A density of states-based approach to determine temperature-dependent aggregation rates.

Here, we establish an approach to determine temperature-dependent aggregation rates in terms of thermostatistical quantities, which can be obtained directly from flat-histogram and statistical temperature algorithms considering the density of states of the system. Our approach is validated through simulations of an Ising-like model with anisotropically interacting particles at temperatures close to its first-order phase transition. Quantitative comparisons between the numerically obtained forward and reverse rates to approximate analytical expressions corroborate its use as a model-independent approach.

Ligancy effects on nucleation kinetics.

Nucleation of particles into crystalline structures can be observed in a wide range of systems from metallic and metal-organic compounds to colloidal and polymeric patch particles. Here, we perform kinetic Monte Carlo simulations to study the nucleation kinetics of particles with different ligancies z at constant supersaturation s. This approach allows one to determine several physico-chemical quantities as a function of s, including the growth probability P(n), the critical nucleus size n*, and the stationary nucleation rate Js. Our numerical results are rationalized in terms of a self-consistent nucleation theory where both n* and Js present a non-trivial dependence on s, but which can be determined from the values of effective z-dependent parameters.

Regarding loads after spinal fusion, every level should be seen separately: a musculoskeletal analysis.

INTRODUCTION: The number of spinal fusion surgeries is steadily increasing and biomechanical consequences are still in debate. The aim of this study is to provide biomechanical insights into the sagittal balance of the spine and to compare spinal load before and after spinal fusion. METHOD: The joint reaction forces of 52 patients were analyzed in proximo-distal and antero-posterior direction from the levels T12-L1 to L5-S1 using musculoskeletal simulations. RESULTS: In 104 simulations, pre-surgical forces were equal to post-surgical. The levels L4-L5 and T12-L1, however, showed increased spinal forces compression forces with higher sagittal displacement. Improved restauration of sagittal balance was accompanied by lower spinal load. AP shear stress, interestingly decreased with sagittal imbalance. CONCLUSION: Imbalanced spines have a risk of increased compression forces at Th12-L1. L4-L5 always has increased spinal loads. These slides can be retrieved under Electronic Supplementary Material.

On the challenges and opportunities facing fish biology: a discussion of five key knowledge gaps.

Many fish species face increasing challenges associated with climate change and overfishing. At the same time, aquaculture is becoming vital for food security. Gaining a deeper understanding of the basic biology of fish is therefore more important than ever. Here we synthesize and summarize key questions, opportunities and challenges in fish biology highlighted during a round-table discussion at the 50th Anniversary Symposium of The Fisheries Society of the British Isles, held at the University of Exeter, U.K., in July 2017. We identified several knowledge gaps but also key opportunities for fish biology to inform food security, for collective behaviour, evolutionary history and trait correlations to predict responses to environmental change and for novel analytical approaches to mine existing data sets. Overall, more integrative approaches through stronger collaborations across different fields are needed to advance our understanding of the basic biology of fish.

Importance of non-affine viscoelastic response in disordered fibre networks.

Disordered fibre networks are ubiquitous in nature and have a wide range of industrial applications as novel biomaterials. Predicting their viscoelastic response is straightforward for affine deformations that are uniform over all length scales, but when affinity fails, as has been observed experimentally, modelling becomes challenging. Here we present a numerical methodology, related to an existing framework for amorphous packings, to predict the steady-state viscoelastic spectra and degree of affinity for disordered fibre networks driven at arbitrary frequencies. Applying this method to a peptide gel model reveals a monotonic increase of the shear modulus as the soft, non-affine normal modes are successively suppressed as the driving frequency increases. In addition to being dominated by fibril bending, these low frequency network modes are also shown to be delocalised. The presented methodology provides insights into the importance of non-affinity in the viscoelastic response of peptide gels, and is easily extendible to all types of fibre networks.

Universality in the morphology and mechanics of coarsening amyloid fibril networks.

