The neuropsychology of sentence processing: Where do we stand?

In the early 1980s, sentence comprehension deficits were attributed to a loss of syntactic knowledge in agrammatic Broca's aphasics and to a short-term memory deficit in conduction aphasics. Findings in the remainder of the decade called both of these claims into question and presented general difficulties for the group study approach. Results from case studies support the representational independence of syntactic and semantic information but the interaction of these knowledge sources during processing. Working memory is still considered to provide critical constraints on sentence comprehension, but the capacity involved appears to be largely independent of the phonological storage involved in word list recall. Current computational approaches to sentence comprehension provide the means of accounting for the interaction of multiple sources of information and working memory requirements, but have yet to be tested against neuropsychological findings.     

Experiences and lessons learned as a Chair of anatomy—An 18-year journey

In 1998, I was appointed Chair of the Department of Anatomy at Monash University in Melbourne, Australia. On commencing as Chair, I had three main goals: (a) to maintain and extend the high quality of anatomy teaching in the medical program; (b) to introduce significantly more developmental biology, cell biology, and neuroscience into our existing Bachelor of Science major in human anatomy; and (c) to establish an active research program in the department. Over the next 18 years, I worked with staff and students at all levels of the university to turn this vision into a reality, with the Monash Department of Anatomy and Developmental Biology now arguably the top ranked anatomy department in Australia. During my tenure, countless challenges were faced and while some errors were made, and a good number of goals were never realized the general outcome was a vibrant scholarly environment where that rich nexus of research and teaching was realized. This personal account provides some insights into that 18-year journey, which I hope may prove useful for current and future Chairs of anatomy. For me personally, it was definitely a journey worth taking.     

Upscaling communication skills training – lessons learned from international initiatives

ObjectiveTo collect experiences and to identify the main facilitators and barriers for the implementation process of large scale communication training programs.MethodsUsing a multiple case study design, data was collected from leaders of the individual programs in Australia, Ireland, Austria and Denmark. The RE-AIM framework was used to evaluate the components: Reach, Effectiveness, Adoption, Implementation, and Maintenance of the programs.ResultsThe programs, all based on the Calgary-Cambridge Guide, succeeded in reaching the intended target groups corresponding to between 446 and 3000 healthcare workers. New courses are planned and so far the outcome of the intervention has been investigated in two countries. The fact that implementation, including educating trainers, relies on a few individuals was identified as the main challenge.ConclusionLarge scale communication training programs based on the Calgary-Cambridge Guide can be implemented and adopted in multiple different healthcare settings across a national health system culture. The importance of standardized trainer education and adaption of the programs to clinical practice was highlighted.Practice ImplicationsIn order to address the sustainability of the programs and to allow the intervention to scale up, it is important to prioritise and allocate resources at the political and organizational level.     

Challenges and lessons learned from clinical pharmacogenetic implementation of multiple gene–drug pairs across ambulatory care settings

PurposeIncorporating a patient’s genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene–drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners.MethodsWe compared common measures collected within each of the pharmacogenetic implementations as well as solicited feedback from stakeholders to identify challenges, successes, and lessons learned.ResultsWe identified several challenges related to trial design and implementation, and learned valuable lessons. Most notably, case discussions are effective for prescriber education, prescribers need clear concise guidance on genotype-based actions, having genotype results available at the time of the patient–prescriber encounter helps optimize the ability to act on them, children prefer noninvasive sample collection, and study participants are willing to answer patient-reported outcomes questionnaires if they are not overly burdensome, among others.ConclusionThe lessons learned from implementing three gene–drug pairs in ambulatory care settings will help shape future pharmacogenetic clinical trials and clinical implementations.     

The immune pathogenesis of experimental autoimmune encephalomyelitis: lessons learned for multiple sclerosis?

