1,721,015 research outputs found
Dataset CTS GAP-43 study including gene counts
No full textGrowth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as ‘regenerators’ or ‘non-regenerators’ based on post-surgical epidermal re-innervation. Data were collected clinically and using histological analysis of skin biopsies
database CTS GAP-43 study
No full textGrowth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration.
Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as ‘regenerators’ or ‘non-regenerators’ based on post-surgical epidermal re-innervation.
Data were collected clinically and using histological analysis of skin biopsies
Beyond mimesis: nature in contemporary classical music
No full textMusic has been connected to nature from ancient times, both materially and philosophically, with the idea of mimesis as an aesthetic principle guiding composers over the same period. Since the turn of the twentieth century, composers have, however, had a more ambivalent relationship with the traditional aesthetics of representation, particularly as high modernism reached into abstraction and alienation from the natural world. By contrast, in the present era of climate change, there is renewed interest in engaging with nature and communicating this engagement to audiences. Yet composers face distinct challenges: how can music inspired by nature be composed without falling back on modes of expression familiar from the Romantic period? Will giving prominence to nature overshadow the composer’s personal voice?
This dissertation explores these questions, considering both the survival of an aesthetics inspired by nature throughout the twentieth century and the vibrancy of contemporary ecocentric compositional methods. David Rothenberg has argued that composers facing inspiration from nature must choose between composing directly from natural sound or emulating, evoking, and being inspired by nature’s operations, as Cage proposed to “imitate nature in its manner of operation”. Using this argument as a starting point, this dissertation examines how various composers - primarily focusing on key case studies such as Kaija Saariaho, Liza Lim, and the author - have integrated scientific research, historical recordings, electronic, and aleatoric techniques. They aim to expand the boundaries of mimesis and decenter the human without compromising their creative voices. Ultimately, I argue that we can develop a new approach to nature in music that encompasses the challenges faced by composers in the twenty-first century
The role of nerve pathology in the development of persistent pain in Whiplash Associated Disorders
Full text linkThe World Health Organization reported the global burden of non-fatal road traffic
collisions affects between 20-50 million people each year. Whiplash Associated
Disorders (WAD) commonly occur after motor vehicle collisions and often include
symptoms of pain and psychological distress. The most common type is WAD grade
2 (WAD2), which includes neck symptoms and musculoskeletal signs (e.g.,
tenderness and impaired neck movement) in the absence of a frank nerve injury on
routine diagnostic testing (electrodiagnostic tests, traditional neurological
examination). Contrary to the previous definition, new evidence demonstrates signs
of nerve injury in patients with WAD2.
My research builds upon this evidence to answer novel objectives in a longitudinal
cohort study assessing the temporal development of nerve pathology and its
predictive ability in WAD2. To begin, I completed two systematic reviews of the
literature integrating current evidence to inform the design of my longitudinal cohort
study. The first systematic review summarised our current understanding of nerve
pathology and neuropathic pain in people with WAD. My second systematic review
aggregated the findings of blood-based biomarkers of nerve pathology to identify the
most promising marker to measure within my cohort.
The findings from the longitudinal cohort study in WAD2 identified approximately
one-third of participants with acute signs of neuropathic pain. In addition, I
identified nearly two-thirds of participants with acute functional nerve pathology
using quantitative sensory testing and neurological assessments. These measures
improved six-months after injury but did not fully recover. Serum neurofilament
light chain was elevated acutely but was comparable to controls six-months after
injury. Intraepidermal nerve fibre densities from skin biopsies remained preserved in
WAD2 participants acutely and six-months after whiplash injury. Transcriptional
blood profiling six-months after injury revealed significant gene dysregulation for
moderate/severe persistent pain versus minimal persistent pain when stratified by
sex.
These novel insights help improve our understanding of the heterogenous nature of
WAD2 and reveal important implications to better manage such patients
Exploring the molecular underpinnings of neuropathic pain in primary afferent subtypes
Full text linkDorsal root ganglia (DRG) neurons have been well described for their role in driving both acute and chronic pain. With cell bodies clustered in the spinal column, these neurons project from the periphery into the dorsal horn. Subtypes convert a range of stimuli into electrical signals, and have been traditionally defined by size, histological markers, projection pathways, and electrophysiological phenotypes. With the advance of sequencing technologies, DRG transcriptomes have been examined through whole ganglia, single cell, and more recently, deep subpopulation sequencing in naïve lines. Here, we study the deep transcriptional profiles of multiple murine DRG populations in acute and chronic pain states while considering sex interactions.
We have exploited currently available transgenics to label and purify subtypes after injury for high throughput sequencing. Using bulk tissue samples, we are able to circumvent the issues of low transcript coverage and drop-outs seen with single cell datasets, increasing our power to detect changes in gene expression.
In one experiment, we have studied the molecular changes in five populations, classified by their functional and molecular signatures in naive states. These include general nociceptors, peptidergic nociceptors, non-peptidergic nociceptors, C-LTMRs, and Ad + AB-RA-LTMRs. We see both stereotyped and unique subtype signatures in injured states after nerve injury at both an acute and chronic timepoint. While all populations contribution to a general injury signature, subtype enrichment changes can also be seen, possibly driven by the loss of transected NP neurons by 4 weeks. Within populations, there is not a strong intersection of sex and injury, but sex differences in na\"ive states - particularly in Ad + AB-RA-LTMRs - still contribute to differences in injured neurons.
Using an SNI model of neuropathic pain, ipsilateral DRG contain both injured and intact neurons. The contributions of these populations to pain have yet to be delineated. Mirroring the techniques above, we next used an Atf3creERT2 line to label and sort fluorescent neurons prior to RNA-seq. We have complemented this with a pilot snATAC-seq study, showing that neurons cluster by subtype in naive and injured states.
We have curated this data into an accessible, online platform. Together, this contributes a resource to the pain community to probe subpopulation and sex-specific differences after nerve injury at multiple timepoints
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Introduction to a special issue on big data and pain
Full text linkThis special issue comprised 7 articles from leaders in the field that focus on “big pain data”, the large datasets and the associated methods for data analysis that are currently emerging in pain research. This collection of articles highlights the power and potential as well as points of caution that multi-disciplinary research utilising big data and their associated methods and interpretations present for pain research
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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