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Knowledge of the quantum response of materials is essential for designing light–matter interactions at the nanoscale. Here, the authors report a theory for understanding the impact of metallic quantum response on acoustic graphene plasmons and how such response could be inferred from measurements.

Here the authors show that radiation emitted by individual electrons can be controlled by shaping the electron wavepacket. They present feasible examples for applications including collimated and monochromatic X-ray emission from specially shaped electrons.

The main aim of this paper is to review existing European policies relevant to the biomass value chains and examine how their main objectives support or align with the five core objectives (pillars) identified under the 2018 Bioeconomy Strategy. The paper also discusses key challenges that restrict the compliance of the policies to the Strategy, identifies policy gaps and provides recommendations for future policy formation.A structured review was conducted of over ninety policies relevant to the biomass, bioprocessing and biobased products. The value chain approach was used as a tool to harmonise these sectors under a common bioeconomy framework and provides an understanding of how key activities and challenges are being addressed. Several gaps were identified in relation to these challenges in each stage, at land use stage a lack of European-wide harmonised characterisation of marginal land and integration among sectoral policies targeting soil quality and financial measures incentivising the uptake of sustainable soil improvers. At the biomass production stage, inadequate policy support was found for waste mobilisation and valorisation. Furthermore, there is a lack of policy provisions and financial support improving collaborations among value chain actors to overcome the complexity associated with harmonising biomass logistics and conversion processes. Finally, regarding the end use stage, policy interventions targeting the distribution and standardisation of the wide, available range of biobased products and services remain limited. Based on this gap analysis, a set of recommendations was produced outlining ways in which policy measures can be updated through introducing either financial, regulatory or information provisions, or formulating novel policies altogether. These recommendations were made following the value chain analysis approach, which addresses specific challenges in relation to the five core objectives of the Bioeconomy Strategy, with the aim of further increasing the level of coherence among sectoral policies.

Genome recoding with quadruplet codons requires a +1-frameshift-suppressor tRNA able to insert an amino acid at quadruplet codons of interest. Here the authors identify the mechanisms resulting in +1 frameshifting and the steps of the elongation cycle in which it occurs.

With federal political parties increasingly interested in new options for dental services, it’s worth exploring two policy solutions to expand dental care into the public realm. Denticare would be a universal dental program for all Canadian residents. Denticaid would be a public dental insurance program for all Canadian children and uninsured adults. This paper estimates the costs of each option through micro-costing, which identifies the likely resources patients would use in each program and sums each unit cost in a given year to generate the estimated annual clinical cost. With no dental record-level information available for academic research, these estimates rely on survey data on oral health collected from across Canada. In particular, this paper uses the Canadian Community Health Survey (CCHS) and the Canadian Health Measures Survey (CHMS), both released by Statistics Canada. When neither survey contains the necessary data to inform assumptions and costing, data from similar high-income jurisdictions are used. Denticare’s costs are estimated using four key variables: the expected number of Canadians using dental services in a given year, the expected number of visits per year, the probability of dental treatments used per visit and the expected price of dental treatments. The first variable is based on Statistics Canada’s 2016 census data, multiplied by their 2019 overall provincial population estimates. The second relies mostly on the CCHS question “when was the last time you visited the dentist?” The third variable uses Australian data and the fourth integrates data from a variety of provincial dental fee guides. High, low and baseline cost scenarios are included, with each province and territory’s clinical costs projected five years after implementation in all three scenarios. To project future changes 1 in service costs, the rate of price increase is calculated from changes between the 2015 and 2019 suggested fee schedules. Methods for micro-costing the denticaid program are similar to the denticare model and the variables are mostly treated similarly. However, the population variable is manipulated to account only for individuals without private dental insurance. There are limitations to this approach. The CCHS is only a telephone survey and does not collect dental data from across every province. The lack of pan-Canadian service-level use data meant that data from an Australian survey was used in its place. This model could not account for the effects of income on the frequency with which any particular dental treatment category is accessed per visit. Australia also covers most dental treatments for children, so use of dental services could be higher than what could be expected in Canada. To obtain a more exact picture, provincial governments should try to collect service-level data on dental use and dental practice activity. However, this paper does provide Canadian policy-makers interested in exploring some sort of public dental care program with a rigorous estimation of the reimbursement of clinical costs for the options of both denticare and denticaid programs.

Background: High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Consumption of dark chocolate, which is high in flavonoids that may reduce CVD risk, is an attractive intervention to reduce to BP. Additionally, the use of mobile health (mHealth) technologies (eg, telehealth, smartphones, and wearable devices) can improve outcomes in patients with CVD. Objective: The purpose of this study was to investigate the impact of dark chocolate intake on BP, subject use of mHealth, and integration of mHealth into a clinical trial. Methods: The COCOA-BP (ChOcolate COnsumption And Blood Pressure) study was a prospective, single-center, pre-/postintervention study that enrolled 62 healthy volunteers. The study consisted of 3 phases: smartwatch/smart BP monitor familiarization and washout from chocolate (week 1); control (week 2); and intervention (weeks 3 and 4). During the intervention phase, subjects consumed 50 g of dark chocolate per day. The primary endpoint was change in resting systolic BP between the intervention and control phases. Additional endpoints included device accuracy and correlation with physical activity. Results: Mean resting systolic BP was 116.4 mm Hg before chocolate intake among 62 participants (mean age 37 years; 61% female). After chocolate intake, mean resting systolic BP was 116.0 mm Hg (difference –0.4; P = .69). These findings suggest that 2 weeks of dark chocolate intake did not reduce resting systolic BP. There was poor agreement between mHealth device and standard (nurse-performed) measurements. Conclusion: In this study, short-term dark chocolate intake did not seem to reduce BP. mHealth technology shows great potential for use in clinical studies, but challenges related to device accuracy and compliance need to be addressed.

