Traumatic rupture of the thoracic aorta presenting as transient paraplegia.

PubMed

Eaves, C C

1990-01-01

A patient involved in a high-speed motor vehicle accident presented paraplegic to the emergency department. He was noted to have an abnormal chest x-ray and, subsequently, underwent aortography which revealed aortic transection. The patient's paraplegia resolved spontaneously prior to definitive aortic repair hours later. Aortic rupture presenting as paraplegia is a rare association, but one an emergency physician should be cognizant of, especially in the case of blunt or decelerating trauma.

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping.

PubMed

Beetz, Christian; Koch, Nicole; Khundadze, Mukhran; Zimmer, Geraldine; Nietzsche, Sandor; Hertel, Nicole; Huebner, Antje-Kathrin; Mumtaz, Rizwan; Schweizer, Michaela; Dirren, Elisabeth; Karle, Kathrin N; Irintchev, Andrey; Alvarez, Victoria; Redies, Christoph; Westermann, Martin; Kurth, Ingo; Deufel, Thomas; Kessels, Michael M; Qualmann, Britta; Hübner, Christian A

2013-10-01

Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival.

Rare presentations of hyperthyroidism--Basedow's paraplegia and pancytopenia.

PubMed

Chen, Yi-Hsien; Lin, Hung-Jung; Chen, Kuo-Tai

2009-02-01

Typical presentations of hyperthyroidism are palpitation, nervousness, tremor, malaise, and weight loss. Hyperthyroidism affects nearly every system in the body, and some patients may manifest neurologic or hematologic symptoms. Atypical presentations of hyperthyroidism often pose a great challenge in diagnosis and treatment. We report a case of Basedow's paraplegia and pancytopenia that was precipitated by hyperthyroidism. The unusual manifestations led to unnecessary examinations and delayed the treatment of hyperthyroidism. The classical symptoms of Basedow's paraplegia are subacute symmetric weakness of the lower extremities with areflexia and sparing sensation or sphincter involvement. Control of the hyperthyroidism mitigated the neurologic and hematologic complications and prevented unnecessary studies.

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

PubMed Central

Beetz, Christian; Koch, Nicole; Khundadze, Mukhran; Zimmer, Geraldine; Nietzsche, Sandor; Hertel, Nicole; Huebner, Antje-Kathrin; Mumtaz, Rizwan; Schweizer, Michaela; Dirren, Elisabeth; Karle, Kathrin N.; Irintchev, Andrey; Alvarez, Victoria; Redies, Christoph; Westermann, Martin; Kurth, Ingo; Deufel, Thomas; Kessels, Michael M.; Qualmann, Britta; Hübner, Christian A.

2013-01-01

Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature–inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival. PMID:24051375

Cardiovascular disease risk factors in persons with paraplegia: the Stockholm spinal cord injury study.

PubMed

Wahman, Kerstin; Nash, Mark S; Westgren, Ninni; Lewis, John E; Seiger, Ake; Levi, Richard

2010-03-01

To examine cardiovascular disease risk factors and risk clusters in Swedish persons with traumatic wheelchair-dependent paraplegia. Prospective examination. A total of 135 individuals aged 18-79 years with chronic (>or= 1 year) post-traumatic paraplegia. Cardiovascular disease risk factors; dyslipidemia, impaired fasting glucose, hypertension, overweight, smoking, and medication usage for dyslipidemia, hypertension, and diabetes mellitus, were analyzed according to authoritative guidelines. Stepwise regression tested the effects of age, gender, and injury characteristics on cardiovascular disease risks. High-prevalence risk factors were dyslipidemia (83.1%), hypertension (39.3%), and overweight (42.2%) with pervasive clustering of these risks. Being older was related to increased cardiovascular disease risk, except for dyslipidemia. Hypertension was more common in low-level paraplegia. Prevalence of impaired fasting glucose was lower than previously reported after paraplegia. A high percentage of persons being prescribed drug treatment for dyslipidemia and hypertension failed to reach authoritative targets for cardiovascular disease risk reduction. Swedish persons with paraplegia are at high risk for dyslipidemia, hypertension, and overweight. Impaired fasting glucose was not as common as reported in some previous studies. Pharmacotherapy for dyslipidemia and hypertension often failed to achieve recommended targets. Population-based screening and therapeutic countermeasures to these cardiovascular disease risks are indicated.

Tractor seating for operators with paraplegia.

PubMed

Wilhite, C S; Field, W E; Jaramillo, M

2017-01-01

This feasibility study explored the utility of using a pressure mapping instrument to explore the variable of pressure under subjects sitting on a commonly used tractor seat, and four other cushion interventions. The research model used single-subject with repeated measures during simulated tractor operation. In examining the graphical images and pressure mapping data available from the instrument; the contour tractor seat used in this study was not sufficient in redistributing pressure for people with paraplegia operating tractors, putting them at greater risk for acquiring a pressure ulcer. The use of pressure mapping equipment to study seated pressure within dynamic environments is achievable, and further studies need to be performed and replicated in simulated or in vivo environments. The data in this study suggest people with paraplegia operating agricultural equipment may not have acceptable pressure distribution using the manufacturer's installed seat and must rely on adding wheelchair cushions or other materials to the seat surface to create acceptable pressure distribution. However, doing so changes other aspects of the seating micro or macro climate that can also be problematic.

[Risk factors for the development of rotator cuff tears in individuals with paraplegia : A cross-sectional study].

PubMed

Pepke, W; Brunner, M; Abel, R; Almansour, H; Gerner, H J; Hug, A; Zeifang, F; Kentar, Y; Bruckner, T; Akbar, M

2018-02-27

Shoulder pain and rotator cuff tears are highly prevalent among wheelchair dependent individuals with paraplegia. The purpose of this study was to identify potential risk factors associated with the development of rotator cuff tears in this population. A total of 217 wheelchair dependent individuals with paraplegia were included in this cross-sectional study (level of evidence III). The mean age of this population was 47.9 years and the mean duration of wheelchair dependence was 24.1 years. Each individual was asked to complete a questionnaire designed to identify risk factors for rotator cuff tears and underwent a standardized clinical examination with the documentation of the Constant-Murley shoulder outcome score and magnetic resonance imaging (MRI) of both shoulder joints. MRI analysis revealed at least one rotator cuff tear in 93 patients (43%). Multiple logistic regression analysis identified the following factors to be associated with the presence of rotator cuff tear: patient age, duration of spinal cord injury/wheelchair dependence, gender, and wheelchair athletic activity. Neither BMI nor the level of spinal cord injury was found to pose a risk factor in the population studied. With respect to patient age, the risk of developing a rotator cuff tear increased by 11% per annum. In terms of duration of spinal cord injury, the analysis revealed a 6% increased risk per year of wheelchair dependence (OR = 1.06). Females had a 2.6-fold higher risk of developing rotator cuff tears than males and wheelchair sport activity increased the risk 2.3-fold. There is a high prevalence of rotator cuff tears in wheel-chair dependent persons with paraplegia. Risk factors such as age, gender, duration of paraplegia, and wheel chair sport activity seem to play an important role in the development of rotator cuff tears.

Genetics Home Reference: spastic paraplegia type 3A

MedlinePlus

... on PubMed or Free article on PubMed Central Blackstone C. Cellular pathways of hereditary spastic paraplegia. Annu ... PP, Soderblom C, Tao-Cheng JH, Stadler J, Blackstone C. SPG3A protein atlastin-1 is enriched in ...

Problems and perspectives in paraplegia

NASA Technical Reports Server (NTRS)

Nashold, B.

1974-01-01

Improved clinical treatment of the paraplegic, developed during World War II, has reduced the overall mortality rate from close to 100 percent to 30 percent. Despite major clinical improvements, mainly in treatment of the acute phase of paraplegia, and despite greater rehabilitation efforts, the spinal injured person is never rehabilitated in the sense that he reaches an optimum and stays there. He is always exposed to the constant threat of deterioration of his physiological, sociological, and psychological state.

A large primary vaginal calculus in a woman with paraplegia.

PubMed

Avsar, Ayse Filiz; Keskin, Huseyin Levent; Catma, Tuba; Kaya, Basak; Sivaslioglu, Ahmet Akın

2013-01-01

The study aimed to report a primary vaginal stone, an extremely rare entity, without vesicovaginal fistula in a woman with disability. We describe the case of a large primary vaginal calculus in a 22-year-old woman with paraplegia, which, surprisingly, was not diagnosed until she was examined under general anesthesia during a preparation for laparoscopy for an adnexal mass. The stone had not been identified by physical examination with the patient in a recumbent position or by transabdominal ultrasonography and pelvic tomography during the preoperative preparation. Vaginoscopy was not performed because the vagina was completely filled with the mass. As a result of its size and hard consistency, a right-sided episiotomy was performed and a 136-g stone was removed using ring forceps. A vesicovaginal fistula was excluded. There was no evidence of a foreign body or other nidus on the cut section of the stone, and it was determined to be composed of 100% struvite (ammonium magnesium phosphate). Culture of urine obtained via catheter showed Escherichia coli. After the surgical removal of the calculus without complications, a program of intermittent catheterization was started. The follow-up period was uneventful, and the patient was symptom free at 6 months after the operation. We postulate that the calculus formed as a consequence of urinary contamination of the vagina in association with incontinence and prolonged maintenance in a recumbent posture. This report is important because it highlights that, although vaginal stones are very rare, their possibility should be considered in the differential diagnosis of individuals with long-term paraplegia.

Increased cardiovascular disease risk in Swedish persons with paraplegia: The Stockholm spinal cord injury study.

PubMed

Wahman, Kerstin; Nash, Mark S; Lewis, John E; Seiger, Ake; Levi, Richard

2010-05-01

Comparison of prevalence of cardiovascular disease risks in persons with chronic traumatic paraplegia with those in the general population. Cross-sectional comparative study. A total of 135 individuals, age range 18-79 years, with chronic (> or = 1 year) traumatic paraplegia. The prevalences of diabetes mellitus, dyslipidaemia, hypertension, overweight, and smoking, were assessed in the study population and were compared with an age- and gender-matched sample of the general population in the region under study. History of myocardial infarction and medication for dyslipidaemia, hypertension, and diabetes mellitus were also recorded. chi2 tests were used to compare the paraplegic cohort with the general population sample. Significantly more persons with paraplegia reported a history of myocardial infarction (5.9%) than those in the comparison group (0.7%). The prevalences of diabetes mellitus (5.9%), dyslipidaemia (11.1%), and hypertension (14.1%) were also significantly higher in the paraplegic group, as were drug treatment for these disorders. Persons with paraplegia report increased prevalences of diabetes mellitus, hypertension, and dyslipidaemia, in particular, compared with the general population. Population-based screening and therapeutic counter-measures for these conditions may therefore be particularly indicated for this patient group.

Paraplegia after contrast media application: a transient or devastating rare complication? Case report.

PubMed

Mielke, Dorothee; Kallenberg, Kai; Hartmann, Marius; Rohde, Veit

2016-05-01

The authors report the case of a 76-year-old man with a spinal dural arteriovenous fistula. The patient suffered from sudden repeated reversible paraplegia after spinal digital subtraction angiography as well as CT angiography. Neurotoxicity of contrast media (CM) is the most probable cause for this repeated short-lasting paraplegia. Intolerance to toxicity of CM to the vulnerable spinal cord is rare, and probably depends on the individual patient. This phenomenon is transient and can occur after both intraarterial and intravenous CM application.

Upper limb function in persons with long term paraplegia and implications for independence: Part II.

PubMed

Pentland, W E; Twomey, L T

1994-04-01

Research has shown that wheelchair use in long term paraplegia is associated with upper limb pain and degeneration that interferes with the independent performance of activities of daily living. This paper proposes a model to explain the development of upper limb problems in persons with long term paraplegia, and one that will guide in the prevention and management of this type of long term complication.

A comparison of 2 circuit exercise training techniques for eliciting matched metabolic responses in persons with paraplegia.

PubMed

Nash, Mark S; Jacobs, Patrick L; Woods, Jeffrey M; Clark, James E; Pray, Tanya A; Pumarejo, Alex E

2002-02-01

To test whether acute metabolic (VO(2)), chronotropic (heart rate), and perceptual (rating of perceived exertion; RPE) responses to exercise by persons with paraplegia differ when the exercise is on a multistation isoinertial exercise system (MultiGym) or on a customized system of Thera-Band resistance bands (ElasticGym). Within-subjects comparison of 2 treatments. Academic medical center. Sixteen men and 1 woman with complete paraplegia (T4-L1), as defined by the American Spinal Injury Association. A circuit resistance training (CRT) program for persons with paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises used for training and testing used 6 resistance maneuvers at 50% of the 1-repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were habituated to both conditions for 2 weeks before testing on randomized nonconsecutive days. VO(2) (L/min) was measured by portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by the Borg Scale of Perceived Exertion (6-20). No significant effects of test condition on average VO(2) or heart rate were observed, with differences between conditions reflecting only .08L/min and 6.4 beats/min, respectively. Average RPE was significantly higher in testing under the ElasticGym condition (P < .05). CRT on a customized ElasticGym system elicited acute metabolic and chronotropic responses that did not differ from responses to exercise on a MultiGym, though RPE was greater with the ElasticGym. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

A case of acute paraplegia that improved with dialysis.

PubMed

Rajendiran, Govarthanan; Jayabalan, Rajamahesh; Chandrahasan, Saravanan; Mani, Ashwin Kumar

2008-01-01

Acute severe hyperkalemia can present as acute paraplegia independent of cardiac effects, even though cardiac muscle is more sensitive to serum potassium changes. We managed a patient with acute hyperkalemic paralysis who did not have threatening cardiac/electrocardiographic manifestations. The limb weakness became normal after hemodialysis.

Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

PubMed

Newton, Timothy; Allison, Rachel; Edgar, James R; Lumb, Jennifer H; Rodger, Catherine E; Manna, Paul T; Rizo, Tania; Kohl, Zacharias; Nygren, Anders O H; Arning, Larissa; Schüle, Rebecca; Depienne, Christel; Goldberg, Lisa; Frahm, Christiane; Stevanin, Giovanni; Durr, Alexandra; Schöls, Ludger; Winner, Beate; Beetz, Christian; Reid, Evan

2018-05-01

Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.

A case of acute paraplegia that improved with dialysis

PubMed Central

Rajendiran, Govarthanan; Jayabalan, Rajamahesh; Chandrahasan, Saravanan; Mani, Ashwin Kumar

2008-01-01

Acute severe hyperkalemia can present as acute paraplegia independent of cardiac effects, even though cardiac muscle is more sensitive to serum potassium changes. We managed a patient with acute hyperkalemic paralysis who did not have threatening cardiac/electrocardiographic manifestations. The limb weakness became normal after hemodialysis. PMID:19826591

Co-segregation of Huntington disease and hereditary spastic paraplegia in 4 generations.

PubMed

Panas, Marios; Karadima, Georgia; Kalfakis, Nikolaos; Vassilopoulos, Dimitris

2011-07-01

Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons.

Hereditary spastic paraplegia.

PubMed

Blackstone, Craig

2018-01-01

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Cellular pathways of hereditary spastic paraplegia.

PubMed

Blackstone, Craig

2012-01-01

Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticulum, as well as intracellular membrane trafficking and distribution as primary defects underlying the HSPs, with clear relevance for other long axonopathies affecting peripheral nerves and lower motor neurons.

[A case of leptomeningeal melanomatosis with acute paraplegia and multiple cranial nerve palsies].

PubMed

Hattori, Kasumi; Matsuda, Nozomu; Murakami, Takenobu; Ito, Eiichi; Ugawa, Yoshikazu

2017-12-27

A 62-year-old man with acute paraplegia was transferred to our hospital. He had flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no meningeal irritation signs. MRI of the spinal canal showed swellings of the conus medullaris and the cauda equine, and also contrast enhancement of the spinal meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment. The lymph node was swollen in his right axilla. The biopsy specimen from the right axillary lymph node revealed metastasis of malignant melanoma histologically. Careful check-up of his whole body found a malignant melanoma in the subungual region of the right ring finger. Repeated cytological examination revealed melanoma cells in the CSF, confirming the diagnosis of leptomeningeal melanomatosis. His consciousness was gradually deteriorated. His family members chose supportive care instead of chemotherapy or surgical therapy after full information about his conditions. Finally, he died 60 days after transfer to our hospital. This is a rare case of leptomenigeal melanomatosis presenting with acute paraplegia and multiple cranial nerve palsies. Careful follow-up and repeated studies are vital for the early diagnosis of leptomenigeal melanomatosis in spite of atypical clinical presentation.

Clinical indicators of paraplegia underplay universal spinal cord neuronal injury from transient aortic occlusion.

PubMed

Bell, Marshall T; Puskas, Ferenc; Bennett, Daine T; Cleveland, Joseph C; Herson, Paco S; Mares, Joshua M; Meng, Xainzhong; Weyant, Michael J; Fullerton, David A; Brett Reece, T

2015-08-27

Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically. Copyright © 2015 Elsevier B.V. All rights reserved.

Hereditary spastic paraplegia: clinical principles and genetic advances.

PubMed

Fink, John K

2014-07-01

Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP. Neuropathological studies, albeit limited to only a few genetic types of HSP, have identified axon degeneration involving the distal ends of the corticospinal tracts and fasciculus gracilis fibers. In this review, the author highlights the clinical and genetic features of HSP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78)

PubMed Central

Estrada-Cuzcano, Alejandro; Martin, Shaun; Chamova, Teodora; Synofzik, Matthis; Timmann, Dagmar; Holemans, Tine; Andreeva, Albena; Reichbauer, Jennifer; De Rycke, Riet; Chang, Dae-In; van Veen, Sarah; Samuel, Jean; Schöls, Ludger; Pöppel, Thorsten; Mollerup Sørensen, Danny; Asselbergh, Bob; Klein, Christine; Zuchner, Stephan; Jordanova, Albena; Vangheluwe, Peter; Tournev, Ivailo; Schüle, Rebecca

2017-01-01

Abstract Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders characterized by progressive spasticity of the lower limbs due to degeneration of the corticospinal motor neurons. In a Bulgarian family with three siblings affected by complicated hereditary spastic paraplegia, we performed whole exome sequencing and homozygosity mapping and identified a homozygous p.Thr512Ile (c.1535C > T) mutation in ATP13A2. Molecular defects in this gene have been causally associated with Kufor-Rakeb syndrome (#606693), an autosomal recessive form of juvenile-onset parkinsonism, and neuronal ceroid lipofuscinosis (#606693), a neurodegenerative disorder characterized by the intracellular accumulation of autofluorescent lipopigments. Further analysis of 795 index cases with hereditary spastic paraplegia and related disorders revealed two additional families carrying truncating biallelic mutations in ATP13A2. ATP13A2 is a lysosomal P5-type transport ATPase, the activity of which critically depends on catalytic autophosphorylation. Our biochemical and immunocytochemical experiments in COS-1 and HeLa cells and patient-derived fibroblasts demonstrated that the hereditary spastic paraplegia-associated mutations, similarly to the ones causing Kufor-Rakeb syndrome and neuronal ceroid lipofuscinosis, cause loss of ATP13A2 function due to transcript or protein instability and abnormal intracellular localization of the mutant proteins, ultimately impairing the lysosomal and mitochondrial function. Moreover, we provide the first biochemical evidence that disease-causing mutations can affect the catalytic autophosphorylation activity of ATP13A2. Our study adds complicated hereditary spastic paraplegia (SPG78) to the clinical continuum of ATP13A2-associated neurological disorders, which are commonly hallmarked by lysosomal and mitochondrial dysfunction. The disease presentation in our patients with hereditary spastic paraplegia was dominated by an adult-onset lower

Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.

PubMed

Benfield, Jon; Maknojia, Asif; Epstein, Franklin

2016-03-01

Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.

Converging cellular themes for the hereditary spastic paraplegias.

PubMed

Blackstone, Craig

2018-05-10

Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking. Published by Elsevier Ltd.

Audio-visual distraction as an adjunct to standby anaesthesia in persons with paraplegia: a case series of five operations.

PubMed

Ayub, Khurram; Corrigan, Ruth A; Misra, Jyoti; Galitzine, Svetlana

2018-01-01

Persons with paraplegia present complex challenges to anaesthetists. Complications experienced by these patients can require major orthoplastic surgery such as excision of infected bone and soft tissue due to pressure sores and soft tissue reconstruction. Anaesthetic strategies deemed both safe and acceptable to this population are essential. We report a case series of five procedures in four patients with complete chronic spinal cord injury (CSCI) who underwent operations in lateral position under standby anaesthesia and audio-visual distraction (AVD) with minimal sedation. Patients' experience was formally assessed as part of the ongoing AVD service evaluation in our institution. All stated that they were not concerned in the operating theatre and felt "comfortable" or "very comfortable" throughout. All patients rated the experience as "better" than their previous experience with general anaesthesia and felt "very satisfied" with their anaesthetic. Importantly, all patients would recommend sedation with AVD to other patients. To our knowledge, this is the first report of AVD application as an adjunct to standby anaesthesia during major surgery in persons with paraplegia. Patient feedback was extremely positive, therefore it is likely that by making standby anaesthesia more acceptable to patients the use of AVD could reduce anaesthetic risk in this complex patient group.

Autosomal recessive mutilating sensory neuropathy with spastic paraplegia maps to chromosome 5p15.31-14.1.

PubMed

Bouhouche, Ahmed; Benomar, Ali; Bouslam, Naima; Ouazzani, Reda; Chkili, Taïeb; Yahyaoui, Mohamed

2006-02-01

Autosomal recessive ulcero-mutilating neuropathy with spastic paraplegia is a very rare disease since only few cases were described up to date. We report in this study a consanguineous Moroccan family with four affected males with this syndrome. The disease onset was in early infancy, with spastic paraplegia and sensory loss leading to mutilating acropathy. Electrophysiological studies revealed a severe axonal sensory neuropathy, magnetic resonance imaging ruled out compression of spinal cord and biological investigations showed decreased levels of Apo B, total cholesterol and triglycerides. A genomewide search was conducted in this family and linkage was found to chromosome 5p. Analysis of recombination events and LOD score calculation map the responsible gene in a 25 cM genetic interval between markers D5S2054 and D5S648. A maximum LOD score value of 3.92 was obtained for all markers located in this candidate interval. This study establishes the presence of a locus for autosomal recessive mutilating sensory neuropathy with spastic paraplegia on chromosome 5p15.31-14.1.

Car Transfer and Wheelchair Loading Techniques in Independent Drivers with Paraplegia

PubMed Central

Haubert, Lisa Lighthall; Mulroy, Sara J.; Hatchett, Patricia E.; Eberly, Valerie J.; Maneekobkunwong, Somboon; Gronley, Joanne K.; Requejo, Philip S.

2015-01-01

Car transfers and wheelchair (WC) loading are crucial for independent community participation in persons with complete paraplegia from spinal cord injury, but are complex, physically demanding, and known to provoke shoulder pain. This study aimed to describe techniques and factors influencing car transfer and WC loading for individuals with paraplegia driving their own vehicles and using their personal WCs. Sedans were the most common vehicle driven (59%). Just over half (52%) of drivers place their right leg only into the vehicle prior to transfer. Overall, the leading hand was most frequently placed on the driver’s seat (66%) prior to transfer and the trailing hand was most often place on the WC seat (48%). Vehicle height influenced leading hand placement but not leg placement such that drivers of higher profile vehicles were more likely to place their hand on the driver’s seat than those who drove sedans. Body lift time was negatively correlated with level of injury and age and positively correlated with vehicle height and shoulder abduction strength. Drivers who transferred with their leading hand on the steering wheel had significantly higher levels of shoulder pain than those who placed their hand on the driver’s seat or overhead. The majority of participants used both hands (62%) to load their WC frame, and overall, most loaded their frame into the back (62%) vs. the front seat. Sedan drivers were more likely to load their frame into the front seat than drivers of higher profile vehicles (53 vs. 17%). Average time to load the WC frame (10.7 s) was 20% of the total WC loading time and was not related to shoulder strength, frame weight, or demographic characteristics. Those who loaded their WC frame into the back seat had significantly weaker right shoulder internal rotators. Understanding car transfers and WC loading in independent drivers is crucial to prevent shoulder pain and injury and preserve community participation. PMID:26442253

Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report.

PubMed

Gormeli, Cemile Ayse; Sarac, Kaya; Ozdemir, Zeynep Maras; Gormeli, Gokay; Kahraman, Aysegul Sagir; Kahraman, Bayram; Oztanir, Mustafa Namik; Karadag, Nese

2016-09-01

Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits.

Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia.

PubMed

Sweet, Laurene A; OʼNeill, Lindsey M; Dobbs, Matthew B

2014-01-01

The purpose of this report is to explore assessment and serial casting intervention for painful rigid flatfoot deformities with vertical talus in an adolescent girl with hereditary spastic paraplegia who was nonambulatory. The participant's right foot underwent 2 phases of casting with correction first toward hindfoot inversion and then dorsiflexion. Because of a vertical talus, her left foot required an intermediate casting toward plantar flexion, inversion, and forefoot adduction prior to casting toward dorsiflexion. The patient improved despite the underlying progressive neuromuscular disorder. Pain ameliorated and she returned to supported standing and transfers. Spasticity decreased bilaterally and the flexibility of her foot deformities improved to allow orthotic fabrication in subtalar neutral. Results were maintained at 12 and 16 months. Individualized multiphase serial casting requires further investigation with patients such as those with hereditary spastic paraplegia.

A Telerehabilitation Approach to Enhance Quality of Life Through Exercise Among Adults With Paraplegia: Study Protocol.

PubMed

Sweet, Shane Norman; Rocchi, Meredith; Arbour-Nicitopoulos, Kelly; Kairy, Dahlia; Fillion, Brigitte

2017-10-19

Despite compelling evidence linking physical activity and quality of life among adults with spinal cord injury (SCI), exercise participation rates are extremely low in this population. Unfortunately, a lack of behavioral exercise interventions, in particular theory-based randomized controlled trials (RCT), exists within the SCI literature. A pilot RCT is needed to first examine the feasibility to conduct such interventions and determine the appropriate effect size to inform future full-scale interventions. The overall goal of this pilot RCT is to test an 8-week innovative, video-based telerehabilitation intervention based on self-determination theory and aimed at enhancing the basic psychological needs, motivation, exercise participation, and quality of life‒related outcomes of adults with paraplegia. The objectives are to (1) determine if individuals in the intervention group have greater increases in their basic psychological needs and autonomous motivation and a decrease in controlled motivation compared to the control group, (2) determine whether the intervention group reports greater increases in exercise participation and quality of life‒related variables (eg, life satisfaction, participation in daily/social activities, depressive symptoms) compared to the control group, and (3) examine if adults with paraplegia who received the intervention report improved scores on psychosocial predictors of exercise (eg, action planning) and well-being (eg, positive affect) compared to the control group. We also aimed to examine the implementation characteristics of the intervention (eg, satisfaction with the technology, counselor's ability to foster the psychological needs). Adults with paraplegia (N=24) living in the community will be recruited. All participants will be invited to complete assessments of their psychological needs, motivation, exercise, and quality of life‒related variables at three time points (baseline, 6, and 10 weeks). Following the baseline

Effects of walkbot gait training on kinematics, kinetics, and clinical gait function in paraplegia and quadriplegia.

PubMed

Hwang, Jongseok; Shin, Yongil; Park, Ji-Ho; Cha, Young Joo; You, Joshua Sung H

2018-04-07

The robotic-assisted gait training (RAGT) system has gained recognition as an innovative, effective paradigm to improve functional ambulation and activities of daily living in spinal cord injury and stroke. However, the effects of the Walkbot robotic-assisted gait training system with a specialized hip-knee-ankle actuator have never been examined in the paraplegia and quadriplegia population. The aim of this study was to determine the long-term effects of Walkbot training on clinical for hips and knee stiffness in individuals with paraplegia or quadriplegia. Nine adults with subacute or chronic paraplegia resulting from spinal cord injury or quadriplegia resulting from cerebral vascular accident (CVA) and/or hypoxia underwent progressive conventional gait retraining combined with the Walkbot RAGT for 5 days/week over an average of 43 sessions for 8 weeks. Clinical outcomes were measured with the Functional Ambulation Category (FAC), Modified Rankin Scale (MRS), Korean version of the Modified Barthel Index (K-MBI), Modified Ashworth Scale (MAS). Kinetic and kinematic data were collected via a built-in Walkbot program. Wilcoxon signed-rank tests showed significant positive intervention effects on K-MBI, maximal hip flexion and extension, maximal knee flexion, active torque in the knee joint, resistive torque, and stiffness in the hip joint (P <  0.05). These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. These improvements were associated with functional recovery in gait, balance, mobility and daily activities. These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. This is the first clinical evidence for intensive, long-term effects of the Walkbot RAGT on active or resistive moments and stiffness associated with spasticity and functional

TWIICE - A lightweight lower-limb exoskeleton for complete paraplegics.

PubMed

Vouga, Tristan; Baud, Romain; Fasola, Jemina; Bouri, Mohamed; Bleuler, Hannes

2017-07-01

This paper introduces TWIICE, a lower-limb exoskeleton that enables people suffering from complete paraplegia to stand up and walk again. TWIICE provides complete mobilization of the lower-limbs, which is a first step toward enabling the user to regain independence in activities of the daily living. The tasks it can perform include level and inclined walking (up to 20° slope), stairs ascent and descent, sitting on a seat, and standing up. Participation in the world's first Cybathlon (Zurich, 2016) demonstrated good performance at these demanding tasks. In this paper, we describe the implementation details of the device and comment on preliminary results from a single user case study.

Quantitative and Functional Analyses of Spastin in the Nervous System: Implications for Hereditary Spastic Paraplegia

DTIC Science & Technology

2008-02-27

equivalent levels of expression of the spastin constructs, as assessed by fluorescence intensity of the Sp/AAA antibody staining. Microtu- bule levels...Errico A, Ballabio A, Rugarli EI (2002) Spastin, the protein mutated in au- tosomal dominant hereditary spastic paraplegia, is involved in microtu- bule

GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.

PubMed

Hengel, H; Keimer, R; Deigendesch, W; Rieß, A; Marzouqa, H; Zaidan, J; Bauer, P; Schöls, L

2018-06-07

Various genetic defects can cause intellectual and developmental disabilities (IDD). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive GPT2 mutations have recently been associated with IDD in four families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in five patients from two consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Due to the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hereditary spastic paraplegias: membrane traffic and the motor pathway

PubMed Central

Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

2017-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution — in axonal maintenance and degeneration. PMID:21139634

Hereditary spastic paraplegias: membrane traffic and the motor pathway.

PubMed

Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

2011-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

PubMed Central

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

2016-01-01

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

REEP1 Mutation Spectrum and Genotype/Phenotype Correlation in Hereditary Spastic Paraplegia Type 31

ERIC Educational Resources Information Center

Beetz, Christian; Schule, Rebecca; Deconinck, Tine; Tran-Viet, Khanh-Nhat; Zhu, Hui; Kremer, Berry P. H.; Frints, Suzanna G. M.; van Zelst-Stams, Wendy A. G.; Byrne, Paula; Otto, Susanne; Nygren, Anders O. H.; Baets, Jonathan; Smets, Katrien; Ceulemans, Berten; Dan, Bernard; Nagan, Narasimhan; Kassubek, Jan; Klimpe, Sven; Klopstock, Thomas; Stolze, Henning; Smeets, Hubert J. M.; Schrander-Stumpel, Constance T. R. M.; Hutchinson, Michael; van de Warrenburg, Bart P.; Braastad, Corey; Deufel, Thomas; Pericak-Vance, Margaret; Schols, Ludger; de Jonghe, Peter; Zuchner, Stephan

2008-01-01

Mutations in the receptor expression enhancing protein 1 (REEP1) have recently been reported to cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG31. In a large collaborative effort, we screened a sample of 535 unrelated HSP patients for "REEP1" mutations and copy number variations. We identified 13 novel and 2 known "REEP1"…

Multigeneration family with dominant SPG30 hereditary spastic paraplegia.

PubMed

Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig

2017-11-01

Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clincal review with six additional families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schrander-Stumpel, C.; Hoeweler, C.; Jones, M.

X-linked hydrocephalus (HSAS) (MIM{sup *}307000), MASA syndrome (MIM {sup *}303350), and complicated spastic paraplegia (SPG1) (MIM {sup *}3129000) are closely related. Soon after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS and MASA syndrome show great clinical overlap; DNA linkage analysis places the loci at Xq28. In an increasing number of families with MASA syndrome or HSAS, mutations in L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previousmore » reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with X-linked corpus callosum agenesis and FG syndrome, and the different forms of X-linked complicated spastic paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific mental retardation. We propose to abandon the designation MASA syndrome and use the term HSAS/MASA spectrum, incorporating SPG1. 79 refs., 6 figs., 2 tabs.« less

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11

PubMed Central

Varga, Rita-Eva; Khundadze, Mukhran; Damme, Markus; Nietzsche, Sandor; Hoffmann, Birgit; Stauber, Tobias; Koch, Nicole; Hennings, J. Christopher; Franzka, Patricia; Huebner, Antje K.; Kessels, Michael M.; Biskup, Christoph; Jentsch, Thomas J.; Qualmann, Britta; Braulke, Thomas; Kurth, Ingo; Beetz, Christian; Hübner, Christian A.

