Should We Use Preoperative Epoetin-α in the Mildly Anemic Patient Undergoing Simultaneous Total Knee Arthroplasty?

Simultaneous knee arthroplasty is associated with significant blood loss. To prevent transfusion, three preoperative doses of epoetin-α were offered to mildly anemic simultaneous knee arthroplasty patients. A retrospective review, using ICD-9 codes, identified twenty patients from 2007-2009. Epoetin-α increased hemoglobin levels preoperatively (12.6 to 13.9,

The Use of Epoetin-α in Revision Knee Arthroplasty.

Introduction. To evaluate the efficacy of epoetin-α prior to revision total knee arthroplasty, we hypothesized that epoetin-α will reduce blood transfusion. Methods. Eighty-one patients were compared in this retrospective review; twenty-eight patients received our dosing regimen. All patients were mildly anemic. Epoetin-α to control (1 : 2) patient matching occurred so that one of two attending surgeons, gender, BMI, complexity of surgery, ASA score, and age were similar between groups. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used. Results. Blood transfusion and length of stay were lower in the study group. None of the patients who received epoetin-α underwent transfusion. Hemoglobin increased from 11.97 to 13.8, preoperatively. Hemoglobin at day of surgery and time of discharge were higher. Gender, BMI, ASA score, total and hidden blood losses, calculated blood loss, preop PLT, PT, PTT, and INR were similar between groups. One Epogen patient had an uncomplicated DVT (3.6%). Conclusions. Epoetin-α may have a role in the mildly anemic revision knee patient. It may also decrease patient length of stay allowing for earlier readiness to resume normal activities and/or meet short-term milestones. A randomized study to evaluate the direct and indirect costs of such a treatment methodology in the mildly anemic revision patient may be warranted

Perceptions of competence: Age moderates views of healthy aging and Alzheimer’s disease

Background/Study Context: Older adults have more complex and differentiated views of aging than do younger adults, but less is known about age-related perceptions of Alzheimer’s disease. This study investigated age-related perceptions of competence of an older adult labeled as “in good health” (healthy) or “has Alzheimer’s disease” (AD), using a person-perception paradigm. It was predicted that older adults would provide more differentiated assessments of the two targets than would younger adults.Methods: Younger (n = 86; 18–36 years) and older (n = 66; 61–95 years) adults rated activities of daily living (ADL), instrumental activities of daily living (IADL), and memory abilities of a female target aged 75 years, described as healthy or with AD. Data on anxiety about aging, knowledge of and experience with aging and AD, knowledge of memory aging, and positive and negative biases toward aging and AD were also collected.Results: Older adults perceived the healthy target as more capable of cognitively effortful activities (e.g., managing finances) and as possessing better memory abilities than the AD target. As predicted, these differences were greater than differences between targets perceived by younger adults. The interaction effect remained significant after statistically controlling for relevant variables, including education and gender. Additionally, exploratory analyses revealed that older adults held less positively biased views of AD than younger adults, but negatively biased views were equivalent between age groups.Conclusion: The results demonstrate that mere labels of “healthy” and “Alzheimer’s disease” produce significant and subtle age differences in perceived competencies of older adults, and that biases towards AD vary by age group and valence. Our findings extend the person-perception paradigm to an integrative analysis of aging and AD, are consistent with models of adult development, and complement current research and theory on stereotypes of aging. Future directions for research on perceptions of aging are suggested

wallace 2: a shiny app for modeling species niches and distributions redesigned to facilitate expansion via module contributions

Released 4 years ago, the Wallace EcoMod application (R package wallace) provided an open-source and interactive platform for modeling species niches and distributions that served as a reproducible toolbox and educational resource. wallace harnesses R package tools documented in the literature and makes them available via a graphical user interface that runs analyses and returns code to document and reproduce them. Since its release, feedback from users and partners helped identify key areas for advancement, leading to the development of wallace 2. Following the vision of growth by community expansion, the core development team engaged with collaborators and undertook a major restructuring of the application to enable: simplified addition of custom modules to expand methodological options, analyses for multiple species in the same session, improved metadata features, new database connections, and saving/loading sessions. wallace 2 features nine new modules and added functionalities that facilitate data acquisition from climate-simulation, botanical and paleontological databases; custom data inputs; model metadata tracking; and citations for R packages used (to promote documentation and give credit to developers). Three of these modules compose a new component for environmental space analyses (e.g., niche overlap). This expansion was paired with outreach to the biogeography and biodiversity communities, including international presentations and workshops that take advantage of the software's extensive guidance text. Additionally, the advances extend accessibility with a cloud-computing implementation and include a suite of comprehensive unit tests. The features in wallace 2 greatly improve its expandability, breadth of analyses, and reproducibility options, including the use of emerging metadata standards. The new architecture serves as an example for other modular software, especially those developed using the rapidly proliferating R package shiny, by showcasing straightforward module ingestion and unit testing. Importantly, wallace 2 sets the stage for future expansions, including those enabling biodiversity estimation and threat assessments for conservation.journal articl

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.Peer reviewe

The Use of Preoperative Epoetin-α in Revision Hip Arthroplasty

PURPOSE: To evaluate the efficacy of preoperative epoetin-α on the revision hip arthroplasty patient. We hypothesized that epoetin-α will reduce blood transfusion. A pertinent review of the literature is provided. METHODS: Forty-six patients were retrospectively reviewed. Sixteen patients received epoetin-α. Patients were case matched by age, preoperative hemoglobin, surgery, gender, and BMI. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used. RESULTS: Blood transfusion and length of stay were decreased in the epoetin-α group. Hemoglobin in the intervention group increased from 12.0 to 14.5, preoperatively. Patients who received epoetin-α were 0.78 (RR=0.225) times as likely to receive a transfusion. Number Needed to Treat (NNT) to avoid one allogeneic transfusion was 1.84. Age, Gender, BMI, ASA, total and hidden blood loss, preoperative Iron supplements, preop Hct, preop PLT, PT, PTT, and INR were similar. One (6.0%) patient developed an uncomplicated deep venous thrombosis in the intervention group. CONCLUSIONS: The mildly anemic revision hip arthroplasty patient is at increased risk for transfusion. Epoetin-α increased preoperative hemoglobin counts and reduced transfusions in this study; it also decreased patient length of hospital stay likely allowing for an earlier readiness to resume normal activities and/or meet short-term milestones. A randomized study to evaluate the direct and indirect costs of such a treatment methodology in the mildly anemic revision patient may be warranted

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Brain structural covariance networks in obsessive-compulsive disorder : a graph analysis from the ENIGMA Consortium

In the largest brain structural covariance study of OCD to date, Yun et al. show a less segregated organization of structural covariance networks and a reorganization of brain hubs, including cingulate and orbitofrontal regions, in OCD. The findings point to altered trajectories of brain development and maturation. Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z -score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions