SpikeInterface, a unified framework for spike sorting

Much development has been directed toward improving the performance and automation of spike sorting. This continuous development, while essential, has contributed to an over-saturation of new, incompatible tools that hinders rigorous benchmarking and complicates reproducible analysis. To address these limitations, we developed SpikeInterface, a Python framework designed to unify preexisting spike sorting technologies into a single codebase and to facilitate straightforward comparison and adoption of different approaches. With a few lines of code, researchers can reproducibly run, compare, and benchmark most modern spike sorting algorithms; pre-process, post-process, and visualize extracellular datasets; validate, curate, and export sorting outputs; and more. In this paper, we provide an overview of SpikeInterface and, with applications to real and simulated datasets, demonstrate how it can be utilized to reduce the burden of manual curation and to more comprehensively benchmark automated spike sorters.ISSN:2050-084

Bone Density in Children with Single Ventricle Physiology

Background Children with chronic diseases are at risk for low bone mineral density (BMD). There are no studies of BMD in children with congenital heart disease and particularly SV. Children with this defect are often treated with warfarin, suspected to negatively impact BMD in adults. We assessed BMD in patients with single ventricle (SV) physiology and compared the BMD of subjects taking warfarin to those who were not. Methods Subjects 5-12 years with SV were included. BMD z-scores by dual-energy X-ray absorptiometry (DXA) of the spine and total body less head (TBLH) were obtained. Calcium intake, activity level, height, and Tanner stage were assessed. Linear regression models and t-tests were used to investigate differences between participants and normative data as well as between subjects' subgroups. Results Twenty six subjects were included; 16 took warfarin. Mean BMD z-score at the spine was significantly lower than expected at -1.0±0.2 (p<0.0001), as was the BMD z-score for TBLH at - 0.8±0.2 (p<0.0001). Those results remained significant after adjusting for height. Subjects who were on warfarin tended to have lower BMD at both the spine and TBLH than those who were not, with a z-score difference of 0.6±0.46 at the spine (p=0.106) and a difference of 0.4±0.34 at TBLH (p=0.132). Conclusions BMD is significantly reduced in children with SV. Warfarin appears to lower BMD but the effect is less conclusive. Continued evaluation is recommended for these patients at risk for reduced bone density. Evaluation of other cardiac patients on warfarin therapy should also be considered

The Restyled Federal Rules of Evidence

A lightly edited transcript of the Symposium held at the William & Mary School of Law on October 28, 2011

The Restyled Federal Rules of Evidence

A lightly edited transcript of the Symposium held at the William & Mary School of Law on October 28, 2011

Antiangiogenic Activity of 2-Deoxy-D-Glucose

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies

Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review

The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL

Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks.</p> <p>Methods/Design</p> <p>A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk.</p> <p>Discussion</p> <p>Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.</p> <p>Trial registration</p> <p>This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012.</p

Taxonomy of the order Mononegavirales: second update 2018.

In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival