Update of the MDS research criteria for prodromal Parkinson's disease

The MDS Research Criteria for Prodromal PD allow the diagnosis of prodromal Parkinson's disease using an evidence‐based conceptual framework, which was designed to be updated as new evidence becomes available. New prospective evidence of predictive values of risk and prodromal markers published since 2015 was reviewed and integrated into the criteria. Many of the predictive values (likelihood ratios, LR) remain unchanged. The positive likelihood ratio notably increase for olfactory loss and decreased for substantia nigra hyperechogenicity. Negative likelihood ratio remained largely unchanged for all markers. New levels of diagnostic certainty for neurogenic and symptomatic orthostatic hypotension have been added, which substantially differ in positive likelihood ratio from the original publication. For intermediate strength genetic variants, their age‐related penetrance is now incorporated in the calculation of the positive likelihood ratio. Moreover, apart from prospective studies, evidence from cross‐sectional case‐control genome‐wide association studies is also considered (given their likely lack of confounding and reverse causation), and to account for the effect of multiple low‐penetrance genetic variants polygenic risk scores are added to the model. Diabetes, global cognitive deficit, physical inactivity, and low plasma urate levels in men enter the criteria as new markers. A web‐based prodromal PD risk calculator allows the calculation of probabilities of prodromal PD for individuals. Several promising candidate markers may improve the diagnostic accuracy of prodromal PD in the future

Generalization of auditory sensory and cognitive learning in typically developing children

Despite the well-established involvement of both sensory (“bottom-up”) and cognitive (“top-down”) processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported “far-transfer” to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills

Technologies to Support Assessment of Movement During Video Consultations: Exploratory Study

Background Understanding and assessing patients’ body movements is essential for physical rehabilitation but is challenging in video consultations, as clinicians are frequently unable to see the whole patient or observe the patient as they perform specific movements. Objective The objective of this exploratory study was to assess the use of readily available technologies that would enable remote assessment of patient movement as part of a video consultation. Methods We reviewed the literature and available technologies and chose four technologies (Kubi and Pivo desktop robots, Facebook Portal TV, wide-angle webcam), in addition to help from a friend or a simple mobile phone holder, to assist video consultations. We used 5 standard assessments (sit-to-stand, timed “Up &amp; Go,” Berg Balance Test, ankle range of motion, shoulder range of motion) as the “challenge” for the technology. We developed an evaluation framework of 6 items: efficacy, cost, delivery, patient setup, clinician training and guidance, and safety. The coauthors, including 10 physiotherapists, then took the roles of clinician and patient to explore 7 combinations of 5 technologies. Subsequently, we applied our findings to hypothetical patients based on the researchers’ family members and clinical experience. Results Kubi, which allowed the clinician to remotely control the patient’s device, was useful for repositioning the tablet camera to gain a better view of the patient’s body parts but not for tracking movement. Facebook Portal TV was useful, but only for upper body movement, as it functions based on face tracking. Both Pivo, with automated full body tracking using a mobile phone, and the wide-angle webcam for a laptop or desktop computer show promise. Simple solutions such as having a friend operate a mobile phone and use of a mobile phone holder also have potential. The setup of these technologies will require better instructions than are currently available from suppliers, and successful use will depend on the technology readiness of patients and, to some degree, of clinicians. Conclusions Technologies that may enable clinicians to assess movement remotely as part of video consultations depend on the interplay of technology readiness, the patient’s clinical conditions, and social support. The most promising off-the-shelf approaches seem to be use of wide-angle webcams, Pivo, help from a friend, or a simple mobile phone holder. Collaborative work between patients and clinicians is needed to develop and trial technological solutions to support video consultations assessing movement. </jats:sec

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Fear and Exploration in European Starlings (Sturnus vulgaris): A Comparison of Hand-Reared and Wild-Caught Birds