Peptide hydrogels have important applications as biomaterials and in nanotechnology, but utilization often depends on their mechanical properties for which we currently have no predictive capability. Here we use a peptide model to simulate the formation of percolating amyloid fibril networks and couple these to the elastic network theory to determine their mechanical properties. We find that the time variation of network length scales can be collapsed onto master curves by using a time scaling function that depends on the peptide interaction anisotropy. The same scaling applies to network mechanics, revealing a nonmonotonic dependence of the shear modulus with time. Our structure-function relationship between the peptide building blocks, network morphology, and network mechanical properties can aid in the design of amyloid fibril networks with tailored mechanical properties.

Cost-Effectiveness of Prevention for People at Risk for Dementia: A Scoping Review and Qualitative Synthesis.

Dementia is from an economic perspective a main challenge for economies worldwide because of increasing costs. Since there is no cure in sight, prevention seems the most promising approach for reducing health care cost due to Dementia. On the contrary, approximately 40% of dementias is attributable to modifiable risk factors and first studies showed that multidomain interventions may be effective for preventing dementia. Considering the increasing economic burden, for many health administrations worldwide, cost-effectiveness plays a mayor role. This scoping review wants to bring evidence to the question if prevention for people at risk may be cost-effective. Therefore, the four databases Medline (via Pubmed), CINHAL (via EBSCO), Business Source Complete (via EBSCO), and the Health Economic Evaluation database (HEED) were used to conduct a scoping review using PICO and a systematic search string. 3,629 studies were identified and seven met all inclusion criteria. The included studies showed clear cost-effectiveness for most multidomain interventions. The gained QALYs at mean were 0.08 (SD=0.08) and the intervention average costs 472.20 EUR per Person (SD=74.06 EUR). The Incremental Cost-Effectiveness Ratios varied between -80,427.97 and 104,189.82 EUR per QALY. The three core results are (i) prevention programs focusing on people at risk may be cost-effective and cost-efficient, (ii) multimodal prevention reveal cost saving potential, when the people at risk are defined well, (iii prevention in middle-aged cohorts may be also cost-effective if life-style related risk factors are addressed.

Participants in a peer-based nutrition and health program in Zimbabwe value dialogue, peer support, and tangible action: A qualitative exploration of peer group experiences.

Peer support groups are implemented globally, and viewed as cost-effective, scalable platforms for delivering health and nutrition programming. Quality is important for participation and achieving social and behavior change goals. Little research has explored the perspectives of peer group participants on quality. This manuscript describes community-based implementation research, and associated findings, which was conducted to learn how participants of a nutrition and health program define quality peer groups and how they suggest improving peer groups. In-depth interviews on experiences, benefits, and challenges were conducted with participants of health and nutrition peer groups, including group members (n = 64) and facilitators (n = 30), in three districts in Zimbabwe. Qualitative data were analyzed thematically and preliminary results were presented in six follow-up focus group discussions with interviewees to provide input on results and interpretation. Peer groups met some of participants' needs for knowledge, social support, and visible improvements in their lives and homes. Participants described generally positive experiences that sustained participation and motivated behavior change. They highlighted group dynamics, interactive facilitation, and community recognition which support the credibility and motivation of group facilitators. Implementation could be improved by strengthening family engagement and more hands-on learning for encouraging participation. Local adaptation of group activities can address influences on behavior change and increase relevance to participants' needs. The perspectives of core stakeholders are essential to understand what aspects of peer groups are most important to implement the approach with quality across contexts. Implementation research and continued monitoring to understand participant perspectives should be an integral part of all programs to ensure the application of adult learning principles and an appropriate balance between fidelity and adaptation for local relevance and engagement.

Communication: Non-monotonic supersaturation dependence of the nucleus size of crystals with anisotropically interacting molecules.

We study the nucleation of model two-dimensional crystals formed from anisotropically interacting molecules using kinetic Monte Carlo simulations and the forward flux sampling algorithm. The growth probability P(n) of a cluster of n molecules is measured while the supersaturation s and interaction anisotropy of the molecules are varied, in order to gain insight into the nucleation mechanism. It is found that with increasing degree of interaction anisotropy the nucleus size (defined as the cluster size at which P(n) = 0.5) can increase with increasing s, with sharp jumps at certain s values. Analysis of the cluster shape reveals that nucleation in the system studied is of a non-standard form, in that it embodies elements of both the classical nucleation theory and the density functional theory frameworks.