Canada’s universal health-care system does not include dental care, which presents problems for both low- and middle-income families. According to the latest Statistics Canada data, out-of-pocket dental expenses are increasing steadily. Lower-income workers struggle with a disproportionate share of these costs, leading one in 4.5 Canadians to avoid visits to the dentist. With dental care becoming increasingly unaffordable and private insurance harder to obtain, it’s time for Canada to consider bringing dental services into the public health system. Policy solutions have tended to fluctuate between a fill-in-the-gaps approach or comprehensive restructuring of dental care. This paper examines two new options: universal first-dollar coverage or denticare, and public dental insurance for all those without it or denticaid. Denticare would cover dental treatment with the same eligibility for public health insurance under the medicare system. Denticaid would only provide this to children under 12 and those lacking private insurance. Both denticare and denticaid would lower overall health-care costs, as improved oral hygiene would reduce rates of chronic and serious diseases. Integrating dentistry into the public health system would lead to increased patient contact, more efficient early screening and referrals. Direct clinical costs are estimated through micro-costing of expected annual dental services used. Indirect administrative costs are estimated through average costing based on existing per-patient administrative costs in the Canadian health-care system. Co-payments for both options are based on five household income brackets with the lowest bracket being exempt and the highest paying the maximum rate. The co-payment for advanced procedures would be 50 per cent and 20 per cent for all other services. Everyone over age 17 would have to pay an annual premium to be enrolled in the public plan; the lowest income brackets would be exempt and the highest would pay the maximum of $400. In denticare, public employees would no longer receive workplace dental benefits on the private market, while those same benefits would make them ineligible for denticaid. National clinical costs for a hypothetical denticare program in 2019, including administrative costs, are estimated at $27.50 billion ($737.09 per capita) with an upper estimate of $38.40 billion ($1,029.18 per capita) and a low estimate of $15.50 billion ($415.46 per capita). In all three scenarios, premiums paid by eligible individuals would generate $8.93 billion in annual revenues. After factoring in premiums, co-payments and the replacement of existing dental expenditures, the program’s net cost would be $6.01 billion in 2019, with an upper estimate of $15.09 billion and a lower estimate of negative $3.82 billion. Denticaid’s costs, including administrative costs, would be $15.09 billion ($404.49 per capita) in 2019, with a high scenario of $21.32 billion ($571.34 per capita) and a low scenario of $8.39 billion ($224.98 per capita). Denticaid’s premiums would generate less revenue to offset costs. The program’s net costs are estimated at $$7.47 billion in 2019, with a high estimate of $12.85 billion and a low estimate of $1.79 billion. There are additional challenges to consider, including dental office staffing levels in rural areas, dentists’ operating costs and orthodontic treatments. But none of this should prevent Canada from committing to a denticare program, which out-performs denticaid in terms of efficiency. Both federal and provincial governments would need to be involved in the necessary modifications to the Canada Health Act, with decisions on premiums and co-pays left to individual provinces. After those offsets, the remaining taxbased costs would be a relatively small increase in Canada’s public health spending and millions of Canadians would get access to good oral health.

Objectives: Randomized clinical trials do not include a population that truly reflects a real-world population, due to their inclusion and exclusion criteria. This leads to concerns about the applicability of these studies in a clinical practice. In the present study, we aim to describe the clinical and demographic characteristics, treatment patterns, and clinical outcomes in a population of patients with HER2-positive metastatic breast cancer who received pertuzumab and trastuzumab as first-line treatment in a real-world setting. Methods: The database of the Danish Breast Cancer Group was used to assemble data on patients included in the period April 2013 to August 2017. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A cohort of 291 patients with a median age of 58 years was registered. Hereof 112 (38%) patients with de novo disease (primary disseminated) and 179 (62%) with recurrence. The median follow-up for OS was 24.1 months. The median OS was 41.8 months (95% CI, 37.7 to NE) and the median PFS was 15.8 months (95% CI, 14.0 to 19.9). For de novo patients alone, the median OS was not reached whereas the median PFS was 17.9 months (95% CI, 14.3 to 27.3).Hazard ratios for patients receiving vinorelbine showed comparable results as for the whole population. Conclusion: This heterogeneous patient population in a real-world setting had a PFS comparable with what could be expected from the related randomized trial. The de novo patients had better OS and PFS as compared to patients with recurrence.

Purpose: To describe a novel surgical technique of a combined implantation of an artificial iris and a scleral fixated intraocular lens (IOL) using flanged IOL haptics (“Yamane” technique). Observations: The suturelessly implanted artificial iris-IOL-sandwich was stable with good functional as well as aesthetic results. However, our case showed a postoperative intraocular pressure rise. Conclusions: The presented case demonstrates that a visual as well as cosmetical rehabilitation seems to be possible even after severe, penetrating ocular trauma with profound iris defects. Importance: The sutureless IOL scleral fixation technique can also be used in combination with a sutureless artificial iris implantation. Further studies are needed to evaluate the long-term safety profile and rates of postoperative complications.

The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O2. Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions.

BackgroundIdentification of sex- and age-related differences in the presentation of atypical symptoms at stroke onset may reduce prehospital delay and improve stroke treatment if acknowledged at first contact.AimTo explore sex- and age-related differences in patient-reported typical and atypical symptoms of a stroke.MethodsWe used data from a cross-sectional survey at two non-comprehensive stroke units in the Capital Region of Denmark. Patient-reported symptoms, stroke knowledge, and behavioral response were analyzed by the Chi-square test or a Fisher's exact test separated by sex. Multivariable logistic regression adjusted for covariates were used to explore sex- and age-related differences according to each patient-reported typical or atypical symptoms.ResultsIn total, 479 patients with acute stroke were included (median age 74 years [25th to 75th percentile: 64–80], and 40.1% were women). Female sex was associated with higher odds of presenting with atypical symptoms, such as loss of consciousness (OR 2.12 [95% CI 1.08–4.18]) and nausea/vomiting (OR 2.33 [95% CI 1.24–4.37]), and lower odds of presenting with lower extremity paresis (OR 0.59 [95% CI 0.39–0.89). With each year of age, the odds decreased of presenting with sensory changes (OR 0.95 [95% CI 0.94–0.97]) and upper extremity paresis (OR 0.98 [95% CI 0.96–0.99]), whereas odds of presenting with dysphagia (OR 1.06 [95% CI 1.02–1.11]) increased.ConclusionsPatients of female sex and younger age reported on admission more frequently atypical stroke symptoms. Attention should be drawn to this possible atypical first presentation to facilitate correct identification and early stroke revascularization treatment to improve the outcome for both sexes.

