World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) Core Set Development for Interstitial Lung Disease.

Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94-100% for the three additional PROMs. Thirty-four new 'Personal Factors' emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. 'pf_embarrassed by cough' or 'pf_panic/afraid when can't get a breath'. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11.

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc.

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.

Dye-sensitized solar cells strike back.

Dye-sensitized solar cells (DSCs) are celebrating their 30th birthday and they are attracting a wealth of research efforts aimed at unleashing their full potential. In recent years, DSCs and dye-sensitized photoelectrochemical cells (DSPECs) have experienced a renaissance as the best technology for several niche applications that take advantage of DSCs' unique combination of properties: at low cost, they are composed of non-toxic materials, are colorful, transparent, and very efficient in low light conditions. This review summarizes the advancements in the field over the last decade, encompassing all aspects of the DSC technology: theoretical studies, characterization techniques, materials, applications as solar cells and as drivers for the synthesis of solar fuels, and commercialization efforts from various companies.

Exercise as a multi-modal disease-modifying medicine in systemic sclerosis: An introduction by The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis (G-FoRSS).

Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease whereby its main pathological drivers of disability and damage are vascular injury, inflammatory cell infiltration, and fibrosis. These mechanisms result in diffuse and diverse impairments arising from ischemic circulatory dysfunction leading to painful skin ulceration and calcinosis, neurovascular aberrations hindering gastrointestinal (GI) motility, progressive painful, incapacitating or immobilizing effects of inflammatory and fibrotic effects on the lungs, skin, articular and periarticular structures, and muscle. SSc-related impairments impede routine activities of daily living (ADLs) and disrupt three critical life areas: work, family, social/leisure, and also impact on psychological well-being. Physical activity and exercise are globally recommended; however, for connective tissue diseases, this guidance carries greater impact on inflammatory disease manifestations, recovery, and cardiovascular health. Exercise, through myogenic and vascular phenomena, naturally targets key pathogenic drivers by downregulating multiple inflammatory and fibrotic pathways in serum and tissue, while increasing circulation and vascular repair. G-FoRSS, The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis recognizes the scientific basis of and advocates for education and research of exercise as a systemic and targeted SSc disease-modifying treatment. An overview of biophysiological mechanisms of physical activity and exercise are herein imparted for patients, clinicians, and researchers, and applied to SSc disease mechanisms, manifestations, and impairment. A preliminary guidance on exercise in SSc, a research agenda, and the current state of research and outcome measures are set forth.

Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel "Dual-Soft" PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis.

We describe the design of a novel PDE4 scaffold and the exploration of the dual-soft concept to reduce systemic side effects via rapid elimination: introducing ester functionalities that can be inactivated in blood as well as by the liver (dual-soft) while being stable in human skin. Compound 40 was selected as a clinical candidate as it was potent and rapidly degraded by blood and liver to inactive metabolites and because in preclinical studies it showed high exposure at the target organ: the skin. Preclinical and clinical data are presented confirming the value of the dual-soft concept in reducing systemic exposure.

Additive Manufacturing of Prostheses Using Forest-Based Composites.

A custom-made prosthetic product is unique for each patient. Fossil-based thermoplastics are the dominant raw materials in both prosthetic and industrial applications; there is a general demand for reducing their use and replacing them with renewable, biobased materials. A transtibial prosthesis sets strict demands on mechanical strength, durability, reliability, etc., which depend on the biocomposite used and also the additive manufacturing (AM) process. The aim of this project was to develop systematic solutions for prosthetic products and services by combining biocomposites using forestry-based derivatives with AM techniques. Composite materials made of polypropylene (PP) reinforced with microfibrillated cellulose (MFC) were developed. The MFC contents (20, 30 and 40 wt%) were uniformly dispersed in the polymer PP matrix, and the MFC addition significantly enhanced the mechanical performance of the materials. With 30 wt% MFC, the tensile strength and Young´s modulus was about twice that of the PP when injection molding was performed. The composite material was successfully applied with an AM process, i.e., fused deposition modeling (FDM), and a transtibial prosthesis was created based on the end-user's data. A clinical trial of the prosthesis was conducted with successful outcomes in terms of wearing experience, appearance (color), and acceptance towards the materials and the technique. Given the layer-by-layer nature of AM processes, structural and process optimizations are needed to maximize the reinforcement effects of MFC to eliminate variations in the binding area between adjacent layers and to improve the adhesion between layers.

