Spectral Invariants of Operators of Dirac Type on Partitioned Manifolds

We review the concepts of the index of a Fredholm operator, the spectral flow of a curve of self-adjoint Fredholm operators, the Maslov index of a curve of Lagrangian subspaces in symplectic Hilbert space, and the eta invariant of operators of Dirac type on closed manifolds and manifolds with boundary. We emphasize various (occasionally overlooked) aspects of rigorous definitions and explain the quite different stability properties. Moreover, we utilize the heat equation approach in various settings and show how these topological and spectral invariants are mutually related in the study of additivity and nonadditivity properties on partitioned manifolds.Comment: 131 pages, 9 figure

Current evidence for treatment with nusinersen for spinal muscular atrophy : a systematic review

Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing

Cytokines and chemokines as regulators of skeletal muscle inflammation: presenting the case of Duchenne muscular dystrophy

Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed

Dequantisation of the Dirac Monopole

Using a sheaf-theoretic extension of conventional principal bundle theory, the Dirac monopole is formulated as a spherically symmetric model free of singularities outside the origin such that the charge may assume arbitrary real values. For integral charges, the construction effectively coincides with the usual model. Spin structures and Dirac operators are also generalised by the same technique.Comment: 22 pages. Version to appear in Proc. R. Soc. London

The myokine GDF-15 is a potential biomarker for myositis and associates with the protein aggregates of sporadic inclusion body myositis.

Background: The cytokine growth differentiation factor-15 (GDF-15) has been associated with inflammatory and mitochondrial disease, warranting exploration of its expression in myositis patients. Methods: GDF-15 protein levels are evaluated in 35 idiopathic inflammatory myopathy (IIM) serum samples using enzyme-linked immunosorbent assays, comparing with levels in samples from healthy individuals and from patients with genetically confirmed hereditary muscular dystrophies and mitochondrial disorders. Muscle tissue expression of GDF-15 protein is evaluated using immunofluorescent staining and Western blotting. Results: GDF-15 protein levels are significantly higher in IIM sera (625 +/- 358 pg/ml) than in that of healthy controls (326 +/- 204 pg/ml, p = 0.01). Western blotting confirms increased GDF-15 protein levels in IIM muscle. In skeletal muscle tissue of IIM patients, GDF-15 localizes mostly to small regenerating or denervated muscle fibres. In patients diagnosed with sporadic inclusion body myositis, GDF-15 co-localizes with the characteristic protein aggregates within affected muscle fibres. Conclusions: We describe for the first time that GDF-15 is a myokine upregulated in myositis and present the cytokine as a potential diagnostic serum biomarker

Predicting student outcomes for Washington State middle schools using school counselor's and administrator's racial consciousness and organizational variables

There is disparity in academic performance, truancy, and discipline referrals for students of color as compared to White students within most of this nation's public schools. Literature offers two theories--cultural conflict and racial identity--to explain these disparities. This study examines data collected using the Oklahoma Racial Attitudes Scale (ORAS) from a randomly selected sample of 108 Washington State middle school counselors and assistant principals as well as their school's data as reported by the Office of Superintendent of Public Instruction. Counselors and assistant principals expressed attitudes of racial acceptance and recognized their privilege, but appeared to hold to traditional values. Variables associated with both cultural conflict and racial identity theory correlated with the measures of disproportionality in eighth grade reading achievement on the Washington Assessment of Student Learning (WASL) and unexcused absences; however, only the cultural conflict variables average years of teacher experience teacher/student ratio, were retained through the multiple regression analysis

Achilles tendon injury: incidence, etiologies, treatments, and outcomes

The Achilles tendon is the largest single tendon in the body and critical for common movements. Achilles tendon injuries are common, with rising levels of incidence in the western world. Current trends indicate that levels of Achilles tendon injuries will continue to rise globally. These are also impactful injuries, often resulting in long term alterations in lives and activities. Particularly devastating are the effects of Achilles tendon injury on athletes. The goal of this thesis is to contextualize these injuries and trends, providing a system of categorization for understanding and classifying Achilles tendon injuries. The normal structure and function of the Achilles tendon is introduced, followed by a discussion of a series of factors that can lead to Achilles tendon injury. Achilles tendon injuries are sorted into a clinically relevant framework and the various treatments and outcomes for these injuries are explored, with an eye towards potential areas of further research. Taken together, these analyses show the importance and prevalence of Achilles tendon injuries, some of the inherent challenges in dealing with these injuries, and also demonstrate the necessity for further study and exploration of Achilles tendon injuries