Measuring the menu, not the food: "psychometric" data may instead measure "lingometrics" (and miss its greatest potential).

This is a review of a range of empirical studies that use digital text algorithms to predict and model response patterns from humans to Likert-scale items, using texts only as inputs. The studies show that statistics used in construct validation is predictable on sample and individual levels, that this happens across languages and cultures, and that the relationship between variables are often semantic instead of empirical. That is, the relationships among variables are given a priori and evidently computable as such. We explain this by replacing the idea of "nomological networks" with "semantic networks" to designate computable relationships between abstract concepts. Understanding constructs as nodes in semantic networks makes it clear why psychological research has produced constant average explained variance at 42% since 1956. Together, these findings shed new light on the formidable capability of human minds to operate with fast and intersubjectively similar semantic processing. Our review identifies a categorical error present in much psychological research, measuring representations instead of the purportedly represented. We discuss how this has grave consequences for the empirical truth in research using traditional psychometric methods.

The Ability of DNAJB6b to Suppress Amyloid Formation Depends on the Chaperone Aggregation State.

For many chaperones, a propensity to self-assemble correlates with function. The highly efficient amyloid suppressing chaperone DNAJB6b has been reported to oligomerize. A key question is whether the DNAJB6b self-assemblies or their subunits are active units in the suppression of amyloid formation. Here, we address this question using a nonmodified chaperone. We use the well-established aggregation kinetics of the amyloid ß 42 peptide (Aß42) as a readout of the amyloid suppression efficiency. The experimental setup relies on the slow dissociation of DNAJB6b assemblies upon dilution. We find that the dissociation of the chaperone assemblies correlates with its ability to suppress fibril formation. Thus, the data show that the subunits of DNAJB6b assemblies rather than the large oligomers are the active forms in amyloid suppression. Our results provide insights into how DNAJB6b operates as a chaperone and illustrate the importance of established assembly equilibria and dissociation rates for the design of kinetic experiments.

Nurses' perceptions of patient involvement in shared decision-making in cardiovascular care.

It is important for nurses to involve patients in their own care to enable shared decision-making. This study aimed to explore the perceptions of nurses regarding the degree to which involvement in shared decision-making takes place in clinical settings during consultations. Previous studies have shown that the use of shared decision-making by healthcare professionals can improve their caring practices and the quality of life of their patients. However, studies have also shown little evidence of the existence of shared decision-making in clinical practice. One step forward can be to clarify nurses' perceptions of patient involvement in shared decision-making. Qualitative data were collected from 10 nurses at four Swedish hospitals using a semi-structured, open-ended interview guide. The data were analyzed using inductive latent content analysis. The results showed that the care practices described by the nurses in the study are clearly different from the healthcare policy and scientific vision of shared decision-making. The nurses in the study believe that, with some exceptions, both healthcare professionals and patients prefer to leave decision-making to medical experts. In order to take advantage of the existing potential for improvement of shared decision-making in cardiologic care, healthcare professionals must be given time to seriously listen to and develop an interest in their patients' lifeworlds. Furthermore, the implementation of shared decision-making requires a mutual initiative and development of knowledge about the decision-making process from healthcare professionals and patients.

On the micelle formation of DNAJB6b.

The human chaperone DNAJB6b increases the solubility of proteins involved in protein aggregation diseases and suppresses the nucleation of amyloid structures. Due to such favourable properties, DNAJB6b has gained increasing attention over the past decade. The understanding of how DNAJB6b operates on a molecular level may aid the design of inhibitors against amyloid formation. In this work, fundamental aspects of DNAJB6b self-assembly have been examined, providing a basis for future experimental designs and conclusions. The results imply the formation of large chaperone clusters in a concentration-dependent manner. Microfluidic diffusional sizing (MDS) was used to evaluate how DNAJB6b average hydrodynamic radius varies with concentration. We found that, in 20 mM sodium phosphate buffer, 0.2 mM EDTA, at pH 8.0 and room temperature, DNAJB6b displays a micellar behaviour, with a critical micelle concentration (CMC) of around 120 nM. The average hydrodynamic radius appears to be concentration independent between ∼10 µM and 100 µM, with a mean radius of about 12 nm. The CMC found by MDS is supported by native agarose gel electrophoresis and the size distribution appears bimodal in the DNAJB6b concentration range ∼100 nM to 4 µM.

Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age.

Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.

X-Ray Scattering Reveals Two Mechanisms of Cellulose Microfibril Degradation by Filamentous Fungi.