Experimental autoimmune encephalomyelits (EAE) has been widely studied as a model for multiple sclerosis (MS). EAE also holds a special place in basic autoimmune research. It is induced by immunizing healthy, na?ve mice with neuroantigen. Unlike in spontaneous autoimmune models, one can therefore clearly define the initiation time point, the inducing antigen, the circumstances of the immunization that elicit a pathogenic--or nonpathogenic--T cell response, and many other parameters that are required for the induction and perpetuation of autoimmune central nervous system pathology. In the following, we will provide an overview of our current understanding of the discrete steps that lead to the pathogenesis of EAE, and we will highlight several junctions at which the perpetuation or abortive course of the disease is defined. It has become abundantly clear that the induction of a pathogenic CD4+ T cell response is a necessary requirement for the induction of EAE. However, many downstream mechanisms need to be considered if we want to understand the pathomechanisms that define the variable outcomes of EAE, and by inference, of MS.     

Evolution of a discipline—The changing face of anatomy

This special issue is unlike any other special issue published in this journal's history. You will not find the types of original research in anatomy and evolutionary biology that you are accustomed to seeing adorning the pages of The Anatomical Record. Instead, the articles included cover the past and future of the discipline of anatomy broadly and of the American Association for Anatomy (AAA) more narrowly, and through two specific rhetorical frames: ethics; and diversity, equity, and inclusion. The articles in this issue are divided into two sections. The first section traces the history of anatomy and addresses many of the ethical dilemmas we face as a result of that history. The second section sets the stage for how the discipline and the AAA move forward to create a more diverse, equitable, and inclusive future for students, teachers, colleagues, and everyone else we touch through our work as anatomists. While this is only the beginning of our reconciliation with our past, the future certainly looks bright.     

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

During the last several years, research has produced a significant amount of knowledge concerning the characteristics of human γδ T lymphocytes. Findings regarding the immune functions of these cells, particularly their natural killer cell-like lytic activity against tumor cells, have raised expectations for the therapeutic applications of these cells for cancer. Pharmaceutical companies have produced selective agonists for these lymphocytes, and several teams have launched clinical trials of γδ T cell-based cancer therapies. The findings from these studies include hematological malignancies (follicular lymphoma, multiple myeloma, acute and chronic myeloid leukemia), as well as solid tumors (renal cell, breast and prostate carcinomas), consisting of samples from more than 250 patients from Europe, Japan and the United States. The results of these pioneering studies are now available, and this short review summarizes the lessons learned and the role of γδ T cell-based strategies in the current landscape of cancer immunotherapies.     

The Department of Veterans Affairs’ (VA) implementation of the Virtual Lifetime Electronic Record (VLER): Findings and lessons learned from Health Information Exchange at 12 sites

PurposeWe describe the Department of Veterans Affairs’ (VA) Virtual Lifetime Health Electronic Record (VLER) pilot phase in 12 communities to exchange health information with private sector health care organizations and the Department of Defense (DoD), key findings, lessons, and implications for advancing Health Information Exchanges (HIE), nationally.MethodsA mixed methods approach was used to monitor and evaluate the status of VLER Health Exchange pilot phase implementation from December 2009 through October 2012. Selected accomplishments, contributions, challenges, and early lessons that are relevant to the growth of nationwide HIE are discussed.ResultsVeteran patient and provider acceptance, trust, and perceived value of VLER Health Exchange are found to be high, and usage by providers is steadily growing. Challenges and opportunities to improve provider use are identified, such as better data quality and integration with workflow. Key findings and lessons for advancing HIE are identified.ConclusionsVLER Health Exchange has made great strides in advancing HIE nationally by addressing important technical and policy issues that have impeded scalability, and by increasing trust and confidence in the value and accuracy of HIE among users. VLER Health Exchange has advanced HIE interoperability standards and patient consent policies nationally. Policy, programmatic, technology, and health Information Technology (IT) standards implications to advance HIE for improved delivery and coordination of health care are discussed. The pilot phase success led to VA-wide deployment of this data sharing capability in 2013.     

The face of Ulnar Mammary syndrome?

Ulnar Mammary syndrome (UMS) is an autosomal disorder caused by haploinsufficiency of the TBX3 gene. There is marked intrafamilial variation in expression of the syndrome. We present one three generation family in which the proband has absence of the right ulna and third, fourth and fifth rays in her right hand. Her mother and maternal grandmother have more subtle anomalies while all have a similar facial appearance with a broad nasal tip, a broad jaw, a prominent chin and a tongue frenulum. They have a single base pair insertion (c. 992dup) in TBX3. We compare faces from the handful of published UMS patients which include photographs, this family and four other cases with TBX3 mutations. All have similarities in appearance which we suggest could alert clinicians to the possibility of a TBX3 mutation if individuals present with more subtle features of UMS such as postaxial polydactyly, isolated 5th finger anomalies, delayed puberty in males, breast hypoplasia or short stature with or without growth hormone deficiency.     

