Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice

A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injur

Automated Assessment of Pavlovian Conditioned Freezing and Shock Reactivity in Mice Using the Video Freeze System

The Pavlovian conditioned freezing paradigm has become a prominent mouse and rat model of learning and memory, as well as of pathological fear. Due to its efficiency, reproducibility and well-defined neurobiology, the paradigm has become widely adopted in large-scale genetic and pharmacological screens. However, one major shortcoming of the use of freezing behavior has been that it has required the use of tedious hand scoring, or a variety of proprietary automated methods that are often poorly validated or difficult to obtain and implement. Here we report an extensive validation of the Video Freeze system in mice, a “turn-key” all-inclusive system for fear conditioning in small animals. Using digital video and near-infrared lighting, the system achieved outstanding performance in scoring both freezing and movement. Given the large-scale adoption of the conditioned freezing paradigm, we encourage similar validation of other automated systems for scoring freezing, or other behaviors

Honneth on Social Pathologies: A Critique

Over the last two decades, Axel Honneth has written extensively on the notion of social pathology. He has presented it as a distinctive critical resource of Frankfurt School Critical Theory, in which tradition he places his own work; and as an alternative to the mainstream liberal approaches in political philosophy. In this paper, I review the developments in Honneth's writing about this notion and offer an immanent critique, with a particular focus on his recent major work Freedom's Right. Both his early context-transcendent approach and his more recent immanent approach are found wanting, and his increasing reformism is exposed and criticized. The central distinction in Freedom's Right between social pathologies and misdevelopments is also shown to be unworkable. In addition, I demonstrate that Zurn's influential proposal to characterize the phenomena Honneth identified as social pathologies in terms of a cognitive disconnect does not fit (with Zurn's own description of) these phenomena. While some such phenomena, like what Honneth describes as “Organized Self-Realization,” call out for conceptualization in terms of the notion of social pathology, an alternative characterization of this notion is necessary

Mapping a Novel Black Spot Resistance Locus in the Climbing Rose Brite Eyes™ (‘RADbrite’)

Rose black spot, caused by Diplocarpon rosae, is one of the most devastating foliar diseases of cultivated roses (Rosa spp.). The globally distributed pathogen has the potential to cause large economic losses in the outdoor cultivation of roses. Fungicides are the primary method to manage the disease, but are often viewed unfavorably by home gardeners due to potential environmental and health impacts. As such, rose cultivars with genetic resistance to black spot are highly desired. The tetraploid climbing rose Brite EyesTM (‘RADbrite’) is known for its resistance to black spot. To better characterize the resistance present in Brite EyesTM, phenotyping was conducted on a 94 individual F1 population developed by crossing Brite EyesTM to the susceptible tetraploid rose ‘Morden Blush’. Brite EyesTM was resistant to all D. rosae races evaluated except for race 12. The progeny were either resistant or susceptible to all races (2, 3, 8, 9, 10, 11, and 13) evaluated. The segregation ratio was 1:1 (χ2 = 0.3830, P = 0.5360) suggesting resistance is conferred by a single locus. The roses were genotyped with the WagRhSNP 68K Axiom array and the ‘polymapR’ package was used to construct a map. A single resistance locus (Rdr4) was identified on the long arm of chromosome 5 homoeolog 4. Three resistance loci have been previously identified (Rdr1, Rdr2, and Rdr3). Both Rdr1 and Rdr2 are located on a chromosome 1 homoeolog. The chromosomal location of Rdr3 is unknown, however, races 3 and 9 are virulent on Rdr3. Rdr4 is either a novel gene or an allele of Rdr3 as it provides resistance to races 3 and 9. Due to its broad resistance, Rdr4 is an excellent gene to introgress into new rose cultivars

Recent advances in research on botrytis gray mold of chickpea: summary proceedings of the third working Group Meeting to Discuss Collaborative Research on Botrytis Gray Mold of Chickpea, 15-17 Apr 1996, Pantnagar, Uttar Pradesh, India

The Third Working Group Meet ing on Botrytis Gray Mold of Chickpea reviewed research progress during the last 3 years, in Bangladesh, India, and Nepal. Summaries of these research findings are presented here. The preliminary report on the occurrence of botryt is gray mold of chickpea in Myanmar is noteworthy. Field trials conducted in Bangladesh, India, and Nepal indicate that an integrated disease management, if practised, can reduce disease intensity in chickpea fields, and increase chickpea product ion in disease-prone areas. Recommendations were made for future research priorities

A technical framework for costing health workforce retention schemes in remote and rural areas

<p>Abstract</p> <p>Background</p> <p>Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions.</p> <p>Methods</p> <p>This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.</p> <p>The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management.</p> <p>Results</p> <p>We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed.</p> <p>Conclusions</p> <p>These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.</p

Monitoring and evaluation of human resources for health: an international perspective

BACKGROUND: Despite the undoubted importance of human resources to the functions of health systems, there is little consistency between countries in how human resource strategies are monitored and evaluated. This paper presents an integrated approach for developing an evidence base on human resources for health (HRH) to support decision-making, drawing on a framework for health systems performance assessment. METHODS: Conceptual and methodological issues for selecting indicators for HRH monitoring and evaluation are discussed, and a range of primary and secondary data sources that might be used to generate indicators are reviewed. Descriptive analyses are conducted drawing primarily on one type of source, namely routinely reported data on the numbers of health personnel and medical schools as covered by national reporting systems and compiled by the World Health Organization. Regression techniques are used to triangulate a given HRH indicator calculated from different data sources across multiple countries. RESULTS: Major variations in the supply of health personnel and training opportunities are found to occur by region. However, certain discrepancies are also observed in measuring the same indicator from different sources, possibly related to the occupational classification or to the sources' representation. CONCLUSION: Evidence-based information is needed to better understand trends in HRH. Although a range of sources exist that can potentially be used for HRH assessment, the information that can be derived from many of these individual sources precludes refined analysis. A variety of data sources and analytical approaches, each with its own strengths and limitations, is required to reflect the complexity of HRH issues. In order to enhance cross-national comparability, data collection efforts should be processed through the use of internationally standardized classifications (in particular, for occupation, industry and education) at the greatest level of detail possible

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Expanding the Taxonomy of (Mis-)Recognition in the Economic Sphere

This paper makes a contribution to debates in recognition theory by expanding the taxonomy of (mis-)recognition in the economic sphere. We argue that doing justice to the variety of ways in which recognition is engaged in economic relationships requires: (1) to take into consideration not just the recognition principle of esteem, but also (various aspects of) need and respect; (2) to distinguish a productive from a consumptive dimension with regards to each principle of recognition (need, esteem and respect); (3) and to identify the specific economic relationship at stake (e.g. between consumers and producers, or between employers and employees). In this way, we can account for the diversity of demands for recognition made in the economic sphere, explain what underpins them, and bring structure into these diverse phenomena. What is more, our expanded taxonomy is a useful tool for social pathology theorists. They have to appreciate the full range of variants of misrecognition when diagnosing pathologies of misrecognition in the economic sphere