α1-Antitrypsin deficiency

1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development

Phylogeny and chromosomal diversification in the <i>Dichroplus elongatus</i> species group (Orthoptera, Melanoplinae)

In an attempt to track the chromosomal differentiation in the Dichroplus elongatus species group, we analyzed the karyotypes of four species with classical cytogenetic and mapping several multigene families through fluorescent in situ hybridization (FISH). We improved the taxon sampling of the D. elongatus species group adding new molecular data to infer the phylogeny of the genus and reconstruct the karyotype evolution. Our molecular analyses recovered a fully resolved tree with no evidence for the monophyly of Dichroplus. However, we recovered several stable clades within the genus, including the D. elongatus species group, under the different strategies of tree analyses (Maximum Parsimony and Maximum Likelihood). The chromosomal data revealed minor variation in the D. elongatus species group's karyotypes caused by chromosome rearrangements compared to the phylogenetically related D. maculipennis species group. The karyotypes of D. intermedius and D. exilis described herein showed the standard characteristics found in most Dichroplini, 2n = 23/24, X0♂ XX♀, Fundamental number (FN) = 23/24. However, we noticed two established pericentric inversions in D. intermedius karyotype, raising the FN to 27♂/28♀. A strong variation in the heterochromatic blocks distribution was evidenced at interespecific level. The multigene families' mapping revealed significant variation, mainly in rDNA clusters. These variations are probably caused by micro chromosomal changes, such as movement of transposable elements (TEs) and ectopic recombination. These observations suggest a high genomic dynamism for these repetitive DNA sequences in related species. The reconstruction of the chromosome character "variation in the FN" posits the FN = 23/24 as the ancestral state, and it is hypothesized that variations due to pericentric inversions has arisen independently three times in the evolutionary history of Dichroplus. One of these independent events occurred in the D. elongatus species group, where D. intermedius is the unique case with the highest FN described in the tribe Dichroplini.Centro de Estudios Parasitológicos y de VectoresFacultad de Ciencias Naturales y Muse

A Systematic Review and Meta-analysis of the Impact of Mindfulness-Based Interventions on the Well-Being of Healthcare Professionals

Efforts to improve the wellbeing of healthcare professionals include mindfulness-based interventions (MBIs). To understand the value of such initiatives, we conducted a systematic review and meta-analysis of empirical studies pertaining to the use of MBIs with healthcare professionals. Databases were reviewed from the start of records to January 2016 (PROSPERO registration number: CRD42016032899). Eligibility criteria included empirical analyses of wellbeing outcomes acquired in relation to MBIs. Forty-two papers met the eligibility criteria, consisting of a total of 2,101 participants. Studies were examined for two broad classes of wellbeing outcomes: (a) “negative” mental health measures such as anxiety, depression, and stress; (b) “positive” indices of wellbeing, such as life satisfaction, together with outcomes associated with wellbeing, such as emotional intelligence. MBIs were generally associated with positive outcomes in relation to most measures, and mindfulness does appear to improve the wellbeing of healthcare professionals. However, the quality of the studies was inconsistent, so further research is needed, particularly high-quality randomised control trials

Barriers to implementation of a computerized decision support system for depression: an observational report on lessons learned in "real world" clinical settings

<p>Abstract</p> <p>Background</p> <p>Despite wide promotion, clinical practice guidelines have had limited effect in changing physician behavior. Effective implementation strategies to date have included: multifaceted interventions involving audit and feedback, local consensus processes, marketing; reminder systems, either manual or computerized; and interactive educational meetings. In addition, there is now growing evidence that contextual factors affecting implementation must be addressed such as organizational support (leadership procedures and resources) for the change and strategies to implement and maintain new systems.</p> <p>Methods</p> <p>To examine the feasibility and effectiveness of implementation of a computerized decision support system for depression (CDSS-D) in routine public mental health care in Texas, fifteen study clinicians (thirteen physicians and two advanced nurse practitioners) participated across five sites, accruing over 300 outpatient visits on 168 patients.</p> <p>Results</p> <p>Issues regarding computer literacy and hardware/software requirements were identified as initial barriers. Clinicians also reported concerns about negative impact on workflow and the potential need for duplication during the transition from paper to electronic systems of medical record keeping.</p> <p>Conclusion</p> <p>The following narrative report based on observations obtained during the initial testing and use of a CDSS-D in clinical settings further emphasizes the importance of taking into account organizational factors when planning implementation of evidence-based guidelines or decision support within a system.</p

Tutorial : applying machine learning in behavioral research

Machine-learning algorithms hold promise for revolutionizing how educators and clinicians make decisions. However, researchers in behavior analysis have been slow to adopt this methodology to further develop their understanding of human behavior and improve the application of the science to problems of applied significance. One potential explanation for the scarcity of research is that machine learning is not typically taught as part of training programs in behavior analysis. This tutorial aims to address this barrier by promoting increased research using machine learning in behavior analysis. We present how to apply the random forest, support vector machine, stochastic gradient descent, and k-nearest neighbors algorithms on a small dataset to better identify parents of children with autism who would benefit from a behavior analytic interactive web training. These step-by-step applications should allow researchers to implement machine-learning algorithms with novel research questions and datasets

Do We Practice What We Preach? A Review of Actual Clinical Practice with Regards to Preconception Care Guidelines

Objectives: To review what past studies have found with regard to existing clinical practices and approaches to providing preconception care. Methods: A literature review between 1966 and September 2005 was performed using Medline. Key words included preconception care, preconception counseling, preconception surveys, practice patterns, pregnancy outcomes, prepregnancy planning, and prepregnancy surveys. Results: There are no current national recommendations that fully address preconception care; as a result, there is wide variability in what is provided clinically under the rubric of preconception care. Conclusions: In 2005, the Centers for Disease Control and Prevention sponsored a national summit regarding preconception care and efforts are underway to develop a uniform set of national recommendations and guidelines for preconception care. Understanding how preconception care is presently incorporated and manifested in current medical practices should help in the development of these national guidelines. Knowing where, how, and why some specific preconception recommendations have been successfully adopted and translated into clinical practice, as well as barriers to implementation of other recommendations or guidelines, is vitally important in developing an overarching set of national guidelines. Ultimately, the success of these recommendations rests on their ability to influence and shape women's health policy

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

Policy and practice impacts of applied research: a case study analysis of the New South Wales Health Promotion Demonstration Research Grants Scheme 2000-2006

BackgroundIntervention research provides important information regarding feasible and effective interventions for health policy makers, but few empirical studies have explored the mechanisms by which these studies influence policy and practice. This study provides an exploratory case series analysis of the policy, practice and other related impacts of the 15 research projects funded through the New South Wales Health Promotion Demonstration Research Grants Scheme during the period 2000 to 2006, and explored the factors mediating impacts.MethodsData collection included semi-structured interviews with the chief investigators (n = 17) and end-users (n = 29) of each of the 15 projects to explore if, how and under what circumstances the findings had been used, as well as bibliometric analysis and verification using documentary evidence. Data analysis involved thematic coding of interview data and triangulation with other data sources to produce case summaries of impacts for each project. Case summaries were then individually assessed against four impact criteria and discussed at a verification panel meeting where final group assessments of the impact of research projects were made and key influences of research impact identified.ResultsFunded projects had variable impacts on policy and practice. Project findings were used for agenda setting (raising awareness of issues), identifying areas and target groups for interventions, informing new policies, and supporting and justifying existing policies and programs across sectors. Reported factors influencing the use of findings were: i) nature of the intervention; ii) leadership and champions; iii) research quality; iv) effective partnerships; v) dissemination strategies used; and, vi) contextual factors.ConclusionsThe case series analysis provides new insights into how and under what circumstances intervention research is used to influence real world policy and practice. The findings highlight that intervention research projects can achieve the greatest policy and practice impacts if they address proximal needs of the policy context by engaging end-users from the inception of projects and utilizing existing policy networks and structures, and using a range of strategies to disseminate findings that go beond traditional peer review publications.<br /