T-cell-based immunotherapy of melanoma: what have we learned and how can we improve?

The lack of effective treatment for advanced stage melanoma by conventional therapies, such as radiation and chemotherapy, has highlighted the need to develop alternative therapeutic strategies. Among them, immunotherapy has attracted much attention because of the potential role played by immunological events in the clinical course of melanoma and the availability of well-characterized melanoma antigens to target melanoma lesions with immunological effector mechanisms. In recent years, T-cell-based immunotherapy has been emphasized, in part because of the disappointing results of the antibody-based trials conducted in the early 1980s, and in part because of the postulated major role played by T-cells in tumor growth control. In this review, the characteristics of antibody and T-cell-defined melanoma antigens will first be described, with emphasis on those used in clinical trials. Following a review of the current immunization and immunomonitoring strategies, the results from the T-cell-based immunotherapy clinical trials conducted to date will be reviewed.     

The neuropsychology of adult obsessive–compulsive disorder: A meta-analysis

A vast and heterogeneous body of literature on the neuropsychology of obsessive–compulsive disorder (OCD) has accumulated in recent decades, yielding inconsistent results. In an attempt to quantitatively summarize the literature, we conducted a meta-analysis of 115 studies (including 3452 patients), comparing adult OCD patients with healthy controls on tests of 10 neuropsychological domains. Across studies, medium mean effect sizes were found for all executive function subdomains, processing speed, and sustained attention. Small effect sizes were found for visuospatial abilities and working memory. A large effect size was found for non-verbal memory whereas a small effect size was found for verbal memory, where only the former was found to be associated with impairments in executive functions. Moderators of effect sizes were also investigated. Results are discussed in terms of their clinical significance as well as their implications for current neurobiological models of OCD and methodological caveats.     

The habitat of Paracoccidioides brasiliensis: how far from solving the riddle?

When trying to understand the pathophysiology of any infectious agent, one key piece of information is the determination of its habitat. In the case of Paracoccidioides brasiliensis, the precise location of the fungus' environmental niche remains undefined despite the efforts of various research groups. This review summarizes recent studies on the ecology of P. brasiliensis and certain facets of paracoccidioidomycosis. Studies on the juvenile form of paracoccidioidomycosis in children less than 13 years of age, the characterization of the ecological factors in the 'reservarea' where the infection is acquired and the presence of P. brasiliensis in the nine-banded armadillo (Dasypus novemcinctus), are all helping to pinpoint the microniche of this pathogen. The application of molecular biology techniques based on the amplification of nucleic acids will also hopefully help in establishing the precise habitat of P. brasiliensis.     

The impact of diabetes on cognition: what can be learned from rodent models?

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.     

Animal models in autoimmune diseases: lessons learned from mouse models for Sjögren's syndrome

The mouse model is the one of the most frequently used and well-established animal models, and is currently used in many research areas. To date, various mouse models have been utilized to elucidate underlying causes of multifactorial autoimmune conditions, including pathological immune components and specific signaling pathways. This review summarizes the more recent mouse models for Sj?gren’s syndrome, a systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands, such as the salivary and lacrimal glands, and loss of secretory function, resulting in dry mouth and dry eyes in patients. Although every Sj?gren’s syndrome mouse model resembles the major symptoms or phenotypes of Sj?gren’s syndrome conditions in humans, the characteristics of each model are variable. Moreover, to date, there is no single mouse model that can completely replicate the human conditions. However, unique features of each mouse model provide insights into the roles of potential etiological and immunological factors in the development and progression of Sj?gren’s syndrome. Here, we will overview the Sj?gren’s syndrome mouse models. Lessons from these mouse models will aid us to understand underlying immune dysregulation in autoimmune diseases in general, and will guide us to direct future research towards appropriate diagnostic and therapeutic strategies.