Introduction and AimData remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH.MethodThis study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA2DS2-VASc and CCI was not adjusted for age.ResultsA total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs. 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs. 39.4% women), p = 0.009. Women were older (mean age 81.9 vs. 76.9 years, p < 0.001). CHA2DS2-VASc and CCI were similar in men and women.Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs. 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8;15] vs. 14 [10;15] p = 0.003).Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [aOR] = 0.52, p = 0.007) but not for surgical clot removal (aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week (aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration (aOR = 1.48, p = 0.10), ability to walk at 3 months (aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27).ConclusionSignificant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes.

Objective To estimate the modern contraceptive prevalence rate (mCPR) and its predictors among young women aged 15–24 years.Design Cross-sectional analysis of Adolescent Youth Project baseline survey.Setting 29 municipalities within Lumbini Province and Sudurpaschim Province in Western Nepal.Participants 683 young women aged 15–24 years who were living in the catchment area of the selected 30 private OK network health facilities at the study sites from November to December 2019 and who provided informed consent or assent.Outcome measure mCPR among young women aged 15–24 years.Results The mean age of the respondents was 19 years, 61.7% never had sex and 63.9% were unmarried. The mCPR was 11.9% (95% CI 9.5 to 14.8). Of those who reported using a modern method of contraception, injectables (37.9%) were the most common, followed by male condom (35.9%) and implants (8.8%). Majority (86.4%) of the respondents reported currently not using any method of contraception. In the binary logistic regression analysis, the odds of contraceptive use were higher among women aged 20–24 years (adjusted OR (AOR)=5.50, 95% CI 2.94 to 10.29) and those of Janajati caste/ethnicity (AOR=2.08, 95% CI 1.16 to 3.71), while the odds were lower among women who faced high level of barriers (individual, family/societal, service provider and health facility barriers) to contraceptive use (AOR=0.36, 95% CI 0.14 to 0.98).Conclusions The mCPR among young women aged 15–24 years was low but similar to the national level. Sexual and reproductive health programmes aiming to improve the mCPR in this population of young women should consider the reported level of sexual activity. Reaching young women to improve their knowledge and self-efficacy for contraception is critical to ensure they can access contraception when needed. The focus should be on reaching not just young women but also key influencers and service providers and making health facilities adolescent-friendly to reduce barriers to contraceptive uptake and to realise self-efficacy.

BackgroundFoam rolling has been shown to acutely improve joint range of motion (ROM). However, limited knowledge exists on the chronic and residual effects. The primary purpose of this study was to examine the chronic and residual effects of a 2-week roller–massager intervention on ankle dorsiflexion ROM and dynamic balance.MethodsForty-two participants (24.3 ± 2.5 years, 33 males, 9 females) were randomly assigned to either roller-massage (RM) or control group (= no intervention). Ankle ROM was assessed with the weight-bearing lunge test (WBLT) and dynamic balance with the Y-Balance test for both limbs. The RM group was instructed to roll their calf muscles for three sets of 60 s per leg on 6 days a week over 2 weeks. Acute effects were measured during baseline testing for dorsiflexion ROM and dynamic balance immediately after foam rolling. Chronic and residual effects were measured 1 day and 7 days after the intervention period. Multivariate ANOVA was performed for post-hoc comparisons to determine acute, chronic, and residual effects.ResultsSignificant acute and chronic foam rolling effects (p

Whereas typical Crohn’s disease is confined to the terminal ileum and presents with abdominal pain and diarrhea, gastroduodenal manifestations of Crohn’s disease are rare, with often asymptomatic patient presentations and inconclusive diagnostic testing. It is, however, a more severe form of Crohn’s disease and thus warrants treatment with steroids and biologics much earlier than its ileocolonic counterpart. We present the case of a young, otherwise healthy, male with newly diagnosed ileocolonic Crohn’s disease with concurrent gastroduodenal involvement that initially failed management with biologic agents. We discuss the clinical manifestations and often obscure pathology of gastroduodenal Crohn’s disease and highlight the necessity of performing a concurrent esophagogastroduodenoscopic evaluation on newly diagnosed ileocolonic Crohn’s disease to assess the presence of upper gastrointestinal involvement.

Objectives. The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo, a supra-annular self-expanding bioprosthetic aortic valve. Background. While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL. Methods. The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo. Results. The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months (P

BackgroundAlthough the proper use of hygiene and personal protective equipment (PPE) is paramount for preventing the spread of diseases such as COVID-19, health care personnel have been shown to use incorrect techniques for donning/doffing of PPE and hand hygiene, leading to a large number of infections among health professionals. Education and training are difficult owing to the social distancing restrictions in place, shortages of PPE and testing material, and lack of evidence on optimal training. Virtual reality (VR) simulation can offer a multisensory, 3-D, fully immersive, and safe training opportunity that addresses these obstacles. ObjectiveThe aim of this study is to explore the short- and long-term effectiveness of a fully immersive VR simulation versus a traditional learning method regarding a COVID-19–related skill set and media-specific variables influencing training outcomes. MethodsThis was a prospective, randomized controlled pilot study on medical students (N=29; intervention VR training, n=15, vs control video-based instruction, n=14) to compare the performance of hand disinfection, nasopharyngeal swab taking, and donning/doffing of PPE before and after training and 1 month later as well as variables of media use. ResultsBoth groups performed significantly better after training, with the effect sustained over one month. After training, the VR group performed significantly better in taking a nasopharyngeal swab, scoring a median of 14 out of 17 points (IQR 13-15) versus 12 out of 17 points (IQR 11-14) in the control group, P=.03. With good immersion and tolerability of the VR simulation, satisfaction was significantly higher in the VR group compared to the control group (median score of User Satisfaction Evaluation Questionnaire 27/30, IQR 23-28, vs 22/30, IQR 20-24, in the control group; P=.01). ConclusionsVR simulation was at least as effective as traditional learning methods in training medical students while providing benefits regarding user satisfaction. These results add to the growing body of evidence that VR is a useful tool for acquiring simple and complex clinical skills.