Experiences of physical activity and exercise in individuals with systemic sclerosis: A qualitative study.

INTRODUCTION: Exercise is emerging as an important part of the treatment in systemic sclerosis-patients with no-mild lung involvement. However, it has not been studied how patients experience physical activity and exercises. We thus explored and described experiences of physical activity/exercises in systemic sclerosis-individuals. METHOD: Sixteen systemic sclerosis-patients were purposefully recruited to represent variation in gender, age, and lung disease. Semi-structured individual interviews were performed, transcribed and analyzed with qualitative content analysis. RESULTS: Three themes (categories) emerged: 1) Essential for life and health (An effective treatment, Reduces fear of deterioration, and Feeling healthy and satisfied with oneself); 2) Disease-related hinders and other barriers (Disease consequences, Risk of worsening, and Non-disease related barriers); and 3) Self-care and/or support (Self-confidence in physical activity/exercise, and, Education and support from healthcare and other). CONCLUSIONS: Physical activity/exercises were experienced as essential for life and health and as an effective treatment. It reduced fear of deterioration and made the participants feel healthy and satisfied with oneself. However, participants also experienced disease-related barriers like shortness of breath and pain, and they expressed a risk of worsening. Participants felt confidence in their physical activity/exercises and expressed that education and support from healthcare could be facilitating. Our findings add new knowledge about how systemic sclerosis-patients perceive physical activity/exercise and can contribute to the development of patient education and PA/exercise programs.

Attractant or Repellent? Behavioral Responses to Mammalian Blood Odor and to a Blood Odor Component in a Mesopredator, the Meerkat (Suricata suricatta).

It is well-established that the odor of mammalian blood is attractive to top predators such as tigers and wolves and aversive to prey species such as mice and rats. Recent studies have shown that the mammalian blood odor component trans-4,5-epoxy-(E)-2-decenal (TED) elicits corresponding behavioral responses in these two groups of mammals. Here we assess whether a mesopredator, that is, a small-bodied carnivorous mammal that is both predator and prey, is attracted to or repelled by the odor of mammalian blood and TED. To this end, we assessed the behavior of a group of 15 captive meerkats (Suricata suricatta) when presented with wooden logs that were impregnated either with horse blood or with TED, and compared it to their behavior toward a fruity odor (iso-pentyl acetate) and a near-odorless solvent (diethyl phthalate). We found that the meerkats displayed significantly more interactions with the odorized wooden logs such as sniffing and pawing when these were impregnated with the two prey-associated odors compared to the two non-prey-associated odors. Most importantly, no significant difference was found in the number of interactions with the wooden logs impregnated with horse blood and TED, respectively. These results demonstrate that meerkats, despite being small-bodied mesopredators, are clearly attracted to the odor of mammalian blood. Further, the results suggest that a single blood odor component can be as efficient as the odor of real blood in eliciting behavioral responses in this herpestid mammal, similar to previous findings in feline and canine top predators.

Aerobic and resistance exercise in systemic sclerosis: State of the art.

