Measuring organisational readiness for patient engagement (MORE) : an international online Delphi consensus study

Date of Acceptance: 28/01/2015. © 2015 Oostendorp et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedWidespread implementation of patient engagement by organisations and clinical teams is not a reality yet. The aim of this study is to develop a measure of organisational readiness for patient engagement designed to monitor and facilitate a healthcare organisation’s willingness and ability to effectively implement patient engagement in healthcarePeer reviewedFinal Published versio

MyosinVIIa Interacts with Twinfilin-2 at the Tips of Mechanosensory Stereocilia in the Inner Ear

In vertebrates hearing is dependent upon the microvilli-like mechanosensory stereocilia and their length gradation. The staircase-like organization of the stereocilia bundle is dynamically maintained by variable actin turnover rates. Two unconventional myosins were previously implicated in stereocilia length regulation but the mechanisms of their action remain unknown. MyosinXVa is expressed in stereocilia tips at levels proportional to stereocilia length and its absence produces staircase-like bundles of very short stereocilia. MyosinVIIa localizes to the tips of the shorter stereocilia within bundles, and when absent, the stereocilia are abnormally long. We show here that myosinVIIa interacts with twinfilin-2, an actin binding protein, which inhibits actin polymerization at the barbed end of the filament, and that twinfilin localization in stereocilia overlaps with myosinVIIa. Exogenous expression of myosinVIIa in fibroblasts results in a reduced number of filopodia and promotes accumulation of twinfilin-2 at the filopodia tips. We hypothesize that the newly described interaction between myosinVIIa and twinfilin-2 is responsible for the establishment and maintenance of slower rates of actin turnover in shorter stereocilia, and that interplay between complexes of myosinVIIa/twinfilin-2 and myosinXVa/whirlin is responsible for stereocilia length gradation within the bundle staircase

The Unconserved Groucho Central Region Is Essential for Viability and Modulates Target Gene Specificity

Groucho (Gro) is a Drosophila corepressor required by numerous DNA-binding repressors, many of which are distributed in gradients and provide positional information during development. Gro contains well-conserved domains at its N- and C-termini, and a poorly conserved central region that includes the GP, CcN, and SP domains. All lethal point mutations in gro map to the conserved regions, leading to speculation that the unconserved central domains are dispensable. However, our sequence analysis suggests that the central domains are disordered leading us to suspect that the lack of lethal mutations in this region reflects a lack of order rather than an absence of essential functions. In support of this conclusion, genomic rescue experiments with Gro deletion variants demonstrate that the GP and CcN domains are required for viability. Misexpression assays using these same deletion variants show that the SP domain prevents unrestrained and promiscuous repression by Gro, while the GP and CcN domains are indispensable for repression. Deletion of the GP domain leads to loss of nuclear import, while deletion of the CcN domain leads to complete loss of repression. Changes in Gro activity levels reset the threshold concentrations at which graded repressors silence target gene expression. We conclude that co-regulators such as Gro are not simply permissive components of the repression machinery, but cooperate with graded DNA-binding factors in setting borders of gene expression. We suspect that disorder in the Gro central domains may provide the flexibility that allows this region to mediate multiple interactions required for repression

Twenty-first century brain banking. Processing brains for research: the Columbia University methods

Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research

fMR-adaptation indicates selectivity to audiovisual content congruency in distributed clusters in human superior temporal cortex

<p>Abstract</p> <p>Background</p> <p>Efficient multisensory integration is of vital importance for adequate interaction with the environment. In addition to basic binding cues like temporal and spatial coherence, meaningful multisensory information is also bound together by content-based associations. Many functional Magnetic Resonance Imaging (fMRI) studies propose the (posterior) superior temporal cortex (STC) as the key structure for integrating meaningful multisensory information. However, a still unanswered question is how superior temporal cortex encodes content-based associations, especially in light of inconsistent results from studies comparing brain activation to semantically matching (congruent) versus nonmatching (incongruent) multisensory inputs. Here, we used fMR-adaptation (fMR-A) in order to circumvent potential problems with standard fMRI approaches, including spatial averaging and amplitude saturation confounds. We presented repetitions of audiovisual stimuli (letter-speech sound pairs) and manipulated the associative relation between the auditory and visual inputs (congruent/incongruent pairs). We predicted that if multisensory neuronal populations exist in STC and encode audiovisual content relatedness, adaptation should be affected by the manipulated audiovisual relation.</p> <p>Results</p> <p>The results revealed an occipital-temporal network that adapted independently of the audiovisual relation. Interestingly, several smaller clusters distributed over superior temporal cortex within that network, adapted stronger to congruent than to incongruent audiovisual repetitions, indicating sensitivity to content congruency.</p> <p>Conclusions</p> <p>These results suggest that the revealed clusters contain multisensory neuronal populations that encode content relatedness by selectively responding to congruent audiovisual inputs, since unisensory neuronal populations are assumed to be insensitive to the audiovisual relation. These findings extend our previously revealed mechanism for the integration of letters and speech sounds and demonstrate that fMR-A is sensitive to multisensory congruency effects that may not be revealed in BOLD amplitude per se.</p

Differences in selectivity to natural images in early visual areas (V1–V3)

