A review of the development of the education service in the borough of Chesterfield 1944-1967

The thesis examines the growth of the Education Service in the Excepted District of the Borough of chesterfield from 1944 to I967. The negotiations leading to the granting of Excepted District status and the formulation of the Scheme of Delegation are discussed, together with the establishment of Managing and Governing bodies of schools and the production of the Development plan for the Borough. The Major and Minor works building programmes are examined and related to the proposals of the Development plan. The evolution of a transfer procedure is described end an analysis is made of the philosophy of Secondary Education maintained by the Borough Education Officer of the day which gave rise to a system of Secondary Schools which attracted interest and acknowledgement at national level and of the factors which caused dissatisfaction with the system in the late 1950's. The resulting discussion leading towards the reorganisation of Secondary Education and the effect of Circulars 10/65 and 10/66 on the decisions of the Council are also examined. The growth of Special Services, Further Education and the Youth Service and the Library Service within the functions delegated by the Scheme of Divisional Administration is outlined. The introduction of i.t.a. and French in the Primary Schools is included in the survey. The successful growth of the service in all its aspects is shown to be a justification for the belief expressed in 1944 that the small Authority of Chesterfield was well able to manage its own affairs within the Scheme of Delegation. The influence of the Borough's geographical position within N.E. Derbyshire, together with the willingness of the Local Education Authority to support bids for the provision of various establishments serving the Borough and N.E. Derbyshire, thus augmenting the development of the Borough Education Service, is analysed

Spirituality and/or religious faith: A means for coping with the effects of amyotrophic lateral sclerosis/motor neuron disease?

OBJECTIVE: The notion of spirituality/religious belief is recognized internationally as a domain within end-of-life care and is important in patients' and carers' quality-of-life. When faced with incurable illness, patients often become more philosophical about their life; many seek comfort in spiritual or religious philosophies. Our intention was to understand how personal spirituality and religious faith might help those living with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) cope with their impending death. METHOD: Unsolicited narratives (internet and print-published) written by individuals diagnosed with the terminal condition of ALS/MND were analyzed thematically. Narratives from 161 individuals diagnosed with ALS/MND written over a period of 37 years (from 1968 to 2005) were included. RESULTS: Our findings reveal that religious faith sustains and helps people to avoid despair, and personal spirituality helps them make sense of what is happening to them. SIGNIFICANCE OF RESULTS: The use of personal narratives by people with ALS/MND has provided a vehicle for sharing their deepest spiritual and religious thoughts with others. The place of spirituality and religious faith within ALS/MND care should not be underestimated. Assessment of religious or spiritual needs should become a routine part of practice and is the responsibility of all members of the multidisciplinary team

Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias

The PARAChute project: remote monitoring of posture and gait for fall prevention

Falls in the elderly are a major public health problem due to both their frequency and their medical and social consequences. In France alone, more than two million people aged over 65 years old fall each year, leading to more than 9 000 deaths, in particular in those over 75 years old (more than 8 000 deaths). This paper describes the PARAChute project, which aims to develop a methodology that will enable the detection of an increased risk of falling in community-dwelling elderly. The methods used for a remote noninvasive assessment for static and dynamic balance assessments and gait analysis are described. The final result of the project has been the development of an algorithm for movement detection during gait and a balance signature extracted from a force plate. A multicentre longitudinal evaluation of balance has commenced in order to validate the methodologies and technologies developed in the project

Explosive vent sites on mercury: Commonplace multiple eruptions and their implications

Explosive volcanic vents are widespread on Mercury. Compound volcanic vents comprise multiple individual vents, and probably formed through multiple events. We demonstrate that ~70% of the volcanic vent sites on Mercury that have been imaged with sufficient resolution to resolve their internal features are compound vents that have probably undergone multiple eruptions. Interior characteristics of compound vents, such as cross-cutting relationships, contrasts in small scale impact cratering, and other textural detail, as well as the asymmetry of surrounding faculae, suggest that activity occurred over a prolonged but so far unquantified period of time. We use multiple case studies to highlight the migration of eruption centres at these sites. At the Nathair Facula vent, small-scale interior pits suggest the location of the most recent activity

Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art

Altered RNA metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including RNA/protein toxic gain-of-function and/or protein loss-of-function. Genetic mutations that cause neurodegenerative disorders disrupt healthy gene expression at diverse levels, from chromatin remodelling, transcription, splicing, through to axonal transport and repeat-associated non-ATG (RAN) translation. We address neurodegeneration in repeat expansion disorders [Huntington's disease, spinocerebellar ataxias, C9ORF72-related amyotrophic lateral sclerosis (ALS)] and in diseases caused by deletions or point mutations (spinal muscular atrophy, most subtypes of familial ALS). Some neurodegenerative disorders exhibit broad dysregulation of gene expression with the synthesis of hundreds to thousands of abnormal messenger RNA (mRNA) molecules. However, the number and identity of aberrant mRNAs that are translated into proteins – and how these lead to neurodegeneration – remain unknown. The field of RNA biology research faces the challenge of identifying pathophysiological events of dysregulated gene expression. In conclusion, we discuss current research limitations and future directions to improve our characterization of pathological mechanisms that trigger disease onset and progression

Impaired mitochondrial anti-oxidant defence in amyotrophic lateral sclerosis

In this study a candidate-generating approach was first employed, using proteomics to identify mitochondrial proteins whose expression changed in the presence of mutant SODI in a wellvalidated model of SOD I-related familial amyotrophic lateral sclerosis (ALS). Proteins whose expression changed in a mutant-specific fashion had functions potentially relevant to the pathogenesis of ALS including roles in apoptosis, protein processing and anti-oxidant defence. I then validated selected protein changes of interest by Western blotting in mitochondrial preparations of further NSC34 cells and G93A transgenic mouse spinal cord. Peroxiredoxin 3 (Prx 3), a thioredoxin-dependent hydroperoxidase, was down-regulated in NSC34 cells expressing two different species of mutant SOD I and in 90 d G93A transgenic mouse whole spinal cord. Immunostaining for Prx 3 and the known mitochondrial matrix protein HSP60 in NSC34 cells revealed co-localizing staining patterns, confirming the expected mitochondrial localization of Prx 3. Prx 3 immunohistochemistry confirmed its expression within the mitochondria of human and murine spinal motor neurons, establishing potential relevance to the human disease. Q-PCR was then used to show a down regulation of Prx 3 mRNA in spinal motor neurons from patients with both sporadic and SOD I-related FALS. The small drug molecule ebselen was identified as a peroxiredoxin mimic and was shown selectively to protect motor neuronal cells expressing two different species of mutant human SOD I against apoptosis induced by withdrawal of serum. Finally, having postulated that ebselen may act by up-regulating anti-oxidant protein transcription as well as acting as an anti-oxidant in its own right, ebselen was shown to induce transcription of the anti-oxidant response element (ARE), an oxidative stress-sensitive promoter sequence common to many anti-oxidant response genes, including members of the peroxiredoxin family and the proteins which maintain them in their active, reduced state. Examination of the sequence 5' to the Prx 3 gene revealed a putative ARE response element.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The effects of vibrotactile biofeedback training on trunk sway in Parkinson's disease patients

Contains fulltext : 109818.pdf (publisher's version ) (Open Access)BACKGROUND: Postural instability in Parkinson's disease (PD) can lead to falls, injuries and reduced quality of life. We investigated whether balance in PD can improve by offering patients feedback about their own trunk sway as a supplement to natural sensory inputs. Specifically, we investigated the effect of artificial vibrotactile biofeedback on trunk sway in PD. METHODS: Twenty PD patients were assigned to a control group (n = 10) or biofeedback group (n = 10). First, all patients performed two sets of six gait tasks and six stance tasks (pre-training assessment). Subsequently, all subjects trained six selected tasks five times (balance training). During this training, the feedback group received vibrotactile feedback of trunk sway, via vibrations delivered at the head. After training, both groups repeated all twelve tasks (post-training assessment). During all tasks, trunk pitch and roll movements were measured with angular velocity sensors attached to the lower trunk. Outcomes included sway angle and sway angular velocity in the roll and pitch plane, and task duration. RESULTS: Overall, patients in the feedback group had a significantly greater reduction in roll (P = 0.005) and pitch (P < 0.001) sway angular velocity. Moreover, roll sway angle increased more in controls after training, suggesting better training effects in the feedback group (P < 0.001). CONCLUSIONS: One session of balance training in PD using a biofeedback system showed beneficial effects on trunk stability. Additional research should examine if these effects increase further after more intensive training, how long these persist after training has stopped, and if the observed effects carry over to non-trained tasks