2015-01-01

Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice. PMID:26284655

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

PubMed

Varga, Rita-Eva; Khundadze, Mukhran; Damme, Markus; Nietzsche, Sandor; Hoffmann, Birgit; Stauber, Tobias; Koch, Nicole; Hennings, J Christopher; Franzka, Patricia; Huebner, Antje K; Kessels, Michael M; Biskup, Christoph; Jentsch, Thomas J; Qualmann, Britta; Braulke, Thomas; Kurth, Ingo; Beetz, Christian; Hübner, Christian A

2015-08-01

Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

Public financing of IVF: a review of policy rationales.

PubMed

Mladovsky, Philipa; Sorenson, Corinna

2010-06-01

There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed.

Clinical and genetic study of hereditary spastic paraplegia in Canada.

PubMed

Chrestian, Nicolas; Dupré, Nicolas; Gan-Or, Ziv; Szuto, Anna; Chen, Shiyi; Venkitachalam, Anil; Brisson, Jean-Denis; Warman-Chardon, Jodi; Ahmed, Sohnee; Ashtiani, Setareh; MacDonald, Heather; Mohsin, Noreen; Mourabit-Amari, Karim; Provencher, Pierre; Boycott, Kym M; Stavropoulos, Dimitri J; Dion, Patrick A; Ray, Peter N; Suchowersky, Oksana; Rouleau, Guy A; Yoon, Grace

2017-02-01

To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP. We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65). A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset ( p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04-548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes ( p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI ( p = 0.014). The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.

Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

PubMed

Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

2013-08-01

In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship Between Hand Contact Angle and Shoulder Loading During Manual Wheelchair Propulsion by Individuals with Paraplegia

PubMed Central

Mulroy, Sara J.; Ruparel, Puja; Hatchett, Patricia E.; Haubert, Lisa Lighthall; Eberly, Valerie J.; Gronley, JoAnne K.

2015-01-01

Background: Shoulder loading during manual wheelchair propulsion (WCP) contributes to the development of shoulder pain in individuals with spinal cord injury (SCI). Objective: To use regression analysis to investigate the relationships between the hand contact angle (location of the hand on the pushrim at initial contact and release during the push phase of the WCP cycle) with propulsion characteristics, pushrim forces, and shoulder kinetics during WCP in individuals with paraplegia. Methods: Biomechanical data were collected from 222 individuals (198 men and 24 women) with paraplegia from SCI during WCP on a stationary ergometer at a self-selected speed. The average age of participants was 34.7 years (±9.3), mean time since SCI was 9.3 years (±6.1), and average body weight was 74.4 kg (±15.9). The majority (n = 127; 56%) of participants had lower level paraplegia (T8 to L5) and 95 (42%) had high paraplegia (T2 to T7). Results: Increased push arc (mean = 75.3°) was associated with greater velocity (R = 0.384, P < .001) and cycle distance (R = 0.658, P < .001) and reduced cadence (R = -0.419, P < .001). Initial contact angle and hand release angles were equally associated with cycle distance and cadence, whereas a more anterior release angle was associated with greater velocity (R = 0.372, P < .001). When controlling for body weight, a more posterior initial contact angle was associated with greater posterior shoulder net joint force (R = 0.229, P = .001) and greater flexor net joint moment (R = 0.204, P = .002), whereas a more anterior hand release angle was significantly associated with increased vertical (R = 0.270, P < .001) and greater lateral (R = .293, P < .001) pushrim forces; greater shoulder net joint forces in all 3 planes — posterior (R = 0.164, P = .015), superior (R = 0.176, P = .009), and medial (R = 0.284, P < .001); and greater external rotator (R = 0.176, P = .009) and adductor (R = 0.259, P = .001) net joint moments. Conclusions: Current

Relationship Between Hand Contact Angle and Shoulder Loading During Manual Wheelchair Propulsion by Individuals with Paraplegia.

PubMed

Requejo, Philip Santos; Mulroy, Sara J; Ruparel, Puja; Hatchett, Patricia E; Haubert, Lisa Lighthall; Eberly, Valerie J; Gronley, JoAnne K

2015-01-01

Shoulder loading during manual wheelchair propulsion (WCP) contributes to the development of shoulder pain in individuals with spinal cord injury (SCI). To use regression analysis to investigate the relationships between the hand contact angle (location of the hand on the pushrim at initial contact and release during the push phase of the WCP cycle) with propulsion characteristics, pushrim forces, and shoulder kinetics during WCP in individuals with paraplegia. Biomechanical data were collected from 222 individuals (198 men and 24 women) with paraplegia from SCI during WCP on a stationary ergometer at a self-selected speed. The average age of participants was 34.7 years (±9.3), mean time since SCI was 9.3 years (±6.1), and average body weight was 74.4 kg (±15.9). The majority (n = 127; 56%) of participants had lower level paraplegia (T8 to L5) and 95 (42%) had high paraplegia (T2 to T7). Increased push arc (mean = 75.3°) was associated with greater velocity (R = 0.384, P < .001) and cycle distance (R = 0.658, P < .001) and reduced cadence (R = -0.419, P <.001). Initial contact angle and hand release angles were equally associated with cycle distance and cadence, whereas a more anterior release angle was associated with greater velocity (R = 0.372, P < .001). When controlling for body weight, a more posterior initial contact angle was associated with greater posterior shoulder net joint force (R = 0.229, P = .001) and greater flexor net joint moment (R = 0.204, P = .002), whereas a more anterior hand release angle was significantly associated with increased vertical (R = 0.270, P < .001) and greater lateral (R = .293, P < .001) pushrim forces; greater shoulder net joint forces in all 3 planes - posterior (R = 0.164, P = .015), superior (R = 0.176, P = .009), and medial (R = 0.284, P < .001); and greater external rotator (R = 0.176, P = .009) and adductor (R = 0.259, P = .001) net joint moments. Current clinical practice guidelines recommend using long, smooth

Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions

PubMed Central

Wedding, Iselin Marie; Koht, Jeanette; Tran, Gia Tuong; Misceo, Doriana; Selmer, Kaja Kristine; Holmgren, Asbjørn; Frengen, Eirik; Bindoff, Laurence; Tallaksen, Chantal M. E.; Tzoulis, Charalampos

2014-01-01

Spastic paraplegia 7 is an autosomal recessive disorder caused by mutations in the gene encoding paraplegin, a protein located at the inner mitochondrial membrane and involved in the processing of other mitochondrial proteins. The mechanism whereby paraplegin mutations cause disease is unknown. We studied two female and two male adult patients from two Norwegian families with a combination of progressive external ophthalmoplegia and spastic paraplegia. Sequencing of SPG7 revealed a novel missense mutation, c.2102A>C, p.H 701P, which was homozygous in one family and compound heterozygous in trans with a known pathogenic mutation c.1454_1462del in the other. Muscle was examined from an additional, unrelated adult female patient with a similar phenotype caused by a homozygous c.1047insC mutation in SPG7. Immunohistochemical studies in skeletal muscle showed mosaic deficiency predominantly affecting respiratory complex I, but also complexes III and IV. Molecular studies in single, microdissected fibres showed multiple mitochondrial DNA deletions segregating at high levels (38–97%) in respiratory deficient fibres. Our findings demonstrate for the first time that paraplegin mutations cause accumulation of mitochondrial DNA damage and multiple respiratory chain deficiencies. While paraplegin is not known to be directly associated with the mitochondrial nucleoid, it is known to process other mitochondrial proteins and it is possible therefore that paraplegin mutations lead to mitochondrial DNA deletions by impairing proteins involved in the homeostasis of the mitochondrial genome. These studies increase our understanding of the molecular pathogenesis of SPG7 mutations and suggest that SPG7 testing should be included in the diagnostic workup of autosomal recessive, progressive external ophthalmoplegia, especially if spasticity is present. PMID:24466038

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

PubMed Central

Féron, F.; Cochrane, J.; Bassingthwaighte, L.; Bayliss, C.; Davies, W.; Fronek, P.; Gray, C.; Kerr, G.; Licina, P.; Nowitzke, A.; Perry, C.; Silburn, P.A.S.; Urquhart, S.; Geraghty, T.

2008-01-01

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post

Five-Year Longitudinal Bone Evaluations in Individuals With Chronic Complete Spinal Cord Injury

PubMed Central

Garland, Douglas E; Adkins, Rodney H; Stewart, Charles A

2008-01-01

Background/Objectives: Knowledge of spinal cord injury (SCI) bone changes has been derived primarily through cross-sectional studies, many of which are controvertible. Longitudinal studies are sparse, and long-term longitudinal chronic studies are unavailable. The objective of this study was to provide a clearer perception of chronic longitudinal bone variations in people with complete SCI. Methods: Bone status of 31 individuals with chronic, complete SCI was assessed twice using dual-energy x-ray absorptiometry at an average interval of 5.06 ± 0.9 years. Because the sample of women was small (4), the primary analyses of change and comparisons of those with paraplegia vs tetraplegia were confined to the male participants. Results: Spine Z-scores showed a significant increase (P < 0.0001). The average Z-scores, initial and follow-up, were within the normal range. Hip Z-scores also showed a significant increase (P < 0.0001), and hip bone mineral density (BMD) increased in 48% of the participants. Knee BMD and lower extremity total bone mineral showed significant decreases (P < 0.003 and P < 0.02, respectively), but increases were seen in 33% and 26% at the respective sites. Individuals with tetraplegia had significantly lower values across all regions (P < 0.0001), and changes were significantly different compared with paraplegia (P < 0.0001). Bone values and changes in men vs women, despite the small sample of women, showed highly significant differences (P < 0.003–0.002). Conclusion: Chronic effects of complete SCI do not exclusively result in continued loss of BMD or a static state of lowered BMD; gain in BMD may occur. The nature and magnitude of the effects of complete SCI on BMD vary by site, with sex and level of injury, which has implications for treatment and its assessment. PMID:19086712

Active lower limb orthosis with one degree of freedom for people with paraplegia.

PubMed

Gloger, Michal; Obinata, Goro; Genda, Eiichi; Babjak, Jan; Pei, Yanling

2017-07-01

The main challenges of designing devices for paraplegic walking can be summarized into three groups, stability and comfort, high efficiency or low energy consumption, dimensions and weight. A new economical device for people with paraplegia which tackles all problems of the three groups is introduced in this paper. The main idea of this device is based on HALO mechanism. HALO is compact passive medial hip joint orthosis with contralateral hip and ankle linkage, which keeps the feet always parallel to the ground and assists swinging the leg. The medial hip joint is equipped with one actuator in the new design and the new orthosis is called @halo. Due to this update, we can achieve more stable and smoother walking patterns with decreased energy consumption of the users, yet maintain its compact and lightweight features. It is proven by the results from preliminary experiments with able-bodied subjects during which the same device with and without actuator was evaluated. Waddling and excessive vertical elevation of the center of gravity were decreased by 40% with significantly smaller standard deviations in case of the active orthosis. There was 52% less energy spent by the user wearing @halo which was calculated from the vertical excursion difference. There was measured 38.5% bigger impulse in crutches while using passive orthosis. The new @halo device is the first active orthosis for lower limbs with just one actuated degree of freedom for users with paraplegia.

Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation.

PubMed

Kawarai, Toshitaka; Miyamoto, Ryosuke; Mori, Atsuko; Oki, Ryosuke; Tsukamoto-Miyashiro, Ai; Matsui, Naoko; Miyazaki, Yoshimichi; Orlacchio, Antonio; Izumi, Yuishin; Nishida, Yoshihiko; Kaji, Ryuji

2015-12-15

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Unusual Presentation of a Primary Ewing's Sarcoma of the Spine with Paraplegia: A Case Report.

PubMed

Kannan, Karthik Kailash; Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

2015-03-01

Ewing's sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing's sarcoma in the spine is very rare. Ewing's sarcoma occurring in the spine is divided into two types, Ewing's sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing's sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing's sarcoma and patient was started on combination chemotherapy and radiotherapy.

Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: implications for cardiovascular risk.

PubMed

Rosado-Rivera, Dwindally; Radulovic, M; Handrakis, John P; Cirnigliaro, Christopher M; Jensen, A Marley; Kirshblum, Steve; Bauman, William A; Wecht, Jill Maria

2011-01-01

Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n=20; TETRA: C4-C8), high paraplegia (n=10; HP: T2-T5), low paraplegia (n=9; LP: T7-T12), and non-SCI controls (n=10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P<0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P<0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P<0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P<0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P<0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated.

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

PubMed Central

Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

2014-01-01

Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26−/− mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

Rationales for Commonly "Challenged" Taught Books.

ERIC Educational Resources Information Center

Shugert, Diane P., Ed.; And Others

1983-01-01

Intended for teachers, this focused journal issue contains separate rationales for teaching books that have been challenged as appropriate instructional materials. Following a discussion of the purpose for rationales and suggestions for using them, the journal presents rationales for teaching the following books: "To Kill a Mockingbird,""The Diary…

Full Body Gait Analysis May Improve Diagnostic Discrimination Between Hereditary Spastic Paraplegia and Spastic Diplegia: A Preliminary Study

ERIC Educational Resources Information Center

Bonnefoy-Mazure, A.; Turcot, K.; Kaelin, A.; De Coulon, G.; Armand, S.

2013-01-01

Hereditary spastic paraplegia (HSP) and spastic diplegia (SD) patients share a strong clinical resemblance. Thus, HSP patients are frequently misdiagnosed with a mild form of SD. Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD. Previous analysis has focused on the lower-body…

Hemorrhagic thoracic schwannoma presenting with intradural hematoma and acute paraplegia after spinal manipulation therapy.

PubMed

Hdeib, Alia; Goodwin, C Rory; Sciubba, Daniel; Bydon, Ali; Wolinsky, Jean-Paul; Witham, Timothy; Gokaslan, Ziya L

2016-01-01

Hemorrhagic conversion of spinal schwannomas represents a rare occurrence; also rare is the development of a spinal intradural hematoma after spinal manipulation therapy. We report a unique presentation of paraplegia in a patient who underwent spinal manipulation therapy and was found to have a hemorrhagic thoracic schwannoma at time of surgery in the setting of anti-platelet therapy use. In patients with spinal schwannomas, tumor hemorrhage is a rare occasion, which can be considered in the setting of additive effects of spinal manipulation therapy and antiplatelet therapy.

A muscle-driven approach to restore stepping with an exoskeleton for individuals with paraplegia.

PubMed

Chang, Sarah R; Nandor, Mark J; Li, Lu; Kobetic, Rudi; Foglyano, Kevin M; Schnellenberger, John R; Audu, Musa L; Pinault, Gilles; Quinn, Roger D; Triolo, Ronald J

2017-05-30

Functional neuromuscular stimulation, lower limb orthosis, powered lower limb exoskeleton, and hybrid neuroprosthesis (HNP) technologies can restore stepping in individuals with paraplegia due to spinal cord injury (SCI). However, a self-contained muscle-driven controllable exoskeleton approach based on an implanted neural stimulator to restore walking has not been previously demonstrated, which could potentially result in system use outside the laboratory and viable for long term use or clinical testing. In this work, we designed and evaluated an untethered muscle-driven controllable exoskeleton to restore stepping in three individuals with paralysis from SCI. The self-contained HNP combined neural stimulation to activate the paralyzed muscles and generate joint torques for limb movements with a controllable lower limb exoskeleton to stabilize and support the user. An onboard controller processed exoskeleton sensor signals, determined appropriate exoskeletal constraints and stimulation commands for a finite state machine (FSM), and transmitted data over Bluetooth to an off-board computer for real-time monitoring and data recording. The FSM coordinated stimulation and exoskeletal constraints to enable functions, selected with a wireless finger switch user interface, for standing up, standing, stepping, or sitting down. In the stepping function, the FSM used a sensor-based gait event detector to determine transitions between gait phases of double stance, early swing, late swing, and weight acceptance. The HNP restored stepping in three individuals with motor complete paralysis due to SCI. The controller appropriately coordinated stimulation and exoskeletal constraints using the sensor-based FSM for subjects with different stimulation systems. The average range of motion at hip and knee joints during walking were 8.5°-20.8° and 14.0°-43.6°, respectively. Walking speeds varied from 0.03 to 0.06 m/s, and cadences from 10 to 20 steps/min. A self-contained muscle

Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24.

PubMed

Schüle, R; Bonin, M; Dürr, A; Forlani, S; Sperfeld, A D; Klimpe, S; Mueller, J C; Seibel, A; van de Warrenburg, B P; Bauer, P; Schöls, L

2009-06-02

Hereditary spastic paraplegias (HSP) are genetically exceedingly heterogeneous. To date, 37 genetic loci for HSP have been described (SPG1-41), among them 16 loci for autosomal dominant disease. Notwithstanding, further genetic heterogeneity is to be expected in HSP, as various HSP families do not link to any of the known HSP loci. In this study, we aimed to map the disease locus in a German family segregating autosomal dominant complicated HSP. A genome-wide linkage analysis was performed using the GeneChip Mapping 10Kv2.0 Xba Array containing 10,204 SNP markers. Suggestive loci were further analyzed by mapping of microsatellite markers. One locus on chromosome 12q23-24, termed SPG36, was confirmed by high density microsatellite fine mapping with a significant LOD score of 3.2. SPG36 is flanked by markers D12S318 and D12S79. Linkage to SPG36 was excluded in >20 additional autosomal dominant HSP families. Candidate genes were selected and sequenced. No disease-causing mutations were identified in the coding regions of ATXN2, HSPB8, IFT81, Myo1H, UBE3B, and VPS29. SPG36 is complicated by a sensory and motor neuropathy; it is therefore the eighth autosomal dominant subtype of complicated HSP. We report mapping of a new locus for autosomal dominant hereditary spastic paraplegia (HSP) (SPG36) on chromosome 12q23-24 in a German family with autosomal dominant HSP complicated by peripheral neuropathy.

Mutations in the KIAA0196 Gene at the SPG8 Locus Cause Hereditary Spastic Paraplegia

PubMed Central

Valdmanis, Paul N.; Meijer, Inge A.; Reynolds, Annie; Lei, Adrienne; MacLeod, Patrick; Schlesinger, David; Zatz, Mayana; Reid, Evan; Dion, Patrick A.; Drapeau, Pierre; Rouleau, Guy A.

2007-01-01

Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. The eighth HSP locus, SPG8, is on chromosome 8p24.13. The three families previously linked to the SPG8 locus present with relatively severe, pure spastic paraplegia. We have identified three mutations in the KIAA0196 gene in six families that map to the SPG8 locus. One mutation, V626F, segregated in three large North American families with European ancestry and in one British family. An L619F mutation was found in a Brazilian family. The third mutation, N471D, was identified in a smaller family of European origin and lies in a spectrin domain. None of these mutations were identified in 500 control individuals. Both the L619 and V626 residues are strictly conserved across species and likely have a notable effect on the structure of the protein product strumpellin. Rescue studies with human mRNA injected in zebrafish treated with morpholino oligonucleotides to knock down the endogenous protein showed that mutations at these two residues impaired the normal function of the KIAA0196 gene. However, the function of the 1,159-aa strumpellin protein is relatively unknown. The identification and characterization of the KIAA0196 gene will enable further insight into the pathogenesis of HSP. PMID:17160902

Short-term effects of upper extremity circuit resistance training on muscle strength and functional independence in patients with paraplegia.

PubMed

Yildirim, Adem; Sürücü, Gülseren Dost; Karamercan, Ayşe; Gedik, Dilay Eken; Atci, Nermin; Dülgeroǧlu, Deniz; Özgirgin, Neşe

2016-11-21

A number of exercises to strengthen the upper extremities are recommended to increase functional independence and quality of life (QoL) in patients with paraplegia. Circuit resistance training (CRT) is a type of progressive resistive exercise performed repeatedly at fixed mechanical exercise stations. The aim of this study was to investigate the potential benefits of CRT for upper extremity muscle strength, functional independence, and QoL in patients with paraplegia. Twenty-six patients with paraplegia who were participating in a conventional rehabilitation program at a tertiary education and research hospital were enrolled in this study. The participants were randomly assigned to two groups. The exercise group participated in the CRT program, which consisted of repetitive exercises for the upper extremities performed at fixed mechanical stations 5 sessions per week for 6 weeks, in addition to conventional rehabilitation. Participants in the control group received only conventional rehabilitation over the same period. We compared the groups with respect to QoL, as well as isokinetic muscle test outcomes in the upper extremities, using the Functional Independence Measure (FIM) and Borg's scale. We observed significant increases in scores on the physical component of the FIM, Borg's scale, and QoL in both the exercise and control groups. Furthermore, the large majority of isokinetic values were significantly more improved in the exercise group compared to the control group. When post-treatment outcomes were compared between the groups, improvements in scores on the physical component of the FIM and in most isokinetic values were significantly greater in the exercise group. This study showed that CRT has positive effects on muscle strength in the upper extremities and the physical disability components of the FIM when added to conventional rehabilitation programs for paraplegic patients. However, we observed no significant improvement in QoL scores after adding CRT

A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia: A 30-year diagnostic delay caused by misleading biochemical findings.

PubMed

Koutsis, Georgios; Lynch, David S; Tucci, Arianna; Houlden, Henry; Karadima, Georgia; Panas, Marios

2015-08-15

To present a Greek family in which 5 male and 2 female members developed progressive spastic paraplegia. Plasma very long chain fatty acids (VLCFA) were reportedly normal at first testing in an affected male and for over 30 years the presumed diagnosis was hereditary spastic paraplegia (HSP). Targeted next generation sequencing (NGS) was used as a further diagnostic tool. Targeted exome sequencing in the proband, followed by Sanger sequencing confirmation; mutation segregation testing in multiple family members and plasma VLCFA measurement in the proband. NGS of the proband revealed a novel frameshift mutation in ABCD1 (c.1174_1178del, p.Leu392Serfs*7), bringing an end to diagnostic uncertainty by establishing the diagnosis of adrenomyeloneuropathy (AMN), the myelopathic phenotype of X-linked adrenoleukodystrophy (ALD). The mutation segregated in all family members and the diagnosis of AMN/ALD was confirmed by plasma VLCFA measurement. Confounding factors that delayed the diagnosis are presented. This report highlights the diagnostic utility of NGS in patients with undiagnosed spastic paraplegia, establishing a molecular diagnosis of AMN, allowing proper genetic counseling and management, and overcoming the diagnostic delay that can be rarely caused by false negative VLCFA analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

PubMed Central

Rainier, Shirley; Chai, Jing-Hua; Tokarz, Debra; Nicholls, Robert D.; Fink, John K.

2003-01-01

The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications. PMID:14508710

Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.

PubMed

López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor

2015-11-15

Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. Copyright © 2015 Elsevier B.V. All rights reserved.

Loss of Function of Glucocerebrosidase GBA2 Is Responsible for Motor Neuron Defects in Hereditary Spastic Paraplegia

PubMed Central

Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L.; Gonzalez, Michael A.; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

2013-01-01

Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. PMID:23332916

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

PubMed

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-07-25

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

Paraplegia after myocardial revascularization. Case report.

PubMed

Nigro Neto, Caetano; Iza, Milton Patricio Chango; Tardelli, Maria Angela

2010-01-01

Developments in anesthesiology have improved safety indices. Several techniques and agents are used to control the hemodynamic response and minimize adverse effects triggered by surgical stimuli in patients undergoing cardiac procedures. This is a 70 years old male patient, 1.74 m, 75 kg, ASA III, and NYHA II. The patient had controlled dyslipedemia, type II diabetes mellitus, and hypertension; history of smoking, peripheral vascular disease, and myocardial infarction 20 years ago. The patient underwent revascularization with the left internal mammary artery and saphenous grafts with extracorporeal circulation with intermittent clamping of the aorta. During the first 24 hours in the ICU, the patient developed hemodynamic instability, sudden hypotension, and atrial fibrillation. Twenty-six hours after the end of the surgery, the patient was awake, hemodynamically stable, and with good respiratory dynamics, being extubated. The patient was talkative and oriented, but immobile and negative reflexes in the lower limbs. Neurological evaluation showed: cranial nerves without changes, no complaints of pain below the hips, preserved superficial and deep sensitivity, adequate distal perfusion without edema, and flaccid paraplegia below T8. The echocardiogram did not show any changes. CT scan of the lumbosacral spine was negative for compressive mass in the epidural space or adjacent to it. Anterior spinal artery syndrome should be considered in procedures with manipulation of the aorta. Prevention, especially in patients at risk, is necessary. Computed tomography, for the differential diagnosis, and MRI, to localize the lesion, are important.

The DALY, context and the determinants of the severity of disease: an exploratory comparison of paraplegia in Australia and Cameroon.

PubMed

Allotey, Pascale; Reidpath, Daniel; Kouamé, Aka; Cummins, Robert

2003-09-01

This paper summarises the findings of an empirical investigation of some of the technical and social assumptions on which the disability adjusted life year (DALY) is based. The objectives of the study were to examine the notion that the burden of disease is broadly similar without regard to country, environment, gender or socio-economic status and to develop detailed descriptions of the experiences of the burden of disease as they related to these contextual factors. The study was a multi-factorial exploratory study employing qualitative and quantitative techniques to obtain data on the effects of country (development), environment (urban versus rural), gender and socio-economic status on people with paraplegia. The data provided an extensive and detailed compilation of context rich descriptions of living with paraplegia. Striking features of the data were the differences between countries with respect to the impact of the health conditions on functioning and highlight a context in which paraplegia of like clinical severity can be fatal in one environment and not in another. While there has been some focus on the control of social determinants of disease, there has been little work on the social determinants of the severity of disease. The underlying assumptions of the DALY, which ignore context in the assessment of the burden of disease, risk exacerbating inequalities by undervaluing the burden of disease in less-developed countries. There is a need to continue to subject the development of indicators to rigorous debate to determine a balance between the assumption of a global "average social milieu" and the treatment of each individual as belonging to their own context in the assessment of population health in order for indicators to be meaningful cross-culturally.

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation

PubMed Central

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2014-01-01

Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration. PMID:25365221

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

PubMed Central

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-01-01

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function. DOI: http://dx.doi.org/10.7554/eLife.23882.001 PMID:28742022

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.

PubMed

Chang, Jaerak; Lee, Seongju; Blackstone, Craig

2014-12-01

Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration.

The influence of shoulder pain on functional limitation, perceived health, and depressive mood in patients with traumatic paraplegia

PubMed Central

Wang, Jia-Chi; Chan, Rai-Chi; Tsai, Yun-An; Huang, Wen-Cheng; Cheng, Henrich; Wu, Han-Lin

2015-01-01

Objective To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. Design Cross sectional and comparative investigation using the unified questionnaire. Setting Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. Participants Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). Outcome measures Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. Results Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r = 0.278, P = 0.017) and lower self-perceived health scores (r = −0.433, P < 0.001) but not SCIM scores (P = 0.342). Conclusion Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels. PMID:25296991

Using Rasch motor FIM individual growth curves to inform clinical decisions for persons with paraplegia.

PubMed

Pretz, C R; Kozlowski, A J; Charlifue, S; Chen, Y; Heinemann, A W

2014-09-01

A longitudinal retrospective study. To better understand individual-level temporal change in functional status for participants with paraplegia in the National Spinal Cord Injury Database (NSCID), as measured by Rasch Transformed Motor Functional Indepedence Measure (FIM) scores. Multicenter/Multistate longitudinal study across the United States. Non-linear random effects modeling, that is, individual growth curve analysis of retrospective data obtained from the National Institute on Disability and Rehabilitation Research (NIDRR) NSCID. We generated non-linear individual level trajectories of recovery for Rasch Transformed Motor FIM scores that rise rapidly from inpatient rehabilitation admission to a plateau. Trajectories are based on relationships between growth parameters and patient and injury factors: race, gender, level of education at admission, age at injury, neurological level at discharge, American Spinal Injury Association Impairment Scale (AIS) at discharge, days from injury to first system inpatient rehabilitation admission, rehabilitation length of stay, marital status and etiology. On the basis of study results, an interactive tool was developed to represent individual level longitudinal outcomes as trajectories based upon an individual's given baseline characteristics, that is, information supplied by the covariates and provides a robust description of temporal change for those with paraplegia within the NSCID. This methodology allows researchers and clinicians to generate and better understand patient-specific trajectories through the use of an automated interactive tool where a nearly countless number of longitudinal paths of recovery can be explored. Projected trajectories holds promise in facilitating planning for inpatient and outpatient services, which could positively impact long term outcomes.

Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia.

PubMed

Hashimoto, Yutaka; Shirane, Michiko; Matsuzaki, Fumiko; Saita, Shotaro; Ohnishi, Takafumi; Nakayama, Keiichi I

2014-05-09

Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with hereditary spastic paraplegia (HSP), and protrudin is therefore also referred to as spastic paraplegia (SPG) 33. We have now generated mice that express a transgene for dual epitope-tagged protrudin under control of a neuron-specific promoter, and we have subjected highly purified protrudin-containing complexes isolated from the brain of these mice to proteomics analysis to identify proteins that associate with protrudin. Protrudin was found to interact with other HSP-related proteins including myelin proteolipid protein 1 (SPG2), atlastin-1 (SPG3A), REEP1 (SPG31), REEP5 (similar to REEP1), Kif5A (SPG10), Kif5B, Kif5C, and reticulon 1, 3, and 4 (similar to reticulon 2, SPG12). Membrane topology analysis indicated that one of three hydrophobic segments of protrudin forms a hydrophobic hairpin domain similar to those of other SPG proteins. Protrudin was found to localize predominantly to the tubular endoplasmic reticulum (ER), and forced expression of protrudin promoted the formation and stabilization of the tubular ER network. The protrudin(G191V) mutant, which has been identified in a subset of HSP patients, manifested an increased intracellular stability, and cells expressing this mutant showed an increased susceptibility to ER stress. Our results thus suggest that protrudin contributes to the regulation of ER morphology and function, and that its deregulation by mutation is a causative defect in HSP.

Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.

PubMed

Martin, Elodie; Schüle, Rebecca; Smets, Katrien; Rastetter, Agnès; Boukhris, Amir; Loureiro, José L; Gonzalez, Michael A; Mundwiller, Emeline; Deconinck, Tine; Wessner, Marc; Jornea, Ludmila; Oteyza, Andrés Caballero; Durr, Alexandra; Martin, Jean-Jacques; Schöls, Ludger; Mhiri, Chokri; Lamari, Foudil; Züchner, Stephan; De Jonghe, Peter; Kabashi, Edor; Brice, Alexis; Stevanin, Giovanni

2013-02-07

Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Unusual Presentation of a Primary Ewing’s Sarcoma of the Spine with Paraplegia: A Case Report

PubMed Central

Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

2015-01-01

Ewing’s sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing’s sarcoma in the spine is very rare. Ewing’s sarcoma occurring in the spine is divided into two types, Ewing’s sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing’s sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing’s sarcoma and patient was started on combination chemotherapy and radiotherapy. PMID:25954672

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.

PubMed

Fink, John K

2013-09-01

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals of diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Postmortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including (1) axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); (2) endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); (3) mitochondrial function (e.g. SPG13/chaperonin 60/heat-shock protein 60, SPG7/paraplegin; and mitochondrial ATP6); (4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); (5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin), "mutilating sensory neuropathy with spastic paraplegia" owing to CcT5 mutation and presumably SPG18/ERLIN2); (6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); (7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and (8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E, SPG52/AP4S1, and

Loss of Association of REEP2 with Membranes Leads to Hereditary Spastic Paraplegia

PubMed Central

Esteves, Typhaine; Durr, Alexandra; Mundwiller, Emeline; Loureiro, José L.; Boutry, Maxime; Gonzalez, Michael A.; Gauthier, Julie; El-Hachimi, Khalid H.; Depienne, Christel; Muriel, Marie-Paule; Acosta Lebrigio, Rafael F.; Gaussen, Marion; Noreau, Anne; Speziani, Fiorella; Dionne-Laporte, Alexandre; Deleuze, Jean-François; Dion, Patrick; Coutinho, Paula; Rouleau, Guy A.; Zuchner, Stephan; Brice, Alexis; Stevanin, Giovanni; Darios, Frédéric

2014-01-01

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurological conditions. Their main pathogenic mechanisms are thought to involve alterations in endomembrane trafficking, mitochondrial function, and lipid metabolism. With a combination of whole-genome mapping and exome sequencing, we identified three mutations in REEP2 in two families with HSP: a missense variant (c.107T>A [p.Val36Glu]) that segregated in the heterozygous state in a family with autosomal-dominant inheritance and a missense change (c.215T>A [p.Phe72Tyr]) that segregated in trans with a splice site mutation (c.105+3G>T) in a family with autosomal-recessive transmission. REEP2 belongs to a family of proteins that shape the endoplasmic reticulum, an organelle that was altered in fibroblasts from an affected subject. In vitro, the p.Val36Glu variant in the autosomal-dominant family had a dominant-negative effect; it inhibited the normal binding of wild-type REEP2 to membranes. The missense substitution p.Phe72Tyr, in the recessive family, decreased the affinity of the mutant protein for membranes that, together with the splice site mutation, is expected to cause complete loss of REEP2 function. Our findings illustrate how dominant and recessive inheritance can be explained by the effects and nature of mutations in the same gene. They have also important implications for genetic diagnosis and counseling in clinical practice because of the association of various modes of inheritance to this new clinico-genetic entity. PMID:24388663

STARPROBE: Scientific rationale

NASA Technical Reports Server (NTRS)

Underwood, J. H. (Editor); Randolph, J. E. (Editor)

1982-01-01

The scientific rationale and instrumentation problems in the areas of solar internal dynamics and relativity, solar plasma and particle dynamics, and solar atmosphere structure were studied. Current STARPROBE mission and system design concepts are summarized.