The revision of EU legislation will ban the use of wild-caught animals in scientific procedures. This change is partially predicated on the assumption that captive-rearing produces animals with reduced fearfulness. Previously, we have shown that hand-reared starlings (Sturnus vulgaris) indeed exhibit reduced fear of humans compared to wild-caught conspecifics. Here, we asked whether this reduction in fear in hand-reared birds is limited to fear of humans or extends more generally to fear of novel environments and novel objects. Comparing 6–8 month old birds hand-reared in the lab with age-matched birds caught from the wild as fledged juveniles a minimum of 1 month previously, we examined the birds' initial reactions in a novel environment (a small cage) and found that wild-caught starlings were faster to initiate movement compared to the hand-reared birds. We interpret this difference as evidence for greater escape motivation in the wild-caught birds. In contrast, we found no differences between hand-reared and wild-caught birds when tested in novel object tests assumed to measure neophobia and exploratory behaviour. Moreover, we found no correlations between individual bird's responses in the different tests, supporting the idea that these measure different traits (e.g. fear and exploration). In summary, our data show that developmental origin affects one measure of response to novelty in young starlings, indicative of a difference in either fear or coping style in a stressful situation. Our data contribute to a growing literature demonstrating effects of early-life experience on later behaviour in a range of species. However, since we did not find consistent evidence for reduced fearfulness in hand-reared birds, we remain agnostic about the welfare benefits of hand-rearing as a method for sourcing wild birds for behavioural and physiological research

Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis

The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically

The link between volcanism and plutonism in epizonal magma systems; high-precision U–Pb zircon geochronology from the Organ Mountains caldera and batholith, New Mexico

The Organ Mountains caldera and batholith expose the volcanic and epizonal plutonic record of an Eocene caldera complex. The caldera and batholith are well exposed, and extensive previous mapping and geochemical analyses have suggested a clear link between the volcanic and plutonic sections, making this an ideal location to study magmatic processes associated with caldera volcanism. Here we present high-precision thermal ionization mass spectrometry U–Pb zircon dates from throughout the caldera and batholith, and use these dates to test and improve existing petrogenetic models. The new dates indicate that Eocene volcanic and plutonic rocks in the Organ Mountains formed from ~44 to 34 Ma. The three largest caldera-related tuff units yielded weighted mean [superscript 206]Pb/[superscript 238]U dates of 36.441 ± 0.020 Ma (Cueva Tuff), 36.259 ± 0.016 Ma (Achenback Park tuff), and 36.215 ± 0.016 Ma (Squaw Mountain tuff). An alkali feldspar granite, which is chemically similar to the erupted tuffs, yielded a synchronous weighted mean [superscript 206]Pb/[superscript 238]U date of 36.259 ± 0.021 Ma. Weighted mean [superscript 206]Pb/[superscript 238]U dates from the larger volume syenitic phase of the underlying Organ Needle pluton range from 36.130 ± 0.031 to 36.071 ± 0.012 Ma, and the youngest sample is 144 ± 20 to 188 ± 20 ka younger than the Squaw Mountain and Achenback Park tuffs, respectively. Younger plutonism in the batholith continued through at least 34.051 ± 0.029 Ma. We propose that the Achenback Park tuff, Squaw Mountain tuff, alkali feldspar granite and Organ Needle pluton formed from a single, long-lived magma chamber/mush zone. Early silicic magmas generated by partial melting of the lower crust rose to form an epizonal magma chamber. Underplating of the resulting mush zone led to partial melting and generation of a high-silica alkali feldspar granite cap, which erupted to form the tuffs. The deeper parts of the chamber underwent continued recharge and crystallization for 144 ± 20 ka after the final eruption. Calculated magmatic fluxes for the Organ Needle pluton range from 0.0006 to 0.0030 km3/year, in agreement with estimates from other well-studied plutons. The petrogenetic evolution proposed here may be common to many small-volume silicic volcanic systems

Application of Surface wave methods for seismic site characterization

Surface-wave dispersion analysis is widely used in geophysics to infer a shear wave velocity model of the subsoil for a wide variety of applications. A shear-wave velocity model is obtained from the solution of an inverse problem based on the surface wave dispersive propagation in vertically heterogeneous media. The analysis can be based either on active source measurements or on seismic noise recordings. This paper discusses the most typical choices for collection and interpretation of experimental data, providing a state of the art on the different steps involved in surface wave surveys. In particular, the different strategies for processing experimental data and to solve the inverse problem are presented, along with their advantages and disadvantages. Also, some issues related to the characteristics of passive surface wave data and their use in H/V spectral ratio technique are discussed as additional information to be used independently or in conjunction with dispersion analysis. Finally, some recommendations for the use of surface wave methods are presented, while also outlining future trends in the research of this topic

Elevated levels of β-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren's disease cells are regulated by tension in vitro

BACKGROUND: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that β-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in β-catenin and fibronectin levels. METHODS: Western blots of β-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed. RESULTS: Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in β-catenin and fibronectin levels, including a transient increase in β-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and β-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices. CONCLUSION: Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of β-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension