Project description:Evidence-based practice is critical but challenging in mental health. Rigorous research-proven interventions often do not yield expected results in the clinical practice. This study aimed to explore factors contributing to the effectiveness of Occupational Connections (OC)-an intervention for promotion of engagement in meaningful occupations in serious mental illness (SMI)-based on case series study of three quasi-experimental studies. The studies focused on people with SMI, admitted to intensive mental health services participated in the OC, as well as on a control condition group. Similar evaluation procedures throughout these studies addressed primary outcomes of participation dimensions and recovery orientation, as well as secondary outcomes of functional capacity, cognition, and symptom severity. Patterns of changes in outcome measures varied between the three studies as to direction and extension. In the OC groups, 29-60% of the outcome measurements were changed, in comparison to 29-43% of measurements in the control groups. The secondary outcomes were consistently improved in the OC (18-100% of measurements) in comparison to the control (18-67%). The analysis of the studies revealed that clinical effectiveness of participation-oriented intervention varied dependent on interplay between the clinical context, clinician actions, served persons' characteristics, and evidence-building process. These factors should be considered to maximize research benefits for practice.
Project description:Despite the remarkable health achievements of Japan's universal health coverage since 1961, along with numerous social programs to ensure financial protection, a growing proportion of the older population reportedly experiences financial hardship for essential health care. The socio-behavioral and economic situation of the households in need and the effective policy interventions remain unknown. To identify the reasons behind older persons' financial hardship and the effective policy interventions, we performed a questionnaire survey of social workers in all hospitals, local government offices and social service agencies across six prefectures in Kansai region. Data from 553 respondents revealed that the financial difficulties related to health care are often closely intertwined with social and mental health hardships experienced by older people and their families. Notably, potentially helpful programs including 'free/low-cost medical treatment program' and the adult guardianship system for dementia were infrequently used. Moreover, male, social workers at local offices/agencies, and less than 10 years' professional experience associated with infrequent use of key protective programs. To close the gap between policy and practice, policies should focus on clients' daily living needs, and new frontline social workers should receive lifelong training that incorporates their own backgrounds, experiences, and values, including the use of anti-oppressive gerontological approaches.Supplementary informationThe online version contains supplementary material available at 10.1007/s10615-023-00914-x.
Project description:DNA polymerase (dpol) β has served as a model for structural, kinetic, and computational characterization of the DNA synthesis reaction. The laboratory directed by Samuel H. Wilson has utilized a multifunctional approach to analyze the function of this enzyme at the biological, chemical, and molecular levels for nearly 50 years. Over this time, it has become evident that correlating static crystallographic structures of dpol β with solution kinetic measurements is a daunting task. However, aided by computational and spectroscopic approaches, novel and unexpected insights have emerged. While dpols generally insert wrong nucleotides with similar poor efficiencies, their capacity to insert the right nucleotide depends on the identity of the dpol. Accordingly, the ability to choose right from wrong depends on the efficiency of right, rather than wrong, nucleotide insertion. Structures of dpol β in various liganded forms published by the Wilson laboratory, and others, have provided molecular insights into the molecular attributes that hasten correct nucleotide insertion and deter incorrect nucleotide insertion. Computational approaches have bridged the gap between structures of intermediate complexes and provided insights into this basic and essential chemical reaction.
Project description:Total-evidence dating (TED) allows evolutionary biologists to incorporate a wide range of dating information into a unified statistical analysis. One might expect this to improve the agreement between rocks and clocks but this is not necessarily the case. We explore the reasons for such discordance using a mammalian dataset with rich molecular, morphological and fossil information. There is strong conflict in this dataset between morphology and molecules under standard stochastic models. This causes TED to push divergence events back in time when using inadequate models or vague priors, a phenomenon we term 'deep root attraction' (DRA). We identify several causes of DRA. Failure to account for diversified sampling results in dramatic DRA, but this can be addressed using existing techniques. Inadequate morphological models also appear to be a major contributor to DRA. The major reason seems to be that current models do not account for dependencies among morphological characters, causing distorted topology and branch length estimates. This is particularly problematic for huge morphological datasets, which may contain large numbers of correlated characters. Finally, diversification and fossil sampling priors that do not incorporate all the available background information can contribute to DRA, but these priors can also be used to compensate for DRA. Specifically, we show that DRA in the mammalian dataset can be addressed by introducing a modest extra penalty for ghost lineages that are unobserved in the fossil record, for instance by assuming rapid diversification, rare extinction or high fossil sampling rate; any of these assumptions produces highly congruent divergence time estimates with a minimal gap between rocks and clocks. Under these conditions, fossils have a stabilizing influence on divergence time estimates and significantly increase the precision of those estimates, which are generally close to the dates suggested by palaeontologists.This article is part of the themed issue 'Dating species divergences using rocks and clocks'.