Mushroom-forming fungi (Agaricomycetes) employ enzymatic and nonenzymatic cellulose degradation mechanisms, the latter presumably relying on Fenton-generated radicals. The effects of the two mechanisms on the cellulose microfibrils structure remain poorly understood. We examined cellulose degradation caused by litter decomposers and wood decomposers, including brown-rot and white-rot fungi and one fungus with uncertain wood decay type, by combining small- and wide-angle X-ray scattering. We also examined the effects of commercial enzymes and Fenton-generated radicals on cellulose using the same method. We detected two main degradation or modification mechanisms. The first characterized the mechanism used by most fungi and resembled enzymatic cellulose degradation, causing simultaneous microfibril thinning and decreased crystalline cellulose. The second mechanism was detected in one brown-rot fungus and one litter decomposer and was characterized by patchy amorphogenesis of crystalline cellulose without substantial thinning of the fibers. This pattern did not resemble the effect of Fenton-generated radicals, suggesting a more complex mechanism is involved in the destruction of cellulose crystallinity by fungi. Furthermore, our results showed a mismatch between decay classifications and cellulose degradation patterns and that even within litter decomposers two degradation mechanisms were found, suggesting higher functional diversity under current ecological classifications of fungi. IMPORTANCE Cellulose degradation by fungi plays a fundamental role in terrestrial carbon cycling, but the mechanisms by which fungi cope with the crystallinity of cellulose are not fully understood. We used X-ray scattering to analyze how fungi, a commercial enzyme mix, and a Fenton reaction-generated radical alter the crystalline structure of cellulose. Our data revealed two mechanisms involved in crystalline cellulose degradation by fungi: one that results in the thinning of the cellulose fibers, resembling the enzymatic degradation of cellulose, and one that involves amorphogenesis of crystalline cellulose by yet-unknown pathways, resulting in a patchy-like degradation pattern. These results pave the way to a deeper understanding of cellulose degradation and the development of novel ways to utilize crystalline cellulose.

α-Synuclein Interaction with Lipid Bilayer Discs.

α-Synuclein (aSyn) is a 140 residue long protein present in presynaptic termini of nerve cells. The protein is associated with Parkinson's disease, in which case it has been found to self-assemble into long amyloid fibrils forming intracellular inclusions that are also rich in lipids. Furthermore, its synaptic function is proposed to involve interaction with lipid membranes, and hence, it is of interest to understand aSyn-lipid membrane interactions in detail. In this paper we report on the interaction of aSyn with model membranes in the form of lipid bilayer discs. Using a combination of cryogenic transmission electron microscopy and small-angle neutron scattering, we show that circular discs undergo a significant shape transition after the adsorption of aSyn. When aSyn self-assembles into fibrils, aSyn molecules desorb from the bilayer discs, allowing them to recover to their original shape. Interestingly, the desorption process has an all-or-none character, resulting in a binary coexistence of circular bilayer discs with no adsorbed aSyn and deformed bilayer discs having a maximum amount of adsorbed protein. The observed coexistence is consistent with the recent finding of cooperative aSyn adsorption to anionic lipid bilayers.

A novel X-ray diffraction approach to assess the crystallinity of regenerated cellulose fibers.

Here, a new accurate approach is presented to quantify the degree of crystallinity of regenerated cellulose textile fibers using wide-angle X-ray scattering. The approach is based on the observation that the contributions to the scattering from crystalline and amorphous domains of the fibers can be separated due to their different degree of orientation with respect to the fiber direction. The method is tested on Ioncell-F fibers, dry jet wet spun with different draw ratios from an ionic liquid solution. The analysis output includes, apart from an accurate estimate of the fiber crystallinity, the degrees of orientation of the cellulose nanocrystals and the cellulose chains in the amorphous domains.

Amyloid ß 42 fibril structure based on small-angle scattering.

Amyloid fibrils are associated with a number of neurodegenerative diseases, including fibrils of amyloid ß42 peptide (Aß42) in Alzheimer's disease. These fibrils are a source of toxicity to neuronal cells through surface-catalyzed generation of toxic oligomers. Detailed knowledge of the fibril structure may thus facilitate therapeutic development. We use small-angle scattering to provide information on the fibril cross-section dimension and shape for Aß42 fibrils prepared in aqueous phosphate buffer at pH = 7.4 and pH 8.0 under quiescent conditions at 37 °C from pure recombinant Aß42 peptide. Fitting the data using a continuum model reveals an elliptical cross-section and a peptide mass-per-unit length compatible with two filaments of two monomers, four monomers per plane. To provide a more detailed atomistic model, the data were fitted using as a starting state a high-resolution structure of the two-monomer arrangement in filaments from solid-state NMR (Protein Data Bank ID 5kk3). First, a twofold symmetric model including residues 11 to 42 of two monomers in the filament was optimized in terms of twist angle and local packing using Rosetta. A two-filament model was then built and optimized through fitting to the scattering data allowing the two N-termini in each filament to take different conformations, with the same conformation in each of the two filaments. This provides an atomistic model of the fibril with twofold rotation symmetry around the fibril axis. Intriguingly, no polydispersity as regards the number of filaments was observed in our system over separate samples, suggesting that the two-filament arrangement represents a free energy minimum for the Aß42 fibril.