INTRODUCTION: Patients with systemic sclerosis (SSc) experience reduced exercise capacity and muscle strength compared with healthy subjects. There are also indications of reduced levels of physical activity. OBJECTIVE: To present the current knowledge of physical exercise in SSc. RESULTS: Most studies presently available [three case studies, one single subject experimental design, one study comparing patients with healthy controls, one quasi experimental design (pre-post), two clinical trials and two random controlled trials] have included small samples of patients, mostly composed of patients with and without pulmonary involvement. It seems that patients with SSc without pulmonary involvement are able to perform and benefit from aerobic exercises of at least moderate intensity. Exercise tolerance, aerobic capacity, walking distance, muscle strength and muscle function as well as health-related quality of life (HRQL) have been found to be improved after participation in programmes including aerobic exercise and aerobic exercise combined with resistance exercises. Improvements seem to be only partially retained at follow up. Patients with pulmonary involvement may also experience improved muscle strength, physical and aerobic capacity, as well as HRQL following exercise. CONCLUSIONS: Patients with SSc without pulmonary involvement can be recommended to be as physically active as the general population. Patients with mild pulmonary involvement can be recommended to be physically active by engaging in exercises of moderate intensity and to participate in moderate-load resistance exercises. Health professionals should inform patients with SSc about the importance of physical activity and avoidance of a sedentary lifestyle.

Film Extrusion of Crambe abyssinica/Wheat Gluten Blends.

Crambe abyssinica is a plant with potential for use in industrial (non-food) plant oil production. The side stream from this oil production is a high-protein crambe meal that has limited value, as it is not fit for food or feed use. However, it contains proteins that could potentially make it a suitable raw material for higher-value products. The purpose of this study was to find methods of making this side stream into extruded films, showing that products with a higher value can be produced. The study mainly considered the development of material compositions and methods of preparing and extruding the material. Wheat gluten was added as a supportive protein matrix material, together with glycerol as a plasticizer and urea as a denaturant. The extrudate was evaluated with respect to mechanical (tensile testing) and oxygen barrier properties, and the extrudate structure was revealed visually and by scanning electron microscopy. A denser, more homogeneous material had a lower oxygen transmission rate, higher strength, and higher extensibility. The most homogeneous films were made at an extruder die temperature of 125-130 °C. It is shown here that a film can be extruded with promising mechanical and oxygen barrier properties, the latter especially after a final compression molding step.

Correlation between Al grain size, grain boundary grooves and local variations in oxide barrier thickness of Al/AlOx/Al tunnel junctions by transmission electron microscopy.

A thickness variation of only one Ångström makes a significant difference in the current through a tunnel junction due to the exponential thickness dependence of the current. It is thus important to achieve a uniform thickness along the barrier to enhance, for example, the sensitivity and speed of single electron transistors based on the tunnel junctions. Here, we have observed that grooves at Al grain boundaries are associated with a local increase of tunnel barrier thickness. The uniformity of the barrier thickness along the tunnel junction thus increases with increasing Al grain size. We have studied the effect of oxidation time, partial oxygen pressure and also temperature during film growth on the grain size. The implications are that the uniformity improves with higher temperature during film growth.

Improved oxygenation during standing performance of deep breathing exercises with positive expiratory pressure after cardiac surgery: A randomized controlled trial.

OBJECTIVE: Breathing exercises after cardiac surgery are often performed in a sitting position. It is unknown whether oxygenation would be better in the standing position. The aim of this study was to evaluate oxygenation and subjective breathing ability during sitting vs standing performance of deep breathing exercises on the second day after cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting (n = 189) were randomized to sitting (controls) or standing. Both groups performed 3 × 10 deep breaths with a positive expiratory pressure device. Peripheral oxygen saturation was measured before, directly after, and 15 min after the intervention. Subjective breathing ability, blood pressure, heart rate, and pain were assessed. RESULTS: Oxygenation improved significantly in the standing group compared with controls directly after the breathing exercises (p < 0.001) and after 15 min rest (p = 0.027). The standing group reported better deep breathing ability compared with controls (p = 0.004). A slightly increased heart rate was found in the standing group (p = 0.047). CONCLUSION: After cardiac surgery, breathing exercises with positive expiratory pressure, performed in a standing position, significantly improved oxygenation and subjective breathing ability compared with sitting performance. Performance of breathing exercises in the standing position is feasible and could be a valuable treatment for patients with postoperative hypoxaemia.