Abstract Background Most patients with minor stroke or transient ischemic attack (TIA) are discharged with little or no specialised follow-up. Nonetheless, these patients have a high prevalence of cognitive impairments and a considerable risk of recurrent stroke. Smoking cessation, physical activity, and adherence to antihypertensive and antithrombotic medication are highly recommended in patients with minor stroke and TIA. Evidence suggests that simple encouragement to change lifestyle is ineffective. Behavioural interventions might therefore be needed to support patients in managing their own health post-discharge. Objectives We aim to test the (1) feasibility of randomisation acceptance and an early initiated, client-centred lifestyle and behavioural intervention in a clinical setting, and (2) potential effect of the intervention on arterial blood pressure in patients with minor stroke or TIA and (3) explore the participants experience of barriers and facilitators for health behaviour after a stroke, including perceived needs and social support. Methods We will conduct a randomized controlled pilot trial: Eligible patients with acute minor stroke or TIA (n = 40) will be randomly allocated to either early initiated counselling with four weekly post-discharge follow-up sessions for 12 weeks or usual care. The primary outcome will be program feasibility and to discuss the relevance of arterial blood pressure as primary outcome after 12 weeks intervention. Selected participants will be invited to participate in semi-structured interviews, based on purposeful sampling, to evaluate the intervention and explore their experience of life after a stroke. The interviews will be analysed using a five-step thematic analysis approach. Discussion The study will provide evidence of the feasibility and potential effect of early initiated counselling on cardiovascular risk factors in patients with minor stroke and TIA. Qualitative interviews will contribute with a more nuanced understanding of the barriers and facilitators of health enhancing behaviour. Optimizing health behaviour counselling and providing formal support to the patients’ post-discharge may ease the transition and help more patients adhere to lifestyle and medication recommendations. Trial registration ClinicalTrial.gov , NCT03648957

Plasmonic enhancements of light–matter interactions are generally maximal at short emitter–surface separations. Here, the authors investigate the impact of nonlocality, spill-out, and surface-assisted Landau damping at nanoscale separations using a mesoscopic electrodynamic framework.

Policy and industry decision makers place high priority on the contribution of biomass to the emerging low carbon, circular economy. Optimisation of performance, from the perspectives of environmental, social and economic sustainability and resource efficiency, is essential to successful development and operation of biomass value chains. The complexity of value chains, which comprise interrelated stages from land use to conversion and multiple end products, presents challenges.To date, decision makers have approached from the viewpoints of single market sectors or issues, such as market shares of bioeconomy and reduction of carbon emissions to mitigate climate change. This approach does not achieve a full understanding of value chains and their competitive priorities, limits consumer awareness, and poses risks of sub-optimal performance and under-development of potential local capacity.This paper presents a conceptual framework that combines value chain analysis and competitive priority theory with indicators suitable to measure, monitor and interpret sustainability and resource efficiency at value chain level. The case of biomass Combined Heat and Power (CHP) is used to illustrate how optimisation strategies can be focused to address challenges in value chain stages which will lead to better performance and uptake of sustainably sourced, widely accepted biomass options.

Topological kink modes are peculiar edge excitations that take place at domain boundaries of magnetic fields inside homogeneous materials. Here, the authors experimentally observe kink magnetoplasmons in a 2D electron gas using custom-shaped strong permanent magnets on top of a GaAs/AlGaAs heterojunction.

Binary intermetallic compounds, such as FePd3, attract interests due to their physical, magnetic and catalytic properties. For a better understanding of their hydrogenation properties, both ordered FePd3 and disordered Fe0.25Pd0.75 are studied by several in situ methods, such as thermal analysis, X-ray powder diffraction and neutron powder diffraction, at moderate hydrogen pressures up to 8.0 MPa. FePd3 absorbs small amounts of hydrogen at room temperature and follows Sieverts’ law of hydrogen solubility in metals. [Pd6] octahedral voids are filled up to 4.7(9)% in a statistical manner at 8.00(2) MPa, yielding the hydride FePd3H0.047(9). This is accompanied by decreasing long-range order of Fe and Pd atoms (site occupancy factor of Fe at Wyckoff position 1a decreasing from 0.875(3) to 0.794(4)). This trend is also observed during heating, while the ordered magnetic moment decreases up to the Curie temperature of 495(8) K. The temperature dependences of the magnetic moments of iron atoms in FePd3 under isobaric conditions (p(D2) = 8.2(2) MPa) are consistent with a 3D Ising or Heisenberg model (critical parameter β = 0.28(5)). The atomic and magnetic order and hydrogen content of FePd3 show a complex interplay.

In order to practice sustainable and resource-efficient agriculture, the use of new technologies such as water-retaining polymers is essential. The objective of this study was to evaluate the effect of a polymer incorporated into the soil on gas exchange and yield under different water regimes (WR) in three soybean cultivars. The experiment was conducted at Embrapa Cerrados under field conditions in 2016 and 2017, using three different cultivars (BRS 5980IPRO, NA 5909RG and BRS 7280RR). Soybean cultivars were submitted to four water regimes (representing 30%, 50%, 83% and 100% of evapotranspiration replacement, namely WR1, WR2, WR3 and WR4). No beneficial results were observed in 2016 with Polymer. Most of the reductions in photosynthesis and transpiration by adding the polymer can be attributed to stomatal control, but such reductions did not influence productivity. In 2017, the yield was higher using Polymer in WR4 and WR3 by 40 to 20%, depending on the cultivar. Under severe stress (WR2 and WR1), reduced gas exchange was obtained with Polymer, but the yield was not reduced. These results indicate that Polymer contributed to the prolongation of photosynthetic activity during the reproductive phase of soybean and may represent a potential strategy for increasing yield under moderate drought stress.