Rationales for Challenged Books. [CD-ROM].

ERIC Educational Resources Information Center

National Council of Teachers of English, Urbana, IL.

This CD-ROM presents a collection of over 200 rationales for over 170 works (mainly novels but a few films) for use by teachers combating censorship. Some rationales on the disc are from published sources; others are student papers. Although the materials in the collection range from kindergarten through grade 12, the emphasis is on the middle…

Effects of Role and Assignment Rationale on Attitudes Formed During Peer Tutoring

PubMed Central

Bierman, Karen Linn; Furman, Wyndol

2012-01-01

This study examined the role of contextual factors, such as assignment rationale, on the attitudinal effects of peer tutoring. Fourth-grade children engaged in brief tutoring experiences as either a tutor or tutee. Subjects received four rationales for being selected as tutor or tutee: (a) a competence rationale, (b) a physical characteristic rationale, (c) a chance rationale, or (d) no rationale. As predicted, tutors had more positive attitudes than tutees when they had been given a competence or physical characteristic rationale but not when the tutors were provided a chance rationale or no rationale. Additionally, the tutors’ and tutees’ attitudes were enhanced when no rationale was provided. Results are discussed in terms of their implications for a role-theory analysis of tutoring and their implications for applied programs. PMID:23946549

Effects of Role and Assignment Rationale on Attitudes Formed During Peer Tutoring.

PubMed

Bierman, Karen Linn; Furman, Wyndol

1981-02-01

This study examined the role of contextual factors, such as assignment rationale, on the attitudinal effects of peer tutoring. Fourth-grade children engaged in brief tutoring experiences as either a tutor or tutee. Subjects received four rationales for being selected as tutor or tutee: (a) a competence rationale, (b) a physical characteristic rationale, (c) a chance rationale, or (d) no rationale. As predicted, tutors had more positive attitudes than tutees when they had been given a competence or physical characteristic rationale but not when the tutors were provided a chance rationale or no rationale. Additionally, the tutors' and tutees' attitudes were enhanced when no rationale was provided. Results are discussed in terms of their implications for a role-theory analysis of tutoring and their implications for applied programs.

Teaching Economics to Young Adolescents: A Research-Based Rationale.

ERIC Educational Resources Information Center

Davis, James E.

This booklet presents a research-based rationale for teaching economics at the middle/junior high school level in the United States. Chapter 1, "Introduction," describes the project in which the rationale was developed and outlines the remainder of the document. Chapter 2, "Elements of a Rationale for Middle School Economic Education," presents…

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia

PubMed Central

Khurana, Meetika; Walia, Shefali

2017-01-01

Objective: To determine whether there is any difference between virtual reality game–based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test–post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game–based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure–III (SCIM-III). Results: There was a significant difference for time (p = .001) and Time × Group effect (p = .001) in mFRT scores, group effect (p = .05) in t-shirt test scores, and time effect (p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game–based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training. PMID:29339902

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia.

PubMed

Khurana, Meetika; Walia, Shefali; Noohu, Majumi M

2017-01-01

Objective: To determine whether there is any difference between virtual reality game-based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test-post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game-based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure-III (SCIM-III). Results: There was a significant difference for time ( p = .001) and Time × Group effect ( p = .001) in mFRT scores, group effect ( p = .05) in t-shirt test scores, and time effect ( p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game-based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training.

The credibility of exposure therapy: Does the theoretical rationale matter?

PubMed

Arch, Joanna J; Twohig, Michael P; Deacon, Brett J; Landy, Lauren N; Bluett, Ellen J

2015-09-01

Little is understood about how the public perceives exposure-based therapy (ET) for treating anxiety and trauma-related disorders or how ET rationales affect treatment credibility. Distinct approaches to framing ET are practiced, including those emphasized in traditional cognitive behavioral therapy, acceptance and commitment therapy, and the more recent inhibitory learning model. However, their relative effect on ET's credibility remains unknown. A final sample of 964 U.S. adults provided baseline views of ET. Participants rated ET treatment credibility following a simple ET definition (pre-rationale) and following randomization to rationale modules addressing ET goals, fear, and cognitive strategies from distinct theoretical perspectives (post-rationale). Baseline ET views, symptoms, and sociodemographic characteristics were examined as putative moderators and predictors. At baseline, the majority had never heard of ET. From pre- to post-rationale, ET treatment credibility significantly increased but the rationales' theoretical perspective had little impact. More negative baseline ET views, specific ethnic/racial minority group status, and lower education moderated or predicted greater increases in treatment credibility following the rationale. ET remains relatively unknown as a treatment for anxiety or trauma, supporting the need for direct-to-consumer marketing. Diverse theory-driven rationales similarly increased ET credibility, particularly among those less likely to use ET. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rationales for the Lightning Launch Commit Criteria

NASA Technical Reports Server (NTRS)

Willett, John C. (Editor); Merceret, Francis J. (Editor); Krider, E. Philip; O'Brien, T. Paul; Dye, James E.; Walterscheid, Richard L.; Stolzenburg, Maribeth; Cummins, Kenneth; Christian, Hugh J.; Madura, John T.

2016-01-01

Since natural and triggered lightning are demonstrated hazards to launch vehicles, payloads, and spacecraft, NASA and the Department of Defense (DoD) follow the Lightning Launch Commit Criteria (LLCC) for launches from Federal Ranges. The LLCC were developed to prevent future instances of a rocket intercepting natural lightning or triggering a lightning flash during launch from a Federal Range. NASA and DoD utilize the Lightning Advisory Panel (LAP) to establish and develop robust rationale from which the criteria originate. The rationale document also contains appendices that provide additional scientific background, including detailed descriptions of the theory and observations behind the rationales. The LLCC in whole or part are used across the globe due to the rigor of the documented criteria and associated rationale. The Federal Aviation Administration (FAA) adopted the LLCC in 2006 for commercial space transportation and the criteria were codified in the FAA's Code of Federal Regulations (CFR) for Safety of an Expendable Launch Vehicle (Appendix G to 14 CFR Part 417, (G417)) and renamed Lightning Flight Commit Criteria in G417.

Effects of prandial challenge on triglyceridemia, glycemia, and pro-inflammatory activity in persons with chronic paraplegia

PubMed Central

Ellenbroek, Dennis; Kressler, Jochen; Cowan, Rachel E.; Burns, Patricia A.; Mendez, Armando J.; Nash, Mark S.

2015-01-01

Context/Objective Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. Design Descriptive trial. Methods Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points −30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. Results Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. Conclusions Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard. PMID:24617559

Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy

PubMed Central

Klebe, Stephan; Depienne, Christel; Gerber, Sylvie; Challe, Georges; Anheim, Mathieu; Charles, Perrine; Fedirko, Estelle; Lejeune, Elodie; Cottineau, Julien; Brusco, Alfredo; Dollfus, Hélène; Chinnery, Patrick F.; Mancini, Cecilia; Ferrer, Xavier; Sole, Guilhem; Destée, Alain; Mayer, Jean-Michel; Fontaine, Bertrand; de Seze, Jérôme; Clanet, Michel; Ollagnon, Elisabeth; Busson, Philippe; Cazeneuve, Cécile; Stevanin, Giovanni; Kaplan, Josseline; Rozet, Jean-Michel; Brice, Alexis

2012-01-01

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18–52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower

A novel mutation in KIF5A in a Malian family with spastic paraplegia and sensory loss.

PubMed

Guinto, Cheick O; Diarra, Salimata; Diallo, Salimata; Cissé, Lassana; Coulibaly, Thomas; Diallo, Seybou H; Taméga, Abdoulaye; Chen, Ke-Lian; Schindler, Alice B; Bagayoko, Koumba; Simaga, Assiatou; Blackstone, Craig; Fischbeck, Kenneth H; Landouré, Guida

2017-04-01

Hereditary spastic paraplegias (HSPs) are well-characterized disorders but rarely reported in Africa. We evaluated a Malian family in which three individuals had HSP and distal muscle atrophy and sensory loss. HSP panel testing identified a novel heterozygous missense mutation in KIF5A (c.1086G>C, p.Lys362Asn) that segregated with the disease (SPG10). Lys362 is highly conserved across species and Lys362Asn is predicted to be damaging. This study shows that HSPs are present in sub-Saharan Africa, although likely underdiagnosed. Increasing efficiency and decreasing costs of DNA sequencing will make it more feasible to diagnose HSPs in developing countries.

Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms

PubMed Central

Julien, Carl; Lissouba, Alexandra; Madabattula, Surya; Fardghassemi, Yasmin; Rosenfelt, Cory; Androschuk, Alaura; Strautman, Joel; Wong, Clement; Bysice, Andrew; O'sullivan, Julia; Rouleau, Guy A.; Drapeau, Pierre; Parker, J. Alex; Bolduc, François V.

2016-01-01

Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases causing progressive gait dysfunction. Over 50 genes have now been associated with HSP. Despite the recent explosion in genetic knowledge, HSP remains without pharmacological treatment. Loss-of-function mutation of the SPAST gene, also known as SPG4, is the most common cause of HSP in patients. SPAST is conserved across animal species and regulates microtubule dynamics. Recent studies have shown that it also modulates endoplasmic reticulum (ER) stress. Here, utilizing null SPAST homologues in C. elegans, Drosophila and zebrafish, we tested FDA-approved compounds known to modulate ER stress in order to ameliorate locomotor phenotypes associated with HSP. We found that locomotor defects found in all of our spastin models could be partially rescued by phenazine, methylene blue, N-acetyl-cysteine, guanabenz and salubrinal. In addition, we show that established biomarkers of ER stress levels correlated with improved locomotor activity upon treatment across model organisms. Our results provide insights into biomarkers and novel therapeutic avenues for HSP. PMID:26744324

A Hereditary Spastic Paraplegia Mouse Model Supports a Role of ZFYVE26/SPASTIZIN for the Endolysosomal System

PubMed Central

Khundadze, Mukhran; Kollmann, Katrin; Koch, Nicole; Biskup, Christoph; Nietzsche, Sandor; Zimmer, Geraldine; Hennings, J. Christopher; Huebner, Antje K.; Symmank, Judit; Jahic, Amir; Ilina, Elena I.; Karle, Kathrin; Schöls, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hübner, Christian A.

2013-01-01

Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells. PMID:24367272

A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system.

PubMed

Khundadze, Mukhran; Kollmann, Katrin; Koch, Nicole; Biskup, Christoph; Nietzsche, Sandor; Zimmer, Geraldine; Hennings, J Christopher; Huebner, Antje K; Symmank, Judit; Jahic, Amir; Ilina, Elena I; Karle, Kathrin; Schöls, Ludger; Kessels, Michael; Braulke, Thomas; Qualmann, Britta; Kurth, Ingo; Beetz, Christian; Hübner, Christian A

2013-01-01

Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells.

Physical therapists' perceptions about patients with incomplete post-traumatic paraplegia adherence to recommended home exercises: a qualitative study.

PubMed

Serpanou, Ismini; Sakellari, Evanthia; Psychogiou, Maria; Zyga, Sofia; Sapountzi-Krepia, Despina

2018-06-08

The overall purpose of physical therapy for patients with spinal cord injury is to improve health-related quality of life. However, poor adherence is a problem in physical therapy and may have negative impact on outcomes. To explore the physical therapists' perspectives about patients with incomplete post-traumatic paraplegia adherence to recommended home exercises. A qualitative content analysis was conducted. Data were collected in a convenience sample using semi-structured interviews. Thirteen registered physical therapists in Athens area participated in the study. Five categories emerged from the data: (1) reasons to recommend home exercise by the physical therapist; (2) obstacles to recommend home exercise by the physical therapist; (3) methods addressing these obstacles; (4) the family's role in the adherence to recommended home exercise; and (5) the impact of financial crisis in adherence to recommended home exercise. All participants found the recommended home exercises essential to rehabilitation and health maintenance, and they value their benefits. They also expressed the obstacles that need to be faced during rehabilitation process in order to promote adherence. Physical therapists should take into account the different obstacles that may prevent patients with incomplete post-traumatic paraplegia adherence to recommended home exercises. These involve the patients and their families, while, financial crisis has also an impact in adherence. In order to overcome these obstacles and increase adherence, communication with patient and family while taking into account the individual's needs, capacities, and resources are essential. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

A non-randomised, controlled clinical trial of an innovative device for negative pressure wound therapy of pressure ulcers in traumatic paraplegia patients.

PubMed

Srivastava, Rajeshwar N; Dwivedi, Mukesh K; Bhagat, Amit K; Raj, Saloni; Agarwal, Rajiv; Chandra, Abhijit

2016-06-01

The conventional methods of treatment of pressure ulcers (PUs) by serial debridement and daily dressings require prolonged hospitalisation, associated with considerable morbidity. There is, however, recent evidence to suggest that negative pressure wound therapy (NPWT) accelerates healing. The commercial devices for NPWT are costly, cumbersome, and electricity dependent. We compared PU wound healing in traumatic paraplegia patients by conventional dressing and by an innovative negative pressure device (NPD). In this prospective, non-randomised trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were recruited. Patients were divided into two groups: group A (n = 24) received NPWT with our NPD, and group B (n = 24) received conventional methods of dressing. All patients were followed up for 9 weeks. At week 9, all patients on NPD showed a statistically significant improvement in PU healing in terms of slough clearance, granulation tissue formation, wound discharge and culture. A significant reduction in wound size and ulcer depth was observed in NPD as compared with conventional methods at all follow-up time points (P = 0·0001). NPWT by the innovative device heals PUs at a significantly higher rate than conventional treatment. The device is safe, easy to apply and cost-effective. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

An Examination on the Chinese Students' Rationales to Receive Their Higher Education in the U.S.

ERIC Educational Resources Information Center

Chao, Chiang-Nan

2017-01-01

This research attempts to explore the rationales why so many Chinese students choose to study abroad and why the United States is their preferred destination. This population is small, but a vital component of university life at many colleges and a much needed source of financial revenue. A total of 380 students completed a questionnaire yielding…

An anthology: Rationale for a US ballistic missile defense (1969 - 1984)

NASA Astrophysics Data System (ADS)

Tircuit, E. C.

1985-04-01

This anthology is a selection and short synopsis of representative articles on the rationale for a US ballistic missile defense (BMD). Unclassified articles and documents were reviewed and analyzed to identify and include nine representative articles in the anthology. The anthology reduces the search for quality material on the subject and documents the fundamental rationale for a BMD. The author concluded that the fundamental rationale for a US BMD is to deter nuclear war. In addition, specific rationale for a US BMD is provided in the anthology. Finally, an extensive bibliography is included in the anthology to enhance further research on the subject.

Anterior spinal artery syndrome. Paraplegia following segmental ischaemic injury to the spinal cord after oesophagectomy.

PubMed

Djurberg, H; Haddad, M

1995-04-01

A case of unexpected paraplegia after oesophageal resection under general anaesthesia combined with epidural analgesia and intra-operative intercostal block is described. Patients with compromised cardiovascular and respiratory function undergoing thoracic or major abdominal surgery can benefit significantly intra-operatively from a combination of general anaesthesia and regional analgesia. The continued use of regional analgesia into the postoperative period offers even more advantages. General anaesthesia administered before regional analgesia may, however, mask complications related to the regional technique and delay the instigation of corrective measures. The blood supply to the anterior part of the spinal cord, through the artery of Adamkiewicz, may be impaired intra-operatively leading to neurological sequelae known as the anterior spinal artery syndrome, characterised by loss of motor function with intact or partially intact sensory function. Patients at risk of developing the syndrome can be identified pre-operatively.

Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

PubMed

Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

2018-05-02

Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

Vertebral osteomyelitis and epidural abscess caused by gas gangrene presenting with complete paraplegia: a case report.

PubMed

Akagawa, Manabu; Kobayashi, Takashi; Miyakoshi, Naohisa; Abe, Eiji; Abe, Toshiki; Kikuchi, Kazuma; Shimada, Yoichi

2015-04-11

Gas gangrene is most often caused by Clostridium perfringens infection. Gas gangrene is a medical emergency that develops suddenly. The mortality rate is higher with trunk involvement than with involvement of the extremities, which carries a better prognosis. With respect to vertebral involvement, there are few reports in the literature. The purpose of this paper is to report a very rare case of vertebral osteomyelitis caused by gas gangrene. A 78-year-old Japanese woman with diabetes mellitus was admitted to our hospital with the chief complaints of back pain, dysuria, and complete paralysis of both legs. A computed tomography scan showed soft tissue swelling anterolaterally at intervertebral disc level T11/12 and a gas-containing epidural abscess that compressed her spinal cord. Cultures later grew Clostridium perfringens and Escherichia coli. Hemilaminectomy was done from T10 to T12, and an epidural abscess was removed. She went on to have fusion surgery 6 weeks after the initial operation and subsequently experienced complete pain relief. She was discharged 2 months later, at which time she was able to walk with a cane. Examination 18 months after surgery showed normal gait without a cane. Discitis caused by gas gangrene infection was successfully treated by immediate debridement and subsequent fusion surgery.

Cannabinoids for spasticity due to multiple sclerosis or paraplegia: A systematic review and meta-analysis of randomized clinical trials.

PubMed

da Rovare, Victoria P; Magalhães, Gabriel P A; Jardini, Guilherme D A; Beraldo, Matheus L; Gameiro, Mariel O; Agarwal, Arnav; Luvizutto, Gustavo José; Paula-Ramos, Lucas; Camargo, Samira Esteves Afonso; de Oliveira, Luciane Dias; Bazan, Rodrigo; El Dib, Regina

2017-10-01

Spasticity remains highly prevalent in patients with spinal cord injury and multiple sclerosis. To summarize the effects of cannabinoids compared with usual care, placebo for spasticity due to multiple sclerosis (MS) or paraplegia. Searches of MEDLINE, EMBASE, CENTRAL and LILACS to March 2017 were performed to identify randomized controlled trials. The primary outcomes were spasticity and spasm frequency. The criteria were any patient with MS and spasticity affecting upper or lower limbs or both, and that had a confirmed diagnosis of MS based on validated criteria, or however defined by the authors of the included studies. 16 trials including 2597 patients were eligible. Moderate-certainty evidence suggested a non-statistically significant decrease in spasticity (standardized mean difference (SMD) 0.36 [confidential interval (CI) 95% -0.17 to 0.88; p=0.18; I2=88%]), and spasm frequency (SMD 0.04 [CI 95% -0.15 to 0.22]). There was an increase in adverse events such as dizziness (risk ratio (RR) 3.45 [CI 95% 2.71-4.4; p=0.20; I2=23%]), somnolence (RR 2.9 [CI 95% 1.98-4.23; p=0.77; I2=0%]), and nausea (RR 2.25 [CI 95% 1.62-3.13; p=0.83; I2=0%]). There is moderate certainty evidence regarding the impact of cannabinoids in spasticity (average 0.36 more spasticity; 0.17 fewer to 0.88 more) due to multiple sclerosis or paraplegia, and in adverse events such as dizziness (419 more dizziness/1000 over 19 weeks), somnolence (127 more somnolence/1000 over 19 weeks), and nausea (125 more somnolence/1000 over 19 weeks). Copyright © 2017. Published by Elsevier Ltd.

Education about Aging: A Rationale.

ERIC Educational Resources Information Center

Wass, Hannelore; And Others

1981-01-01

Reviews studies on children's and adolescents' attitudes about aging. Analyzes media content such as children's literature, textbooks, and public television programs to determine how older persons are portrayed. Provides a rationale for systematic education about aging in the public schools. (Author)

Weight Bearing Over-ground Stepping in an Exoskeleton with Non-invasive Spinal Cord Neuromodulation after Motor Complete Paraplegia.

PubMed

Gad, Parag; Gerasimenko, Yury; Zdunowski, Sharon; Turner, Amanda; Sayenko, Dimitry; Lu, Daniel C; Edgerton, V Reggie

2017-01-01

We asked whether coordinated voluntary movement of the lower limbs could be regained in an individual having been completely paralyzed (>4 year) and completely absent of vision (>15 year) using two novel strategies-transcutaneous electrical spinal cord stimulation at selected sites over the spine as well as pharmacological neuromodulation by buspirone. We also asked whether these neuromodulatory strategies could facilitate stepping assisted by an exoskeleton (EKSO, EKSO Bionics, CA) that is designed so that the subject can voluntarily complement the work being performed by the exoskeleton. We found that spinal cord stimulation and drug enhanced the level of effort that the subject could generate while stepping in the exoskeleton. In addition, stimulation improved the coordination patterns of the lower limb muscles resulting in a more continuous, smooth stepping motion in the exoskeleton along with changes in autonomic functions including cardiovascular and thermoregulation. Based on these data from this case study it appears that there is considerable potential for positive synergistic effects after complete paralysis by combining the over-ground step training in an exoskeleton, combined with transcutaneous electrical spinal cord stimulation either without or with pharmacological modulation.

Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 4. Effect on physical self-concept and depression.

PubMed

Guest, R S; Klose, K J; Needham-Shropshire, B M; Jacobs, P L

1997-08-01

To determine whether persons with spinal cord injury (SCI) paraplegia who participated in an electrical stimulation walking program experienced changes in measures of physical self-concept and depression. Before-after trial. Human SCI applied research laboratory. Volunteer sample of 12 men and 3 women with SCI paraplegia, mean age 28.75 +/- 6.6yrs and mean duration of injury 3.8 +/- 3.2yrs. Thirty-two FNS ambulation training sessions using a commercially available system (Parastep 1). The hybrid system consists of a microprocessor-controlled stimulator and a modified walking frame with finger-operated switches that permit the user to control the stimulation parameters and activate the stepping. The Tennessee Self-Concept Scale (TSCS) and the Beck Depression Inventory (BDI) were administered before and after training. Only the Physical Self subscale of the TSCS was analyzed. After training, individual interviews were performed to assess participants' subjective reactions to the training program. A repeated measures analysis of variance indicated that desired directional and statistically significant changes occurred on the Physical Self subscale of the TSCS (F(1,14) = 8.54, p < .011) and on the BDI (F(1,14) = 5.42, p < .035). Subsequent to the ambulation training program there were statistically significant increases in physical self-concept scores and decreases in depression scores.

Rationale for Student Dress Codes: A Review of School Handbooks

ERIC Educational Resources Information Center

Freeburg, Elizabeth W.; Workman, Jane E.; Lentz-Hees, Elizabeth S.

2004-01-01

Through dress codes, schools establish rules governing student appearance. This study examined stated rationales for dress and appearance codes in secondary school handbooks; 182 handbooks were received. Of 150 handbooks containing a rationale, 117 related dress and appearance regulations to students' right to a non-disruptive educational…

Bioethics: A Rationale and a Model

ERIC Educational Resources Information Center

Barman, Charles R.; Rusch, John J.

1978-01-01

Discusses the rationale for and development of an undergraduate bioethics course. Based on experiences with the course, general suggestions are offered to instructors planning to add bioethics to existing curricula. (MA)

Shoulder Strength and Physical Activity Predictors of Shoulder Pain in People With Paraplegia From Spinal Injury: Prospective Cohort Study

PubMed Central

Hatchett, Patricia; Eberly, Valerie J.; Lighthall Haubert, Lisa; Conners, Sandy; Requejo, Philip S.

2015-01-01

Background Shoulder joint pain is a frequent secondary complaint for people following spinal cord injury (SCI). Objective The purpose of this study was to determine predictors of shoulder joint pain in people with paraplegia. Methods/Design A 3-year longitudinal study was conducted. Participants were people with paraplegia who used a manual wheelchair for at least 50% of their mobility and were asymptomatic for shoulder pain at study entry. Participants were classified as having developed shoulder pain if they experienced an increase of ≥10 points on the Wheelchair User's Shoulder Pain Index in the 3-year follow-up period. Measurements of maximal isometric shoulder torques were collected at study entry (baseline), 18 months, and 3 years. Daily activity was measured using a wheelchair odometer, and self-reported daily transfer and raise frequency data were collected by telephone every 6 weeks. Results Two hundred twenty-three participants were enrolled in the study; 39.8% developed shoulder pain over the 3-year follow-up period. Demographic variables and higher activity levels were not associated with shoulder pain onset. Baseline maximal isometric torque (normalized by body weight) in all shoulder muscle groups was 10% to 15% lower in participants who developed shoulder pain compared with those who remained pain-free. Lower shoulder adduction torque was a significant predictor of shoulder pain development (log-likelihood test=11.38), but the model explained only 7.5% of shoulder pain onset and consequently is of limited clinical utility. Limitations Time since SCI varied widely among participants, and transfer and raise activity was measured by participant recall. Conclusions Participants who developed shoulder pain had decreased muscle strength, particularly in the shoulder adductors, and lower levels of physical activity prior to the onset of shoulder pain. Neither factor was a strong predictor of shoulder pain onset. PMID:25721123

Ossified ligamentum flavum causing neurological deficit above the level of post-tuberculous kyphotic deformity.

PubMed

Subramani, Suresh; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Shanmuganathan, Rajasekaran

2017-01-01

Late onset paraplegia is a rare complication of spinal tuberculosis. Disease reactivation and cord compression by internal gibbus are the common causes for neurological deficit. We report a patient with post-tubercular kyphotic deformity in whom the late onset paraplegia is caused by ossified ligamentum flavum above the level of kyphotic deformity. The deficit was attributable to the ossified ligamentum flavum and she recovered completely following posterior decompression and instrumented posterolateral fusion. To the best of our knowledge, this is the first report of this unusual cause of late onset paraplegia.

"Socialized Music": Historical Formations of Community Music through Social Rationales

ERIC Educational Resources Information Center

Yerichuk, Deanna

2014-01-01

This article traces the formation of community music through professional and scholarly articles over the last century in North America, and argues that community music has been discursively formed through social rationales, although the specific rationales have shifted. The author employs an archaeological framework inspired by Michel Foucault to…

Late onset Pott's paraplegia in patients with upper thoracic sharp kyphosis.

PubMed

Zhang, Zhengfeng

2012-02-01

The purpose of this study was to determine the clinical results of patients with late onset upper thoracic sharp Pott's kyphosis and to predict the prognosis for Pott's paraplegics. The study included five patients who developed late onset upper thoracic (T1-T4) sharp Pott's kyphosis/kyphoscoliosis within a period from 19 to 37 years after the active disease was healed. The kyphosis angle of the patients ranged from 95° to 105°. Among them, three patients suffered onset of paraplegia ranging from 26 to 31 years after spinal tuberculosis was healed. The duration of neurological deterioration before surgery ranged from four to five years. All patients underwent decompressive surgery with an attempt to correct the curve. Neurological status was evaluated using the ASIA impairment classification and the motor score. Postoperatively, kyphosis correction ranged from 20° to 30° for five patients. No neurological deficit occurred in two patients with normal neurological status. Two ASIA D paraplegics remained unchanged after surgery and no further improvement was found at one year follow-up. One ASIA C paralysis deteriorated neurologically to ASIA B after surgery and persisted to a deterioration of neurological status at one year follow-up. Upper thoracic sharp Pott's kyphosis and neurological deficits occur progressively. The neurological recovery or improvement of Pott's paraplegics with upper thoracic severe sharp kyphosis results in poor prognosis after decompressive surgery.

Artificial gait in complete spinal cord injured subjects: how to assess clinical performance.

PubMed

Pithon, Karla Rocha; Abreu, Daniela Cristina Carvalho de; Vasconcelos-Neto, Renata; Martins, Luiz Eduardo Barreto; Cliquet, Alberto

2015-02-01

Adapt the 6 minutes walking test (6MWT) to artificial gait in complete spinal cord injured (SCI) patients aided by neuromuscular electrical stimulation. Nine male individuals with paraplegia (AIS A) participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96) explained 96% of the variation in the distance walked. The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance.

Recovery of supraspinal control of leg movement in a chronic complete flaccid paraplegic man after continuous low-frequency pelvic nerve stimulation and FES-assisted training

PubMed Central

Possover, Marc; Forman, Axel

2017-01-01

Introduction: More than 30 years ago, functional electrical stimulation (FES) was developed as an orthotic system to be used for rehabilitation for SCI patients. In the present case report, FES-assisted training was combined with continuous low-frequency stimulation of the pelvic somatic nerves in a SCI patient. Case Presentation: We report on unexpected findings in a 41-year-old man with chronic complete flaccid paraplegia, since he was 18 years old, who underwent spinal stem cell therapy and a laparoscopic implantation of neuroprosthesis (LION procedure) in the pelvic lumbosacral nerves. The patient had complete flaccid sensomotoric paraplegia T12 as a result of a motor vehicle accident in 1998. In June 2011, he underwent a laparoscopic implantation of stimulation electrodes to the sciatic and femoral nerves for continuous low-frequency electrical stimulation and functional electrical stimulation of the pelvic nerves. Neither intraoperative direct stimulation of the pelvic nerves nor postoperative stimulation induced any sensation or muscle reactions. After 2 years of passive continuous low-frequency stimulation, the patient developed progressive recovery of electrically assisted voluntary motor functions below the lesions: he was first able to extend the right knee and 6 months later, the left. He is currently capable of voluntary weight-bearing standing and walking (with voluntary knee movements) about 50 m with open cuff crutches and drop foot braces. Discussion: Our findings suggest that continuous low-frequency pelvic nerve stimulation in combination with FES-assisted training might induce changes that affect both the upper and the lower motor neuron and allow supra- and infra-spinal inputs to engage residual spinal and peripheral pathways. PMID:28503316

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

PubMed

Martino, G; Ivanenko, Y; Serrao, M; Ranavolo, A; Draicchio, F; Rinaldi, M; Casali, C; Lacquaniti, F

2018-03-01

A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

PubMed Central

Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

2015-01-01

We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

Moral and Instrumental Rationales for Affirmative Action in Five National Contexts

ERIC Educational Resources Information Center

Moses, Michele S.

2010-01-01

The author's primary aims are to clarify the differing rationales for affirmative action that have emerged in five nations--France, India, South Africa, the United States, and Brazil--and to make the case for the most compelling rationales, whether instrumentally or morally based. She examines the different social contexts surrounding the…

Attitudes towards Affirmative Action: Effects of Procedural Rationale and Candidates' Qualifications.

ERIC Educational Resources Information Center

Mann, Jeffrey A.; Fasolo, Peter M.

This study examined whether individuals in higher education who are exposed to a hiring rationale based on a diversity value (minority group differences are valuable and should be relevant criteria for employment decisions in higher education) will rate affirmative action as fairer than those exposed to a compensation rationale (minority status is…

SPG3A-linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism.

PubMed

Terada, Tatsuhiro; Kono, Satoshi; Ouchi, Yasuomi; Yoshida, Kenichi; Hamaya, Yasushi; Kanaoka, Shigeru; Miyajima, Hiroaki

2013-04-01

SPG3A-linked hereditary spastic paraplegia (HSP) is a rare autosomal dominant motor disorder caused by a mutation in the SPG3A gene, and is characterized by progressive motor weakness and spasticity in the lower limbs, without any other neurological abnormalities. SPG3A-linked HSP caused by a R239C mutation has been reported to present a pure phenotype confined to impairment of the corticospinal tract. However, there is still a debate about the etiology of this motor deficit with regard to whether it is peripheral or central. We herein report two patients who were heterozygous for a R239C mutation in the SPG3A gene. Two middle-aged Japanese sisters had been suffering from a pure phenotype of HSP since their childhood. Both patients had a significant decrease in glucose metabolism in the frontal cortex medially and dorsolaterally in a [(18)F]-fluorodeoxyglucose (FDG) positron emission photography (PET) study and low scores on the Frontal Assessment Battery. A real-time PCR analysis in normal subjects showed the frontal cortex to be the major location where SPG3A mRNA is expressed. The present finding that the frontal glucose hypometabolism was associated with frontal cognitive impairment indicates that widespread neuropathology associated with mutations in the SPG3A gene may be present more centrally than previously assumed.

Why Do Higher Education Institutions Internationalize? An Investigation of the Multilevel Determinants of Internationalization Rationales

ERIC Educational Resources Information Center

Seeber, Marco; Cattaneo, Mattia; Huisman, Jeroen; Paleari, Stefano

2016-01-01

In recent decades internationalization has risen to prominence in higher education institutions (HEIs). Scholars have identified several rationales for internationalization. There is however a lack of conceptual understanding and empirical evidence for which rationale(s) for internationalization are chosen by a given HEI and why. The goal of this…

Training for Corrections: Rationale and Techniques.

ERIC Educational Resources Information Center

Southern Illinois Univ., Carbondale. Center for the Study of Crime, Delinquency and Corrections.