Cold thermopeaking-induced drift of nase Chondrostoma nasus larvae.

Research on how intermittent water releases from hydropower plants affect the early life stages of fish has advanced in the last years, focusing not only on the direct impacts of rapid flow changes (hydropeaking), but also on the short-term fluctuations in water temperature (thermopeaking). Flow and thermal fluctuations caused by hydropeaking may affect fish movement patterns and migration at critical stages of a species' life cycle, e.g., by inducing passive downstream drift. Using two experimental outdoor channels, we investigated how nase (Chondrostoma nasus, Cypriniformes) larvae respond to a rapid drop in water temperature during hydropeaking (simulating a cold thermopeaking event), reaching on average 5.5 °C under peak flow (maximum discharge) conditions, in comparison with a hydropeaking treatment with a constant water temperature regime. Responses of fish larvae were analyzed during acclimation, up-ramping (increase in discharge), peak flow and down-ramping (decrease in discharge) phases. Fish drift increased during peak flow in the cold thermopeaking treatment compared to hydropeaking. Higher drift rates were also negatively associated with pronounced water temperature drops during peak flow conditions. In addition, the starting temperature of the experiment influenced drift during up-ramping. Overall, the results suggest that cold thermopeaking may increase drift in the early life stages of cypriniform fish compared with hydropeaking with stable water temperature. Hence, monitoring and active water temperature adjustments following hydropower releases should be adopted as strategies to mitigate power plant-related impacts on aquatic organisms. Supplementary Information: The online version contains supplementary material available at 10.1007/s00027-023-00955-x.

[A training program for dementia trainers: does this program have practical relevance?]. / Ausbildungsmodell für M.A.S-Trainer : Eine Praxisevaluierung.

BACKGROUND: Specific curricula for professionals working in various settings with persons with dementia have been developed and implemented into practice. In this study, the practical relevance of a teaching program for the M.A.S (Morbus Alzheimer syndrome) dementia trainer was evaluated. The curriculum was developed in 2002 within a scientific project. The goal was that care professionals and noncare professionals learn how to support and train persons with dementia and their caregivers. The task of the trainer is to support the functional and emotional resources of the person with dementia employing stage-specific training according to principles of the theory of retrogenesis. Trainers are also able to support family caregivers in their difficult day-to-day care for the person with dementia. With this training and support program, persons with dementia can train their residual capacities and develop a life perspective which enables them to cope with the long duration of Alzheimer's disease. MATERIALS AND METHODS: The curriculum for the training methodology is based in the theory of retrogenesis. The 1-year training course is held in the form of modules and includes the following topics: (1) stages of dementia and medical aspects, (2) communication with persons with dementia, (3) stage-specific retrogenic training, (4) physical training for the elderly and persons with dementia, (5) coaching family caregivers through the long disease duration, and (6) care issues for persons without education in care. M.A.S trainers were questioned after they had concluded the teaching program successfully and had the chance to apply the content of the teaching program in their practical work. A short questionnaire was sent via e-mail or a telephone interview was performed. RESULTS: A total of 279 trainers graduated and were certified. Of these, 140 persons (53.6% of the population) could be questioned after an average of 2.69 years after completion of the course: 93.6% of trainees were still using the principles of the teaching course successfully; of these, 56% were working in the function of a trainer full time and 44% used the principles within their work environment (mainly in the nursing home environment). CONCLUSION: The study found that the majority of questioned trainers are still using the principles taught in the course successfully with persons with dementia living at home and the content was found to be relevant for practice. The content of the teaching course, applying principles of retrogenesis, which was originally designed for persons with dementia living at home, can also be successfully applied in the nursing home environment. Increasing interest has been shown by institutions employing professionals whose task it is to keep persons with dementia active and interested as well as physically functioning at their best possible level. As a consequence, persons with dementia perceive higher quality of life and exhibit fewer behavior problems which complicate care. More research is needed to accumulate evidence and to support these findings.

Evaluation of Mass Sensitive Micro-Array biosensors for their feasibility in multiplex detection of low molecular weight toxins using mycotoxins as model compounds.