On the Cluster Formation of α-Synuclein Fibrils.

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson's disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d = 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.

Strong inhibition of peptide amyloid formation by a fatty acid.

The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer's and Parkinson's disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68-78 of the protein α-synuclein involved in Parkinson's disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of NACore. This inhibitory effect manifests itself through a prolongation of the lag phase of the peptide fibrillation. The effect is greatest when the fatty acid is present from the beginning of the process together with the monomeric peptide. Cryogenic transmission electron microscopy revealed the presence of nonfibrillar clusters among NACore fibrils formed in the presence of linoleic acid. We argue that the observed inhibitory effect on fibrillation is due to co-association of peptide oligomers and fatty acid aggregates at the early stage of the process. An important aspect of this mechanism is that it is nonmonomeric peptide structures that associate with the fatty acid aggregates. Similar mechanisms of action could be relevant in amyloid formation occurring in vivo, where the aggregation takes place in a lipid-rich environment.

Multiscale Structural Elucidation of Peptide Nanotubes by X-Ray Scattering Methods.

This mini-review presents the structural investigations of the self-assembled peptide nanotubes using X-ray scattering techniques. As compared to electron microscopy, scattering methods enable studies of nanotubes in solution under the appropriate physicochemical conditions and probe their formation mechanism. In addition, a combination of X-ray scattering methods allow the elucidation of structural organization from the molecular scale to the dimension of nanotubes.

SAXS/WAXS Investigation of Amyloid-ß(16-22) Peptide Nanotubes.

This brief report presents an X-ray scattering investigation of self-assembled nanotubes formed by a short peptide. X-ray scattering methods enable multiscale structural elucidation of these nanotubes in solution under the same conditions involved in the self-assembly process. In particular, the dimensions of nanotubes and the crystalline organization within their walls can be determined quantitatively. This is illustrated in the case of amyloid-ß(16-22) peptide nanotubes.

The 3Rs in animal welfare bodies at Swedish universities - knowledge, attitudes, implementation.

The implementation of the 3Rs (replacement, reduction and refinement) is emphasized in EU Directive 2010/63. The task of the animal welfare bodies (AWB) is to strengthen animal welfare and develop the 3Rs at research animal facilities. In 2016, we surveyed the knowledge on, attitudes towards and implementation of the 3Rs within AWBs at eight major Swedish universities. Based on responses of 34 closed-ended questions from 44 of 90 AWB members, the overall attitude towards the 3Rs was positive. AWB members did not believe that the 3Rs slow down innovation or result in increased costs, and refinement was considered beneficial for research quality. AWB members were particularly positive towards refinement questions in the survey. A majority of the AWB members predicted that alternative methods will never replace animal use. Researchers as a group represented in the AWBs were significantly less positive towards the 3Rs compared to the group of veterinarians. The tasks of the AWBs, e.g., giving advice on the 3Rs and following up on animal use in projects, were often not carried out in the AWB or not known by the respondents. Our results indicate a need for more practical and regulatory guidance and support to the AWBs. To reach the goal of the EU Directive to phase out animal use in research and education, we suggest that technical expertise in replacement techniques is included in the AWBs. We emphasize the need to strengthen the awareness of the 3Rs among researchers at Swedish universities.

Adsorption of Anionic Dyes Using a Poly(styrene-block-4-vinylpyridine) Block Copolymer Organogel.

An organogel was prepared by chemically cross-linking a poly(styrene-block-4-vinylpyridine) diblock copolymer using dibromododecane in dimethylformamide. Analysis of the prominent structure peak in small-angle X-ray scattering along with the results of light scattering and rheological profile suggests the bridging of the spherical micelles to one another to form an interconnected network after gelation. The use of this organogel as a selective adsorbent for removing anionic dyes from individual aqueous dye solutions and in a mixture of cationic and anionic dye solutions has shown more than 90% removal of the anionic dyes within 2 h. The regeneration and reusability studies showed that even after 20 cycles, the adsorption property of the organogel holds extremely well still beyond 90%. These results are indicative of the potential use of poly(styrene-block-4-vinylpyridine) organogel for the anionic ions removal in wastewater treatment.

Influence of clinical setting and cat characteristics on indirectly measured blood pressure and pulse rate in healthy Birman, Norwegian Forest, and Domestic Shorthair cats.