A manual focuses on how to teach in inservice training programs for professional personnel in correctional agencies. A chapter on rationale discusses training objectives and curriculum. A second chapter covers learning environment, lesson plans, and learning problems. One, on teaching techniques, covers lecture, group discussion, case study,…

Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach.

PubMed

Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L; Shah, Veena R; Dave, Shruti D; Dixit, Satyajit B; Tiwari, Bharat B; Shah, Harda H

2016-01-01

Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 10(4)/μL and mean CD34+ of 0.35%, CD45-/90+ and CD45-/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs.

Forum: The Rise of International Large-Scale Assessments and Rationales for Participation

ERIC Educational Resources Information Center

Addey, Camilla; Sellar, Sam; Steiner-Khamsi, Gita; Lingard, Bob; Verger, Antoni

2017-01-01

This Forum discusses the significant growth of international large-scale assessments (ILSAs) since the mid-1990s. Addey and Sellar's contribution ("A Framework for Analysing the Multiple Rationales for Participating in International Large-Scale Assessments") outlines a framework of rationales for participating in ILSAs and examines the…

Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia.

PubMed

Bouhouche, A; Benomar, A; Bouslam, N; Chkili, T; Yahyaoui, M

2006-05-01

Mutilating sensory neuropathy with spastic paraplegia is a very rare disease with both autosomal dominant and recessive modes of inheritance. We previously mapped the locus of the autosomal recessive form to a 25 cM interval between markers D5S2048 and D5S648 on chromosome 5p. In this candidate interval, the Cct5 gene encoding the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (CCT) was the most obvious candidate gene since mutation in the Cct4 gene encoding the CCT delta subunit has been reported to be associated with autosomal recessive mutilating sensory neuropathy in mutilated foot (mf) rat mutant. A consanguineous Moroccan family with four patients displaying mutilating sensory neuropathy associated with spastic paraplegia was investigated. To identify the disease causing gene, the 11 coding exons of the Cct5 gene were screened for mutations by direct sequencing in all family members including the four patients, parents, and six at risk relatives. Sequence analysis of the Cct5 gene revealed a missense A492G mutation in exon 4 that results in the substitution of a highly conserved histidine for arginine amino acid 147. Interestingly, R147 was absent in 384 control matched chromosomes tested. This is the first disease causing mutation that has been identified in the human CCT subunit genes; the mf rat mutant could serve as an animal model for studying these chaperonopathies.

A Rationale for Building a Comprehensive Science Program for Inner-City Education.

ERIC Educational Resources Information Center

Martin, Charles Arthur

The intent of this dissertation was to develop a science curriculum from an inner-city perspective. Five units and a rationale for inner-city education are included. The units include both physical and biological science topics. The units are as follows: (1) Rationale for Building a Comprehensive Science Program for Inner-City Education; (2) With…

Clinical phenotype of hereditary spastic paraplegia due to KIF1C gene mutations across life span.

PubMed

Yücel-Yılmaz, Didem; Yücesan, Emrah; Yalnızoğlu, Dilek; Oğuz, Kader Karlı; Sağıroğlu, Mahmut Şamil; Özbek, Uğur; Serdaroğlu, Esra; Bilgiç, Başar; Erdem, Sevim; İşeri, Sibel Aylin Uğur; Hanağası, Haşmet; Gürvit, Hakan; Özgül, Rıza Köksal; Dursun, Ali

2018-06-01

Hereditary spastic paraplegias (HSPs) are a group of genetic disorders resulting in pyramidal tract impairment, predominantly in lower limbs. KIF1C gene has recently been identified as one of the genetic causes of HSP and associated with pure or complicated HSP. We present three patients with complicated HSP from two unrelated families, who had early onset progressive cerebellar signs and developed pyramidal tract signs during follow-up. Whole exome sequencing in these patients followed by segregation analysis identified novel truncating KIF1C mutations (c.463C> T; p.R155 ∗ and c.2478delA; p.Ala828Argfs ∗ 13). Neuroimaging findings showed cerebral and upper cervical spinal atrophy, bilateral symmetrical pyramidal tract involvement, and focal cerebral white matter lesions. Patients with KIF1C mutations may present with cerebellar signs and pyramidal findings may emerge later, therefore complicated HSP should be considered in the differential diagnosis of unidentified cases with cerebellar dysfunction. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[When a patient falls (asleep) and can't get up: conversion disorder - paraplegia following general anesthesia].

PubMed

Mason, Chawla LaToya

This case report describes the rare occurrence of paraplegia caused by conversion disorder in a woman who received general anesthesia for breast surgery. A 46-year-old healthy woman received general anesthesia for excision of a left breast fibroepithelial lesion. In the post-anesthesia care unit, she reported bilateral loss of both sensation and motor function below the knees. Physical signs and symptoms did not correlate with any anatomical or neurological patterns; imaging revealed no abnormalities. Psychiatric consultation was performed wherein familial stressor circumstances were identified, leading to diagnosis and management of conversion disorder. Conversion disorder is characterized by alteration of physical function due to expression of an underlying psychological ailment. Its diagnosis requires thorough evaluation including appropriate workup to exclude organic causes. The meshing together of anesthesiology and psychiatry - as demonstrated by this case report - offers an opportunity to highlight important information pertaining to the definition, diagnosis, and management of conversion disorder as it may be encountered in the postanesthesia recovery period. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

How might acupuncture work? A systematic review of physiologic rationales from clinical trials.

PubMed

Moffet, Howard H

2006-07-07

Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions.

Hereditary Spastic Paraplegia-Linked REEP1 Modulates ER-Mitochondria Contacts

PubMed Central

Lim, Youngshin; Cho, Il-Taeg; Schoel, Leah J.; Cho, Ginam; Golden, Jeffrey A.

2015-01-01

Objective Mutations in receptor expression enhancing protein 1 (REEP1) are associated with hereditary spastic paraplegias (HSPs). Although axonal degeneration is thought to be a predominant feature in HSP, the role of REEP1 mutations in degeneration is largely unknown. Previous studies have implicated a role for REEP1 in the ER, whereas others localized REEP1 with mitochondria. We sought to resolve the cellular localization of REEP1 and to further elucidate the pathobiology underlying REEP1 mutations in patients. Methods A combination of cellular imaging and biochemical approaches was used to refine the cellular localization of REEP1. Next, Reep1 mutations associated with HSP were functionally tested in neuritic growth and degeneration assays using mouse cortical culture. Finally, a novel assay was developed and used with wild type and mutant Reep1s to measure the interactions between the ER and mitochondria. Results We found that REEP1 is present at the ER-mitochondria interface, and it contains subdomains for mitochondrial as well as ER localization. Knockdown of Reep1 and the expression of pathological Reep1 mutations resulted in neuritic growth defects and degeneration. Finally, using our novel split-RLuc8 assay, we show REEP1 facilitates ER-mitochondria interactions, a function diminished by disease-associated mutations. Interpretation Our data potentially reconcile the current conflicting reports regarding REEP1 being either an ER or a mitochondrial protein. Furthermore, our results connect, for the first time, the disrupted ER-mitochondria interactions to a failure in maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a new tool to identify potential drugs for multiple neurodegenerative diseases with ER-mitochondria interaction defects. PMID:26201691

Supplement use in sport: is there a potentially dangerous incongruence between rationale and practice?

PubMed Central

Petróczi, Andrea; Naughton, Declan P

2007-01-01

Background Supplement use by athletes is complex and research supports the alarming notion of misinformed decisions regarding supplements. Hypothesis A frequent divergence between the type of supplements chosen by athletes and the rationale dictating the supplement use is hypothesized. Thus, a potentially dangerous incongruence may exist between rationale and practice. Testing the hypothesis In the continued absence of reliable data on supplement use, an alternative approach of studying the reasons underlying supplement use in athletes is proposed to determine whether there is an incongruence between rationale and practice. Existing data from large scale national surveys can be used to investigate this incongruence. Implications of the hypothesis In this report, analyses of distinctive patterns between the use and rationale for use of supplements among athletes are recommended to explore this potentially dangerous phenomenon. PMID:17535442

Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

PubMed Central

Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

2012-01-01

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait.

PubMed

Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

1997-03-01

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity.

Social Stories[TM]: A Possible Theoretical Rationale

ERIC Educational Resources Information Center

Reynhout, Georgina; Carter, Mark

2011-01-01

Social Stories[TM] are an intervention widely used with individuals with autism spectrum disorders (ASD). This paper discusses a possible theoretical rationale that might account for the purported efficacy of Social Stories[TM]. Attributes of individuals with ASD in relation to Social Story intervention including difficulties with theory of mind…

Adhesives: Test Method, Group Assignment, and Categorization Guide for High-Loading Rate Applications - History and Rationale

DTIC Science & Technology

2017-04-20

Categorization Guide for High -Loading- Rate Applications – History and Rationale by Robert Jensen, David Flanagan, Daniel DeSchepper, and Charles...Adhesives: Test Method, Group Assignment, and Categorization Guide for High -Loading- Rate Applications – History and Rationale by Robert Jensen...Categorization Guide for High - Loading-Rate Applications – History and Rationale 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic responses, and experiences.

PubMed

Accardi, Michelle; Cleere, Colleen; Lynn, Steven Jay; Kirsch, Irving

2013-10-01

In this study participants were provided with either the standard rationale that accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne, 1962) or a rationale that presented hypnosis as a nondeceptive placebo, consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The effects of the placebo and standard rationales were highly comparable with respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective, and involuntariness measures of hypnotic responding; as well as a variety of subjective experiences during hypnosis, as measured by the Phenomenology of Consciousness Inventory (Pekala, 1982). Differences among correlations were not evident when measures were compared across groups. However, indices of hypnotic responding were correlated with attitudes in the hypnosis but not the placebo condition, and, generally speaking, the link between subjective experiences during hypnosis and measures of hypnotic responding were more reliable in the placebo than the hypnosis group. Researcher findings are neutral with respect to providing support for altered state versus sociocognitive models of hypnosis.

Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.

PubMed

Peddareddygari, Leema Reddy; Hanna, Philip A; Igo, Robert P; Luo, Yuqun A; Won, Sungho; Hirano, Michio; Grewal, Raji P

2016-01-01

Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.

Burn from car seat heater in a man with paraplegia: case report

PubMed Central

Benjamin, Cheryl; Gittler, Michelle; Lee, Ray

2011-01-01

Objective/background Heated car seats are a common feature in newer automobiles. They are increasingly being recognized as potential hazards as there have been multiple reports of significant burns to its users. The potential for harm is considerably increased in those with impaired sensation with the possibility of a devastating injury. Methods Case report and literature review. Results A 26-year-old male with a T8 ASIA A paraplegia presented to the outpatient clinic for management of a hip burn. Two weeks prior to his visit he was driving a 2004 Jeep Cherokee for approximately 30 minutes. He was unaware that the driver's side seat warmer was set on high. He denied that his seat belt was in direct contact with the skin of his right hip. He presented to an acute care hospital that evening with a hip burn where he was prescribed silver sulfadiazine cream and instructed to apply it until his scheduled follow-up clinic visit. In clinic, the hip wound was unstageable with approximately 95% eschar. A dressing of bismuth tribromophenate in petrolatum was applied to the wound and he was instructed to change the dressing daily. This was later changed to an antimicrobial alginate dressing. The ulcer eventually healed. Conclusions This case illustrates the significant risk of car seat heaters in individuals with spinal cord injuries or neurological impairment who have decreased sensation. Additionally, it highlights an atypical area of potential for burn. Furthermore, it emphasizes the need for a heightened awareness for this unique and dangerous situation. PMID:21756574

Electrical treatment of spinal cord injuries in the 18th and 19th centuries.

PubMed

Silver, John R; Weiner, M-F

2013-05-01

Two centuries ago, electricity was being used for the treatment of paraplegia and trials were taking place in France. This study aims to identify cases of traumatic paraplegia treated with electricity in the 19th century in order to assess the therapeutic benefit. Only four such cases were identified, none with a complete transection of the spinal cord since these patients would have died from pressure sores and urinary tract infections. The personalities involved, William Gull, William Erb, Guillaume Duchenne and Cyril Henry Golding Bird are portrayed and contemporaneous views on electrotherapy analysed. While the four patients apparently benefited from the treatment, the lack of follow-up and the incomplete data prevented a definitive conclusion on the therapeutic value of electrical treatment in traumatic paraplegia.

Kinematic gait deficits at the trunk and pelvis: characteristic features in children with hereditary spastic paraplegia.

PubMed

Adair, Brooke; Rodda, Jillian; McGinley, Jennifer L; Graham, H Kerr; Morris, Meg E

2016-08-01

To examine the kinematic gait deviations at the trunk and pelvis of children with hereditary spastic paraplegia (HSP). This exploratory observational study quantified gait kinematics for the trunk and pelvis from 11 children with HSP (7 males, 4 females) using the Gait Profile Score and Gait Variable Scores (GVS), and compared the kinematics to data from children with typical development using a Mann-Whitney U test. Children with HSP (median age 11y 4mo, interquartile range 4y) demonstrated large deviations in the GVS for the trunk and pelvis in the sagittal and coronal planes when compared to the gait patterns of children with typical development (p=0.010-0.020). Specific deviations included increased range of movement for the trunk in the coronal plane and increased excursion of the trunk and pelvis in the sagittal plane. In the transverse plane, children with HSP demonstrated later peaks in posterior pelvic rotation. The kinematic gait deviations identified in this study raise questions about the contribution of muscle weakness in HSP. Further research is warranted to determine contributing factors for gait dysfunction in HSP, especially the relative influence of spasticity and weakness. © 2016 Mac Keith Press.

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12

PubMed Central

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

Teacher Grading Decisions: Influences, Rationale, and Practices

ERIC Educational Resources Information Center

Kunnath, Joshua P.

2017-01-01

This mixed-methods study applied a decision-making theoretical framework to an investigation of teacher grading in a large urban school district in California. A sample of 251 high school teachers of core subjects were surveyed, and 15 teachers participated in four focus group interviews in order provide data on the influences, rationale, and…

Learning Rationales and Virtual Reality Technology in Education.

ERIC Educational Resources Information Center

Chiou, Guey-Fa

1995-01-01

Defines and describes virtual reality technology and differentiates between virtual learning environment, learning material, and learning tools. Links learning rationales to virtual reality technology to pave conceptual foundations for application of virtual reality technology education. Constructivism, case-based learning, problem-based learning,…

Effects of Providing a Rationale for Learning a Lesson on Students' Motivation and Learning in Online Learning Environments

ERIC Educational Resources Information Center

Shin, Tae Seob

2010-01-01

This study examined whether providing a rationale for learning a particular lesson influences students' motivation and learning in online learning environments. A mixed-method design was used to investigate the effects of two types of rationales (former student vs. instructor rationales) presented in an online introductory educational psychology…

Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North Americanmore » kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.« less

Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morales, J. P.; Taylor, P. R.; Bell, R. E.

2007-09-15

Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, generalmore » in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.« less

Rationale and Roadmap for Moon Exploration

NASA Astrophysics Data System (ADS)

Foing, B. H.; ILEWG Team

We discuss the different rationale for Moon exploration. This starts with areas of scientific investigations: clues on the formation and evolution of rocky planets, accretion and bombardment in the inner solar system, comparative planetology processes (tectonic, volcanic, impact cratering, volatile delivery), records astrobiology, survival of organics; past, present and future life. The rationale includes also the advancement of instrumentation: Remote sensing miniaturised instruments; Surface geophysical and geochemistry package; Instrument deployment and robotic arm, nano-rover, sampling, drilling; Sample finder and collector. There are technologies in robotic and human exploration that are a drive for the creativity and economical competitivity of our industries: Mecha-electronics-sensors; Tele control, telepresence, virtual reality; Regional mobility rover; Autonomy and Navigation; Artificially intelligent robots, Complex systems, Man-Machine interface and performances. Moon-Mars Exploration can inspire solutions to global Earth sustained development: In-Situ Utilisation of resources; Establishment of permanent robotic infrastructures, Environmental protection aspects; Life sciences laboratories; Support to human exploration. We also report on the IAA Cosmic Study on Next Steps In Exploring Deep Space, and ongoing IAA Cosmic Studies, ILEWG/IMEWG ongoing activities, and we finally discuss possible roadmaps for robotic and human exploration, starting with the Moon-Mars missions for the coming decade, and building effectively on joint technology developments.

Duration and functional outcome of spinal cord injury rehabilitation in the Netherlands.

PubMed

Post, Marcel W M; Dallmeijer, Annet J; Angenot, Edmond L D; van Asbeck, Floris W A; van der Woude, Lucas H V

2005-01-01

This study describes the length of stay (LOS) and functional outcome of spinal cord injury (SCI) in the Netherlands and its determinants. Data of 157 patients from eight rehabilitation centers were available. Mean age was 40.0 years and 76.4% were traumatic injuries, 39.8% had tetraplegia, and 69.9% had a motor complete SCI. Median LOS was 240 days (interquartile range 164-322). Median motor Functional Independence Measure (FIM) scores at discharge were 37.3 for persons with complete tetraplegia and 69.7 for persons with complete paraplegia. Level and completeness of injury, bed rest because of pressure sores, and LOS were predictors of motor FIM scores. Duration of SCI rehabilitation in the Netherlands is long compared with the literature. Functional outcome appears slightly better in persons with complete tetraplegia, but not in persons with complete paraplegia when compared with data from the United States. International studies are necessary to reveal strengths and weaknesses of SCI rehabilitation systems in different countries.

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the

Invitation to the Birthday Party: Rationale and Description

ERIC Educational Resources Information Center

Ginsburg, Herbert P.; Pappas, Sandra

2016-01-01

Educators in many countries around the world have a strong interest in improving early childhood mathematics education, one component of which is formative assessment. Unlike summative assessment, this approach can provide teachers with information useful for understanding and teaching individual children. This paper describes the rationale for…

Modeling Axonal Defects in Hereditary Spastic Paraplegia with Human Pluripotent Stem Cells

PubMed Central

Denton, Kyle R.; Xu, Chongchong; Shah, Harsh; Li, Xue-Jun

2016-01-01

BACKGROUND Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor neuron axons is implicated in several debilitating disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Since the discovery of the first HSP gene, SPAST that encodes spastin, over 70 distinct genetic loci associated with HSP have been identified. How the mutations of these functionally diverse genes result in axonal degeneration and why certain axons are affected in HSP remains largely unknown. The development of induced pluripotent stem cell (iPSC) technology has provided researchers an excellent resource to generate patient-specific human neurons to model human neuropathologic processes including axonal defects. METHODS In this article, we will frst review the pathology and pathways affected in the common forms of HSP subtypes by searching the PubMed database. We will then summurize the findings and insights gained from studies using iPSC-based models, and discuss the challenges and future directions. RESULTS HSPs, a heterogeneous group of genetic neurodegenerative disorders, are characterized by lower extremity weakness and spasticity that result from retrograde axonal degeneration of cortical motor neurons. Recently, iPSCs have been generated from several common forms of HSP including SPG4, SPG3A, and SPG11 patients. Neurons derived from HSP iPSCs exhibit disease-relevant axonal defects, such as impaired neurite outgrowth, increased axonal swellings, and reduced axonal transport. CONCLUSION These patient-derived neurons offer unique tools to study the pathogenic mechanisms and explore the treatments for rescuing axonal defects in HSP, as well as other diseases involving axonopathy. PMID:27956894

Rationale of Early Adopters of Fossil Fuel Divestment

ERIC Educational Resources Information Center

Beer, Christopher Todd

2016-01-01

Purpose: This research uses the social science perspectives of institutions, ecological modernization and social movements to analyze the rationale used by the early-adopting universities of fossil fuel divestment in the USA. Design/methodology/approach: Through analysis of qualitative data from interviews with key actors at the universities that…

Structure, Citizenship, and Professionalism: Exploring Rationale Development as Part of Graduate Education in Social Studies

ERIC Educational Resources Information Center

Hawley, Todd S.; Pifel, A. Robert; Jordan, Adam W.

2012-01-01

This article details an interpretive, qualitative interview study that explored rationales developed by seven social studies graduate students, all experienced teachers, at a large Midwestern university. Interviews revealed three common themes regarding the influence of the rationale development process. The three themes were: providing structure,…

Pilot Aircraft Interface Objectives/Rationale

NASA Technical Reports Server (NTRS)

Shively, Jay

2010-01-01

Objective: Database and proof of concept for guidelines for GCS compliance a) Rationale: 1) Provide research test-bed to develop guidelines. 2) Modify GCS for NAS Compliance to provide proof of concept. b) Approach: 1) Assess current state of GCS technology. 2) Information Requirements Definition. 3) SME Workshop. 4) Modify an Existing GCS for NAS Compliance. 5) Define exemplar UAS (choose system to develop prototype). 6) Define Candidate Displays & Controls. 7) Evaluate/ refine in Simulations. 8) Demonstrate in flight. c) Deliverables: 1) Information Requirements Report. 2) Workshop Proceedings. 3) Technical Reports/ papers on Simulations & Flight Demo. 4) Database for guidelines.

Building "Applied Linguistic Historiography": Rationale, Scope, and Methods

ERIC Educational Resources Information Center

Smith, Richard

2016-01-01

In this article I argue for the establishment of "Applied Linguistic Historiography" (ALH), that is, a new domain of enquiry within applied linguistics involving a rigorous, scholarly, and self-reflexive approach to historical research. Considering issues of rationale, scope, and methods in turn, I provide reasons why ALH is needed and…

Logistic Approximation to the Normal: The KL Rationale

ERIC Educational Resources Information Center

Savalei, Victoria

2006-01-01

A rationale is proposed for approximating the normal distribution with a logistic distribution using a scaling constant based on minimizing the Kullback-Leibler (KL) information, that is, the expected amount of information available in a sample to distinguish between two competing distributions using a likelihood ratio (LR) test, assuming one of…

Oral Health Promotion in Schools: Rationale and Evaluation

ERIC Educational Resources Information Center

Kizito, Alex; Caitlin, Meredith; Wang, Yili; Kasangaki, Arabat; Macnab, Andrew J.

2014-01-01

Purpose: The purpose of this paper is to explain the rationale and potential for the WHO health promoting schools (HPS) to improve children's oral health, and describe validated quantitative methodologies and qualitative approaches to measure program impact. Design/Methodology/Approach: Critical discussion of the impact of poor oral health and…

Novel Compound Heterozygous Spatacsin Mutations in a Greek Kindred with Hereditary Spastic Paraplegia SPG11 and Dementia.

PubMed

Fraidakis, Matthew J; Brunetti, Maura; Blackstone, Craig; Filippi, Massimo; Chiò, Adriano

2016-01-01

SPG11 belongs to the autosomal recessive hereditary spastic paraplegias (HSP) and presents during childhood or puberty with a complex clinical phenotype encompassing learning difficulties, ataxia, peripheral neuropathy, amyotrophy, and mental retardation. We hereby present the case of a 30-year-old female patient with complex autosomal recessive HSP with thinning of the corpus callosum (TCC) and dementia that was compound heterozygous with two novel mutations in the SPG11 gene. Sequence analysis of the SPG11 gene revealed two novel mutations in a compound heterozygous state in the index patient (c.2431C>T/p.Gln811Ter and c.6755_6756insT/p.Glu2252Aspfs*88). MRI showed abnormal TCC, white matter (WM) hyperintensities periventricularly, and the 'ears of the lynx' sign. Diffusion tensor imaging showed a mild-to-moderate decrease in fractional anisotropy and an increase in mean diffusivity in WM compared to age-matched controls, while magnetic resonance spectroscopy showed abnormal findings in affected WM with a decrease in N-acetyl-aspartate in WM regions of interest. This is the first SPG11 kindred from the Greek population to be reported in the medical literature. © 2016 S. Karger AG, Basel.

Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.

PubMed

Orlacchio, A; Patrono, C; Gaudiello, F; Rocchi, C; Moschella, V; Floris, R; Bernardi, G; Kawarai, T

2008-05-20

To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.

"ComPost": A Writing Program Newsletter and Its Rationale.

ERIC Educational Resources Information Center

Hall, Dennis R.

1993-01-01

Discusses the development and rationale of "ComPost," a weekly newsletter of the Composition Program at the University of Louisville. Suggests that a vehicle like ComPost can promote the communications that contribute to accomplishing collegiality and genuine program consensus. (RS)

Soft Power as a Policy Rationale for International Education in the UK: A Critical Analysis

ERIC Educational Resources Information Center

Lomer, Sylvie

2017-01-01

This article presents the results of a textual analysis conducted on policy discourses on international students in the UK between 1999 and 2013. A number of rationales for and against increasing their numbers have been made, which have largely remained consistent over changing political administrations. One key rationale is that international…

Market Failures and the Rationale for National Parks.

ERIC Educational Resources Information Center

Turner, Robert W.

2002-01-01

Discusses how market failures can, in principle, be used to justify national parks. States the best rationale is based on existence or nonuse values instead of the recreational aspects. Shows more evidence (costs of providing and operating the parks and the magnitude of nonuse values) is needed before the case becomes compelling. (JEH)

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing

PubMed Central

Lynch, David S; Koutsis, Georgios; Tucci, Arianna; Panas, Marios; Baklou, Markella; Breza, Marianthi; Karadima, Georgia; Houlden, Henry

2016-01-01

Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients. PMID:26374131

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing.

PubMed

Lynch, David S; Koutsis, Georgios; Tucci, Arianna; Panas, Marios; Baklou, Markella; Breza, Marianthi; Karadima, Georgia; Houlden, Henry

2016-06-01

Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients.

Documenting the rationale and psychometric characteristics of patient reported outcomes for labeling and promotional claims: the PRO Evidence Dossier.

PubMed

Revicki, Dennis A; Gnanasakthy, Ari; Weinfurt, Kevin

2007-05-01

The Food and Drug Administration (FDA) and European Medicines Agency (EMEA) are willing to consider including information on patient reported outcomes (PROs) in product labeling and advertising. Pharmaceutical industry researchers must provide sufficient evidence supporting PRO benefit before an approval may be granted. This report describes the purpose and content of a PRO Evidence Dossier, which consists of important information supporting PRO claims. The dossier should be completed by pharmaceutical industry or other researchers to document the planning of the PRO assessment strategy, psychometric evidence, desired target labeling statements, and the clinical trial evidence of PRO benefits. The systematic reporting and documentation of information on the rationale for including PROs, rationale for the selection of specific PRO instruments, evidence on the psychometric qualities of the PRO measures, and guidelines for interpreting PRO findings will facilitate achieving a PRO labeling or promotional claim. Combining all the relevant information into a single document will facilitate the review and evaluation process for clinical and regulatory reviewers. The PRO Evidence Dossier may also be helpful to industry and academic researchers in identifying further information that will need to be developed to support the clinical development program and the PRO endpoints.

What Is Implementation Research? Rationale, Concepts, and Practices

ERIC Educational Resources Information Center

Bhattacharyya, Onil; Reeves, Scott; Zwarenstein, Merrick

2009-01-01

Despite the growing knowledge base on evidence-based practices in social work and medicine, there is a large gap between what is known and what is consistently done. Implementation research is the study of methods to promote the uptake of research findings into routine practice. In this article, we describe the rationale for implementation…

Constructing a Theory- and Evidence-Based Treatment Rationale for Complex eHealth Interventions: Development of an Online Alcohol Intervention Using an Intervention Mapping Approach.

PubMed

Brendryen, Håvar; Johansen, Ayna; Nesvåg, Sverre; Kok, Gerjo; Duckert, Fanny

2013-01-23

rationale for Balance, the alcohol intervention reported herein, provides an intervention blueprint that will aid in interpreting the results from future program evaluations. It will ease comparisons of program rationales across interventions, and may assist intervention development. By putting just-in-time therapy within a complete theoretical and practical context, including the tunnel delivery strategy and the self-regulation perspective, we have contributed to an understanding of how multiple delivery strategies in eHealth interventions can be combined. Additionally, this is a call for action to improve the reporting practices within eHealth research. Possible ways to achieve such improvement include using a systematic and structured approach, and for intervention reports to be published after peer-review and separately from evaluation reports.

Constructing a Theory- and Evidence-Based Treatment Rationale for Complex eHealth Interventions: Development of an Online Alcohol Intervention Using an Intervention Mapping Approach

PubMed Central

Johansen, Ayna; Nesvåg, Sverre; Kok, Gerjo; Duckert, Fanny

2013-01-01

. Conclusions The descriptions of the treatment rationale for Balance, the alcohol intervention reported herein, provides an intervention blueprint that will aid in interpreting the results from future program evaluations. It will ease comparisons of program rationales across interventions, and may assist intervention development. By putting just-in-time therapy within a complete theoretical and practical context, including the tunnel delivery strategy and the self-regulation perspective, we have contributed to an understanding of how multiple delivery strategies in eHealth interventions can be combined. Additionally, this is a call for action to improve the reporting practices within eHealth research. Possible ways to achieve such improvement include using a systematic and structured approach, and for intervention reports to be published after peer-review and separately from evaluation reports. PMID:23612478

Stanton's "The Solitude of Self": A Rationale for Feminism.

ERIC Educational Resources Information Center

Campbell, Karlyn Kohrs

1980-01-01

Examines Elizabeth Cady Stanton's speech, "The Solitude of Self," as a philosophical statement of the principles underlying the nineteenth century struggle for woman's rights in the United States. Analyzes the lyric structure and tone of the speech and its tragic, existential rationale for feminism. (JMF)

Data book: Space station/base food system study. Book 3: Study selection rationale sheets

NASA Technical Reports Server (NTRS)

1970-01-01

The supporting rationale sheets are presented which were utilized in the selection and support of the concepts considered in the final phase of the study. Each concept, conceived to fulfill a specific function of the food system, was assessed in terms of the eight critical factors depicted on the rationale sheet. When weighted and totaled, the resulting selection factor was used as a guide in making the final decision.

A beginner's guide to writing the nursing conceptual model-based theoretical rationale.

PubMed

Gigliotti, Eileen; Manister, Nancy N

2012-10-01

Writing the theoretical rationale for a study can be a daunting prospect for novice researchers. Nursing's conceptual models provide excellent frameworks for placement of study variables, but moving from the very abstract concepts of the nursing model to the less abstract concepts of the study variables is difficult. Similar to the five-paragraph essay used by writing teachers to assist beginning writers to construct a logical thesis, the authors of this column present guidelines that beginners can follow to construct their theoretical rationale. This guide can be used with any nursing conceptual model but Neuman's model was chosen here as the exemplar.

Rationale for Incorporating Health and Safety into the Curriculum.

ERIC Educational Resources Information Center

Fleischman, Marvin

1988-01-01

Presents a philosophical commentary on the need and rationale for incorporating safety and health into the chemical engineering curriculum. Proposes safety and health assessments as useful teaching methods. Describes an approach to bringing safety and health into undergraduate engineering curricula. Gives examples of integration of these curricula…

Case-Based Capture and Reuse of Aerospace Design Rationale

NASA Technical Reports Server (NTRS)

Leake, David B.

2001-01-01

The goal of this project was to apply artificial intelligence techniques to facilitate capture and reuse of aerospace design rationale. The project combined case-based reasoning (CBR) and concept maps (CMaps) to develop methods for capturing, organizing, and interactively accessing records of experiences encapsulating the methods and rationale underlying expert aerospace design, in order to bring the captured knowledge to bear to support future reasoning. The project's results contribute both principles and methods for effective design-aiding systems that aid capture and access of useful design knowledge. The project has been guided by the tenets that design-aiding systems must: (1) Leverage a designer's knowledge, rather than attempting to replace it; (2) Be able to reflect different designers' differing conceptualizations of the design task, and to clarify those conceptualizations to others; (3) Include capabilities to capture information both by interactive knowledge modeling and during normal use; and (4) Integrate into normal designer tasks as naturally and unobtrusive as possible.

Instilling positive beliefs about disabilities: pilot testing a novel experiential learning activity for rehabilitation students.

PubMed

Silverman, Arielle M; Pitonyak, Jennifer S; Nelson, Ian K; Matsuda, Patricia N; Kartin, Deborah; Molton, Ivan R

2018-05-01

To develop and test a novel impairment simulation activity to teach beginning rehabilitation students how people adapt to physical impairments. Masters of Occupational Therapy students (n = 14) and Doctor of Physical Therapy students (n = 18) completed the study during the first month of their program. Students were randomized to the experimental or control learning activity. Experimental students learned to perform simple tasks while simulating paraplegia and hemiplegia. Control students viewed videos of others completing tasks with these impairments. Before and after the learning activities, all students estimated average self-perceived health, life satisfaction, and depression ratings among people with paraplegia and hemiplegia. Experimental students increased their estimates of self-perceived health, and decreased their estimates of depression rates, among people with paraplegia and hemiplegia after the learning activity. The control activity had no effect on these estimates. Impairment simulation can be an effective way to teach rehabilitation students about the adaptations that people make to physical impairments. Positive impairment simulations should allow students to experience success in completing activities of daily living with impairments. Impairment simulation is complementary to other pedagogical methods, such as simulated clinical encounters using standardized patients. Implication of Rehabilitation It is important for rehabilitation students to learn how people live well with disabilities. Impairment simulations can improve students' assessments of quality of life with disabilities. To be beneficial, impairment simulations must include guided exposure to effective methods for completing daily tasks with disabilities.