Mycotoxins produced by Fusarium species including trichothecenes, zearalenone and fumonisins, can co-contaminate food and feed throughout the supply chain, including cereal grains and animal feeds. There is an increasing demand to enhance global food security by improving the monitoring of mycotoxins throughout our food supply chain. For time and cost-efficient analysis, rapid tests capable of detecting multiple toxins from a single sample are ideal. Considering these current trends in mycotoxin testing, this project examined the feasibility of using both a portable and non-portable mass-based biosensor for multiplex mycotoxin detection. The biosensor was a mass sensitive microarray (MSMA) which consisted of 4 × 16 miniaturized mass sensitive transducer pixels based on solidly mounted resonator (SMR) technology. Functionalisation of individual pixels on the sensor surface using nano-spotting technology for the simultaneous and semi-quantitative detection of three regulated mycotoxins: T2-toxin (T2) zearalenone (ZEN), and fumonisin B1 (FumB1) was examined. With the integration of portable and non-portable microfluidic devices for antibody and standard sample injections, competitive inhibition assays were developed followed by singleplex and multiplex calibration curves. The characteristics and performance of the MSMA were evaluated including sensitivity which was determined as the concentration causing 50% inhibition. Sensitivity of singleplex assays using the portable microfluidic device (PMD) were 1.3 ng/ml, 2.0 ng/ml and 6.8 ng/ml for T2, FumB1 and ZEN, respectively. Sensitivity of the multiplex assay again using the PMD was 6.1 ng/ml, 3.6 ng/ml and 2.4 ng/ml for T2, FumB1 and ZEN, respectively. The PMD was an easy to use and highly sensitive screening tool which has been demonstrated for the multiplex detection of three regulated mycotoxins. Analysis was in real time and results were fully digital. Since detection of analytes was by mass it was both a label-free and cost-efficient method proposed method of analysis for mycotoxins.

Nursing home structure and association with agitation and use of psychotropic drugs in nursing home residents in three countries: Norway, Austria and England.

BACKGROUND: Understanding the underlying mechanisms and risk factors leading to agitation is crucial to reduce the severity of agitation and increase quality of life. International comparative studies offer special advantages in elucidating environmental risk factors by providing a wider diversity of environmental exposures such as nursing home structures, health care systems and genetic diversity. METHODS: Baseline data for three different intervention studies in Austria (n = 38), England (n = 302) and Norway (n = 163) were combined posthoc. Patients were grouped according to their dementia severity using the global deterioration scale (GDS), functional assessment staging (FAST) and clinical dementia rating (CDR) scales. For the measurement of agitation, the Cohen-Mansfield Agitation Inventory (CMAI) was used. Data analysis was performed using one-way ANOVA, multivariate and linear regression analysis. RESULTS: CMAI scores were available for 503 subjects with dementia. There were significant differences between the nursing home residents in the three countries regarding age, gender and dementia severity (all p values < 0.001). In the multivariate analyses, the level of agitation differed with higher mean scores in the Austrian (mean (SD) score 51.9(21.8)) compared to UK (43.3(16.1)) and Norwegian (41.6(13.2)) nursing homes (p = 0.002). Similarly, the use of psychotropic drugs differed significantly, with a higher proportion of neuroleptics in UK (48%, p < 0.001) and Austrian (52.6%; p = 0.001) compared to Norwegian (19%) nursing homes. CONCLUSION: We found differences in agitation and antipsychotic drug use which are likely related to structural and cultural differences in nursing homes in three European countries. These findings suggest that structural changes can improve quality of care and quality of life for nursing home residents.

Onset of heterogeneous crystal nucleation in colloidal suspensions.

The addition of small 'seed' particles to a supersaturated solution can greatly increase the rate at which crystals nucleate. This process is understood, at least qualitatively, when the seed has the same structure as the crystal that it spawns. However, the microscopic mechanism of seeding by a 'foreign' substance is not well understood. Here we report numerical simulations of colloidal crystallization seeded by foreign objects. We perform Monte Carlo simulations to study how smooth spherical seeds of various sizes affect crystallization in a suspension of hard colloidal particles. We compute the free-energy barrier associated with crystal nucleation. A low barrier implies that nucleation is easy. We find that to be effective crystallization promoters, the seed particles need to exceed a well-defined minimum size. Just above this size, seed particles act as crystallization 'catalysts' as newly formed crystallites detach from the seed. In contrast, larger seed particles remain covered by the crystallites that they spawn. This phenomenon should be experimentally observable and can have important consequences for the control of the resulting crystal size distribution.