Abstract Low back pain is a major public health issue associated with degeneration of the intervertebral disc (IVD). The early stages of degeneration are characterized by the dehydration of the central, gelatinous portion of the IVD, the nucleus pulposus (NP). One possible treatment approach is to replace the NP in the early stages of IVD degeneration with a hydrogel that restores healthy biomechanics while supporting tissue regeneration. The present study evaluates a novel thermosensitive hydrogel based on poly(N‐isopropylacrylamide‐graft‐chondroitin sulfate) (PNIPAAM‐g‐CS) for NP replacement. The hypothesis was tested that the addition of freeze‐dried, calcium crosslinked alginate microparticles (MPs) to aqueous solutions of PNIPAAm‐g‐CS would enable tuning of the rheological properties of the injectable solution, as well as the bioadhesive and mechanical properties of the thermally precipitated composite gel. Further, we hypothesized that the composite would support encapsulated cell viability and differentiation. Structure‐material property relationships were evaluated by varying MP concentration and diameter. The addition of high concentrations (50 mg/mL) of small MPs (20 ± 6 μm) resulted in the greatest improvement in injectability, compressive mechanical properties, and bioadhesive strength of PNIPAAm‐g‐CS. This combination of PNIPAAM‐g‐CS and alginate MPs supported the survival, proliferation, and differentiation of adipose derived mesenchymal stem cells toward an NP‐like phenotype in the presence of soluble GDF‐6. When implanted ex vivo into the intradiscal cavity of degenerated porcine IVDs, the formulation restored the compressive and neutral zone stiffnesses to intact values and resisted expulsion under lateral bending. Overall, results indicate the potential of the hydrogel composite to serve as a scaffold for supporting NP regeneration. This work uniquely demonstrates that encapsulation of re‐hydrating polysaccharide‐based MPs may be an effective method for improving key functional properties of in situ forming hydrogels for orthopedic tissue engineering applications.

Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+ correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3 and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1–1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation.

N1-methylation of G37 is required for a subset of tRNAs to maintain the translational reading-frame. While loss of m1G37 increases ribosomal +1 frameshifting, whether it incurs additional translational defects is unknown. Here, we address this question by applying ribosome profiling to gain a genome-wide view of the effects of m1G37 deficiency on protein synthesis. Using E coli as a model, we show that m1G37 deficiency induces ribosome stalling at codons that are normally translated by m1G37-containing tRNAs. Stalling occurs during decoding of affected codons at the ribosomal A site, indicating a distinct mechanism than that of +1 frameshifting, which occurs after the affected codons leave the A site. Enzyme- and cell-based assays show that m1G37 deficiency reduces tRNA aminoacylation and in some cases peptide-bond formation. We observe changes of gene expression in m1G37 deficiency similar to those in the stringent response that is typically induced by deficiency of amino acids. This work demonstrates a previously unrecognized function of m1G37 that emphasizes its role throughout the entire elongation cycle of protein synthesis, providing new insight into its essentiality for bacterial growth and survival.

Abstract Objective Timely evaluation and initiation of treatment is the key for improving stroke outcomes, although minimizing the time from symptom onset to the first contact with healthcare professionals remains a challenge. We aimed to identify patient‐related factors associated with early hospital arrival. Materials and methods In this cross‐sectional survey, we included patients with stroke or transient ischemic attack admitted directly to one of two noncomprehensive stroke units or transferred to the units from comprehensive stroke centers in the Capital Region of Denmark. Patient‐reported factors associated with early hospital arrival were analyzed using multivariable logistic regression analysis adjusted for age, sex, education, living arrangement, brain location of the stroke, stroke severity, patient‐perceived symptom severity, history of prior stroke, stroke risk factors, and knowledge of stroke symptoms. Results In total, 479 patients with acute stroke were included (median age 74 (25th–75th percentile, 64–80), 40% women), of whom 46.4% arrived within 180 min of symptom onset. Factors associated with early hospital arrival were patients or bystanders choosing emergency medical service (EMS) for the first contact with a medical professional (adjusted odds ratio (OR), 3.41; 95% confidence interval, CI [1.57, 7.35]) or the patient's perceived symptom severity above the median score of 25 on a 100‐point verbal scale (adjusted OR, 2.44; 95% CI [1.57, 3.82]). Living alone reduced the likelihood of early arrival (adjusted OR, 0.53; 95% CI [0.33, 0.86]). Conclusions Only when patients perceived symptoms as severe or when EMS was selected as the first contact, early arrival for stroke treatment was ensured.

Abstract Background Current stroke research suggests that there are differences between females and males regarding incidence, stroke risk factors, stroke severity, outcome, and mortality. The few studies that have investigated sex differences in rehabilitation 8–12 months poststroke found that males are more independent, compared to females. Objectives To investigate if there is a difference in the improvement of independence in activities of daily living (ADL) between females and males in the acute phase (first 2 weeks) of stroke rehabilitation in a Danish population. Methods A prospective cohort study enrolling patients admitted to the hospital's rehabilitation ward with a stroke diagnosis from January 1, 2016, to March 17, 2017. Baseline and follow‐up data regarding the primary outcome, Barthel‐100 index, were analyzed using an adjusted linear mixed model. Results The study included 206 patients (83 females). Females were older at admission and more males lived with a partner. No differences in stroke severity or any of the risk factors were found. There were no differences between female and male scores at baseline. In the adjusted linear mixed model, quantifying the difference between follow‐up and baseline Barthel‐100 score, females increased their Barthel‐100 score by 20.8 points (95% confidence interval (CI) 15.4–26.3) and males with 29.0 points (95% CI 24.6–33.4). Conclusion In a homogeneous sample of stroke survivors undergoing specialized 24‐h stroke rehabilitation for 11–14 days, females were more dependent in ADL than males.

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab.

This article presents an open source software able to convert, display, and process medical images. It differentiates itself from the existing software by its ability to design complex processing pipelines and to wisely execute them on a large databases. An MP3 pipeline can contain unlimited homemade or ready-made processes and can be carried out with a parallel execution system. As a viewer, MP3 allows display of up to four images together and to draw Regions Of Interest (ROI). Two applications showing the strengths of the software are presented as examples: a preclinical study involving Magnetic Resonance Imaging (MRI) data and a clinical one involving Computed Tomography (CT) images. MP3 is downloadable at https://github.com/nifm-gin/MP3.