Talent Search: Purposes, Rationale, and Role in Gifted Education.

ERIC Educational Resources Information Center

Olszewski-Kubilius, Paula

1998-01-01

This paper describes the purpose and rationale of a "talent search" effort to identify gifted students through use of off-level testing. Three components are stressed: diagnosis and evaluation of domains and levels of talent; educational placement and guidance; and talent development opportunities. Research supporting the talent-search…

Treating alcoholism through a narrative approach. Case study and rationale.

PubMed Central

Kaminsky, D.; Rabinowitz, S.; Kasan, R.

1996-01-01

A case study illustrates the narrative or story-telling approach to treating alcoholism. We discuss the rationale for this method and describe how it could be useful in family practice for treating people with alcohol problems. PMID:8653035

Mobility Outcomes Following Five Training Sessions with a Powered Exoskeleton

PubMed Central

Hartigan, Clare; Kandilakis, Casey; Dalley, Skyler; Clausen, Mike; Wilson, Edgar; Morrison, Scott; Etheridge, Steven

2015-01-01

Background: Loss of legged mobility due to spinal cord injury (SCI) is associated with multiple physiological and psychological impacts. Powered exoskeletons offer the possibility of regained mobility and reversal or prevention of the secondary effects associated with immobility. Objective: This study was conducted to evaluate mobility outcomes for individuals with SCI after 5 gait-training sessions with a powered exoskeleton, with a primary goal of characterizing the ease of learning and usability of the system. Methods: Sixteen subjects with SCI were enrolled in a pilot clinical trial at Shepherd Center, Atlanta, Georgia, with injury levels ranging from C5 complete to L1 incomplete. An investigational Indego exoskeleton research kit was evaluated for ease of use and efficacy in providing legged mobility. Outcome measures of the study included the 10-meter walk test (10MWT) and the 6-minute walk test (6MWT) as well as measures of independence including donning and doffing times and the ability to walk on various surfaces. Results: At the end of 5 sessions (1.5 hours per session), average walking speed was 0.22 m/s for persons with C5-6 motor complete tetraplegia, 0.26 m/s for T1-8 motor complete paraplegia, and 0.45 m/s for T9-L1 paraplegia. Distances covered in 6 minutes averaged 64 meters for those with C5-6, 74 meters for T1-8, and 121 meters for T9-L1. Additionally, all participants were able to walk on both indoor and outdoor surfaces. Conclusions: Results after only 5 sessions suggest that persons with tetraplegia and paraplegia learn to use the Indego exoskeleton quickly and can manage a variety of surfaces. Walking speeds and distances achieved also indicate that some individuals with paraplegia can quickly become limited community ambulators using this system. PMID:26364278

Case-Based Capture and Reuse of Aerospace Design Rationale

NASA Technical Reports Server (NTRS)

Leake, David B.

1998-01-01

The goal of this project is to apply artificial intelligence techniques to facilitate capture and reuse of aerospace design rationale. The project applies case-based reasoning (CBR) and concept mapping (CMAP) tools to the task of capturing, organizing, and interactively accessing experiences or "cases" encapsulating the methods and rationale underlying expert aerospace design. As stipulated in the award, Indiana University and Ames personnel are collaborating on performance of research and determining the direction of research, to assure that the project focuses on high-value tasks. In the first five months of the project, we have made two visits to Ames Research Center to consult with our NASA collaborators, to learn about the advanced aerospace design tools being developed there, and to identify specific needs for intelligent design support. These meetings identified a number of task areas for applying CBR and concept mapping technology. We jointly selected a first task area to focus on: Acquiring the convergence criteria that experts use to guide the selection of useful data from a set of numerical simulations of high-lift systems. During the first funding period, we developed two software systems. First, we have adapted a CBR system developed at Indiana University into a prototype case-based reasoning shell to capture and retrieve information about design experiences, with the sample task of capturing and reusing experts' intuitive criteria for determining convergence (work conducted at Indiana University). Second, we have also adapted and refined existing concept mapping tools that will be used to clarify and capture the rationale underlying those experiences, to facilitate understanding of the expert's reasoning and guide future reuse of captured information (work conducted at the University of West Florida). The tools we have developed are designed to be the basis for a general framework for facilitating tasks within systems developed by the Advanced Design

The Effects of Rationales, Differential Reinforcement, and a Guided Compliance Procedure to Increase Compliance among Preschool Children

ERIC Educational Resources Information Center

Wilder, David A.; Myers, Kristin; Nicholson, Katie; Allison, Janelle; Fischetti, Anthony T.

2012-01-01

Previous research suggests that rationales, or statements describing why a child should comply with a caregiver-delivered instruction, are ineffective at increasing compliance. In the current study, we compared the effects of rationales to a differential reinforcement procedure and a guided compliance procedure. The results indicated that…

A Psychological Rationale for Adventure Therapy with Hospitalized Adolescents.

ERIC Educational Resources Information Center

Gillis, H. L.; And Others

The purpose of this study was to examine the Wechsler Intelligence Scale for Children-Revised (WISC-R) profiles of two treatment populations and present a theoretical rationale for using adventure therapy. Data for the first group were obtained from the psychological testing records of 150 randomly selected inpatients (81 males, 69 females)…

Throwing Caution to the Wind: Rationales for Risky Behavior.

ERIC Educational Resources Information Center

de La Rue, Denise; Ruback, R. Barry

There appears to be a tendency for people who have not been victimized by negative life events to perceive themselves as less vulnerable to victimization than others. Research has revealed this unrealistic optimism in risk perception. A study on rationales for risky behaviors was conducted to identify reasons other than this illusion of…

Developing a Language Learning Rationale for African Language Tutorials.

ERIC Educational Resources Information Center

Dwyer, David

1999-01-01

Presents a rationale for the supervised tutorial component of the African language program at Michigan State University. The supervised tutorial is one of two modes through which African languages are offered at Michigan State University. The other, which is teacher led, is offered for high enrollment languages such as Arabic, Swahili, and Hausa.…

Introducing ICT in Schools in England: Rationale and Consequences

ERIC Educational Resources Information Center

Hammond, Michael

2014-01-01

This paper provides a critical perspective on the attempts to promote the use of information and communication technology (ICT) in teaching and learning in England. It describes the rationale given for the introduction of ICT in terms of its potential to impact on educational standards to contribute to developing a curriculum which has more…

A complete hard X-ray selected sample of local, luminous AGNs

NASA Astrophysics Data System (ADS)

Burtscher, Leonard; Davies, Ric; Lin, Ming-yi; Orban de Xivry, Gilles; Rosario, David

2016-08-01

Choosing a very well defined sample is essential for studying the AGN phenomenon. Only the most luminous AGNs can be expected to require a coherent feeding mechanism to sustain their activity and since host galaxy properties and AGN activity are essentially uncorrelated, nuclear scales must be resolved in order to shed light on the feeding mechanisms of AGNs. For these reasons we are compiling a sample of the most powerful, local AGNs. In this talk we present our on-going programme to observe a complete volume limited sample of nearby active galaxies selected by their 14-195 keV luminosity, and outline its rationale for studying the mechanisms regulating gas inflow and outflow.

Rationales Shaping International Linkages in Higher Education: A Qualitative Case Study of the ASU-ITESM Strategic Alliance

ERIC Educational Resources Information Center

Camacho Lizarraga, Monica Irene

2011-01-01

This qualitative case study examines the rationales of the relationship between Arizona State University (ASU)--an American public research university--and Tecnologico de Monterrey (ITESM), a Mexican private not for profit research university. The focus of the study is to document the different meanings participants attached to the rationales of…

Strength Training. Rationale for Current Guidelines for Adult Fitness Programs.

ERIC Educational Resources Information Center

Feigenbaum, Matthew S.; Pollock, Michael L.

1997-01-01

Strength training is an effective method of developing musculoskeletal strength and is often prescribed for fitness, health, and for prevention and rehabilitation of orthopedic injuries. This paper describes and presents a rationale for the population-specific strength training guidelines established by major health organizations. (SM)

Subjective Measures of Exercise Intensity to Gauge Substrate Partitioning in Persons With Paraplegia

PubMed Central

Kressler, Jochen; Cowan, Rachel E.; Ginnity, Kelly; Nash, Mark S.

2012-01-01

Background: The Borg Rating of Perceived Exertion (RPE) Scale and talk test (TT) are commonly recommended for persons to gauge exercise intensity. It is not known whether they are suitable to estimate substrate partitioning between carbohydrate and fat in persons with SCI. Objective: Investigate substrate partitioning/utilization patterns associated with RPE and TT. Methods: Twelve participants with chronic paraplegia underwent 2 arm crank exercise tests on nonconsecutive days within 2 weeks. Test 1 was a graded exercise test (GXT) to volitional exhaustion. Test 2 was a 15-minute self-selected steady state (SS) voluntary arm exercise bout simulating a brief, yet typical exercise session. Results: For the GXT, very light intensity exercise (RPE < 9) and TT stage before last positive were associated with highest contribution of fat oxidation (~35%-50%) to total energy expenditure (TEE). Fat oxidation was low at all stages, with the highest rate (0.13 ± 0.07 g/min) occurring at stage 1 (10 W). Corresponding average RPE was 7 ± 2 and the TT was positive for all participants at this stage. For the SS, fuel partitioning throughout exercise was dominated by carbohydrate oxidation (1.47 ± 0.08 g/min), accounting for almost all (~94%) of TEE with only a minute contribution from fat oxidation (0.02 ± 0.004 g/min). A positive TT was associated with an average contribution of fat oxidation of ~10%. Conclusions: RPE but not the TT appears suitable to predict exercise intensities associated with the highest levels of fat oxidation. However, such intensities are below authoritative intensity thresholds for cardiorespiratory fitness promotion, and therefore the applicability of such a prediction for exercise prescriptions is likely limited to individuals with low exercise tolerance. PMID:23459243

Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

PubMed

Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

2006-06-01

The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

Karl Popper and Jean Piaget: A Rationale for Constructivism

ERIC Educational Resources Information Center

Harlow, Steve; Cummings, Rhoda; Aberasturi, Suzanne M.

2006-01-01

The current faddish use of the term constructivism has taken on as many different definitions as the number of people attempting to define it. This essay clarifies the meaning of constructivism through an examination of Karl Popper's and Jean Piaget's theories. The authors provide a rationale for the use of Popper's paradigm of "Three Worlds" and…

A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and Rationale

PubMed Central

Fournié, Guillaume; Høg, Erling; Barnett, Tony; Pfeiffer, Dirk U.; Mangtani, Punam

2017-01-01

Abstract. Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages. PMID:28749769

Corporate incentives for promoting safety belt use : rationale, guidelines, and examples

DOT National Transportation Integrated Search

1982-10-01

This manual was designed to teach the corporate executive successful strategies for implementing and evaluating a successful industry-based program to motivate employee safety belt use. A rationale is given for the general approach; and specific guid...

Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity.

PubMed

Josifova, Dragana J; Monroe, Glen R; Tessadori, Federico; de Graaff, Esther; van der Zwaag, Bert; Mehta, Sarju G; Harakalova, Magdalena; Duran, Karen J; Savelberg, Sanne M C; Nijman, Isaäc J; Jungbluth, Heinz; Hoogenraad, Casper C; Bakkers, Jeroen; Knoers, Nine V; Firth, Helen V; Beales, Philip L; van Haaften, Gijs; van Haelst, Mieke M

2016-06-01

We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation. In mice and humans, KIDINS220 is alternative spliced in the middle region as well as in the last exon. These full-length and KIDINS220 splice variants occur at precise moments in cortical, hippocampal, and motor neuron development, with splice variants similar to the variants seen in our patients and lacking the last exon of KIDINS220 occurring in adult rather than in embryonic brain. We conducted tissue-specific expression studies in zebrafish that resulted in spasms, confirming a functional link with disruption of the KIDINS220 levels in developing neurites. This work reveals a crucial physiological role of KIDINS220 in development and provides insight into how perturbation of the complex interplay of KIDINS220 isoforms and their relative expression can affect neuron control and human metabolism. Altogether, we here show that de novo protein-truncating KIDINS220 variants cause a new syndrome, SINO. This is the first report of KIDINS220 variants causing a human disease. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Use and Rationale of Media Types in Performance-Centered Design.

ERIC Educational Resources Information Center

Schubert, Dave

2002-01-01

Focuses on the convergent rationale and use of media within performance centered design and how that can affect user performance using real-time electronic performance support system appliance design. Discusses the more effective time-based, interactive, and synchronized media types that have become viable with technological advancements.…

A rodent brain-machine interface paradigm to study the impact of paraplegia on BMI performance.

PubMed

Bridges, Nathaniel R; Meyers, Michael; Garcia, Jonathan; Shewokis, Patricia A; Moxon, Karen A

2018-05-31

Most brain machine interfaces (BMI) focus on upper body function in non-injured animals, not addressing the lower limb functional needs of those with paraplegia. A need exists for a novel BMI task that engages the lower body and takes advantage of well-established rodent spinal cord injury (SCI) models to study methods to improve BMI performance. A tilt BMI task was designed that randomly applies different types of tilts to a platform, decodes the tilt type applied and rights the platform if the decoder correctly classifies the tilt type. The task was tested on female rats and is relatively natural such that it does not require the animal to learn a new skill. It is self-rewarding such that there is no need for additional rewards, eliminating food or water restriction, which can be especially hard on spinalized rats. Finally, task difficulty can be adjusted by making the tilt parameters. This novel BMI task bilaterally engages the cortex without visual feedback regarding limb position in space and animals learn to improve their performance both pre and post-SCI.Comparison with Existing Methods: Most BMI tasks primarily engage one hemisphere, are upper-body, rely heavily on visual feedback, do not perform investigations in animal models of SCI, and require nonnaturalistic extrinsic motivation such as water rewarding for performance improvement. Our task addresses these gaps. The BMI paradigm presented here will enable researchers to investigate the interaction of plasticity after SCI and plasticity during BMI training on performance. Copyright © 2018. Published by Elsevier B.V.

Study of Tomography Of Nephrolithiasis Evaluation (STONE): methodology, approach and rationale.

PubMed

Valencia, Victoria; Moghadassi, Michelle; Kriesel, Dana R; Cummings, Steve; Smith-Bindman, Rebecca

2014-05-01

Urolithiasis (kidney stones) is a common reason for Emergency Department (ED) visits, accounting for nearly 1% of all visits in the United States. Computed tomography (CT) has become the most common imaging test for these patients but there are few comparative effectiveness data to support its use in comparison to ultrasound. This paper describes the rationale and methods of STONE (Study of Tomography Of Nephrolithiasis Evaluation), a pragmatic randomized comparative effectiveness trial comparing different imaging strategies for patients with suspected urolithiasis. STONE is a multi-center, non-blinded pragmatic randomized comparative effectiveness trial of patients between ages 18 and 75 with suspected nephrolithiasis seen in an ED setting. Patients were randomized to one of three initial imaging examinations: point-of-care ultrasound, ultrasound performed by a radiologist or CT. Participants then received diagnosis and treatment per usual care. The primary aim is to compare the rate of severe SAEs (Serious Adverse Events) between the three arms. In addition, a broad range of secondary outcomes was assessed at baseline and regularly for six months post-baseline using phone, email and mail questionnaires. Excluding 17 patients who withdrew after randomization, a total of 2759 patients were randomized and completed a baseline questionnaire (n=908, 893 and 958 in the point-of-care ultrasound, radiology ultrasound and radiology CT arms, respectively). Follow-up is complete, and full or partial outcomes were assessed on over 90% of participants. The detailed methodology of STONE will provide a roadmap for comparative effectiveness studies of diagnostic imaging conducted in an ED setting. Published by Elsevier Inc.

[Difficulties in the diagnosis in the case of subacute paraplegia in a woman with Addison-Biermer disease].

PubMed

Szupień, Elzbieta; Ositek, Bozena; Pniewski, Jarosław

2004-01-01

The following paper presents a case of presently rare serious and non-typical subacutely progressing neurological complications in Addison-Biermer disease in a period before the diagnosis, and effective treatment with vitamin B12 in the advanced process of the nervous system impairment. The patient was a 52-year-old woman with the following (increasingly severe) symptoms occurring over a period of 5 weeks, after an earlier non-related operation: paresis of lower limbs (up to paraplegia), slight paresis of upper limbs, sphincters disorder, numbness and the loss of sensation in the upper and lower limbs, and finally mental deterioration. The woman was admitted to a neurological clinic with the suspected Guillain-Bare syndrome. After an interview and medical examination, with the help of some additional tests and resulting clinical picture, it was diagnosed as the Addison-Biermer disorder. A typical treatment was started with vitamin B12 injections, with a neurological improvement within a week, and further gradual improvement over the following 5 weeks of treatment in the clinic (improvement in the strength, sensation in the limbs, functionality of the sphincters, and normalization of the cognitive functions). After 2 months of continuous pharmacological treatment and physical rehabilitation, the patient started to walk with the help of a walker, and after further 2 months, she was able to walk on her own with a crutch.

Quality of life and self-esteem of persons with paraplegia living in São Paulo, Brazil.

PubMed

Blanes, Leila; Carmagnani, Maria Isabel S; Ferreira, Lydia M

2009-02-01

To evaluate the quality of life (QoL) and self-esteem of paraplegic persons. The sample consisted of 60 outpatients with traumatic paraplegia living in São Paulo, Brazil, from whom clinical and demographic data were obtained. QoL was assessed by the 36-item Short-Form (SF-36) health survey questionnaire, and self-esteem was measured by Rosenberg's Self-Esteem (RSE) scale. Statistical analysis was performed using Student's t-test, analysis of variance and Fisher's least significant difference (LSD) test at a significance level of 5%. Participants were predominately men (86.7%) with a mean age of 32.9 (standard deviation [SD] = 9.47) years, low education level and low income. The SF-36 dimensions that received the lowest scores were physical functioning, role physical and role emotional. Cronbach's alpha for the SF-36 questionnaire was 0.80. A significant statistical difference was found between the presence of pressure ulcers and low scores on mental health (P = 0.001), as determined by Student's t-test. The mean self-esteem score was 8.35 and there was a significant statistical difference between low self-esteem scores and occupation (P = 0.008). Participants reported low QoL and self-esteem. The results provide background information that may be useful in the development of strategies to reduce the impact of spinal cord injury (SCI) on the life and health of persons with SCI, improving their QoL.

Non-speech oro-motor exercise use in acquired dysarthria management: regimes and rationales.

PubMed

Mackenzie, Catherine; Muir, Margaret; Allen, Carolyn

2010-01-01

Non-speech oro-motor exercises (NSOMExs) are described in speech and language therapy manuals and are thought to be much used in acquired dysarthria intervention, though there is no robust evidence of an influence on speech outcome. Opinions differ as to whether, and for which dysarthria presentations, NSOMExs are appropriate. The investigation sought to collect development-phase data, in accordance with the Medical Research Council (MRC) evaluation of complex interventions. The aims were to establish the extent of use of NSOMExs in acquired disorders, the exercise regimes in use for dysarthria, with which dysarthric populations, and the anticipated clinical outcomes. A further aim was to determine the influencing rationales where NSOMExs were or were not used in dysarthria intervention. Speech and language therapists throughout Scotland, Wales, and Northern Ireland, working with adult-acquired dysarthria, were identified by their service heads. They received postal questionnaires comprising 21 closed and two open questions, covering respondent biographics, use of NSOMExs, anticipated clinical outcomes, and practice influencing rationales. One hundred and ninety-one (56% response) completed questionnaires were returned. Eighty-one per cent of respondents used NSOMExs in dysarthria. There was no association with years of speech and language therapy experience. Those who used and those who did not use NSOMExs provided similar influencing rationales, including evidence from their own practice, and Higher Education Institute teaching. More experienced speech and language therapists were more likely than those more recently qualified to be guided by results from their own practice. Input from the attended Higher Education Institute was more influential for those less experienced than for those more experienced. Clinical outcome aims were not confined to speech, but also included improvements in movement, sensory awareness, appearance, emotional status, dysphagia and

A Rationale for Mixed Methods (Integrative) Research Programmes in Education

ERIC Educational Resources Information Center

Niaz, Mansoor

2008-01-01

Recent research shows that research programmes (quantitative, qualitative and mixed) in education are not displaced (as suggested by Kuhn) but rather lead to integration. The objective of this study is to present a rationale for mixed methods (integrative) research programs based on contemporary philosophy of science (Lakatos, Giere, Cartwright,…

Ethnicity and British Colonialism; The Rationale for Racially-Based Schools

ERIC Educational Resources Information Center

Whitehead, Clive

2005-01-01

This paper examines the rationale for ethnic schooling in former British colonial territories in East Africa and Southeast Asia. Critics, especially of British rule in Malaya and Singapore, have traditionally claimed that ethnic schools were established as part of a British political strategy of "divide et impera". An examination the…

New knowledge network evaluation method for design rationale management

NASA Astrophysics Data System (ADS)

Jing, Shikai; Zhan, Hongfei; Liu, Jihong; Wang, Kuan; Jiang, Hao; Zhou, Jingtao

2015-01-01

Current design rationale (DR) systems have not demonstrated the value of the approach in practice since little attention is put to the evaluation method of DR knowledge. To systematize knowledge management process for future computer-aided DR applications, a prerequisite is to provide the measure for the DR knowledge. In this paper, a new knowledge network evaluation method for DR management is presented. The method characterizes the DR knowledge value from four perspectives, namely, the design rationale structure scale, association knowledge and reasoning ability, degree of design justification support and degree of knowledge representation conciseness. The DR knowledge comprehensive value is also measured by the proposed method. To validate the proposed method, different style of DR knowledge network and the performance of the proposed measure are discussed. The evaluation method has been applied in two realistic design cases and compared with the structural measures. The research proposes the DR knowledge evaluation method which can provide object metric and selection basis for the DR knowledge reuse during the product design process. In addition, the method is proved to be more effective guidance and support for the application and management of DR knowledge.

Developing Pre-Technical Secondary Education Programs: Rationale, Content, and Methodology.

ERIC Educational Resources Information Center

Georgia State Univ., Atlanta. Dept. of Vocational and Career Development.

This guide outlines the rationale, content, and methodology of a three-part high technology program that was developed in Georgia to provide secondary school students with training in the areas of electronics and electromechanical and mechanical technologies. Discussed first are the Georgia Initiative, the impact of high technology and the role of…

Rationale for the Cultural Construction of School Mental Health Programming

ERIC Educational Resources Information Center

Arora, Prerna G.; Nastasi, Bonnie K.; Leff, Stephen S.

2017-01-01

The implementation of evidence-based psychological programming to meet the needs of a global population has been impeded by the translation of theories and research findings across populations and settings without due consideration of cultural factors. The purpose of this article is to discuss the rationale for use of partnership-based methods in…

Getting inside acupuncture trials - Exploring intervention theory and rationale

PubMed Central

2011-01-01

Background Acupuncture can be described as a complex intervention. In reports of clinical trials the mechanism of acupuncture (that is, the process by which change is effected) is often left unstated or not known. This is problematic in assisting understanding of how acupuncture might work and in drawing together evidence on the potential benefits of acupuncture. Our aim was to aid the identification of the assumed mechanisms underlying the acupuncture interventions in clinical trials by developing an analytical framework to differentiate two contrasting approaches to acupuncture (traditional acupuncture and Western medical acupuncture). Methods Based on the principles of realist review, an analytical framework to differentiate these two contrasting approaches was developed. In order to see how useful the framework was in uncovering the theoretical rationale, it was applied to a set of trials of acupuncture for fatigue and vasomotor symptoms, identified from a wider literature review of acupuncture and early stage breast cancer. Results When examined for the degree to which a study demonstrated adherence to a theoretical model, two of the fourteen selected studies could be considered TA, five MA, with the remaining seven not fitting into any recognisable model. When examined by symptom, five of the nine vasomotor studies, all from one group of researchers, are arguably in the MA category, and two a TA model; in contrast, none of the five fatigue studies could be classed as either MA or TA and all studies had a weak rationale for the chosen treatment for fatigue. Conclusion Our application of the framework to the selected studies suggests that it is a useful tool to help uncover the therapeutic rationale of acupuncture interventions in clinical trials, for distinguishing between TA and MA approaches and for exploring issues of model validity. English language acupuncture trials frequently fail to report enough detail relating to the intervention. We advocate using

Meeting a Moral Imperative: A Rationale for Teaching the Holocaust

ERIC Educational Resources Information Center

Lindquist, David H.

2011-01-01

A primary rationale for studying the Holocaust (Shoah) involves the opportunity to consider the moral implications that can be drawn from examining the event. Studying the Shoah forces students to consider what it means to be human and humane by examining the full continuum of individual behavior, from "ultimate evil" to "ultimate good". This…

The ‘grey’ assessment practice of IA screening: Prevalence, influence and applied rationale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bidstrup, Morten, E-mail: Bidstrup@plan.aau.dk

Research focusing on the practices surrounding screening in Impact Assessment (IA) is limited. Yet, it has been found that development proposals sometimes are adjusted through an informal dialog with IA practitioners prior to or during screening. Such practice is often referred to as ‘grey IA’ in Denmark. This article explores the prevalence, influence and applied rationale of grey IA. Through a questionnaire, data was collected from 121 IA practitioners working within the fields of environmental impact assessment and strategic environmental assessment. It was found that grey IA is a common practice, which influences the outcomes of formal screening procedures throughmore » consideration of impacts on neighbours and spatial zones of protection. Grey IA is to some extent motivated by the opportunity to save the resources required for full-scale IA, but an additional ‘green’ rationale also exists. Grey IA may influence the effectiveness of IA systems, but further research is needed before any conclusions can be made. - Highlights: • Screening procedures may function as an informal, ‘grey’ assessment. • Grey assessment is common and influences formal screening outcomes. • Grey assessment is motivated by an opportunity to cut IA costs. • Yet, an environmental, ‘green’ rationale for grey assessment also exists.« less

Cultural Variables Underlying Obesity in Latino Men: Design, Rationale and Participant Characteristics from the Latino Men's Health Initiative.

PubMed

Sanchez-Johnsen, Lisa; Craven, Meredith; Nava, Magdalena; Alonso, Angelica; Dykema-Engblade, Amanda; Rademaker, Alfred; Xie, Hui

2017-08-01

Overweight and obesity are associated with significant health problems and rates of obesity are high among Latino men. This paper describes the design, rationale and participant characteristics of the key demographic variables assessed in an NIH-funded study (R21-CA143636) addressing culture and several obesity-related variables (diet, physical activity, and body image) among Mexican and Puerto Rican men using a community-based participatory research framework. Participants completed objective measures (height, weight, body fat, hip, waist), a health and culture interview, a diet questionnaire, and used an accelerometer to measure their level of physical activity. A total of 203 participants completed the measures and the health and culture interview and 193 completed all study components. Puerto Ricans were older than Mexicans (p < .0001) and there were significant differences in marital status (p < .05), country of birth (p < .05), smoking (p < .05) and work status (p < .001). There were no significant differences in religion, education, health insurance, Body Mass Index, body fat, hip and waist measurements, and the language preference of the interview. Results have implications for the development of a future intervention that incorporates the role of cultural factors into a community participatory obesity intervention for Latino men.

Child Development and Social Studies Curriculum Design: Toward a Rationale.

ERIC Educational Resources Information Center

Knox, Gary A.

This paper is a working draft of a study which has examined the accumulated research on child growth and development. The draft is designed as an input paper to enable the Marin Social Studies Project to refine its rationale and criteria for a recommended K-12 social studies program of curriculum options. Identification of the capabilities of…

Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.

PubMed

Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

2015-01-01

A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Coercion or Compulsion?: Rationales behind Informal Payments for Education in Azerbaijan

ERIC Educational Resources Information Center

Lepisto, Eric; Kazimzade, Elmina

2009-01-01

Although informal payments are necessary for education systems in many countries, they prohibit education accessibility and equity in Eastern Europe and neighboring states. Exploring the rationales and the relationships is a promising approach for understanding corruption in education and ensuring educational equity. In this article, rationales…

Accuracy and completeness of drug information in Wikipedia medication monographs.

PubMed

Reilly, Timothy; Jackson, William; Berger, Victoria; Candelario, Danielle

The primary objective of this study was to determine the accuracy and completeness of drug information on Wikipedia and Micromedex compared with U.S. Food and Drug Administration-approved U.S. product inserts. The top 10 brand and top 10 generic medications from the 2012 Institute for Health Informatics' list of top 200 drugs were selected for evaluation. Wikipedia medication information was evaluated and compared with Micromedex in 7 sections of drug information; the U.S. product inserts were used as the standard comparator. Wikipedia demonstrated significantly lower completeness and accuracy scores compared with Micromedex (mean composite scores 18.55 vs. 38.4, respectively; P <0.01). No difference was found between the mean composite scores for brand versus generic drugs in either reference (17.8 vs. 19.3, respectively [P = 0.62], for Wikipedia; 39.2 vs. 37.6, [P = 0.06] for Micromedex). Limitations to these results include the speed with which information is edited on Wikipedia, that there was no evaluation of off-label information, and the limited number of drugs that were evaluated. Wikipedia lacks the accuracy and completeness of standard clinical references and should not be a routine part of clinical decision making. More research should be conducted to evaluate the rationale for health care providers' use of Wikipedia. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms

PubMed Central

Fink, John K.

2014-01-01

Hereditary spastic paraplegia (HSP) is a syndrome designation describing inherited disorders in which lower extremity weakness and spasticity are the predominant symptoms. There are more than 50 genetic types of HSP. HSP affects individuals diverse ethnic groups with prevalence estimates ranging from 1.2 to 9.6 per 100,000 [39, 70, 77, 154, 185]. Symptoms may begin at any age. Gait impairment that begins after childhood usually worsens very slowly over many years. Gait impairment that begins in infancy and early childhood may not worsen significantly. Post mortem studies consistently identify degeneration of corticospinal tract axons (maximal in the thoracic spinal cord) and degeneration of fasciculus gracilis fibers (maximal in the cervico-medullary region). HSP syndromes thus appear to involve motor-sensory axon degeneration affecting predominantly (but not exclusively) the distal ends of long central nervous system (CNS) axons. In general, proteins encoded by HSP genes have diverse functions including axon transport (e.g. SPG30/KIF1A, SPG10/KIF5A and possibly SPG4/Spastin); endoplasmic reticulum morphology (e.g. SPG3A/Atlastin, SPG4/Spastin, SPG12/reticulon 2, and SPG31/REEP1, all of which interact); mitochondrial function (e.g. SPG13/chaperonin 60/heat shock protein 60, SPG7/paraplegin; and mitochondrial ATP6; 4) myelin formation (e.g. SPG2/Proteolipid protein and SPG42/Connexin 47); 5) protein folding and ER-stress response (SPG6/NIPA1, SPG8/K1AA0196 (Strumpellin), SGP17/BSCL2 (Seipin) [113-115], “mutilating sensory neuropathy with spastic paraplegia” due to CcT5 mutation and presumably SPG18/ERLIN2); 6) corticospinal tract and other neurodevelopment (e.g. SPG1/L1 cell adhesion molecule and SPG22/thyroid transporter MCT8); 7) fatty acid and phospholipid metabolism (e.g. SPG28/DDHD1, SPG35/FA2H, SPG39/NTE, SPG54/DDHD2, and SPG56/CYP2U1); and 8) endosome membrane trafficking and vesicle formation (e.g. SPG47/AP4B1, SPG48/KIAA0415, SPG50/AP4M1, SPG51/AP4E

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

Relationship of physical therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: The SCIRehab project

PubMed Central

Teeter, Laura; Gassaway, Julie; Taylor, Sally; LaBarbera, Jacqueline; McDowell, Shari; Backus, Deborah; Zanca, Jeanne M.; Natale, Audrey; Cabrera, Jordan; Smout, Randall J.; Kreider, Scott E. D.; Whiteneck, Gale

2012-01-01

Background/objective Examine associations of type and quantity of physical therapy (PT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and at 1 year post-injury. Methods Physical therapists delivering routine care documented details of PT interventions provided. Regression modeling was used to predict outcomes at discharge and 1 year post-injury for a 75% subset; models were validated with the remaining 25%. Injury subgroups also were examined: motor complete low tetraplegia, motor complete paraplegia, and American Spinal Injury Association (ASIA) Impairment Scale (AIS) D motor incomplete tetra-/paraplegia. Results PT treatment variables explain more variation in three functionally homogeneous subgroups than in the total sample. Among patients with motor complete low tetraplegia, higher scores for the transfer component of the discharge motor Functional Independence Measure () are strongly associated with more time spent working on manual wheelchair skills. Being male is the most predictive variable for the motor FIM score at discharge for patients with motor complete paraplegia. Admission ASIA lower extremity motor score (LEMS) and change in LEMS were the factors most predictive for having the primary locomotion mode of “walk” or “both (walk and wheelchair)” on the discharge motor FIM for patients with AIS D injuries. Conclusion Injury classification influences type and quantity of PT interventions during inpatient SCI rehabilitation and is a strong predictor of outcomes at discharge and 1 year post-injury. The impact of PT treatment increases when patient groupings become more homogeneous and outcomes become specific to the groupings. Note This is the second of nine articles in the SCIRehab series. PMID:23318034

Rationale and methodology of a collaborative learning project in congenital cardiac care

PubMed Central

Wolf, Michael J.; Lee, Eva K.; Nicolson, Susan C.; Pearson, Gail D.; Witte, Madolin K.; Huckaby, Jeryl; Gaies, Michael; Shekerdemian, Lara S.; Mahle, William T.