Project description:BackgroundIt may take 15 years or longer before research evidence is integrated into clinical practice. This evidence-to-practice gap has deleterious effects on patients as well as research and clinical processes. Bringing clinical knowledge into the research process, however, has the potential to close the evidence-to-practice gap. The NEUROTRANS-Project attempts to bring research and practice together by focusing on two groups that usually operate separately in their communities: general practitioners and neuroscientists. Although both groups focus on dementia as an area of work, they do so in different contexts and without opportunities to share their expertise. Finding new treatment pathways for patients with dementia will require an equal knowledge exchange among researchers and clinicians along with the integration of that knowledge into research processes, so that both groups will benefit from the expertise of the other.MethodsThe NEUROTRANS-Project uses a qualitative, multi-stage research design to explore how neuroscientists and general practitioners (GPs) approach dementia. Using a grounded theory methodology, it analyzes semi-structured interviews, case vignettes, focus groups with GPs in Saxony-Anhalt, Germany, and informal conversations with, and observations of, neuroscientists from the German Center for Neurodegenerative Diseases in Magdeburg.ResultsThe NEUROTRANS-Project identified a clear division of labor between two highly specialized professional groups. Neuroscientists focus abstractly on nosology whereas general practitioners tend to patient care following a hermeneutic approach integrating the patients' perspective of illness. These different approaches to dementia create a barrier to constructive dialogue and the capacity of these groups to do research together with a common aim. Additionally, the broader system of research funding and health care within which the two groups operate reinforces their divide thereby limiting joint research capacity.ConclusionsOvercoming barriers to research collaboration between general practitioners and neuroscientists requires a shift in perspective in which both groups actively engage with the other's viewpoints to facilitate knowledge circulation (KC). Bringing 'art into science and science into art', i.e. amalgamating the hermeneutic approach with the perspective of nosology, is the first step in developing joint research agendas that have the potential to close the evidence-to-practice gap.
Project description:Despite early predictions and rapid progress in research, the introduction of personal genomics into clinical practice has been slow. Several factors contribute to this translational gap between knowledge and clinical application. The evidence available to support genetic test use is often limited, and implementation of new testing programs can be challenging. In addition, the heterogeneity of genomic risk information points to the need for strategies to select and deliver the information most appropriate for particular clinical needs. Accomplishing these tasks also requires recognition that some expectations for personal genomics are unrealistic, notably expectations concerning the clinical utility of genomic risk assessment for common complex diseases. Efforts are needed to improve the body of evidence addressing clinical outcomes for genomics, apply implementation science to personal genomics, and develop realistic goals for genomic risk assessment. In addition, translational research should emphasize the broader benefits of genomic knowledge, including applications of genomic research that provide clinical benefit outside the context of personal genomic risk.
Project description:Nucleosome structure and stability affect genetic accessibility by altering the local chromatin morphology. Recent FRET experiments on nucleosomes have given valuable insight into the structural transformations they can adopt. Yet, even if performed under seemingly identical conditions, experiments performed in bulk and at the single molecule level have given mixed answers due to the limitations of each technique. To compare such experiments, however, they must be performed under identical conditions. Here we develop an experimental framework that overcomes the conventional limitations of each method: single molecule FRET experiments are carried out at bulk concentrations by adding unlabeled nucleosomes, while bulk FRET experiments are performed in microplates at concentrations near those used for single molecule detection. Additionally, the microplate can probe many conditions simultaneously before expending valuable instrument time for single molecule experiments. We highlight this experimental strategy by exploring the role of selective acetylation of histone H3 on nucleosome structure and stability; in bulk, H3-acetylated nucleosomes were significantly less stable than non-acetylated nucleosomes. Single molecule FRET analysis further revealed that acetylation of histone H3 promoted the formation of an additional conformational state, which is suppressed at higher nucleosome concentrations and which could be an important structural intermediate in nucleosome regulation.
Project description:Measuring the pace at which speciation and extinction occur is fundamental to understanding the origin and evolution of biodiversity. Both the fossil record and molecular phylogenies of living species can provide independent estimates of speciation and extinction rates, but often produce strikingly divergent results. Despite its implications, the theoretical reasons for this discrepancy remain unknown. Here, we reveal a conceptual and methodological basis able to reconcile palaeontological and molecular evidence: discrepancies are driven by different implicit assumptions about the processes of speciation and species evolution in palaeontological and neontological analyses. We present the "birth-death chronospecies" model that clarifies the definition of speciation and extinction processes allowing for a coherent joint analysis of fossil and phylogenetic data. Using simulations and empirical analyses we demonstrate not only that this model explains much of the apparent incongruence between fossils and phylogenies, but that differences in rate estimates are actually informative about the prevalence of different speciation modes.
Project description:The understanding of complex biological networks often relies on both a dedicated layout and a topology. Currently, there are three major competing layout-aware systems biology formats, but there are no software tools or software libraries supporting all of them. This complicates the management of molecular network layouts and hinders their reuse and extension. In this paper, we present a high-level overview of the layout formats in systems biology, focusing on their commonalities and differences, review their support in existing software tools, libraries and repositories and finally introduce a new conversion module within the MINERVA platform. The module is available via a REST API and offers, besides the ability to convert between layout-aware systems biology formats, the possibility to export layouts into several graphical formats. The module enables conversion of very large networks with thousands of elements, such as disease maps or metabolic reconstructions, rendering it widely applicable in systems biology.
Project description:Despite continuous updates of the human reference genome, there are still hundreds of unresolved gaps which account for about 5% of the total sequence length. Given the availability of whole genome de novo assemblies, especially those derived from long-read sequencing data, gap-closing sequences can be determined. By comparing 17 de novo long-read sequencing assemblies with the human reference genome, we identified a total of 1,125 gap-closing sequences for 132 (16.9% of 783) gaps and added up to 2.2 Mb novel sequences to the human reference genome. More than 90% of the non-redundant sequences could be verified by unmapped reads from the Simons Genome Diversity Project dataset. In addition, 15.6% of the non-reference sequences were found in at least one of four non-human primate genomes. We further demonstrated that the non-redundant sequences had high content of simple repeats and satellite sequences. Moreover, 43 (32.6%) of the 132 closed gaps were shown to be polymorphic; such sequences may play an important biological role and can be useful in the investigation of human genetic diversity.