calcium. Both young women and a group of older persons of both sexes were included to study the influence of age and sex. In total, 53 healthy women and men were included: a group of 23 younger women (median age 30) and an older group of 15 women and 15 men (median age 66). The study period was 4 weeks; each participant completed four treatment regimens randomly: CaCO(3), CaCO(3 )+ 1,200 IU of cholecalciferol, milk, and placebo. All regimens were distributed three times a day and consisted of 1,200 mg of elementary calcium. The 24-hour urine calcium excretion was used as a method. Total urinary calcium excretion rates (mmol/day) were as follows (mean +/- SD): placebo 4.41 +/- 2.17, milk 5.17 +/- 2.33, CaCO(3) 5.83 +/- 2.03, and CaCO(3 )+ D 6.06 +/- 2.46. All regimens compared to placebo were significant. Addition of cholecalciferol to the CaCO(3) regimen increased calcium excretion but insignificantly: 0.27 +/- 2.84 mmol/day. The increase in calcium excretion during the milk regimen was significant only for the old group: 0.96 vs. 0.28 mmol/day. No other difference was found according to age and sex. The bioavailability of calcium carbonate and milk was demonstrated. Additional cholecalciferol (1,200 IU) to individuals in positive calcium balance with serum 25(OH)D levels >50 nmol/L only marginally increased calcium absorption in a short-term intervention.

It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33 % of the Danish population). Current age of probands was 20–65 years and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4 %) were affected with IDDM. The sex difference in the parental-offspring IDDM transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 ± 0.6 and 5.7 ± 0.9 %, RR = 2.40, 95 % CI 1.30–4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 ± 1.8 and 3.6 ± 1.0 %; RR = 2.27, 95 % CI 1.21–4.25; p = 0.006). No such relation was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM. [Diabetologia (1998) 41: 666–673]

Low-energy neutrons are essential for the analysis and characterization of materials and magnetic structures. However, both continuous (reactor-based) and pulsed (spallation-based) sources of such neutrons suffer from low fluence. Steering and lensing devices could improve this situation dramatically, so increasing spatial resolution, detectable sample volume limits and even perhaps opening the way for the construction of a neutron microscope. Neutron optics have to date exploited either Bragg diffraction1,2, such as bent crystals, or reflection, as in mirror3 guides or a Kumakhov lens4,5. Refractive optics remain an attractive alternative as they would permit full use of the beam cross-section, allow a compact and linear installation and, because of similarity to conventional optics, enable the use of commercial design and simulation tools. These advantages notwithstanding, single-element refractive optics have previously been considered impractical as they are too weakly focusing, too absorptive and too dispersive. Inspired by the recent demonstration6 of a compound refractive lens (CRL) for high-energy X-rays, we have designed, built and tested a prototype CRL for 9–20-A neutrons by using readily available optical components: our CRL has gains greater than 15 and focal lengths of 1–6 m, well matched to small-angle neutron scattering.

This communication reviews the evidence for the pivotal role of protein kinase C in ischemic myocardial preconditioning. It is believed that several intracellular signalling pathways via receptor-coupled phospholipase C and its "cross-talk" with phospholipase D converge to activation of protein kinase C isotypes which is followed by phosphorylation of until now (a number of) unknown target proteins which produce the protective state of ischemic preconditioning. After briefly introducing the general biochemical properties of protein kinase C, its isotypes and the limitations of the methodology used to investigate the role of protein kinase C, studies are discussed in which pharmacological inhibition and activation and (immunore) activity and/or isotypes measurements of protein kinase C isotypes were applied to assess the role of activation of protein kinase C in ischemic myocardial preconditioning. It is concluded that definitive proof for the involvement of protein kinase C in preconditioning requires future studies which must focus on the isotype(s) of protein kinase C that are activated, the duration of action, cellular translocation sites and the identity and stability (of covalently bound phosphate) of phosphorylated substrate proteins.

We compare the results of small angle neutron scattering on the flux line lattice (FLL) obtained in the borocarbide superconductor LuNi2B2C with the applied field along the c- and a-axes. For H‖c the temperature dependence of the FLL structural phase transition from square to hexagonal symmetry was investigated. Above 10 K the transition onset field. H 2(T), rises sharply, bending away from H c2(T) in contradiction to theoretical predictions of the two merging. For H‖a a first order FLL reorientation transition is observed at H tr=3–3.5 kOe. Below H tr the FLL nearest neighbor direction is parallel to the b-axis, and above H tr to the c-axis. This transition cannot be explained using nonlocal corrections to the London model.