Erratum: The Dynamics of Coalition Formation on Complex Networks.

This corrects the article DOI: 10.1038/srep13386.

Large area mass analyzer instrument for the chemical analysis of interstellar dust particles.

A new instrument to analyze the chemical composition of dust particles in situ in space has been developed. The large target area ( approximately 0.2 m(2)) makes this instrument well suited for detecting a statistically significant number of interstellar dust grains or other dust particles with a low flux. The device is a reflectron-type time-of-flight mass spectrometer that uses only flat electrodes for the generation of the parabolic potential. The instrument analyzes the ions from the impact generated plasma due to hypervelocity dust impacts onto a solid target surface. The SIMION ion optics software package is used to investigate different potential field configurations and optimize the mass resolution and focusing of the ions. The cylindrically symmetric instrument operates with six ring electrodes and six annular electrodes biased to different potentials to create the potential distribution of the reflectron. The laboratory model of the instrument has been fabricated and tested. Hypervelocity dust impacts are simulated by laser ablation using a frequency doubled Nd:YAG laser with approximately 8 ns pulse length. The experimental data show typical mass resolution m/Deltam approximately 200.

Amyloid Fibril Solubility.

It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.

The Dynamics of Coalition Formation on Complex Networks.

Complex networks describe the structure of many socio-economic systems. However, in studies of decision-making processes the evolution of the underlying social relations are disregarded. In this report, we aim to understand the formation of self-organizing domains of cooperation ("coalitions") on an acquaintance network. We include both the network's influence on the formation of coalitions and vice versa how the network adapts to the current coalition structure, thus forming a social feedback loop. We increase complexity from simple opinion adaptation processes studied in earlier research to more complex decision-making determined by costs and benefits, and from bilateral to multilateral cooperation. We show how phase transitions emerge from such coevolutionary dynamics, which can be interpreted as processes of great transformations. If the network adaptation rate is high, the social dynamics prevent the formation of a grand coalition and therefore full cooperation. We find some empirical support for our main results: Our model develops a bimodal coalition size distribution over time similar to those found in social structures. Our detection and distinguishing of phase transitions may be exemplary for other models of socio-economic systems with low agent numbers and therefore strong finite-size effects.

The neglected half of Alzheimer disease: cognitive and functional concomitants of severe dementia.

OBJECTIVE: Traditional mental status and psychometric assessments bottom out in the late stages of Alzheimer disease (AD). A method adapted from cognitive testing in infants, the Ordinal Scales of Psychological Development was modified (M-OSPD) and applied to a severely demented population. The concurrent validity of this method was tested in comparison with Functional Assessment Staging (FAST). Internal consistency as a measure for reliability was also determined. DESIGN: Cross sectional study. SETTING: Subjects were generally evaluated in their residence, usually a nursing home or a private home. PATIENTS: Severely cognitively impaired subjects who fulfilled criteria for probable AD were studied. MEASUREMENTS: Evaluation consisted of clinical global, mental status, functional, and cognitive assessments including the Global Deterioration Scale (GDS) and the Mini-Mental State Examination (MMSE). RESULTS: Seventy patients were evaluated. Traditional mental status assessments (eg, the MMSE) manifested virtually uniform bottom scores in all GDS stage 7 subjects (n = 46), and GDS stage 6 subjects had MMSE scores within one standard deviation unit of zero. In contrast, the M-OSPD scale continued to show results in the last stages of the disease. The Spearman correlation coefficient between the M-OSPD total score and the 11 FAST substages represented in this sample was -0.77 (P < 0.001). CONCLUSIONS: The results indicate that patients who are functionally more impaired also show continuing increments in cognitive loss. These cognitive and functional assessments for measuring the magnitude of deterioration in AD can be applied to the estimated half-million nursing home residents presently labeled "untestable" with the goal of optimization of care and residual capacities.