High-level regions of the ventral visual pathway respond more to intact objects compared to scrambled objects. The aim of this study was to determine if this selectivity for objects emerges at an earlier stage of processing. Visual areas (V1–V3) were defined for each participant using retinotopic mapping. Participants then viewed intact and scrambled images from different object categories (bottle, chair, face, house, shoe) while neural responses were measured using fMRI. Our rationale for using scrambled images is that they contain the same low-level properties as the intact objects, but lack the higher-order combinations of features that are characteristic of natural images. Neural responses were higher for scrambled than intact images in all regions. However, the difference between intact and scrambled images was smaller in V3 compared to V1 and V2. Next, we measured the spatial patterns of response to intact and scrambled images from different object categories. We found higher within-category compared to between category correlations for both intact and scrambled images demonstrating distinct patterns of response. Spatial patterns of response were more distinct for intact compared to scrambled images in V3, but not in V1 or V2. These findings demonstrate the emergence of selectivity to natural images in V3

Analysis of rainfall seasonality from observations and climate models

Two new indicators of rainfall seasonality based on information entropy, the relative entropy (RE) and the dimensionless seasonality index (DSI), together with the mean annual rainfall, are evaluated on a global scale for recently updated precipitation gridded datasets and for historical simulations from coupled atmosphere--ocean general circulation models. The RE provides a measure of the number of wet months and, for precipitation regimes featuring a distinct wet and dry season, it is directly related to the duration of the wet season. The DSI combines the rainfall intensity with its degree of seasonality and it is an indicator of the extent of the global monsoon region. We show that the RE and the DSI are fairly independent of the time resolution of the precipitation data, thereby allowing objective metrics for model intercomparison and ranking. Regions with different precipitation regimes are classified and characterized in terms of RE and DSI. Comparison of different land observational datasets reveals substantial difference in their local representation of seasonality. It is shown that two-dimensional maps of RE provide an easy way to compare rainfall seasonality from various datasets and to determine areas of interest. Models participating to the Coupled Model Intercomparison Project platform, Phase 5, consistently overestimate the RE over tropical Latin America and underestimate it in West Africa, western Mexico and East Asia. It is demonstrated that positive RE biases in a general circulation model are associated with excessively peaked monthly precipitation fractions, too large during the wet months and too small in the months preceding and following the wet season; negative biases are instead due, in most cases, to an excess of rainfall during the premonsoonal months

Design of a randomized controlled study of a multi-professional and multidimensional intervention targeting frail elderly people

<p>Abstract</p> <p>Background</p> <p>Frail elderly people need an integrated and coordinated care. The two-armed study "Continuum of care for frail elderly people" is a multi-professional and multidimensional intervention for frail community-dwelling elderly people. It was designed to evaluate whether the intervention programme for frail elderly people can reduce the number of visits to hospital, increase satisfaction with health and social care and maintain functional abilities. The implementation process is explored and analysed along with the intervention. In this paper we present the study design, the intervention and the outcome measures as well as the baseline characteristics of the study participants.</p> <p>Methods/design</p> <p>The study is a randomised two-armed controlled trial with follow ups at 3, 6 and 12 months. The study group includes elderly people who sought care at the emergency ward and discharged to their own homes in the community. Inclusion criteria were 80 years and older <it>or </it>65 to 79 years with at least one chronic disease and dependent in at least one activity of daily living. Exclusion criteria were acute severely illness with an immediate need of the assessment and treatment by a physician, severe cognitive impairment and palliative care. The intention was that the study group should comprise a representative sample of frail elderly people at a high risk of future health care consumption. The intervention includes an early geriatric assessment, early family support, a case manager in the community with a multi-professional team and the involvement of the elderly people and their relatives in the planning process.</p> <p>Discussion</p> <p>The design of the study, the randomisation procedure and the protocol meetings were intended to ensure the quality of the study. The implementation of the intervention programme is followed and analysed throughout the whole study, which enables us to generate knowledge on the process of implementing complex interventions. The intervention contributes to early recognition of both the elderly peoples' needs of information, care and rehabilitation and of informal caregivers' need of support and information. This study is expected to show positive effects on frail elderly peoples' health care consumption, functional abilities and satisfaction with health and social care.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01260493">NCT01260493</a></p

Functional characterization of the human myosin-7a motor domain

Myosin-7a participates in auditory and visual processes. Defects in MYO7A, the gene encoding the myosin-7a heavy chain, are causative for Usher syndrome 1B, the most frequent cause of deaf-blindness in humans. In the present study, we performed a detailed kinetic and functional characterization of the isolated human myosin-7a motor domain to elucidate the details of chemomechanical coupling and the regulation of motor function. A rate-limiting, slow ADP release step causes long lifetimes of strong actin-binding intermediates and results in a high duty ratio. Moreover, our results reveal a Mg2+-sensitive regulatory mechanism tuning the kinetic and mechanical properties of the myosin-7a motor domain. We obtained direct evidence that changes in the concentration of free Mg2+ ions affect the motor properties of human myosin-7a using an in vitro motility assay system. Our results suggest that in a cellular environment, compartment-specific fluctuations in free Mg2+ ions can mediate the conditional switching of myosin-7a between cargo moving and tension bearing modes