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45–6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99–3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07–2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28–0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25–2.21]) and Asian (1.51 [1.28–1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34–3.15]).

The 2019 MacKinnon report, commissioned by the Alberta government, recommended ending fee-for-service (FFS) as the model for paying primary care physicians because of its significant and inherent inefficiencies. Since then, the COVID-19 pandemic has also demonstrated the value of moving Alberta’s family physicians to an alternative payment (APP) model. While the MacKinnon report was in favour of enacting legislation to change the compensation model, this paper instead recommends offering physicians a choice of alternative payment programs as an incentive to move on voluntarily from an FFS system. Other provinces have attempted to reform physicians’ pay using a quadruple aim model for health-care improvement, which identifies the major points policy- makers must examine in instituting a replacement for FFS. The quadruple aim model is four-pronged and encompasses patient experience, population health, care team wellbeing and cost reductions. Alberta Health Services already uses the quadruple aim model to improve patient care and quality outcomes, although the MacKinnon report focused primarily on reducing costs. However, reforming doctors’ compensation is not just about the amount they should be paid; it must also consider that the method of compensation has a profound impact on both cost and quality of care received. Meanwhile, the self-isolation and social distancing measures for both doctors and patients, established with the arrival of the COVID-19 pandemic, have put Alberta’s doctors on a policy roller-coaster. Applying the FFS compensation model during the pandemic has resulted in the use of virtual care codes such as telehealth billing and in-person limited assessment codes. However, these codes were immediately problematic because they do not adequately account for complex patient care that requires longer visits, after-hours premiums and the Rural Remote Northern Program. During a pandemic is not the right time to embark on physician compensation reform. This gives the government time to reconsider the controversial approach taken prior to the COVID-19 pandemic. The need for compensation reform in Alberta is driven by the reality that Alberta has the highest proportion of physicians on FFS along with some of the highest FFS payments per physician in Canada. Meanwhile, family physicians in other provinces are now more likely to be covered by an APP rather than the former FFS system. The problem with FFS is that it tends to encourage physicians to create volume in number of patients seen per day, in order to increase compensation. Thus, it also encourages more diagnostic testing, which increases costs to the health-care system. In general, physicians compensated under FFS have much less incentive to consider costs when treating patients. The argument for legislating pay reform is poorly justified. No other province has legislated physicians out of the FFS system, and that is not a route Alberta should take, either. Nova Scotia has brought in a one-size-fits-all APP, while Ontario implemented a menu of higher paying APPs that produced greater downstream cost savings, making APPs an increasingly attractive payment option to family physicians. Ontario’s approach would be better for Alberta because it improves patients’ overall experience with primary care, their care outcomes and the wellbeing of those who care for the patients. Alberta should offer a menu of APP models tailored to primary care so that the family doctors themselves can choose the best model for their own practices. As this paper has demonstrated in its comparison of the experiences of other provinces, and as the COVID-19 affirms, the menu approach is the model most strongly aligned with the goals of quadruple aim.

The fundamental, or first, band gap is of unmatched importance in the study of photonic crystals. Here, we address precisely where this gap can be opened in the band structure of three-dimensional photonic crystals. Although strongly constrained by symmetry, this problem cannot be addressed directly with conventional band-symmetry analysis due to the existence of a photonic polarization vortex at zero frequency. We develop an approach for overcoming the associated symmetry singularity by incorporating fictitious, auxiliary longitudinal modes. Our strategy also enables us to extend recent developments in symmetry-based topological analysis to the fundamental gap of three-dimensional photonic crystals. Exploiting this, we systematically study the topology of the minimal fundamental gaps. This reveals the existence of topological gap obstructions that push the fundamental gap higher than what a conventional analysis would suggest. Our work demonstrates that topology can play a crucial role in the opening of the fundamental photonic gap and informs future theoretical and experimental searches for conventional and topological band gaps in three-dimensional photonic crystals.

In this introductory essay, a number of cautionary reminders are suggested for any historian seeking to trace the reception of European music theory outside of its traditional borders. Using a range of examples from Medieval Arabic music theory, Jean-Philippe Rameau’s theory of harmony, and Schenkerian theory, it is shown that a global dissemination and absorption of music-theoretical ideas is rarely a straightforward process of import and export. Perspectives drawn from contemporary theories of cultural transfer and postcolonialism offer some suggestive ways to think about the migration of a music theory across cultures as a more dialogical process in which notions of hybridity and agency play important roles. // In dieser Einleitung wird eine Reihe von Zusammenhängen aufgezeigt, die dort zur Zurückhaltung mahnen sollen, wo Historiker*innen versuchen die Rezeption europäischer Musiktheorie außerhalb ihrer traditionellen Grenzen nachzuvollziehen. Es wird gezeigt, dass die globale Verbreitung und Rezeption musiktheoretischer Ideen selten als schlichte Import- oder Exportvorgänge verstanden werden können, wie anhand von Beispielen aus der mittelalterlichen arabischen Musiktheorie, der Harmonielehre Jean-Philippe Rameaus und Heinrich Schenkers Theorie veranschaulicht wird. Perspektiven aus den Bereichen der Kulturtransferforschung und postkolonialer Forschung erlauben es, die transkulturelle Migration einer musikalischen Theorie als einen stärker dialogischen Prozess zu verstehen, in dem die Phänomene der Hybridität und der Handlungsmacht (agency) eine wichtige Rolle einnehmen.

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016.

The greatest challenge in accelerating the realisation of a sustainable and competitive bioeconomy is to demonstrate that enshrining sustainability principles at the very heart of a production line can generate value and improve its overall system. Strategies for reducing emissions, pollutants, indirect land use change or soil depreciation are all perceived as costs or necessary inconveniences to comply with stringent, climate change-focused policy frameworks. System dynamics modelling and competitive priorities are tools that can accurately and intelligently expand on the cross-value chain approach, which integrates both technical and environmental performances, to address the issue of harmonising sustainability and technical operations as one overall dimension of performance. A stock-and-flow model is developed to map a full biofuel value chain and quantitatively and coherently integrate factors of emissions, carbon, land, production, and technology. As such, environmental and operational impacts of innovative practices are measured, and subsequently linked to a qualitative framework of competitive priorities, as defined by transparency, quality, innovation and flexibility. Sustainability and productivity functions are found to reinforce each other when all competitive priorities are optimised. Equally, the framework provides a clear understanding of trade-offs engendered by value chain interventions. Advantages and limitations in the accessibility, scope and transferability of the multi-pronged analytical approach are discussed.

The SHFT device is a novel running wearable consisting of two pods connected to your smartphone issuing several running metrics based on accelerometer and gyroscope technology. The purpose of this study was to investigate the reliability and validity of the power output (PO) metric produced by the SHFT device. To assess reliability, 12 men ran on an outdoor track at 10.5 km·h−1 and 12 km·h−1 on two consecutive days. To assess validity, oxygen uptake (VO2) and SHFT data from eight men and seven women were collected during incremental submaximal running tests on an indoor treadmill on one to four separate days (34 tests in total). SHFT reliability on the outdoor track was strong with coefficients of variance (CV) of 1.8% and 2.4% for 10.5 and 12 km·h−1, respectively. We observed a very strong linear relationship between PO and VO2 (r2 = 0.54) within subjects, and a very strong linear relationship within each subject within each treadmill test (r2 = 0.80). We conclude that SHFT provides a reliable running power estimate and that a very strong relationship between SHFT-Power and metabolic rate exists, which places SHFT as one of the leading commercially available running power meters.

Abstract Background The purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation. Methods Cerebrospinal fluid (CSF) from patients with acute ischemic stroke (n = 21) and controls (n = 21) was collected by lumbar puncture. miRNA analysis was performed with three different methods: 1) Trizol RNA extraction followed by Illumina Next Generation Sequencing (NGS) on all small RNAs, 2) Exiqon RNA extraction protocol and miRNA qPCR assays, and 3) validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and Applied Biosystems qPCR assays. Results NGS detected 71 frequently expressed miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly higher in CSF of stroke patients compared to controls. When dividing stroke patients into groups according to infarct size several brain-enriched miRNAs (miR-9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and qPCR (Applied Biosystems) but was only statistically significant in some of the measurement platforms. Conclusions Several brain-enriched miRNAs are elevated in the CSF three days after stroke onset, suggesting that these miRNAs reflect the brain damage caused by ischemia. The expression differences seem, however, limited to patients with larger ischemic brain injury, which argues against the use of CSF miRNAs as diagnostic biomarkers of stroke based on current methods.

Purpose: The purpose of this systematic literature review was to examine whether different assessment methods contribute to the variance in delirium incidence detected in populations of patients with acute stroke. Specifically, the aim was to address the influence of (1) choice of assessment tool, (2) frequency of assessment, and (3) type of health professional doing the assessment. Methods: We searched MEDLINE, EMBASE, and PsycINFO and included pro- and retrospective cohort studies assessing delirium during hospitalization of adult acute stroke patients. Results: In 30 articles, 24 unique populations were identified and included in the review. Delirium incidence ranged from 1.4% to 75.6% in total and a chi-square test showed a significant heterogeneity across studies (χ 2 = 536.5, df = 23, P

Objective To compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.Design Using publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.Results In 2014–2016, 115 NASs were approved by EMA or FDA or both; 74/115 were new chemical entities and 41 new biological/biotechnology entities; 82/115 were approved by both agencies, 24 only by FDA and nine only by EMA. Simultaneous submission occurred for 52/115; 13/52 received expedited review by both agencies and 18 only by FDA; 8/52 received conditional approval from both agencies, 2/52 only from FDA and 1/52 only from EMA; 17/52 were designated as orphans by both agencies and 10/52 by FDA only; 31/52 indications were approved as submitted and 21 changed by EMA and 29/46 were approved as submitted (six not assessed) and 17/46 changed by FDA. Median FDA review timelines were 319 days compared with 409 days for EMA.Conclusions There was general agreement in EMA / FDA conditional approvals. FDA used expedited pathways and orphan designation more often than EMA, suggesting stricter EMA criteria or definitions for these designations or less flexible processes. Despite consistency in submitted indications, there was lack of concordance in approved indications, which should be further investigated. FDA review times are faster because of a wider range of expedited pathways and the two-step EMA process; this may change with recent revisions to EMA accelerated assessment guidelines and the launch of Priority Medicines.

At a time when branding new, occasionally innovative but often only catchy terms has become a familiar activity of researchers, companies and policymakers alike, it is necessary to reflect on which of these concepts is actually worthwhile, provides analytic value and in effect describes something new. This new special section Defining concepts of the digital society seeks to foster a platform that discusses and validates these overarching frameworks and theories. Based on the latest research, yet broad in scope, the contributions offer effective tools to analyse the digital society. Their authors offer concise articles that portray and critically discuss individual concepts such as algorithmic governance, datafication, platformisation, privacy with an interdisciplinary mindset. Each article contextualises their respective origin and academic traditions, analyses their contemporary usage in different research approaches and discusses their social, political, cultural, ethical or economic relevance and impact as well as their analytical value. The special section is a continuing project that will expand the collection of concepts in 2020 and beyond. We sincerely hope that it will grow into a valuable forum for making sense of the digital transformation and a pertinent resource for researchers, teachers, students and practitioners.

Background: High-intensity interval training (HIIT) is superior to moderate-intensity continuous training in improving cardiorespiratory fitness in patients with cardiovascular disease, but is it safe, feasible and effective in patients with stroke? We investigated feasibility and effect of early, home-based HIIT in patients with lacunar stroke combined with usual care vs. usual care, only.Methods: Patients with minor stroke (severity: 55/58 point on the Scandinavian Stroke Scale) were randomized to HIIT or usual care in a randomized, controlled trial. We measured the following outcomes at baseline and post-intervention: cardiorespiratory fitness monitored as power output from the Graded Cycling Test with Talk Test (GCT-TT; primary outcome), physical activity, fatigue, depression, well-being, stress, cognition, endothelial function, blood pressure, body mass index, and biomarkers.Results: We included 71 patients (mean age 63.7 ± 9.2), 49 men, 31 in intervention group. Home-based HIIT was feasible with no reported adverse events in relation to the intervention. No significant change between the groups in GCT-TT power output was detected (p = 0.90). The change in time spent on vigorous-intensity activity was 2 h/week and 0.6 h/week, intervention and usual care, respectively (p = 0.045). There were no significant differences between groups in the remaining secondary outcomes.Conclusion: HIIT was feasible and safe in patients with lacunar stroke. Patients can engage early in home-based HIIT when involved in choosing exercise modality and guided by weekly motivational phone calls. Within 3 months, HIIT did, however, not yield effect on cardiorespiratory fitness. We await further evaluation of long-term effects of this intervention on continued regular physical exercise and cardiovascular event.Clinical Trial Registration:https://clinicaltrials.gov, identifier NCT02731235

Plant dehydrins (DNHs) belong to the LEA (Late Embryogenesis Abundant) protein family and are involved in responses to multiple abiotic stresses. DHNs are classified into five subclasses according to the organization of three conserved motifs (K-; Y-; and S-segments). In the present study, the DHN protein family was characterized by molecular phylogeny, exon/intron organization, protein structure, and tissue-specificity expression in eight Fabaceae species. We identified 20 DHN genes, encompassing three (YnSKn, SKn, and Kn) subclasses sharing similar gene organization and protein structure. Two additional low conserved DHN Φ-segments specific to the legume SKn-type of proteins were also found. The in silico expression patterns of DHN genes in four legume species (Arachis duranensis, A. ipaënsis, Glycine max, and Medicago truncatula) revealed that their tissue-specific regulation is associated with the presence or absence of the Y-segment. Indeed, DHN genes containing a Y-segment are mainly expressed in seeds, whereas those without the Y-segment are ubiquitously expressed. Further qRT-PCR analysis revealed that, amongst stress responsive dehydrins, a SKn-type DHN gene from A. duranensis (AdDHN1) showed opposite response to biotic and abiotic stress with a positive regulation under water deficit and negative regulation upon nematode infection. Furthermore, transgenic Arabidopsis lines overexpressing (OE) AdDHN1 displayed improved tolerance to multiple abiotic stresses (freezing and drought) but increased susceptibility to the biotrophic root-knot nematode (RKN) Meloidogyne incognita. This contradictory role of AdDHN1 in responses to abiotic and biotic stresses was further investigated by qRT-PCR analysis of transgenic plants using a set of stress-responsive genes involved in the abscisic acid (ABA) and jasmonic acid (JA) signaling pathways and suggested an involvement of DHN overexpression in these stress-signaling pathways.

Quinoa stands out as an excellent crop in the Cerrado region for cultivation in the off-season or irrigated winter season. Here, we tested the effects of different water regimes on the agronomic characteristics, physiology, and grain quality of different elite quinoa genotypes under field conditions. The experiment was conducted under field conditions at Embrapa Cerrados (Planaltina, DF, Brazil). The experimental design was in randomized blocks, in a split-plot scheme, with four replications. The plots were composed of 18 quinoa genotypes and modified BRS Piabiru (the currently used genotype), and the split-plots were divided into 4 different water regimes. The following variables were evaluated: productivity and productivity per unit of applied water (PUAA), plant height, flavonoids, anthocyanins, gas exchange, chlorophyll, leaf proline, and relative water content. Our results showed that water regimes between 309 and 389 mm can be recommended for quinoa in the Cerrado region. CPAC6 and CPAC13 presented the highest yield and PUAA under high and intermediate WRs, and hence were the most suitable for winter growth under irrigation. CPAC17 is most suitable for off-season growth under rainfed conditions, as it presented the highest PUAA under the low WRs (247 and 150). CPAC9 stood out in terms of accumulation of flavonoids and anthocyanins in all WRs. Physiological analyses revealed different responses of the genotypes to water restriction, together with symptoms of stress under lower water regimes. Our study reinforces the importance of detailed analyses of the relationship between productivity, physiology, and water use when choosing genotypes for planting and harvest in different seasons.

A plasma microreactor dedicated to chemical synthesis has been conceived and developed using soft-lithography techniques. In this study, we propose to use highly reactive species created by the plasma discharge to replace traditionally used chemical initiators. A dielectric barrier discharge plasma was generated under atmospheric pressure and then dispersed into a continuous liquid phase with a T-junction geometry. Injected metal electrodes made it possible for in situ optical observations with an intensified charge-coupled device camera. No signal was detected when analyzing the exhaust liquid by electron spin resonance (ESR) spectroscopy. Numerical simulations confirmed that only low quantities of hydroxyl radicals could diffuse into the liquid phase, giving a concentration of DMPO-OH of 10−6 mol/l, below the detection limit of ESR.

Background: Clopidogrel is a commonly prescribed antiplatelet drug in patients with stents and histories of arterial vascular disease. It generally has a favorable side effect profile with increasing bleeding risk as the main concern as an adverse event.Case Presentation: A 19-year-old previously healthy male presented to the neurological intensive care unit with a subarachnoid hemorrhage requiring a flow diverting stent to secure the aneurysm. The patient was stable for 2 weeks and had no changes to management or medication within 48 h of antiplatelet therapy. Within hours of first-time dosing of clopidogrel, the patient experienced a syncopal episode and dyspnea. He was difficult to arouse and using accessory muscles to breath with an otherwise benign exam. He was hypoxic with bibasilar crackles requiring bilevel positive airway pressure (BiPap). Imaging showed bilateral pulmonary edema and he was diagnosed with moderate acute respiratory distress syndrome (ARDS). Infectious, cardiogenic, and contrast-induced ARDS were ruled out. Upon cessation of clopidogrel, his pulmonary function and mental status improved.Conclusions: This is the first reported case of a young and immunocompetent patient's severe pulmonary edema leading to acute respiratory distress syndrome in association with first- time dosing of clopidogrel.