Atomic scale dynamics of a solid state chemical reaction directly determined by annular dark-field electron microscopy.

Dynamic processes, such as solid-state chemical reactions and phase changes, are ubiquitous in materials science, and developing a capability to observe the mechanisms of such processes on the atomic scale can offer new insights across a wide range of materials systems. Aberration correction in scanning transmission electron microscopy (STEM) has enabled atomic resolution imaging at significantly reduced beam energies and electron doses. It has also made possible the quantitative determination of the composition and occupancy of atomic columns using the atomic number (Z)-contrast annular dark-field (ADF) imaging available in STEM. Here we combine these benefits to record the motions and quantitative changes in the occupancy of individual atomic columns during a solid-state chemical reaction in manganese oxides. These oxides are of great interest for energy-storage applications such as for electrode materials in pseudocapacitors. We employ rapid scanning in STEM to both drive and directly observe the atomic scale dynamics behind the transformation of Mn3O4 into MnO. The results demonstrate we now have the experimental capability to understand the complex atomic mechanisms involved in phase changes and solid state chemical reactions.

Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids.

To progress from the laboratory to commercial applications, it will be necessary to develop industrially scalable methods to produce large quantities of defect-free graphene. Here we show that high-shear mixing of graphite in suitable stabilizing liquids results in large-scale exfoliation to give dispersions of graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show the exfoliated flakes to be unoxidized and free of basal-plane defects. We have developed a simple model that shows exfoliation to occur once the local shear rate exceeds 10(4) s(-1). By fully characterizing the scaling behaviour of the graphene production rate, we show that exfoliation can be achieved in liquid volumes from hundreds of millilitres up to hundreds of litres and beyond. The graphene produced by this method performs well in applications from composites to conductive coatings. This method can be applied to exfoliate BN, MoS2 and a range of other layered crystals.

A method for producing site-specific TEM specimens from low contrast materials with nanometer precision.

A method that enables high precision extraction of transmission electron microscope (TEM) specimens in low contrast materials has been developed. The main idea behind this work is to produce high contrast markers on both sides of and close to the area of interest. The markers are filled during the depositing of the protective layer. The marker material can be of either Pt or C depending on which one gives the highest contrast. It is thereby possible to distinguish the location of the area of interest during focused ion beam (FIB) milling and ensure that the TEM sample is extracted precisely at the desired position. This method is generally applicable and enables FIB/scanning electron microscope users to make high quality TEM specimens from small features and low contrast materials without a need for special holders. We explain the details of this method and illustrate its potential by examples from three different types of materials.

Electrolytes for dye-sensitized solar cells based on interhalogen ionic salts and liquids.

In this paper, we report on the preparation of interhalogen ionic liquids of the general formula [K+]XY2-, where K+=1,3-dialkylimidazolium, 1,2,3-trialkylimidazolium, or N-alkylpyridinium; XY2-=IBr2- or I2Br-. These compounds were characterized in solution and the solid state by NMR, IR, Raman, and mass spectroscopy. The crystal structure of the compound [Me2BuIm]IBr2 (7) shows that the IBr2- anion has a linear Br-I-Br structure. Indications of an equilibrium between different forms of XY2- anions in solution are observed. Interhalogen ionic salts and liquids were used as electrolyte components for encapsulated monolithic dye-sensitized solar cells. Overall light-to-electricity conversion efficiencies up to 6.4%, 5.0%, and 2.4% at 1000 W/m2 were achieved by using electrolytes based on interhalogen ionic salts and gamma-butyrolactone, glutaronitrile, or native ionic liquids as solvents, respectively. Moreover, in terms of stability, the cell performance lost 9-14% of the initial performance after 1000 h illumination at 350 W/m2.