BACKGROUND: Measured indirect blood pressure (BP) results in cats in a clinical environment might be affected by stress and characteristics of the cats. HYPOTHESIS: To investigate the influence of clinical setting, cat characteristics, and life situation on BP and pulse rate (PR) in healthy cats. ANIMALS: Ninety-four healthy Domestic Shorthair, Birman and Norwegian Forest cats. METHODS: Blood pressure measured by high-definition oscillometry in 3 settings: cat placed in its own carrier with veterinarian present; cat placed in carrier with owner alone present; and cat placed on table with veterinarian present. Statistical analyses were performed using mixed linear models. RESULTS: Systolic BP (SBP) did not differ among settings. Higher mean arterial pressure (MAP), diastolic BP (DBP), and PR were found when measurements were performed with cat placed on table, rather than in carrier. Coefficients of variation (CVs) higher for SBP, MAP, DBP, and PR when measured with cat placed on table than in carrier. Birman cats had lower BP than other breeds. Systolic BP, MAP, DBP, and PR increased with age. Cats allowed outdoors had lower PR than cats living strictly indoors. CONCLUSION AND CLINICAL IMPORTANCE: No difference in SBP was found among settings, but measuring BP with the cat placed on the examination table gave higher MAP, DBP, PR, and CV than measuring BP with the cat in its carrier. Breed affected BP, with lower BP in Birman cats than other breeds. Blood pressure increased with age. Pulse rate was lower in cats allowed outdoors than cats living strictly indoors.

Slow Dissolution Kinetics of Model Peptide Fibrils.

Understanding the kinetics of peptide self-assembly is important because of the involvement of peptide amyloid fibrils in several neurodegenerative diseases. In this paper, we have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench. Due to the low concentrations involved, the experimental method of choice was isothermal titration calorimetry (ITC). We show that the dissolution is a strikingly slow and reaction-limited process, that can be timescale separated from other rapid processes associated with dilution in the ITC experiment. We argue that the rate-limiting step of dissolution involves the breaking up of inter-peptide ß-sheet hydrogen bonds, replacing them with peptide-water hydrogen bonds. Complementary pH experiments revealed that the self-assembly involves partial deprotonation of the peptide molecules.

Comparison of small-angle neutron and X-ray scattering for studying cortical bone nanostructure.

In this study, we present a combined small-angle neutron and X-ray scattering (SANS and SAXS) study of the nanoscale structure of cortical bone specimens from three different species. The variation of the scattering cross section of elements across the periodic table is very different for neutrons and X-rays. For X-rays, it is proportional to the electron density while for neutrons it varies irregularly with the atomic number. Hence, combining the two techniques on the same specimens allows for a more detailed interpretation of the scattering patterns as compared to a single-contrast experiment. The current study was performed on bovine, porcine and ovine specimens, obtained in two perpendicular directions with respect to the main axis of the bone (longitudinal and radial) in order to maximise the understanding of the nanostructural organisation. The specimens were also imaged with high resolution micro-computed tomography (micro-CT), yielding tissue mineral density and microstructural orientation as reference. We show that the SANS and SAXS patterns from the same specimen are effectively identical, suggesting that these bone specimens can be approximated as a two-component composite material. Hence, the observed small-angle scattering results mainly from the mineral-collagen contrast, apart from minor features associated with the internal collagen structure.

Patient Centeredness from a Perspective of History of the Present: A Genealogical Analysis.

The overall aim of this study, performed in Sweden, was to problematize the contemporary national and transnational discourse on patient centeredness, which during recent decades has become a given, having become established as a dogma in conversations, writing, and thinking about patients and health care. We did that by showing that ideas such as patient centeredness can be seen differently from the way they are depicted in contemporary discourses about health care. In the presented analysis, we drew on Foucault's concepts of governmentality, 'history of the present' and genealogy. This means that we reflected on contemporary conceptions of how phenomena, such as the care seeker, have been constructed within other discourses about health care. Empirically, we used different health policy documents-government reports from three different historical periods. The analysis showed that contemporary narratives about centeredness are neither more, nor less, care seeker-centered than the narratives of yesteryear. Rather, the phenomenon of the care seeker is given different frames and meanings within the framework of different economic and historical discourses about health care. Our analysis raised questions about the contemporary construction of patient centeredness. In a world with such huge economic differences between nations, as well as between citizens within most nations, the contemporary discourse may be limited as it does not problematize structural issues in the same way as previous discourses had done. Perhaps what is needed today are national and international patient-centered or person-centered discourses which also discuss policies and practices that are population- and social group-centered. In the final discussion of the analysis, we identified a new patient-centered discourse, which views the patient as a resource among other resources. The most important limitation of this type of study is that it is only about discourses and policy issues and not about daily practical activities.