A new combined bodian-luxol technique for staining unmyelinated axons in semithin, resin-embedded peripheral nerves: a comparison with electron microscopy.

peer reviewedaudience: researcher, professionalQuantitation of unmyelinated fibers (UF) in peripheral nerves has classically relied upon ultrastructural morphometry. Because this method is time-consuming, it is not typically performed in routine analysis of nerve biopsies. We applied the Bodian-Luxol technique to detect unmyelinated axons by light microscopy on semithin sections from resin-embedded nerve tissue. Estimates were compared to ultrastructural counts. The staining appeared highly specific for axons. Excellent correlation was found between optic densities and the population of UF larger than 0.5 microm. The smallest profiles detected by light microscopy had a diameter close to 0.6 microm. This new technique is not a substitute for ultrastructural quantitative morphometry of UF, as very small unmyelinated axons, especially regenerating ones, can not be reliably visualized. However, it provides a valuable light microscopic method for evaluating axonal loss among UF

Neuroimaging Biomarkers and Cognitive Function in Non-CNS Cancer and Its Treatment: Current Status and Recommendations for Future Research

Cognitive changes in patients undergoing treatment for non-central nervous system (CNS) cancers have been recognized for several decades, yet the underlying mechanisms are not well understood. Structural, functional and molecular neuroimaging has the potential to help clarify the neural bases of these cognitive abnormalities. Structural magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and positron emission tomography (PET) have all been employed in the study of cognitive effects of cancer treatment, with most studies focusing on breast cancer and changes thought to be induced by chemotherapy. Articles in this special issue of Brain Imaging and Behavior are devoted to neuroimaging studies of cognitive changes in patients with non-CNS cancer and include comprehensive critical reviews and novel research findings. The broad conclusions that can be drawn from past studies and the present body of new research is that there are structural and functional changes associated with cancer and various treatments, particularly systemic cytotoxic chemotherapy, although some cognitive and fMRI studies have identified changes at pre-treatment baseline. Recommendations to accelerate progress include well-powered multicenter neuroimaging studies, a better standardized definition of the cognitive phenotype and extension to other cancers. A systems biology framework incorporating multimodality neuroimaging, genetics and other biomarkers will be highly informative regarding individual differences in risk and protective factors and disease- and treatment-related mechanisms. Studies of interventions targeting cognitive changes are also needed. These next steps are expected to identify novel protective strategies and facilitate a more personalized medicine for cancer patients

Army Energy and Water Reporting System Assessment

There are many areas of desired improvement for the Army Energy and Water Reporting System. The purpose of system is to serve as a data repository for collecting information from energy managers, which is then compiled into an annual energy report. This document summarizes reported shortcomings of the system and provides several alternative approaches for improving application usability and adding functionality. The U.S. Army has been using Army Energy and Water Reporting System (AEWRS) for many years to collect and compile energy data from installations for facilitating compliance with Federal and Department of Defense energy management program reporting requirements. In this analysis, staff from Pacific Northwest National Laboratory found that substantial opportunities exist to expand AEWRS functions to better assist the Army to effectively manage energy programs. Army leadership must decide if it wants to invest in expanding AEWRS capabilities as a web-based, enterprise-wide tool for improving the Army Energy and Water Management Program or simply maintaining a bottom-up reporting tool. This report looks at both improving system functionality from an operational perspective and increasing user-friendliness, but also as a tool for potential improvements to increase program effectiveness. The authors of this report recommend focusing on making the system easier for energy managers to input accurate data as the top priority for improving AEWRS. The next major focus of improvement would be improved reporting. The AEWRS user interface is dated and not user friendly, and a new system is recommended. While there are relatively minor improvements that could be made to the existing system to make it easier to use, significant improvements will be achieved with a user-friendly interface, new architecture, and a design that permits scalability and reliability. An expanded data set would naturally have need of additional requirements gathering and a focus on integrating with other existing data sources, thus minimizing manually entered data

Towards an Energy-Aware Framework for Application Development and Execution in Heterogeneous Parallel Architectures

The Transparent heterogeneous hardware Architecture deployment for eNergy Gain in Operation (TANGO) project’s goal is to characterise factors which affect power consumption in software development and operation for Heterogeneous Parallel Hardware (HPA) environments. Its main contribution is the combination of requirements engineering and design modelling for self-adaptive software systems, with power consumption awareness in relation to these environments. The energy efficiency and application quality factors are integrated into the application lifecycle (design, implementation and operation). To support this, the key novelty of the project is a reference architecture and its implementation. Moreover, a programming model with built-in support for various hardware architectures including heterogeneous clusters, heterogeneous chips and programmable logic devices is provided. This leads to a new cross-layer programming approach for heterogeneous parallel hardware architectures featuring software and hardware modelling. Application power consumption and performance, data location and time-criticality optimization, as well as security and dependability requirements on the target hardware architecture are supported by the architecture

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as ‘chemo fog’. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning. This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research

The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

Background: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin‑2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. Methods: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C &gt; T (p.Arg79*), c.397C &gt; T (p.Gln133*) and c.2489+1G &gt; A (p.?)). Results: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p &lt; 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia–free survival between 4 PKP2 founder variants, including c.1211dup. Conclusions: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.</p