2018-01-01

Background Collaborative learning is a technique through which individuals or teams learn together by capitalizing on one another’s knowledge, skills, resources, experience, and ideas. Clinicians providing congenital cardiac care may benefit from collaborative learning given the complexity of the patient population and team approach to patient care. Rationale and development Industrial system engineers first performed broad-based time-motion and process analyses of congenital cardiac care programs at 5 Pediatric Heart Network core centers. Rotating multidisciplinary team site visits to each center were completed to facilitate deep learning and information exchange. Through monthly conference calls and an in-person meeting, we determined that duration of mechanical ventilation following infant cardiac surgery was one key variation that could impact a number of clinical outcomes. This was underscored by one participating center’s practice of early extubation in the majority of its patients. A consensus clinical practice guideline using collaborative learning was developed and implemented by multidisciplinary teams from the same 5 centers. The 1-year prospective initiative was completed in May 2015, and data analysis is under way. Conclusion Collaborative learning that uses multidisciplinary team site visits and information sharing allows for rapid structured fact-finding and dissemination of expertise among institutions. System modeling and machine learning approaches objectively identify and prioritize focused areas for guideline development. The collaborative learning framework can potentially be applied to other components of congenital cardiac care and provide a complement to randomized clinical trials as a method to rapidly inform and improve the care of children with congenital heart disease. PMID:26995379

Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.

PubMed

Renvoisé, Benoît; Malone, Brianna; Falgairolle, Melanie; Munasinghe, Jeeva; Stadler, Julia; Sibilla, Caroline; Park, Seong H; Blackstone, Craig

2016-12-01

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial.

PubMed

Cesari, Matteo; Landi, Francesco; Calvani, Riccardo; Cherubini, Antonio; Di Bari, Mauro; Kortebein, Patrick; Del Signore, Susanna; Le Lain, Regis; Vellas, Bruno; Pahor, Marco; Roubenoff, Ronenn; Bernabei, Roberto; Marzetti, Emanuele

2017-02-01

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

International Student Recruitment to Universities in England: Discourse, Rationales and Globalisation

ERIC Educational Resources Information Center

Bolsmann, Chris; Miller, Henry

2008-01-01

The recruitment of international students to universities in England has become a central issue in an era of globalisation for university administrators, senior managers, international offices and heads of schools and faculties. We examine the policy rationales for the recruitment of international students to England. Through the use of in-depth…

Roles and Structures for Participation in Higher Education Governance: A Rationale.

ERIC Educational Resources Information Center

Ikenberry, Stanley O.

It is obvious that the roles for participation of faculty, students and administrators in campus governance are inadequately defined and that the organizational structure through which these roles might be performed is deficient. This paper considers the rationale for such faculty and student organizations and examines some issues that have to be…

Pott disease in the thoracolumbar spine with marked kyphosis and progressive paraplegia necessitating posterior vertebral column resection and anterior reconstruction with a cage.

PubMed

Pappou, Ioannis P; Papadopoulos, Elias C; Swanson, Andrew N; Mermer, Matthew J; Fantini, Gary A; Urban, Michael K; Russell, Linda; Cammisa, Frank P; Girardi, Federico P

2006-02-15

Case report. To report on a patient with Pott disease, progressive neurologic deficit, and severe kyphotic deformity, who had medical treatment fail and required posterior/anterior decompression with instrumented fusion. Treatment options will be discussed. Tuberculous spondylitis is an increasingly common disease worldwide, with an estimated prevalence of 800,000 cases. Surgical treatment consisting of extensive posterior decompression/instrumented fusion and 3-level posterior vertebral column resection, followed by anterior debridement/fusion with cage reconstruction. Neurologic improvement at 6-month follow-up (Frankel B to Frankel D), with evidence of radiographic fusion. A 70-year-old patient with progressive Pott paraplegia and severe kyphotic deformity, for whom medical treatment failed is presented. A posterior vertebral column resection, multiple level posterior decompression, and instrumented fusion, followed by an anterior interbody fusion with cage was used to decompress the spinal cord, restore sagittal alignment, and debride the infection. At 6-month follow-up, the patient obtained excellent pain relief, correction of deformity, elimination of the tuberculous foci, and significant recovery of neurologic function.

Treatment of spinal fractures with paraplegia.

PubMed

Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

[Microbiological rationale for using whey on salting salmon caviar].

PubMed

Kim, I N; Shtan'ko, T I

2011-01-01

The paper provides a rationale for the use of whey to salt salmon fishes instead of traditional preservatives, including those exported from low industrial potential countries, which do not undergo comprehensive sanitary and hygienic tests. On the basis of the performed studies, the authors recommend to use whey to salt salmon caviar, which ensures the ecological purity of the product containing the minimum amount of preservatives and other substances that fail to affect its organoleptic properties.

Rationales for the Lightning Flight-Commit Criteria

NASA Technical Reports Server (NTRS)

Willett, John C. (Editor); Merceret, Francis J.; Krider, E. Philip; Dye, James E.; OBrien, T. Paul; Rust, W. David; Walterscheid, Richard L.; Madura, John T.; Christian, Hugh J.

2010-01-01

Since natural and artificially-initiated (or "triggered") lightning are demonstrated hazards to the launch of space vehicles, the American space program has responded by establishing a set of Lightning Flight Commit Criteria (LFCC), also known as Lightning Launch Commit Criteria (LLCC), and associated Definitions to mitigate the risk. The LLCC apply to all Federal Government ranges and similar LFCC have been adopted by the Federal Aviation Administration for application at state-operated and private spaceports. The LLCC and Definitions have been developed, reviewed, and approved over the years of the American space program, progressing from relatively simple rules in the mid-twentieth century (that were inadequate) to a complex suite for launch operations in the early 21st century. During this evolutionary process, a "Lightning Advisory Panel (LAP)" of top American scientists in the field of atmospheric electricity was established to guide it. Details of this process are provided in a companion document entitled "A History of the Lightning Launch Commit Criteria and the Lightning Advisory Panel for America s Space program" which is available as NASA Special Publication 2010-216283. As new knowledge and additional operational experience have been gained, the LFCC/LLCC have been updated to preserve or increase their safety and to increase launch availability. All launches of both manned and unmanned vehicles at all Federal Government ranges now use the same rules. This simplifies their application and minimizes the cost of the weather infrastructure to support them. Vehicle operators and Range safety personnel have requested that the LAP provide a detailed written rationale for each of the LFCC so that they may better understand and appreciate the scientific and operational justifications for them. This document provides the requested rationales

A Rationale for Outdoor Activity as Experiential Education: The Reason for Freezin'.

ERIC Educational Resources Information Center

Kesselheim, A. Donn

John Dewey said, "Learning is thinking about experience". This dictum accurately reflects the rationale for outdoor activity as experiential education. The term "outdoor learning" refers to a set of activities which have the following characteristics in common: environmental contrast (a sharp environmental change for the participant); physical…

AYURVEDIC RATIONALE OF THE SOUTHERN INDIAN VEGETABLE SOUP SAARU OR RASAM

PubMed Central

Vijayalakshmi, B.; Swamy, B.V Kumara; Shantha, T.R.

1998-01-01

Spices are historically known contributions to the world. The credit for identifying the spices with medicinal and culinary values goes to Ayurveda. Saaru or Rasam is a very popular soup used all over southern India. In this paper an attempt has been made to present the ayurvedic rationale behind formulating the receipt of saaru or rasam. PMID:22556843

A Design Rationale Capture Tool to Support Design Verification and Re-use

NASA Technical Reports Server (NTRS)

Hooey, Becky Lee; Da Silva, Jonny C.; Foyle, David C.

2012-01-01

A design rationale tool (DR tool) was developed to capture design knowledge to support design verification and design knowledge re-use. The design rationale tool captures design drivers and requirements, and documents the design solution including: intent (why it is included in the overall design); features (why it is designed the way it is); information about how the design components support design drivers and requirements; and, design alternatives considered but rejected. For design verification purposes, the tool identifies how specific design requirements were met and instantiated within the final design, and which requirements have not been met. To support design re-use, the tool identifies which design decisions are affected when design drivers and requirements are modified. To validate the design tool, the design knowledge from the Taxiway Navigation and Situation Awareness (T-NASA; Foyle et al., 1996) system was captured and the DR tool was exercised to demonstrate its utility for validation and re-use.

Structural annotation of Beta-1,4-N-acetyl galactosaminyltransferase 1 (B4GALNT1) causing Hereditary Spastic Paraplegia 26.

PubMed

Dad, Rubina; Malik, Uzma; Javed, Aneela; Minassian, Berge A; Hassan, Muhammad Jawad

2017-08-30

Beta-1,4-N-acetyl galactosaminyltransferase 1, B4GALNT1, is a GM2/GD2 synthase, involved in the expression of glycosphingolipids (GSLs) containing sialic acid. Mutations in the gene B4GALNT1 cause Hereditary Spastic Paraplegia 26 (HSP26). In present study we have made attempt to predict the potential structural of the human B4GALNT1 protein. The results illustrated that the amino acid sequences of B4GALNT1 are not 100% conserved among selected twenty species. One signal peptide and one transmembrane domain predicted in human wild type B4GALNT1 protein with aliphatic index of 92.76 and theoretical (iso-electric point) pI of 8.93. It was a kind of unstable protein with Grand average of hydropathicity (GRAVY) of -0.127. Various post-translational modifications were also predicted to exist in B4GALNT1 and predicted to interact with different proteins including ST8SIA5, SLC33A1, GLB1 and others. In the final round, reported missense mutations have shown the further decrease in stability of the protein. This in-silico analysis of B4GALNT1 protein will provide the basis for the further studies on structural variations and biological pathways involving B4GALNT1 in the HSP26. Copyright © 2017. Published by Elsevier B.V.

Resolute efforts to cure hepatitis C: Understanding patients' reasons for completing antiviral treatment.

PubMed

Clark, Jack A; Gifford, Allen L

2015-09-01

Antiviral treatment for hepatitis C is usually difficult, demanding, and debilitating and has long offered modest prospects of successful cure. Most people who may need treatment have faced stigma of an illness associated with drug and alcohol misuse and thus may be deemed poor candidates for treatment, while completing a course of treatment typically calls for resolve and responsibility. Patients' efforts and their reasons for completing treatment have received scant attention in hepatitis C clinical policy discourse that instead focuses on problems of adherence and patients' expected failures. Thus, we conducted qualitative interviews with patients who had recently undertaken treatment to explore their reasons for completing antiviral treatment. Analysis of their narrative accounts identified four principal reasons: cure the infection, avoid a bad end, demonstrate the virtue of perseverance through a personal trial, and achieve personal rehabilitation. Their reasons reflect moral rationales that mark the social discredit ascribed to the infection and may represent efforts to restore creditable social membership. Their reasons may also reflect the selection processes that render some of the infected as good candidates for treatment, while excluding others. Explication of the moral context of treatment may identify opportunities to support patients' efforts in completing treatment, as well as illuminate the choices people with hepatitis C make about engaging in care. © US Government 2014.

Complete integrability of information processing by biochemical reactions

NASA Astrophysics Data System (ADS)

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-11-01

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

Complete integrability of information processing by biochemical reactions.

PubMed

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-11-04

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

PubMed

Hassan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vuckovic, Aleksandra

2015-10-13

Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia. Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex. Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

Activation of lower back muscles via FES for pressure sores prevention in paraplegia: a case study.

PubMed

Vanoncini, M; Holderbaum, W; Andrews, B J

2010-04-01

The aim of this paper is to show the feasibility of the use of functional electrical stimulation (FES) applied to the lower back muscles for pressure sores prevention in paraplegia. The hypothesis under study is that FES induces a change in the pressure distribution on the contact area during sitting. Tests were conducted on a paraplegic subject (T5), sitting on a standard wheelchair and cushion. Trunk extensors (mainly the erector spinae) were stimulated using surface electrodes placed on the skin. A pressure mapping system was used to measure the pressure on the sitting surface in four situations: (a) no stimulation; (b) stimulation on one side of the spine only; (c) stimulation on both sides, at different levels; and (d) stimulation at the same level on both sides, during pressure-relief manoeuvres. A session of prolonged stimulation was also conducted. The experimental results show that the stimulation of the erector spinae on one side of the spine can induce a trunk rotation on the sagittal plane, which causes a change in the pressure distribution. A decrease of pressure on the side opposite to the stimulation was recorded. The phenomenon is intensified when different levels of stimulation are applied to the two sides, and such change can be sustained for a considerable time (around 5 minutes). The stimulation did not induce changes during pressure-relief manoeuvres. Finally, from this research we can conclude that the stimulation of the trunk extensors can be a useful tool for pressure sores prevention, and can potentially be used in a routine for pressure sores prevention based on periodical weight shifts.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

Laryngeal High-Speed Videoendoscopy: Rationale and Recommendation for Accurate and Consistent Terminology

ERIC Educational Resources Information Center

Deliyski, Dimitar D.; Hillman, Robert E.; Mehta, Daryush D.

2015-01-01

Purpose: The authors discuss the rationale behind the term "laryngeal high-speed videoendoscopy" to describe the application of high-speed endoscopic imaging techniques to the visualization of vocal fold vibration. Method: Commentary on the advantages of using accurate and consistent terminology in the field of voice research is…

[Spinal cord compression caused by spinal aneurysmal bone cyst (author's transl)].

PubMed

Steimlé, R; Pageaut, G; Jacquet, G; Gehin, P; Sexe, C B

1975-01-01

Spinal aneurysmal bone cyst is sufficiently rare for the authors to report this case with rapid evolution and development of paraplegia. Total removal was achieved, and clinical recovery remained complete six months after operation. The pathogenic, clinical, radiological, histological and therapeutic aspects are briefly reviewed and discussed.

Nutrient Intake and Body Habitus After Spinal Cord Injury: An Analysis by Sex and Level of Injury

PubMed Central

Groah, Suzanne L; Nash, Mark S; Ljungberg, Inger H; Libin, Alexander; Hamm, Larry F; Ward, Emily; Burns, Patricia A; Enfield, Gwen

2009-01-01

Background/Objectives: To examine nutrient intake and body mass index (BMI) in the spinal cord injury (SCI) population according to level of injury and sex. Design: Cross-sectional study conducted at 2 SCI treatment centers. Participants/Methods: Seventy-three community-dwelling individuals with C5-T12 ASIA Impairment Scale (AIS) A or B SCI. Subjects were divided into 4 groups: male tetraplegia (N = 24), male paraplegia (N = 37), female tetraplegia (N = 1), and female paraplegia (N = 11). Mean age was 38 years; 84% were male; 34% were white, 41% were African American, and 25% were Hispanic. Participants completed a 4-day food log examining habitual diet. Dietary composition was analyzed using Food Processor II v 7.6 software. Results: Excluding the 1 woman with tetraplegia, total calorie intake for the other 3 groups was below observed values for the general population. The female paraplegia group tended to have a lower total calorie intake than the other groups, although macronutrient intake was within the recommended range. The male tetraplegia group, male paraplegia group, and the 1 woman with tetraplegia all had higher than recommended fat intake. Intake of several vitamins, minerals, and macronutrients did not meet recommended levels or were excessively low, whereas sodium and alcohol intake were elevated. Using adjusted BMI tables, 74.0% of individuals with SCI were overweight or obese. Conclusions: Women with paraplegia tended to maintain healthier diets, reflected by lower caloric and fat intakes, fewer key nutrients falling outside recommended guidelines, and less overweight or obesity. Individuals with tetraplegia tended to take in more calories and had higher BMIs, and using adjusted BMI, the majority of the population was overweight or obese. The majority of people with SCI would benefit from nutritional counseling to prevent emerging secondary conditions as the population with SCI ages. PMID:19264046

Assessing the Rationales for Educational Reforms: A Test of the Professional Development, Comprehensive Reform, and Direct Instruction Hypotheses. Policy Research Report.

ERIC Educational Resources Information Center

St. John, Edward P.; Manset, Genevieve; Chung, Choong-Geun; Worthington, Kimberly

Educational reforms are advocated based on rationales that emerge from the research literature. However, evaluation studies seldom examine whether the rationales used to argue for a reform actually hold up when empirical evidence is examined after the reform has been implemented. This paper examines survey data from 3 years of analyses of early…

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

PubMed Central

2010-01-01

Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold

Self-rated health appraisal as cultural and identity process: African American elders' health and evaluative rationales.

PubMed

McMullen, Carmit K; Luborsky, Mark R

2006-08-01

We explored self-rated health by using a meaning-centered theoretical foundation. Self-appraisals, such as self-rated health, reflect a cultural process of identity formation, whereby identities are multiple, simultaneously individual and collective, and produced by specific historical formations. Anthropological research in Philadelphia determined (a) how African American elders appraise their health, and (b) how health evaluations reflect cultural and historical experiences within a community. We interviewed and observed 35 adults aged 65 to 80, stratified by gender and self-rated health. We validated theme analysis of focused interview questions against the larger data set of field notes and transcripts. Health appraisal reflected a complex process of adaptation and identity. Criteria for health included: independent functioning, physical condition, control and responsibility for health, and overall feeling. Evaluative rationales that shaped health appraisals were comparisons, restricted possibilities for self-evaluation, and ways of handling adversity. Evaluative rationales mitigated undesirable health identities (including low self-reported health) and provided mechanisms for claiming desired health identities despite adversity. Describing the criteria and evaluative rationales underlying self-appraisals of health extends current understandings of self-rated health and illustrates the sociohistorical context of individual assessments of well-being.

Legitimizing Technical Communication in English Departments: Carolyn Miller's "Humanistic Rationale for Technical Writing"

ERIC Educational Resources Information Center

Moore, Patrick

2006-01-01

Carolyn Miller's oft-cited "Humanistic Rationale for Technical Writing," published in 1979, tries to give technical communication faculty more cultural capital in English departments controlled by literature professors. Miller replaces a positivistic emphasis in technical communication pedagogy with rhetoric. She shows how technical knowledge is…

Plato's Cosmic Theology: A Rationale for a Polytheistic Astrology?

NASA Astrophysics Data System (ADS)

Henriques, André

2015-05-01

Plato's cosmology influenced classical astronomy and religion, but was in turn influenced by the polytheistic context of its time. Throughout his texts, including the cosmological treatise Timaeus, and the discussions on the soul in the Phaedrus, Plato (c.428-c.348 BC) established what can be generalised as Platonic cosmological thought. An understanding of the philosophical and mythical levels of Platonic thought can provide a rationale for polytheistic and astrological worldviews, pointing to some cosmological continuity, alongside major shifts, from ancient Greek religion to the astrological thought of ancient astronomers such as Claudius Ptolemy.

Rationale, design and respondent characteristics of the 2013-2014 New York City Health and Nutrition Examination Survey (NYC HANES 2013-2014).

PubMed

Thorpe, Lorna E; Greene, Carolyn; Freeman, Amy; Snell, Elisabeth; Rodriguez-Lopez, Jesica S; Frankel, Martin; Punsalang, Amado; Chernov, Claudia; Lurie, Elizabeth; Friedman, Mark; Koppaka, Ram; Perlman, Sharon E

2015-01-01

Capacity to monitor non-communicable diseases (NCDs) at state or local levels is limited. Emerging approaches include using biomeasures and electronic health record (EHR) data. In 2004, New York City (NYC) performed a population-based health study on adult residents using biomeasures (NYC Health and Nutrition Examination Study, or NYC HANES), modeled after NHANES. A second NYC HANES was launched in 2013 to examine change over time, evaluate municipal policies, and validate a proposed EHR-based surveillance system. We describe the rationale and methods of NYC HANES 2013-2014. NYC HANES was a population-based, cross-sectional survey of NYC adults using three-stage cluster sampling. Between August 2013 and June 2014, selected participants completed a health interview and physical exam (blood pressure, body mass index, and waist circumference). Fasting biomeasures included diabetes, lipid profiles, kidney function, environmental biomarkers, and select infectious diseases. Of the 3065 households approached, 2742 were eligible and 1827 were successfully screened (67%). A total of 1524 of eligible participants completed the survey (54%), for an overall response rate of 36%. Completing a second NYC HANES a decade after the first study affords an opportunity to understand changes in prevalence, awareness and control of NCDs and evaluate municipal efforts to manage them.

Nature of Science Progression in School Year 1-9: a Case Study of Teachers' Suggestions and Rationales

NASA Astrophysics Data System (ADS)

Leden, Lotta; Hansson, Lena

2017-07-01

The inclusion of nature of science (NOS) in science education has for a long time been regarded as crucial. There is, however, a lack of research on appropriate NOS aspects for different educational levels. An even more neglected area of research is that focusing on teachers' perspectives on NOS teaching at different levels. The aim of this article is to examine NOS progression in the light of teachers' suggestions and rationales. In order to obtain teachers' informed perspectives, we chose to involve six teachers (teaching grades 1-9) in a 3-year research project. They took part in focus group discussions about NOS and NOS teaching as well as implemented jointly planned NOS teaching sessions. Data that this article builds on was collected at the end of the project. The teachers' suggestions for NOS progression often relied on adding more NOS issues at every stage, thereby creating the foundations of a broader but not necessarily deeper understanding of NOS. Five rationales, for if/when specific NOS issues are appropriate to introduce, emerged from the analysis of the teacher discussions. Some of these rationales, including practice makes perfect and increasing levels of depth can potentially accommodate room for many NOS issues in the science classroom, while maturity and experience instead has a restricting effect on NOS teaching. Also, choice of context and teaching approaches play an important role in teachers' rationales for whether specific NOS issues should be included or not at different stages. The article discusses the implications for teacher education and professional development.

Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias

PubMed Central

Morais, Sara; Raymond, Laure; Mairey, Mathilde; Coutinho, Paula; Brandão, Eva; Ribeiro, Paula; Loureiro, José Leal; Sequeiros, Jorge; Brice, Alexis; Alonso, Isabel; Stevanin, Giovanni

2017-01-01

Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness that can be complicated by other neurological or non-neurological signs. Despite a high genetic heterogeneity (>60 causative genes), 40–70% of the families remain without a molecular diagnosis. Analysis of one of the pioneer cohorts of 193 HSP families generated in the early 1990s in Portugal highlighted that SPAST and SPG11 are the most frequent diagnoses. We have now explored 98 unsolved families from this series using custom next generation sequencing panels analyzing up to 70 candidate HSP genes. We identified the likely disease-causing variant in 20 of the 98 families with KIF5A being the most frequently mutated gene. We also found 52 variants of unknown significance (VUS) in 38% of the cases. These new diagnoses resulted in 42% of solved cases in the full Portuguese cohort (81/193). Segregation of the variants was not always compatible with the presumed inheritance, indicating that the analysis of all HSP genes regardless of the inheritance mode can help to explain some cases. Our results show that there is still a large set of unknown genes responsible for HSP and most likely novel mechanisms or inheritance modes leading to the disease to be uncovered, but this will require international collaborative efforts, particularly for the analysis of VUS. PMID:28832565

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report

PubMed Central

Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun

2009-01-01

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter

Development of Functional Electrical Stimulation Rowing: The Rowstim Series.

PubMed

Andrews, Brian; Gibbons, Robin; Wheeler, Garry

2017-11-01

Potentially, functional electrical stimulation (FES)-assisted exercise may have an important therapeutic role in reducing comorbidities associated with spinal cord injury (SCI). Here, we present an overview of these secondary life-threatening conditions, discuss the rationale behind the development of a hybrid exercise called FES rowing, and describe our experience in developing FES rowing technology. FES rowing and sculling are unique forms of adaptive rowing for those with SCI. The paralyzed leg musculature is activated by multiple channels of electrical pulses delivered via self-adhesive electrodes attached to the skin. The stimulated muscle contractions are synchronized with voluntary rowing movements of the upper limbs. A range of steady-state FES rowing exercise intensities have been demonstrated from 15.2 ± 1.8 mL/kg/min in tetraplegia to 22.9 ±7.1 mL/kg/min in paraplegia. We expect that such high levels may help some to achieve significant reductions in the risks to their health, particularly where a dose-response relationship exists as is the case for cardiovascular disease and Type II diabetes. Furthermore, preliminary results suggest that cyclical forces more than 1.5 times body weight are imposed on the leg long bones which may help to reduce the risk of fragility fractures. We have demonstrated the feasibility of FES rowing on land and water using adapted rowing technology that includes; a fixed stretcher indoor ergometer (adapted Concept 2, Model E), a floating stretcher indoor ergometer (adapted Concept 2 Dynamic), a turbine powered water rowing tank, a custom hydraulic sculling simulator and a single scull (adapted Alden 16). This has involved volunteers with paraplegia and tetraplegia with SCI ranging from C4 to T12 AIS A using at least 4-channels of surface electrical stimulation. FES rowers, with SCI, have competed alongside non-SCI rowers over the Olympic distance of 2000 m at the British Indoor Rowing Championships in 2004, 2005, and 2006

Paraplegia-quadriplegia Independently Increases All Percutaneous Nephrolithotomy Complications: A Comparative Study Using the Modified Clavien System.

PubMed

Danawala, Zeeshan A; Singh, Dinesh

2015-05-01

To investigate the perioperative complication rates for paraplegic-quadriplegic patients (PQPs) undergoing percutaneous nephrolithotomy (PCNL) as compared with non-PQPs using a standardized method of complication reporting via the Clavien system. Two hundred thirteen consecutive PCNLs performed by a single surgeon were analyzed. There were 31 and 115 patients separated into PQP and non-PQP groups, respectively. Data collection included demographic and clinical factors, as well as perioperative and delayed complications. Complications were organized by the Clavien grade. All- and initial-procedure complications were analyzed. The rate of adverse events for each Clavien grade was calculated, and statistical comparisons were made. The relationship between PQP and complication severity was investigated using univariate and multivariate analyses. There were 38 and 43 initial-procedure complications in the PQP and non-PQP groups, respectively. The rate of adverse events was higher across the spectrum of Clavien grades for the PQP group, specifically grade 1 (48.4% vs 20.2%; P = .002), grade 2 (22.6% vs 5.3%; P = .004), grade 3b (12.9% vs 2.6%; P = .038), grade 4a (6.5% vs 0%), and grade 4b (9.7% vs 1.8%; P = .066). Approximately 51.6% and 31.5% of PQPs and non-PQPs experienced ≥ 1 complications, respectively (odds ratio = 2.34; P = .05). Multivariate analysis demonstrated paraplegia or quadriplegia status to be an independent risk factor for the development of perioperative complications after adjusting for confounding factors (odds ratio = 2.91; P = .040). PCNL complication rates are higher in PQPs compared with non-PQPs. This study is one of the first in PCNL to use a standardized reporting system to highlight high-risk individuals within the stone population. Copyright © 2015 Elsevier Inc. All rights reserved.

Gait phenotypes in paediatric hereditary spastic paraplegia revealed by dynamic time warping analysis and random forests

PubMed Central

Martín-Gonzalo, Juan Andrés; Rodríguez-Andonaegui, Irene; López-López, Javier; Pascual-Pascual, Samuel Ignacio

2018-01-01

The Hereditary Spastic Paraplegias (HSP) are a group of heterogeneous disorders with a wide spectrum of underlying neural pathology, and hence HSP patients express a variety of gait abnormalities. Classification of these phenotypes may help in monitoring disease progression and personalizing therapies. This is currently managed by measuring values of some kinematic and spatio-temporal parameters at certain moments during the gait cycle, either in the doctor´s surgery room or after very precise measurements produced by instrumental gait analysis (IGA). These methods, however, do not provide information about the whole structure of the gait cycle. Classification of the similarities among time series of IGA measured values of sagittal joint positions throughout the whole gait cycle can be achieved by hierarchical clustering analysis based on multivariate dynamic time warping (DTW). Random forests can estimate which are the most important isolated parameters to predict the classification revealed by DTW, since clinicians need to refer to them in their daily practice. We acquired time series of pelvic, hip, knee, ankle and forefoot sagittal angular positions from 26 HSP and 33 healthy children with an optokinetic IGA system. DTW revealed six gait patterns with different degrees of impairment of walking speed, cadence and gait cycle distribution and related with patient’s age, sex, GMFCS stage, concurrence of polyneuropathy and abnormal visual evoked potentials or corpus callosum. The most important parameters to differentiate patterns were mean pelvic tilt and hip flexion at initial contact. Longer time of support, decreased values of hip extension and increased knee flexion at initial contact can differentiate the mildest, near to normal HSP gait phenotype and the normal healthy one. Increased values of knee flexion at initial contact and delayed peak of knee flexion are important factors to distinguish GMFCS stages I from II-III and concurrence of polyneuropathy

First Reconsideration Decision and Rationale: Nutrient and Sediment TMDLs for the Indian Creek Watershed, Pennsylvania

EPA Pesticide Factsheets

Reconsideration Decision and Rationale: Nutrient and Sediment TMDLs for the Indian Creek Watershed, Pennsylvania: Established by the U.S. Environmental Protection Agency, Region 3, Philadelphia, PA. March 21, 2014. 6 Documents, below

Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP).

PubMed

Baxter, Sally L; Allard, Denise E; Crowl, Christopher; Sherwood, Nina Tang

2014-08-01

Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase. In Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron morphology and function, and most die as pupae. Adult survivors display impaired mobility, reminiscent of the human disease. Here, we show that rearing pupae or adults at reduced temperature (18°C), compared with the standard temperature of 24°C, improves the survival and mobility of adult spastin mutants but leaves wild-type flies unaffected. Flies expressing human spastin with pathogenic mutations are similarly rescued. Additionally, larval cooling partially rescues the larval synaptic phenotype. Cooling thus alleviates known spastin phenotypes for each developmental stage at which it is administered and, notably, is effective even in mature adults. We find further that cold treatment rescues larval synaptic defects in flies with mutations in Flower (a protein with no known relation to Spastin) and mobility defects in flies lacking Kat60-L1, another microtubule-severing protein enriched in the CNS. Together, these data support the hypothesis that the beneficial effects of cold extend beyond specific alleviation of Spastin dysfunction, to at least a subset of cellular and behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique in clinical treatment of acute anoxia, might thus hold additional promise as a therapeutic approach for AD-HSP and, potentially, for other neurodegenerative diseases. © 2014. Published by The Company of Biologists Ltd.

Complete genome sequence of Coriobacterium glomerans type strain (PW2T) from the midgut of Pyrrhocoris apterus L. (red soldier bug)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stackebrandt, Erko; Zeytun, Ahmet; Lapidus, Alla L.

2013-01-01

Coriobacterium glomerans Haas and Ko nig 1988, is the only species of the genus Coriobacterium, family Coriobacteriaceae, order Coriobacteriales, phylum Actinobacteria. The bacterium thrives as an endosymbiont of pyrrhocorid bugs, i.e. the red fire bug Pyrrhocoris apterus L. The rationale for sequencing the genome of strain PW2T is its endosymbiotic life style which is rare among members of Actinobacteria. Here we describe the features of this symbiont, together with the complete genome sequence and its annotation. This is the first complete genome sequence of a member of the genus Coriobacterium and the sixth member of the order Coriobacteriales for whichmore » complete genome sequences are now available. The 2,115,681 bp long single replicon genome with its 1,804 protein-coding and 54 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.« less

Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

PubMed Central

Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I.; Sue, Carolyn M.; Mackay-Sim, Alan

2014-01-01

ABSTRACT Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

The Importance of Rationales for Internationalization at a Local Level--University and Individual

ERIC Educational Resources Information Center

Willis, Ian; Taylor, John

2014-01-01

This study examines rationales for internationalization at a research intensive university in the UK. Internationalization is often described at a macro level without reaching down to explore the individual motivations that may support or constrain internationalization at a particular institution. The article argues that it is important to…

Proposed energy conservation contingency plan: emergency restrictions on advertising lighting. Authorities, need, rationale, and operation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The emergency restrictions on advertising lighting proposed in Energy Conservation Contingency Plan No. 5 of 1977 are presented. A statement is given on the need for rationale and operation of the Contingency Plan.

Effect of Epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study

PubMed Central

Harkema, Susan; Gerasimenko, Yury; Hodes, Jonathan; Burdick, Joel; Angeli, Claudia; Chen, Yangsheng; Ferreira, Christie; Willhite, Andrea; Rejc, Enrico; Grossman, Robert G.; Edgerton, V. Reggie

2011-01-01

Summary Background Repeated periods of stimulation of the spinal cord and training seems to have amplified the ability to consciously control movement. Methods An individual three years post C7-T1 subluxation presented with a complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. Following 170 locomotor training sessions, a 16-electrode array was surgically placed on the dura (L1-S1 cord segments) to allow for chronic electrical stimulation. After implantation and throughout stand retraining with epidural stimulation, 29 experiments were performed. Extensive stimulation combinations and parameters were tested to achieve standing and stepping. Findings Epidural stimulation enabled the human lumbosacral spinal circuitry to dynamically elicit full weight-bearing standing with assistance provided only for balance for 4·25 minutes in a subject with a clinically motor complete SCI. This occurred when using stimulation at parameters optimized for standing while providing bilateral load-bearing proprioceptive input. Locomotor-like patterns were also observed when stimulation parameters were optimized for stepping. In addition, seven months after implantation, the subject recovered supraspinal control of certain leg movements, but only during epidural stimulation. Interpretation Even after a severe low cervical spinal injury, the neural networks remaining within the lumbosacral segments can be reactivated into functional states so that it can recognize specific details of ensembles of sensory input to the extent that it can serve as the source of neural control. In addition, newly formed supraspinal input to this same lumbosacral segments can re-emerge as another source of control. Task specific training with epidural stimulation may have reactivated previously silent spared neural circuits or promoted plasticity. This suggests that these interventions could be a viable clinical approach for

Complete integrability of information processing by biochemical reactions

PubMed Central

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-01-01

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling – based on spin systems – has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis–Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy – based on completely integrable hydrodynamic-type systems of PDEs – which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions. PMID:27812018

Nondamaging Retinal Laser Therapy: Rationale and Applications to the Macula.

PubMed

Lavinsky, Daniel; Wang, Jenny; Huie, Philip; Dalal, Roopa; Lee, Seung Jun; Lee, Dae Yeong; Palanker, Daniel

2016-05-01

Retinal photocoagulation and nondamaging laser therapy are used for treatment of macular disorders, without understanding of the response mechanism and with no rationale for dosimetry. To establish a proper titration algorithm, we measured the range of tissue response and damage threshold. We then evaluated safety and efficacy of nondamaging retinal therapy (NRT) based on this algorithm for chronic central serous chorioretinopathy (CSCR) and macular telangiectasia (MacTel). Retinal response to laser treatment below damage threshold was assessed in pigmented rabbits by expression of the heat shock protein HSP70 and glial fibrillary acidic protein (GFAP). Energy was adjusted relative to visible titration using the Endpoint Management (EpM) algorithm. In clinical studies, 21 eyes with CSCR and 10 eyes with MacTel were treated at 30% EpM energy with high spot density (0.25-diameter spacing). Visual acuity, retinal and choroidal thickness, and subretinal fluid were monitored for 1 year. At 25% EpM energy and higher, HSP70 was expressed acutely in RPE, and GFAP upregulation in Müller cells was observed at 1 month. Damage appeared starting at 40% setting. Subretinal fluid resolved completely in 81% and partially in 19% of the CSCR patients, and visual acuity improved by 12 ± 3 letters. Lacunae in the majority of MacTel patients decreased while preserving the retinal thickness, and vision improved by 10 letters. Heat shock protein expression in response to hyperthermia helps define the therapeutic window for NRT. Lack of tissue damage enables high-density treatment to boost clinical efficacy, therapy in the fovea, and retreatments to manage chronic diseases.

An ecological dynamics rationale to explain home advantage in professional football

NASA Astrophysics Data System (ADS)

Gama, José; Dias, Gonçalo; Couceiro, Micael; Passos, Pedro; Davids, Keith; Ribeiro, João

2016-03-01

Despite clear findings, research on home advantage in team sports lacks a comprehensive theoretical rationale for understanding why this phenomenon is so compelling. The aim of this study was to provide an explanatory theoretical rationale in ecological dynamics for the influence of home advantage observed in research on professional football. We recorded 30 competitive matches and analyzed 13958 passes, from one highly successful team in the Portuguese Premier League, during season 2010/2011. Performance data were analyzed using the Match Analysis Software—Amisco® (version 3.3.7.25), allowing us to characterize team activity profiles. Results were interpreted from an ecological dynamics perspective, explaining how task and environmental constraints of a competitive football setting required performers to continuously co-adapt to teammate behaviors. Despite slight differences in percentage of ball possession when playing home or away, the number of passes achieved by the team, while in possession of the ball, was quite different between home or away venues. When playing at home, the number of passes performed by the team was considerably higher than when playing away. The explanation proposed in this study for a home advantage effect can be understood from studying interpersonal coordination tendencies of team sports players as agents in a complex adaptive system.

Rationale for Content and Method of the Teacher and Teacher-Aide Training Program.

ERIC Educational Resources Information Center

Tennessee Appalachia Educational Cooperative, Oak Ridge.

This document gives the rationale for the content and method of five teacher and teacher-aide training workshops. Results of a questionnaire confirmed the need for improvement in in-service training in the entire Appalachian area and also indicated the kinds of changes needed. Deficiencies in content were identified as: 1) application of…

Writing a Rationale for a Controversial Common Reading Book: Alice Walker's "The Color Purple."

ERIC Educational Resources Information Center

Worthington, Pepper

1985-01-01

Offers a rationale that can be used to defend the assignment of Alice Walker's controversial novel for class reading. Indicates four issues that might evoke calls for censorship: (1) subject matter, (2) vocabulary, (3) grammar, and (4) the epistolary form of the work. (RBW)

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report.

PubMed

Oh, Ja-Young; Do, Hyun Jung; Lee, Seungok; Jang, Ja-Hyun; Cho, Eun-Hae; Jang, Dae-Hyun

2016-12-01

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11 . One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.

Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

PubMed Central

Rinaldi, Carlo; Schmidt, Thomas; Situ, Alan J.; Johnson, Janel O.; Lee, Philip R.; Chen, Ke-lian; Bott, Laura C.; Fadó, Rut; Harmison, George H.; Parodi, Sara; Grunseich, Christopher; Renvoisé, Benoît; Biesecker, Leslie G.; De Michele, Giuseppe; Santorelli, Filippo M.; Filla, Alessandro; Stevanin, Giovanni; Dürr, Alexandra; Brice, Alexis; Casals, Núria; Traynor, Bryan J.; Blackstone, Craig; Ulmer, Tobias S.; Fischbeck, Kenneth H.

2017-01-01

IMPORTANCE The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene. RESULTS We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size (0.29 [0.01] vs 0.26 [0

The declining demand for hospital care as a rationale for duty hour reform.

PubMed

Jena, Anupam B; DePasse, Jacqueline W; Prasad, Vinay

2014-10-01

The regulation of duty hours of physicians in training remains among the most hotly debated subjects in medical education. Although recent duty hour reforms have been chiefly motivated by concerns about resident well-being and medical errors attributable to resident fatigue, the debate surrounding duty hour reform has infrequently involved discussion of one of the most important secular changes in hospital care that has affected nearly all developed countries over the last 3 decades: the declining demand for hospital care. For example, in 1980, we show that resident physicians in US teaching hospitals provided, on average, 1,302 inpatient days of care per resident physician compared to 593 inpatient days in 2011, a decline of 54%. This decline in the demand for hospital care by residents provides an under-recognized economic rationale for reducing residency duty hours, a rationale based solely on supply and demand considerations. Work hour reductions and growing requirements for outpatient training can be seen as an appropriate response to the shrinking demand for hospital care across the health-care sector.

Rationales for expanding minority physician representation in the workforce: a scoping review.

PubMed

Kelly-Blake, Karen; Garrison, Nanibaa' A; Fletcher, Faith E; Ajegba, Brittany; Smith, Nichole; Brafford, Morgann; Bogdan-Lovis, Elizabeth

2018-06-22

The purpose of this study was to conduct a scoping review of the literature and to categorically map a 15-year trajectory of US undergraduate medical education rationales for and approaches to expanding under-represented minority (URM) physician representation in the medical workforce. Further aims were to comparatively examine related justifications and to consider international implications. From 1 June to 31 July 2015, the authors searched the Cochrane Library, ERIC, PsycINFO, PubMed, Scopus, Web of Science and Google Scholar for articles published between 2000 and 2015 reporting rationales for and approaches to increasing the numbers of members of URMs in undergraduate medical school. A total of 137 articles were included in the scoping review. Of these, 114 (83%) mentioned workforce diversity and 73 (53%) mentioned concordance. The patient-physician relationship (n = 52, 38%) and service commitment (n = 52, 38%) were the most commonly cited rationales. The most frequently mentioned approaches to increasing minority representation were pipeline programmes (n = 59, 43%), changes in affirmative action laws (n = 32, 23%) and changes in admission policies (n = 29, 21%). This scoping review of the 2000-2015 literature on strategies for and approaches to expanding URM representation in medicine reveals a repetitive, amplifying message of URM physician service commitment to vulnerable populations in medically underserved communities. Such message repetition reinforces policies and practices that might limit the full scope of URM practice, research and leadership opportunities in medicine. Cross-nationally, service commitment and patient-physician concordance benefits admittedly respond to recognised societal need, yet there is an associated risk for instrumentally singling out members of URMs to fulfil that need. The proceedings of a 2001 US Institute of Medicine symposium warned against creating a deterministic expectation that URM physicians provide care to minority

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.

PubMed

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-Sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2016-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

PubMed Central

Elsayed, Liena E O; Mohammed, Inaam N; Hamed, Ahlam A A; Elseed, Maha A; Johnson, Adam; Mairey, Mathilde; Mohamed, Hassab Elrasoul S A; Idris, Mohamed N; Salih, Mustafa A M; El-sadig, Sarah M; Koko, Mahmoud E; Mohamed, Ashraf Y O; Raymond, Laure; Coutelier, Marie; Darios, Frédéric; Siddig, Rayan A; Ahmed, Ahmed K M A; Babai, Arwa M A; Malik, Hiba M O; Omer, Zulfa M B M; Mohamed, Eman O E; Eltahir, Hanan B; Magboul, Nasr Aldin A; Bushara, Elfatih E; Elnour, Abdelrahman; Rahim, Salah M Abdel; Alattaya, Abdelmoneim; Elbashir, Mustafa I; Ibrahim, Muntaser E; Durr, Alexandra; Audhya, Anjon; Brice, Alexis; Ahmed, Ammar E; Stevanin, Giovanni

2017-01-01

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance. PMID:27601211

ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia

PubMed Central

Cooper, Helen M.; Yang, Yang; Ylikallio, Emil; Khairullin, Rafil; Woldegebriel, Rosa; Lin, Kai-Lan; Euro, Liliya; Palin, Eino; Wolf, Alexander; Trokovic, Ras; Isohanni, Pirjo; Kaakkola, Seppo; Auranen, Mari; Lönnqvist, Tuula; Wanrooij, Sjoerd

2017-01-01

Abstract De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G > A (p.G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood. HSP is a clinically and genetically heterogeneous disorder of the upper motor neurons. Symptoms beginning in early childhood may resemble spastic cerebral palsy. The function of ATAD3A, a mitochondrial inner membrane AAA ATPase, is yet undefined. AAA ATPases form hexameric rings, which are catalytically dependent on the co-operation of the subunits. The dominant-negative patient mutation affects the Walker A motif, which is responsible for ATP binding in the AAA module of ATAD3A, and we show that the recombinant mutant ATAD3A protein has a markedly reduced ATPase activity. We further show that overexpression of the mutant ATAD3A fragments the mitochondrial network and induces lysosome mass. Similarly, we observed altered dynamics of the mitochondrial network and increased lysosomes in patient fibroblasts and neurons derived through differentiation of patient-specific induced pluripotent stem cells. These alterations were verified in patient fibroblasts to associate with upregulated basal autophagy through mTOR inactivation, resembling starvation. Mutations in ATAD3A can thus be dominantly inherited and underlie variable neurological phenotypes, including HSP, with intrafamiliar variability. This finding extends the group of mitochondrial inner membrane AAA proteins associated with spasticity. PMID:28158749

Effects of paraplegia on quality of life and family economy among patients with spinal cord injuries in selected hospitals of Sri Lanka.

PubMed

Kalyani, H H N; Dassanayake, S; Senarath, U

2015-06-01

The study was conducted with the aim of assessing the effects of paraplegia caused by spinal cord injuries on the quality of life of patients and their family economy. A descriptive cross-sectional study. The study was carried out in Accident Service, Orthopedic and Neurosurgery Units of the National Hospital of Sri Lanka and the Spinal Injury Unit of Rehabilitation Hospital Ragama. One hundred traumatic paraplegic patients were included as the study sample. Modified Ferrans and Powers quality of life index: spinal cord injury version was used to measure the quality of life. Pre- and post-family economic data were collected using an interviewer-administered questionnaire. Quality of Life was calculated under four major components. Paraplegics' family component (mean=3.50) and social, economic aspects (mean=3.24) are considerably good when compared with health and functioning (mean=2.83) and psychological (mean=2.78) components. Also the study revealed that expenditures are significantly high (P=0.001) and income is significantly less (P=0.001) after injury than before. Quality of life is relatively good on family and social aspects, whereas the physical and psychological aspects are somewhat poor. Regarding family economy, expenses are significantly high and earnings are significantly less after the injury. Contribution to the income from self-employment shows the most significant decline. Findings suggest that the family economy of such patients should be supported.

Telework rationale and implementation for people with disabilities: considerations for employer policymaking.

PubMed

Moon, Nathan W; Linden, Maureen A; Bricout, John C; Baker, Paul M A

2014-01-01

Telework has been promoted as a viable workplace accommodation for people with disabilities since the 1990s, when information and communication technologies (ICT) had developed sufficiently to facilitate its widespread adoption. This initial research and accompanying policy recommendations were prescriptive in nature and frequently aimed at employers. This article adds to existing policy models for facilitating successful telework outcomes for people with disabilities. Drawing upon two studies by the Rehabilitation Engineering Research Center on Workplace Accommodations, we expound on employee-side considerations in the implementation of telework. Our policy model utilizes established typologies for policy evaluation to develop a process model that considers rationales and implementation factors for telework among people with physical disabilities. Telework may be used as an accommodation for disability, but employee rationales for telework are more complex, involving work-life balance, strategies for pain and fatigue not formally recognized as disability, and expediency in travel and transportation. Implementation of telework as a component of workplace operations is similarly multifaceted, involving non-technology accommodations to realize job restructuring left incomplete by telework. Our model grounds new empirical research in this area. We also renew our call for additional research on effective telework practices for people with disabilities.

The Zambia Children's KS-HHV8 Study: Rationale, Study Design, and Study Methods

PubMed Central

Minhas, Veenu; Crabtree, Kay L.; Chao, Ann; Wojcicki, Janet M.; Sifuniso, Adrian M.; Nkonde, Catherine; Kankasa, Chipepo; Mitchell, Charles D.; Wood, Charles

2011-01-01

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia. PMID:21447476

Actuarial analysis of surgical results: rationale and method.

PubMed

Grunkemeier, G L; Starr, A

1977-11-01

The use of time-related methods of statistical analysis is essential for valid evaluation of the long-term results of a surgical procedure. Accurate comparison of two procedures or two prosthetic devices is possible only when the length of follow-up is properly accounted for. The purpose of this report is to make the technical aspects of the acturial, or life table, method easily accessible to the surgeon, with emphasis on the motivation for and the rationale behind it. This topic is illustrated in terms of heart valve prostheses, a field that is rapidly developing. Both the authors and readers of articles must be aware that controversies surrounding the relative merits of various prosthetic designs or operative procedures can be settled only if proper time-related methods of analysis are utilized.

Ethical Dilemmas in Office Practice: Physician Response and Rationale

PubMed Central

Secundy, Marian Gray

1985-01-01

A survey of black and white family physicians in the District of Columbia is described. The survey provides insight into decision-making processes and the ability to recognize ethical dilemmas in medical practice. Comments were elicited to hypothetical case vignettes typical of ethical conflict in office practice. Findings note physician ability to recognize ethical dilemmas in day-to-day aspects of medical practice. Methods of decision making and rationale for decisions made, however, appear to be inconsistent, nonuniversal, and individualistic without evidence of specific models or criteria. No significant differences were noted between black and white physicians. The need in physician training for clarification and development of criteria is evident. PMID:4078929

Opening minds in Canada: background and rationale.

PubMed

Stuart, Heather; Chen, Shu-Ping; Christie, Romie; Dobson, Keith; Kirsh, Bonnie; Knaak, Stephanie; Koller, Michelle; Krupa, Terry; Lauria-Horner, Bianca; Luong, Dorothy; Modgill, Geeta; Patten, Scott B; Pietrus, Mike; Szeto, Andrew; Whitley, Rob

2014-10-01

To summarize the background and rationale of the approach taken by the Mental Health Commission of Canada's Opening Minds (OM) Anti-Stigma Initiative. The approach taken by OM incorporates a grassroots, community development philosophy, has clearly defined target groups, uses contact-based education as the central organizing element across interventions, and has a strong evaluative component, so that best practices can be identified, replicated, and disseminated. Contact-based education occurs when people who have experienced a mental illness share their personal story of recovery and hope. OM has acted as a catalyst to develop partnerships between community groups who are undertaking anti-stigma work and an interdisciplinary team of academic researchers in 5 universities who are evaluating the results of these programs. Building partnerships with existing community programs and promoting systematic evaluation using standardized approaches and instruments have contributed to our understanding of best practices in the field of anti-stigma programming.

Ancient observation of spinal cord injury: the case of the Assiryan lion.

PubMed

Luvizutto, Gustavo J; Siqueira, Emerson G; Hamamoto Filho, Pedro Tadao; Zétola, Viviane F; Lange, Marcos C; Theive, Hélio A; Resende, Luiz A; Bazan, Rodrigo

2018-05-19

The description of paraplegia is considered a milestone in the history of neurology. The Egyptians provided excellent descriptions of spinal cord injuries, the Bible has several references to paraplegia, and, more recently, the pioneers of neurology described the classic syndromes related to spinal injuries and paraplegia. Here, we describe an ancient observation by the Assyrian people of paraplegia in an animal. In ancient Assyria, lion hunting was a ritualized activity conducted for political and religious purposes. The Lion Hunt of Ashurbanipal, a series of Assyrian palace reliefs from the North Palace at Nineveh dating from approximately 645 BCE, which is now in the British Museum in London, UK, shows King Ashurbanipal hunting lions. Applying modern knowledge of mammalian dermatomes to the images, we reveal a detailed and precise observation of paraplegia following spinal cord injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network

PubMed Central

Park, Seong H.; Zhu, Peng-Peng; Parker, Rell L.; Blackstone, Craig

2010-01-01

Hereditary spastic paraplegias (HSPs; SPG1–45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and atlastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins atlastin-1, spastin, and REEP1 interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP. PMID:20200447

The Rhetoric of Issue Advertising: A Rationale, a Case Study, a Critical Perspective--And More.

ERIC Educational Resources Information Center

Heath, Robert L.

1988-01-01

Supports the use of issue advertising. Argues that speech communication scholars can facilitate the responsible and effective use of issue ads. Reviews critics and proponents of issue advertising. Develops a rationale to guide the practice of issue advertising. Examines issue advertising in the current pro-nuclear campaign. (MS)

Integrating the Beliefs of Dewey, Lewin, and Rogers into a Rationale for Effective Group Leadership.

ERIC Educational Resources Information Center

Grove, Richard W.

1992-01-01

Presents a rationale for effective group leadership grounded in John Withall's articulation of selected beliefs of John Dewey, Kurt Lewin, and Carl Rogers. Teachers and administrators need more and better preparation in collaborative inquiry. Knowledge and skills in collaborative inquiry should undergird the successful functioning of groups of…

The Impact of a Course on Nature of Science Pedagogical Views and Rationales. Comparing Preservice Teachers in Their First Versus Second Experience

NASA Astrophysics Data System (ADS)

Kruse, Jerrid W.; Easter, Jaclyn M.; Edgerly, Hallie S.; Seebach, Colin; Patel, Neal

2017-08-01

This study explored changes in preservice teachers' (PSTs) nature of science pedagogical (NOSP) views and nature of science (NOS) rationales using pre- and post-course written responses as well as interview data. Through systematic analysis, themes were generated and compared to the NOS literature. Comparisons between pre- and post-course data demonstrate improved and deepened NOS views, NOSP views that are more aligned with NOS literature, and a greater number of rationales for including NOS. All participants were enrolled in the "Inquiry and Natures of Science, Technology, and Engineering" (INSTE) course. However, six participants were enrolled in INSTE as their first course in which NOS and NOSP were addressed. The other six participants were enrolled in INSTE as their second course in which NOS and NOSP were addressed, with science methods as their first course in which NOS and NOSP were addressed. By comparing participants enrolled in INSTE as their first course to those enrolled in INSTE as their second course, we observed that NOS understanding seemed to develop in a first experience alongside some NOS rationales, but NOSP views lagged for participants in INSTE as their first course. Participants enrolled in INSTE as their second course developed more robust and literature-aligned NOSP views and more multifaceted NOS rationales. Therefore, this study bolsters arguments that teachers need to receive extended NOS and NOSP instruction.

Rationale for hedging initiatives: Empirical evidence from the energy industry

NASA Astrophysics Data System (ADS)

Dhanarajata, Srirajata

Theory offers different rationales for hedging including (i) financial distress and bankruptcy cost, (ii) capacity to capture attractive investment opportunities, (iii) information asymmetry, (iv) economy of scale, (v) substitution for hedging, (vi) managerial risk aversion, and (vii) convexity of tax schedule. The purpose of this dissertation is to empirically test the explanatory power of the first five theoretical rationales on hedging done by oil and gas exploration and production (E&P) companies. The level of hedging is measured by the percentage of production effectively hedged, calculated based on the concept of delta and delta-gamma hedging. I employ Tobit regression, principal components, and panel data analysis on dependent and raw independent variables. Tobit regression is applied due to the fact that the dependent variable used in the analysis is non-negative. Principal component analysis helps to reduce the dimension of explanatory variables while panel data analysis combines/pools the data that is a combination of time-series and cross-sectional. Based on the empirical results, leverage level is consistently found to be a significant factor on hedging activities, either due to an attempt to avoid financial distress by the firm, or an attempt to control agency cost by debtholders, or both. The effect of capital expenditures and discretionary cash flows are both indeterminable due possibly to a potential mismatch in timing of realized cash flow items and hedging decision. Firm size is found to be positively related to hedging supporting economy of scale hypothesis, which is introduced in past literature, as well as the argument that large firm usually are more sophisticated and should be more willing and more comfortable to use hedge instruments than smaller firms.

Rationale for cannabis-based interventions in the opioid overdose crisis.

PubMed

Lucas, Philippe

2017-08-18

North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions. Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect. Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality. This paper presents an evidence-based rationale for cannabis-based interventions in the opioid overdose crisis informed by research on substitution effect, proposing three important windows of opportunity for cannabis for therapeutic purposes (CTP) to play a role in reducing opioid use and interrupting the cycle towards opioid use disorder: 1) prior to opioid introduction in the treatment of chronic pain; 2) as an opioid reduction strategy for those patients already using opioids; and 3) as an adjunct therapy to methadone or suboxone treatment in order to increase treatment success rates. The commentary explores potential obstacles and limitations to these proposed interventions, and as well as strategies to monitor their impact on public health and safety. The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.

Perceptions of Shared Decision Making Among Patients with Spinal Cord Injuries/Disorders.

PubMed

Locatelli, Sara M; Etingen, Bella; Heinemann, Allen; Neumann, Holly DeMark; Miskovic, Ana; Chen, David; LaVela, Sherri L

2016-01-01

Background: Individuals with spinal cord injuries/disorders (SCI/D) are interested in, and benefit from, shared decision making (SDM). Objective: To explore SDM among individuals with SCI/D and how demographics and health and SCI/D characteristics are related to SDM. Method: Individuals with SCI/D who were at least 1 year post injury, resided in the Chicago metropolitan area, and received SCI care at a Veterans Affairs (VA; n = 124) or an SCI Model Systems facility ( n = 326) completed a mailed survey measuring demographics, health and SCI/D characteristics, physical and mental health status, and perceptions of care, including SDM, using the Combined Outcome Measure for Risk Communication and Treatment Decision-Making Effectiveness (COMRADE) that assesses decision-making effectiveness (effectiveness) and risk communication (communication). Bivariate analyses and multiple linear regression were used to identify variables associated with SDM. Results: Participants were mostly male (83%) and White (70%) and were an average age of 54 years ( SD = 14.3). Most had traumatic etiology, 44% paraplegia, and 49% complete injury. Veteran/civilian status and demographics were unrelated to scores. Bivariate analyses showed that individuals with tetraplegia had better effectiveness scores than those with paraplegia. Better effectiveness was correlated with better physical and mental health; better communication was correlated with better mental health. Multiple linear regressions showed that tetraplegia, better physical health, and better mental health were associated with better effectiveness, and better mental health was associated with better communication. Conclusion: SCI/D and health characteristics were the only variables associated with SDM. Interventions to increase engagement in SDM and provider attention to SDM may be beneficial, especially for individuals with paraplegia or in poorer physical and mental health.

Theoretical rationale for music selection in oncology intervention research: an integrative review.

PubMed

Burns, Debra S

2012-01-01

Music-based interventions have helped patients with cancer improve their quality of life, decrease treatment related distress, and manage pain. However, quantitative findings from music intervention studies are inconsistent. The purpose of this review was to explore the theoretical underpinnings for the selection of the music stimuli used to influence targeted outcomes. It was hypothesized that disparate findings were due in part to the atheoretical nature of music selection and the resulting diversity in music stimuli between and within studies. A systematic research synthesis including a comprehensive database and reference list search resulted in 22 studies. Included studies were compiled into two tables cataloging intervention theory, intervention content, and outcomes. A majority of studies did not provide a rationale or intervention theory for the delivery of music or choice of outcomes. Recorded music was the most common delivery method, but the specific music was rarely included within the report. Only two studies that included a theoretical framework reported null results on at least some of the outcomes. Null results are partially explained by an incomplete or mismatch in intervention theory and music selection and delivery. While the inclusion of an intervention theory does not guarantee positive results, including a theoretical rationale for the use of music, particular therapeutic processes or mechanisms, and the specifics of how music is selected and delivered increases scientific rigor and the probability of clinical translation.

Rationale for windshield glass system specification requirements for shuttle orbiter

NASA Technical Reports Server (NTRS)

Hayashida, K.; King, G. L.; Tesinsiky, J.; Wittenburg, D. R.

1972-01-01

A preliminary procurement specification for the space shuttle orbiter windshield pane, and some of the design considerations and rationale leading to its development are presented. The windshield designer is given the necessary methods and procedures for assuring glass pane structural integrity by proof test. These methods and procedures are fully developed for annealed and thermally tempered aluminosilicate, borosilicate, and soda lime glass and for annealed fused silica. Application of the method to chemically tempered glass is considered. Other considerations are vision requirements, protection against bird impact, hail, frost, rain, and meteoroids. The functional requirements of the windshield system during landing, ferrying, boost, space flight, and entry are included.

Rationale for Students Preparation and Entrepreneurship Education in the Face of Global Economic Crisis in Nigeria

ERIC Educational Resources Information Center

Onuma, Nwite

2016-01-01

The rationale for students preparation in job creation through entrepreneurship education was examined. Problems of unemployment among Nigerian university graduates and challenges to entrepreneurship in the face of global economic crisis were also highlighted. The persistent problem of unemployment among University graduates and its attendant…

Fundamental Fairness in Search of a Legal Rationale in Private College Student Discipline and Expulsions

ERIC Educational Resources Information Center

Beach, John A.

1974-01-01

In discussing the present state of the law concerning judicial review of student expulsion and discipline cases at private colleges and universities and the quest for a satisfactory legal rationale for achieving fundamental fairness in those cases, the author argues that there are nonconstitutional doctrines of public policy and contract law not…

Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation.

PubMed

Kim, Young Kwan; Kameo, Yoshitaka; Tanaka, Sakae; Adachi, Taiji

2017-10-01

To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis?

PubMed Central

Muñoz-Torrico, Marcela; Rendon, Adrian; Centis, Rosella; D'Ambrosio, Lia; Fuentes, Zhenia; Torres-Duque, Carlos; Mello, Fernanda; Dalcolmo, Margareth; Pérez-Padilla, Rogelio; Spanevello, Antonio; Migliori, Giovanni Battista

2016-01-01

ABSTRACT The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae. PMID:27812638

Effect of exoskeletal joint constraint and passive resistance on metabolic energy expenditure: Implications for walking in paraplegia

PubMed Central

Kobetic, Rudi; Triolo, Ronald J.

2017-01-01

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses. These mechanisms added passive resistance to the hip (15 Nm) and knee (6 Nm) joints while the exoskeleton constrained joint motion to the sagittal plane. The average oxygen consumption when walking with the exoskeleton was 22.5 ± 3.4 ml O2/min/kg as compared to 11.7 ± 2.0 ml O2/min/kg when walking without the exoskeleton at a comparable speed. The heart rate and physiological cost index with the exoskeleton were at least 30% and 4.3 times higher, respectively, than walking without it. The maximum average speed achieved with the exoskeleton was 1.2 ± 0.2 m/s, at a cadence of 104 ± 11 steps/min, and step length of 70 ± 7 cm. Average peak hip joint angles (25 ± 7°) were within normal range, while average peak knee joint angles (40 ± 8°) were less than normal. Both hip and knee angular velocities were reduced with the exoskeleton as compared to normal. While the walking speed achieved with the exoskeleton could be sufficient for community ambulation, metabolic energy expenditure was significantly increased and unsustainable for such activities. This suggests that passive resistance, constraining leg motion to the sagittal plane, reciprocally coupling the hip joints, and weight of exoskeleton place considerable limitations on the utility of the device and need to be minimized in future designs of practical hybrid neuroprostheses for walking after paraplegia. PMID:28817701

Effect of exoskeletal joint constraint and passive resistance on metabolic energy expenditure: Implications for walking in paraplegia.

PubMed

Chang, Sarah R; Kobetic, Rudi; Triolo, Ronald J

2017-01-01

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses. These mechanisms added passive resistance to the hip (15 Nm) and knee (6 Nm) joints while the exoskeleton constrained joint motion to the sagittal plane. The average oxygen consumption when walking with the exoskeleton was 22.5 ± 3.4 ml O2/min/kg as compared to 11.7 ± 2.0 ml O2/min/kg when walking without the exoskeleton at a comparable speed. The heart rate and physiological cost index with the exoskeleton were at least 30% and 4.3 times higher, respectively, than walking without it. The maximum average speed achieved with the exoskeleton was 1.2 ± 0.2 m/s, at a cadence of 104 ± 11 steps/min, and step length of 70 ± 7 cm. Average peak hip joint angles (25 ± 7°) were within normal range, while average peak knee joint angles (40 ± 8°) were less than normal. Both hip and knee angular velocities were reduced with the exoskeleton as compared to normal. While the walking speed achieved with the exoskeleton could be sufficient for community ambulation, metabolic energy expenditure was significantly increased and unsustainable for such activities. This suggests that passive resistance, constraining leg motion to the sagittal plane, reciprocally coupling the hip joints, and weight of exoskeleton place considerable limitations on the utility of the device and need to be minimized in future designs of practical hybrid neuroprostheses for walking after paraplegia.

Imaging technique for the complete edentulous patient treated conventionally or with mini implant overdenture

PubMed Central

Meleşcanu Imre, M; Preoteasa, E; Țâncu, AM; Preoteasa, CT

2013-01-01

Rationale. The imaging methods are more and more used in the clinical process of modern dentistry. Once the implant based treatment alternatives are nowadays seen as being the standard of care in edentulous patients, these techniques must be integrated in the complete denture treatment. Aim. The study presents some evaluation techniques for the edentulous patient treated by conventional dentures or mini dental implants (mini SKY Bredent) overdentures, using the profile teleradiography. These offer data useful for an optimal positioning of the artificial teeth and the mini dental implants, favoring to obtain an esthetic and functional treatment outcome. We proposed also a method to conceive a simple surgical guide that allows the prosthetically driven implants placement. Material and method. Clinical case reports were made, highlighting the importance of cephalometric evaluation on lateral teleradiographs in complete edentulous patients. A clinical case that gradually reports the surgical guide preparation (Bredent silicon radio opaque), in order to place the mini dental implants in the best prosthetic and anatomic conditions, was presented. Conclusions. The profile teleradiograph is a useful tool for the practitioner. It allows establishing the optimal site for implant placement, in a good relation with the overdenture. The conventional denture can be easily and relatively costless transformed in a surgical guide used during implant placement. PMID:23599828

Physics Education Research in the United States: A Summary of Its Rationale and Main Findings.

ERIC Educational Resources Information Center

Gonzales-Espada, Wilson J.

2003-01-01

Recognizes how difficult it is for secondary and post-secondary students to make connections between physics and everyday phenomena, rationalize the use of a particular formula for a given problem, and go beyond algebraic substitutions to really make sense of physics in a meaningful way. Provides a rationale for physicists to become involved in…

A rationale for continuing mass antibiotic distributions for trachoma

PubMed Central

Ray, Kathryn J; Porco, Travis C; Hong, Kevin C; Lee, David C; Alemayehu, Wondu; Melese, Muluken; Lakew, Takele; Yi, Elizabeth; House, Jenafir; Chidambaram, Jaya D; Whitcher, John P; Gaynor, Bruce D; Lietman, Thomas M

2007-01-01

Background The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period. Methods We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection. Results Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages. Conclusion Local elimination from a community is

A rationale for continuing mass antibiotic distributions for trachoma.

PubMed

Ray, Kathryn J; Porco, Travis C; Hong, Kevin C; Lee, David C; Alemayehu, Wondu; Melese, Muluken; Lakew, Takele; Yi, Elizabeth; House, Jenafir; Chidambaram, Jaya D; Whitcher, John P; Gaynor, Bruce D; Lietman, Thomas M

2007-08-07

The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period. We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection. Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages. Local elimination from a community is theoretically possible, even in the

Minimum energy efficiency standards for appliances: Old and new economic rationales

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houde, Sebastien; Spurlock, C. Anna

In this study, we revisit Hausman and Joskow (1982)'s economic rationales for appliance minimum energy efficiency standards. In addition to the four market failures they argued could justify appliance standards--energy prices below marginal social cost, consumers underestimating energy prices, consumer discount rates above social discount rates, or principal agent problems--we discuss two additional market failures that are relevant and potentially economically important in this context: market power and innovation market failures. We highlight puzzles uncovered by recent empirical results, and suggest directions future research should take to better understand the normative implications of appliance standards.

Minimum energy efficiency standards for appliances: Old and new economic rationales

DOE PAGES

Houde, Sebastien; Spurlock, C. Anna

2016-09-01

In this study, we revisit Hausman and Joskow (1982)'s economic rationales for appliance minimum energy efficiency standards. In addition to the four market failures they argued could justify appliance standards--energy prices below marginal social cost, consumers underestimating energy prices, consumer discount rates above social discount rates, or principal agent problems--we discuss two additional market failures that are relevant and potentially economically important in this context: market power and innovation market failures. We highlight puzzles uncovered by recent empirical results, and suggest directions future research should take to better understand the normative implications of appliance standards.

Sample of a client intake information protocol: a synopsis and rationale.

PubMed

Green, Shari

2012-11-01

The utilization of standardized comprehensive forms in the field of orofacial myology is crucial as this profession continues to grow and establish assessment and treatment protocols. This article formally presents a comprehensive health history intake form currently in use, and highlights the rationale for each particular question within this form in an effort to explore the evidence-based theory behind each question utilized. Highlighting the importance of obtaining a thorough health history as it pertains to our profession, personally allows the clinician to ultimately best plan a therapeutic strategy and assess the individual criteria necessary for successful orofacial myofunctional habituation.

Do the kinematics of a baulked take-off in springboard diving differ from those of a completed dive.

PubMed

Barris, Sian; Farrow, Damian; Davids, Keith

2013-01-01

Consistency and invariance in movements are traditionally viewed as essential features of skill acquisition and elite sports performance. This emphasis on the stabilization of action has resulted in important processes of adaptation in movement coordination during performance being overlooked in investigations of elite sport performance. Here we investigate whether differences exist between the movement kinematics displayed by five, elite springboard divers (age 17 ± 2.4 years) in the preparation phases of baulked and completed take-offs. The two-dimensional kinematic characteristics of the reverse somersault take-off phases (approach and hurdle) were recorded during normal training sessions and used for intra-individual analysis. All participants displayed observable differences in movement patterns at key events during the approach phase; however, the presence of similar global topological characteristics suggested that, overall, participants did not perform distinctly different movement patterns during completed and baulked dives. These findings provide a powerful rationale for coaches to consider assessing functional variability or adaptability of motor behaviour as a key criterion of successful performance in sports such as diving.

Rationale for Students' Participation in University Governance and Organizational Effectiveness in Ekiti and Ondo States, Nigeria

ERIC Educational Resources Information Center

Akomolafe, C. O.; Ibijola, E. Y.

2012-01-01

The study investigated the rationale for students' participation in university governance and organizational effectiveness. A descriptive research of survey design was adopted. The population consisted of all staff and students of Ekiti State University, Ado Ekiti, Ekiti State and Adekunle Ajasin University, Akungba-Akoko, Ondo State. 700 subjects…

Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

ERIC Educational Resources Information Center

Friedmann, Peter D.; Katz, Elizabeth C.; Rhodes, Anne G.; Taxman, Faye S.; O'Connell, Daniel J.; Frisman, Linda K.; Burdon, William M.; Fletcher, Bennett W.; Litt, Mark D.; Clarke, Jennifer; Martin, Steven S.

2008-01-01

This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment…

Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

PubMed

Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F; Nöthen, Markus M; Munnich, Arnold; Strom, Tim M; Reis, Andre; Colleaux, Laurence

2011-06-10

Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42(∗)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs(∗)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short Stature

PubMed Central

Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H.; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F.; Nöthen, Markus M.; Munnich, Arnold; Strom, Tim M.; Reis, Andre; Colleaux, Laurence

2011-01-01

Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42∗), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs∗20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex. PMID:21620353

Tracing the Rationale Behind UML Model Change Through Argumentation

NASA Astrophysics Data System (ADS)

Jureta, Ivan J.; Faulkner, Stéphane

Neglecting traceability—i.e., the ability to describe and follow the life of a requirement—is known to entail misunderstanding and miscommunication, leading to the engineering of poor quality systems. Following the simple principles that (a) changes to UML model instances ought be justified to the stakeholders, (b) justification should proceed in a structured manner to ensure rigor in discussions, critique, and revisions of model instances, and (c) the concept of argument instantiated in a justification process ought to be well defined and understood, the present paper introduces the UML Traceability through Argumentation Method (UML-TAM) to enable the traceability of design rationale in UML while allowing the appropriateness of model changes to be checked by analysis of the structure of the arguments provided to justify such changes.

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale.

PubMed

Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations.

PubMed

Conceição Pereira, Maria; Loureiro, José Leal; Pinto-Basto, Jorge; Brandão, Eva; Margarida Lopes, Ana; Neves, Georgina; Dias, Pureza; Geraldes, Ruth; Martins, Isabel Pavão; Cruz, Vitor Tedim; Kamsteeg, Erik-Jan; Brunner, Han G; Coutinho, Paula; Sequeiros, Jorge; Alonso, Isabel

2012-01-01

Hereditary spastic paraplegias compose a group of neurodegenerative disorders with a large clinical and genetic heterogeneity. Among the autosomal recessive forms, spastic paraplegia type 11 is the most common. To better understand the spastic paraplegia type 11 mutation spectrum, we studied a group of 54 patients with hereditary spastic paraplegia. Mutation screening was performed by PCR amplification of SPG11 coding regions and intron boundaries, followed by sequencing. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification. We report 13 families with spastic paraplegia type 11 carrying either novel or previously identified mutations. We describe a complex entire SPG11 rearrangement and show that large gene rearrangements are frequent among patients with spastic paraplegia type 11. Moreover, we mapped the deletion breakpoints of three different large SPG11 deletions and provide evidence for Alu microhomology-mediated exon deletion. Our analysis shows that the high number of repeated elements in SPG11 together with the presence of recombination hotspots and the high intrinsic instability of the 15q locus all contribute toward making this genomic region more prone to large gene rearrangements. These findings enlarge the amount of data relating repeated elements with neurodegenerative disorders and highlight their importance in human disease and genome evolution.

A rationale for human operator pulsive control behavior

NASA Technical Reports Server (NTRS)

Hess, R. A.

1979-01-01

When performing tracking tasks which involve demanding controlled elements such as those with K/s-squared dynamics, the human operator often develops discrete or pulsive control outputs. A dual-loop model of the human operator is discussed, the dominant adaptive feature of which is the explicit appearance of an internal model of the manipulator-controlled element dynamics in an inner feedback loop. Using this model, a rationale for pulsive control behavior is offered which is based upon the assumption that the human attempts to reduce the computational burden associated with time integration of sensory inputs. It is shown that such time integration is a natural consequence of having an internal representation of the K/s-squared-controlled element dynamics in the dual-loop model. A digital simulation is discussed in which a modified form of the dual-loop model is shown to be capable of producing pulsive control behavior qualitively comparable to that obtained in experiment.

The Right Not to Hear as a Rationale for Broadcast Regulation: A Review and an Appraisal.

ERIC Educational Resources Information Center

Glasser, Theodore L.; Jassem, Harvey C.

"FCC v. Pacifica Foundation," a 1978 case involving a radio broadcast considered to be indecent, was the first United States Supreme Court litigation using the right of privacy, or the right not to hear, as a rationale for broadcast regulation of programing. The issue of pornography best illustrates the judiciary's understanding of the…

Computer Based Instructional Techniques in Undergraduate Introductory Organic Chemistry: Rationale, Developmental Techniques, Programming Strategies and Evaluation.

ERIC Educational Resources Information Center

Culp, G. H.; And Others

Over 100 interactive computer programs for use in general and organic chemistry at the University of Texas at Austin have been prepared. The rationale for the programs is based upon the belief that computer-assisted instruction (CAI) can improve education by, among other things, freeing teachers from routine tasks, measuring entry skills,…

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Long-term follow-up of HIV seroconverters in microbicide trials - rationale, study design, and challenges in MTN-015.

PubMed

Riddler, Sharon A; Husnik, Marla; Gorbach, Pamina M; Levy, Lisa; Parikh, Urvi; Livant, Edward; Pather, Arendevi; Makanani, Bonus; Muhlanga, Felix; Kasaro, Margaret; Martinson, Francis; Elharrar, Vanessa; Balkus, Jennifer E

2016-09-01

As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort. Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing. MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness. Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.

Understanding the Rationale for Preschool Physical Education: Implications for Practitioners' and Children's Embodied Practices and Subjectivity Formation

ERIC Educational Resources Information Center

McEvilly, Nollaig; Atencio, Matthew; Verheul, Martine; Jess, Mike

2013-01-01

This paper provides an overview of selected academic research literature that underpins contemporary preschool physical education. We highlight and interrogate diverse rationales and beliefs that serve to influence and structure preschool physical education in various forms. We speculate as to how preschool practitioners and children might engage…

Four Rationales of HE Internationalization: Perspectives of U.K. Universities on Attracting Students from Former Soviet Countries

ERIC Educational Resources Information Center

Chankseliani, Maia

2018-01-01

In the context marked by increasing competition between nation-states and universities, expanding individualization, growing influence of nonstate actors, and the new reality of Brexit, this study uses narrative and numeric data to explore the rationales of U.K. higher education (HE) internationalization, specifically motives of attracting…

The VEPSY UPDATED Project: clinical rationale and technical approach.

PubMed

Riva, G; Alcãniz, M; Anolli, L; Bacchetta, M; Baños, R; Buselli, C; Beltrame, F; Botella, C; Castelnuovo, G; Cesa, G; Conti, S; Galimberti, C; Gamberini, L; Gaggioli, A; Klinger, E; Legeron, P; Mantovani, F; Mantovani, G; Molinari, E; Optale, G; Ricciardiello, L; Perpiñá, C; Roy, S; Spagnolli, A; Troiani, R; Weddle, C

2003-08-01

More than 10 years ago, Tart (1990) described virtual reality (VR) as a technological model of consciousness offering intriguing possibilities for developing diagnostic, inductive, psychotherapeutic, and training techniques that can extend and supplement current ones. To exploit and understand this potential is the overall goal of the "Telemedicine and Portable Virtual Environment in Clinical Psychology"--VEPSY UPDATED--a European Community-funded research project (IST-2000-25323, www.cybertherapy.info). Particularly, its specific goal is the development of different PC-based virtual reality modules to be used in clinical assessment and treatment of social phobia, panic disorders, male sexual disorders, obesity, and eating disorders. The paper describes the clinical and technical rationale behind the clinical applications developed by the project. Moreover, the paper focuses its analysis on the possible role of VR in clinical psychology and how it can be used for therapeutic change.

Apoptotic impact on Brugia malayi by sulphonamido-quinoxaline: search for a novel therapeutic rationale.

PubMed

Bhoj, Priyanka S; Ingle, Rahul G; Goswami, Kalyan; Jena, Lingaraj; Wadher, Shailesh

2018-05-01

Human lymphatic filariasis although not fatal but poses serious socioeconomic burden due to associated disability. This is reflected by the huge magnitude of the estimated disability-adjusted life years of about 5.09 million. Therefore, following WHO mandate, our earlier studies on antifilarial drug development revealed the significance of apoptosis. Apoptotic impact has been implicated in anticancer rationale of several drugs. In this study, we explored the antifilarial potential of sulphonamido-quinoxaline compounds, shown to be specific inhibitor for c-Met kinase in human cancer cells. Out of studied compounds, Q4, showing favorable drug-likeness and medicinal chemistry properties on bioinformatics platform along with subsequently recorded lowest IC 100 value, was considered as a suitable antifilarial candidate. Significant apoptosis due to mitochondrial involvement was recorded in drug-treated parasite unlike untreated control. In spite of homology between human c-Met kinase and Brugia malayi counterpart, comparative docking result of this compound showed more favorable binding parameters with the parasitic target. The wide gap between IC 100 and LD 50 values further confirmed the therapeutic safety. We propose sulphonamido-quinoxaline derivative as a lead candidate for antifilarial drug development. Further study is warranted to authenticate parasitic c-Met kinase as a novel therapeutic target reminiscent of anticancer rationale implicating inhibition of proliferation.

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale

PubMed Central

Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583

Better exercise adherence after treatment for cancer (BEAT Cancer) study: Rationale, design, and methods

PubMed Central

Rogers, Laura Q.; McAuley, Edward; Anton, Philip M.; Courneya, Kerry S.; Vicari, Sandra; Hopkins-Price, Patricia; Verhulst, Steven; Mocharnuk, Robert; Hoelzer, Karen

2011-01-01

Most breast cancer survivors do not engage in regular physical activity. Our physical activity behavior change intervention for breast cancer survivors significantly improved physical activity and health outcomes post-intervention during a pilot, feasibility study. Testing in additional sites with a larger sample and longer follow-up is warranted to confirm program effectiveness short and longer term. Importantly, the pilot intervention resulted in changes in physical activity and social cognitive theory constructs, enhancing our potential for testing mechanisms mediating physical activity behavior change. Here, we report the rationale, design, and methods for a two-site, randomized controlled trial comparing the effects of the BEAT Cancer physical activity behavior change intervention to usual care on short and longer term physical activity adherence among breast cancer survivors. Secondary aims include examining social cognitive theory mechanisms of physical activity behavior change and health benefits of the intervention. Study recruitment goal is 256 breast cancer survivors with a history of ductal carcinoma in situ or Stage I, II, or IIIA disease who have completed primary cancer treatment. Outcome measures are obtained at baseline, 3 months (i.e., immediately post-intervention), 6 months, and 12 months and include physical activity, psychosocial factors, fatigue, sleep quality, lower extremity joint dysfunction, cardiorespiratory fitness, muscle strength, and waist-to-hip ratio. Confirming behavior change effectiveness, health effects, and underlying mechanisms of physical activity behavior change interventions will facilitate translation to community settings for improving the health and well-being of breast cancer survivors. PMID:21983625

Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia

PubMed Central

Denton, Kyle R.; Lei, Ling; Grenier, Jeremy; Rodionov, Vladimir; Blackstone, Craig; Li, Xue-Jun

2013-01-01

Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP. PMID:24123785

Secondary School Students Learning from Reflections on the Rationale behind Self-Made Errors: A Field Experiment

ERIC Educational Resources Information Center

Heemsoth, Tim; Heinze, Aiso

2016-01-01

Thus far, it is unclear how students can learn most effectively from their own errors. In this study, reflections on the rationale behind self-made errors are assumed to enhance knowledge acquisition. In a field experiment with pre/post/follow-up design, the authors practiced fractions with 174 seventh- and eighth-grade students who were randomly…

Telemetry: Summary of concept and rationale

NASA Astrophysics Data System (ADS)

1987-12-01

This report presents the concept and supporting rationale for the telemetry system developed by the Consultative Committee for Space Data Systems (CCSDS). The concepts, protocols and data formats developed for the telemetry system are designed for flight and ground data systems supporting conventional, contemporary free-flyer spacecraft. Data formats are designed with efficiency as a primary consideration, i.e., format overhead is minimized. The results reflect the consensus of experts from many space agencies. An overview of the CCSDS telemetry system introduces the notion of architectural layering to achieve transparent and reliable delivery of scientific and engineering sensor data (generated aboard space vehicles) to users located in space or on earth. The system is broken down into two major conceptual categories: a packet telemetry concept and a telemetry channel coding concept. Packet telemetry facilitates data transmission from source to user in a standardized and highly automated manner. It provides a mechanism for implementing common data structures and protocols which can enhance the development and operation of space mission systems. Telemetry channel coding is a method by which data can be sent from a source to a destination by processing it in such a way that distinct messages are created which are easily distinguishable from one another. This allows construction of the data with low error probability, thus improving performance of the channel.

Extracorporeal blood purification therapy for sepsis and systemic inflammation: its biological rationale.

PubMed

Bellomo, R; Baldwin, I; Ronco, C

2001-01-01

EBPTs represent a promising new approach to the adjuvant treatment of severe sepsis, septic shock and MODS. Their technology is rapidly evolving and pilot animal and human studies are now taking place to prepare the territory for the first large randomized controlled trial. The rationale for EBPT is reasonable and the initial data are encouraging. The correct technology and molecular targeting, however, are still being explored. Once the best technology has been determined, it is likely that phase II and phase III trials will be performed to test the hypothesis that these therapies can indeed alter mortality in severe inflammatory multiorgan dysfunction.

The Italian Consensus Conference on Pain in Neurorehabilitation: rationale and methodology

PubMed Central

Tamburin, Stefano; Paolucci, Stefano; Magrinelli, Francesca; Musicco, Massimo; Sandrini, Giorgio

2016-01-01

Pain is very common in the neurorehabilitation setting, where it may not only represent a target for treatment but can also negatively influence rehabilitation procedures directly or through the side effects of painkillers. To date, there are neither guidelines nor consensus on how to assess and treat pain in neurorehabilitation. Because of the very scanty pieces of evidence on this topic, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) was promoted under the auspices of different scientific societies. This article illustrates the rationale, methodology, and topics of the ICCPN. The recommendations of the ICCPN will offer some information on how to deal with pain in neurorehabilitation and may represent the starting point for further studies. PMID:27313474

Consumer Evaluation of Educational Programs: Using Questionnaires Completed by Alumni.

ERIC Educational Resources Information Center

Copeland, H. L.; Hewson, M.; Weiker, G.

This paper describes a method used to evaluate 48 medical residency programs at one institution. It presents the background rationale, logistics, and results obtained by surveying alumni, in the context of their current practice, for relevant data on the value of their training experience. Surveys were sent for 3 years to all alumni of Cleveland…

Rationale for In-Neonatal Intensive Care Unit Administration of Live, Attenuated Rotavirus Vaccination.

PubMed

Briggs-Steinberg, Courtney; Shah, Shetal

2018-06-08

Rotavirus is the most common nonseasonal vaccine preventable illness. Despite increased severity of rotaviral illness in early infancy, most neonatal intensive care units (NICU) do not administer rotavirus vaccination either during the NICU stay at age of eligibility or at discharge as the Advisory Committee on Immunization Practices recommends. In this commentary, we review the rationale for the administration of rotavirus vaccination to premature infants. Further, we outline data supporting vaccine administration at chronologic age while still admitted to the NICU. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol.

PubMed

Fine, Naomi B; Achituv, Michal; Etkin, Amit; Merin, Ofer; Shalev, Arieh Y

2018-01-01

Background : The immediate aftermath of traumatic events is a period of enhanced neural plasticity, following which some survivors remain with post-traumatic stress disorder (PTSD) whereas others recover. Evidence points to impairments in emotional reactivity, emotion regulation, and broader executive functions as critically contributing to PTSD. Emerging evidence further suggests that the neural mechanisms underlying these functions remain plastic in adulthood and that targeted retraining of these systems may enhance their efficiency and could reduce the likelihood of developing PTSD. Administering targeted neurocognitive training shortly after trauma exposure is a daunting challenge. This work describes a study design addressing that challenge. The study evaluated the direct effects of cognitive remediation training on neurocognitive mechanisms that hypothetically underlay PTSD, and the indirect effect of this intervention on emerging PTSD symptoms. Method : We describe a study rationale, design, and methodological choices involving: (a) participants' enrolment; (b) implementation and management of a daily self-administered, web-based intervention; (c) reliable, timely screening and assessment of treatment of eligible survivors; and (d) defining control conditions and outcome measures. We outline the rationale of choices made regarding study sample, timing of intervention, measurements, monitoring participants' adherence, and ways to harmonize and retain interviewers' fidelity and mitigate eventual burnout by repeated contacts with recently traumatized survivors. Conclusion : Early web-based interventions targeting causative mechanisms of PTSD can be informed by the model presented in this paper.

The Rationale for Subsidy of Higher Education in Hong Kong: A Sensible Decision from an Economic Viewpoint

ERIC Educational Resources Information Center

Chan, Shing Yin Amy

2010-01-01

This paper is an attempt to draw the statistical data from reports and documents to reveal the rationale for subsidizing the higher education in Hong Kong. There is a discussion made with reference to educational planning interacting with personal choice. The notion of economics has been noted with consideration of allocation of scarce resources…

Relationship of occupational therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: The SCIRehab Project

PubMed Central

Ozelie, Rebecca; Gassaway, Julie; Buchman, Emily; Thimmaiah, Deepa; Heisler, Lauren; Cantoni, Kara; Foy, Teresa; Hsieh, Ching-Hui (Jean); Smout, Randall J.; Kreider, Scott E. D.; Whiteneck, Gale

2012-01-01

Background/objective Describe associations of occupational therapy (OT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and 1-year post-injury. Methods Occupational therapists at six inpatient rehabilitation centers documented detailed information about treatment provided. Least squares regression modeling was used to predict outcomes at discharge and 1-year injury anniversary for a 75% subset; models were validated with the remaining 25%. Functional outcomes for injury subgroups (motor complete low tetraplegia and motor complete paraplegia) also were examined. Results OT treatment variables explain a small amount of variation in Functional Independence Measure (FIM) outcomes for the full sample and significantly more in two functionally homogeneous subgroups. For patients with motor complete paraplegia, more time spent in clothing management and hygiene related to toileting was a strong predictor of higher scores on the lower body items of the self-care component of the discharge motor FIM. Among patients with motor complete low tetraplegia, higher scores for the FIM lower body self-care items were associated with more time spent on lower body dressing, manual wheelchair mobility training, and bathing training. Active patient participation during OT treatment sessions also was predictive of FIM and other outcomes. Conclusion OT treatments add to explained variance (in addition to patient characteristics) for multiple outcomes. The impact of OT treatment on functional outcomes is more evident when examining more homogeneous patient groupings and outcomes specific to the groupings. Note This is the third of nine articles in the SCIRehab series. PMID:23318035

Exploring the Rationale for Group Music Activities for Parents and Young Children: Parents' and Practitioners' Perspectives

ERIC Educational Resources Information Center

Pitt, Jessica; Hargreaves, David

2017-01-01

Children's Centres are widespread in England and comprise multi-professional staff teams seeking to work with families with children aged 0-5 years. Although parent-child group music sessions appear frequently in Children's Centre activity programmes, the rationale for their inclusion remains unclear. This article presents the results from phase…

Subsidizing Early Childhood Education and Care for Parents on Low Income: Moving beyond the Individualized Economic Rationale of Neoliberalism

ERIC Educational Resources Information Center

Simpson, Donald; Envy, Rose

2015-01-01

Neoliberalism and an associated "new politics of parenting" adopts a predominantly economic rationale which discursively positions early childhood education and care (ECEC) as essential to tackling several social ills by allowing individual parents (particularly young mothers) to improve their labour force participation, thus boosting…

Challenge of handling a Charcot spinal arthropathy with a novel hybrid fibular autograft and expandable cage.

PubMed

Ohana, Nissim; Benharroch, Daniel; Sheinis, Dimitri

2018-04-13

A 26-year-old man, who was paraplegic for 6 years due to a motor vehicle accident, presented to the authors' clinic following his incapacity to withstand a sitting posture, the frequent sensation of "clicks" in his back, and a complaint of back pain while in his wheelchair. On imaging, his dorsal spine showed a complete arthrodesis of the primarily fused vertebrae. However, distal to this segment, a Charcot spinal arthropathy with subluxation of T12-L1 was evident. Repair of this complex, uncommon, late complication of his paraplegia by the frequently used fusion techniques was shown to be inappropriate. A novel and elaborate surgical procedure is presented by which a complete fusion of the affected spine was secured. A left retrodiaphragmatic approach was used. Complete corpectomy of both the T-12 and L-1 vertebrae to the preserved endplates was performed. Most of the patient's fibula was resected and shaped for engrafting. The segment of the fibula was introduced into a mesh cage, before its intramedullary implantation into the T-12 and L-1 vertebrae. This 2-step procedure combined the hybrid use of a fibular autograft and an expandable mesh cage, incorporated one into the other, in an innovative intramedullary position. This intervention allowed the patient to resume his former condition as an extremely physically active patient with paraplegia. Nine years later, an asymptomatic early-stage Charcot spine was found at L5-S1, but no treatment is planned at this point.

Implementing Attachment and Biobehavioral Catch-Up with birth parents: Rationale and case example.

PubMed

Hoye, Julie R; Dozier, Mary

2018-05-25

Attachment and Biobehavioral Catch-Up (ABC) is an intervention designed for vulnerable children and their parents. This intervention enhances parental sensitivity and nurturance with the goal of promoting secure, organized attachments and strong self-regulatory capabilities among children. Here, we provide a brief rationale for the need for such interventions to be delivered to parent-child dyads in the child welfare system. Next, we review specific intervention targets of ABC. We include a case example of two birth parents and their daughter who became involved in Child Protective Services due to domestic violence. © 2018 Wiley Periodicals, Inc.

The role of pulse oximetry in chiropractic practice: a rationale for its use

PubMed Central

Hall, Michael W.; Jensen, Anne M.

2012-01-01

Objective Pulse oximetry is used regularly to assess oxygen saturation levels. The objective of this commentary is to discuss a rationale for using pulse oximetry in chiropractic practice. Discussion Pulse oximetry may offer doctors of chiropractic a way to monitor patients' oxygen saturation levels. Quantification of saturation values with heart rate may give clinical aid to the management of chiropractic patients. Markedly reduced saturation levels may necessitate medical referral, whereas mildly reduced levels could lead to changes in chiropractic management. Conclusions Pulse oximetry has the potential to be an integral part of chiropractic practice. PMID:23204957

The Why and What of ESD: A Rationale for Earth Charter Education (and Naming Some of Its Difficulties)

ERIC Educational Resources Information Center

Preston, Noel

2010-01-01

This article explores Earth Charter education as a form of values education that is integral to education for sustainable development. Initially, it outlines how Earth Charter education rests on an ecocentric worldview and a social analysis of ecojustice--terms that are defined and explained. Moving from this rationale, the article explores issues…

Effective Structured Query Formulation for Session Search

DTIC Science & Technology

2012-11-01

with top frequency are “type of paralysi”, “ quadriplegia paraplegia”, “paraplegia”, “spinal cord injury”, and “quadriplegic tetraplegic”, so the final... quadriplegia paraplegia) 0.004819 paraplegia 0.004819 #combine(spinal cord injury) 0.00241 #combine(quadriplegic tetraplegic) )”, where the

A Rationale and Framework for Establishing a Systems Engineering Community Within the Department of the Army

DTIC Science & Technology

2011-03-01

transition into the ranks of employees. • Make contact not solely with students , but with all those who impact their decision-making: parents, teachers ...SUBTITLE A Rationale and Framework for Establishing a Systems Engineering Community Within the Department of the Army 6. AUTHOR( S ) Alan Clayton...fields the most operationally effective military force in the world. However, fielding such a force has been challenging, as seen by the multiple

A preliminary report of music-based training for adult cochlear implant users: Rationales and development.

PubMed

Gfeller, Kate; Guthe, Emily; Driscoll, Virginia; Brown, Carolyn J

2015-09-01

This paper provides a preliminary report of a music-based training program for adult cochlear implant (CI) recipients. Included in this report are descriptions of the rationale for music-based training, factors influencing program development, and the resulting program components. Prior studies describing experience-based plasticity in response to music training, auditory training for persons with hearing impairment, and music training for CI recipients were reviewed. These sources revealed rationales for using music to enhance speech, factors associated with successful auditory training, relevant aspects of electric hearing and music perception, and extant evidence regarding limitations and advantages associated with parameters for music training with CI users. This informed the development of a computer-based music training program designed specifically for adult CI users. Principles and parameters for perceptual training of music, such as stimulus choice, rehabilitation approach, and motivational concerns were developed in relation to the unique auditory characteristics of adults with electric hearing. An outline of the resulting program components and the outcome measures for evaluating program effectiveness are presented. Music training can enhance the perceptual accuracy of music, but is also hypothesized to enhance several features of speech with similar processing requirements as music (e.g., pitch and timbre). However, additional evaluation of specific training parameters and the impact of music-based training on speech perception of CI users is required.

A preliminary report of music-based training for adult cochlear implant users: rationales and development

PubMed Central

Gfeller, Kate; Guthe, Emily; Driscoll, Virginia; Brown, Carolyn J.

2015-01-01

Objective This paper provides a preliminary report of a music-based training program for adult cochlear implant (CI) recipients. Included in this report are descriptions of the rationale for music-based training, factors influencing program development, and the resulting program components. Methods Prior studies describing experience-based plasticity in response to music training, auditory training for persons with hearing impairment, and music training for cochlear implant recipients were reviewed. These sources revealed rationales for using music to enhance speech, factors associated with successful auditory training, relevant aspects of electric hearing and music perception, and extant evidence regarding limitations and advantages associated with parameters for music training with CI users. This information formed the development of a computer-based music training program designed specifically for adult CI users. Results Principles and parameters for perceptual training of music, such as stimulus choice, rehabilitation approach, and motivational concerns were developed in relation to the unique auditory characteristics of adults with electric hearing. An outline of the resulting program components and the outcome measures for evaluating program effectiveness are presented. Conclusions Music training can enhance the perceptual accuracy of music, but is also hypothesized to enhance several features of speech with similar processing requirements as music (e.g., pitch and timbre). However, additional evaluation of specific training parameters and the impact of music-based training on speech perception of CI users are required. PMID:26561884

Cognitive defusion versus thought distraction: a clinical rationale, training, and experiential exercise in altering psychological impacts of negative self-referential thoughts.

PubMed

Masuda, Akihiko; Feinstein, Amanda B; Wendell, Johanna W; Sheehan, Shawn T

2010-11-01

Using two modes of intervention delivery, the present study compared the effects of a cognitive defusion strategy with a thought distraction strategy on the emotional discomfort and believability of negative self-referential thoughts. One mode of intervention delivery consisted of a clinical rationale and training (i.e., Partial condition). The other mode contained a condition-specific experiential exercise with the negative self-referential thought in addition to the clinical rationale and training (i.e., Full condition). Nonclinical undergraduates were randomly assigned to one of five protocols: Partial-Defusion, Full-Defusion, Partial-Distraction, Full-Distraction, and a distraction-based experimental control task. The Full-Defusion condition reduced the emotional discomfort and believability of negative self-referential thoughts significantly more than other comparison conditions. The positive results of the Full-Defusion condition were also found among participants with elevated depressive symptoms.

A review of the scientific rationale and methods used in the search for other planetary systems

NASA Technical Reports Server (NTRS)

Black, D. C.

1985-01-01

Planetary systems appear to be one of the crucial links in the chain leading from simple molecules to living systems, particularly complex (intelligent?) living systems. Although there is currently no observational proof of the existence of any planetary system other than our own, techniques are now being developed which will permit a comprehensive search for other planetary systems. The scientific rationale for and methods used in such a search effort are reviewed here.

Mission-oriented requirements for updating MIL-H-8501. Volume 2: STI background and rationale. [military rotorcraft

NASA Technical Reports Server (NTRS)

Clement, W. F.; Hoh, R. H.; Mitchell, D. G.; Ferguson, S. W., III

1985-01-01

A supplement to the structure of a new flying and ground handling qualities specification for military rotorcraft structure is presented in order to explain the background and rationale for the specification structure, the proposed forms of criteria, and the status of the existing data base. Critical gaps in the data base for the new structure are defined, and recommendations are provided for the research required to address the most important of these gaps.

ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor in hereditary spastic paraplegia.

PubMed

Nielsen, Troels Tolstrup; Svenstrup, Kirsten; Budtz-Jørgensen, Esben; Eiberg, Hans; Hasholt, Lis; Nielsen, Jørgen E

2012-10-15

Hereditary spastic paraplegia (HSP) confines a group of heterogeneous neurodegenerative disorders characterized by progressive spasticity and lower limb weakness. Age of onset is highly variable even in familial cases with known mutations suggesting that the disease is modulated by other yet unknown parameters. Although progressive gait disturbances, lower limb spasticity and extensor plantar responses are hallmarks of HSP these characteristics are also found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis (ALS). HSP has been linked to ALS and frontotemporal degeneration with motor neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been found in an HSP subtype, and TDP-43 are found in abundance in pathological inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene ATXN2), a polyglutamine containing protein elongated in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering the similarities in the disease phenotype and the neuropathological link between ALS and HSP we hypothesized that intermediate-length CAG/CAA repeats in ATXN2 could be a modulator of HSP. We show that in a cohort of 181 HSP patients 4.9 % of the patients had intermediate-length CAG/CAA repeats in ATXN2 which was not significantly different from the frequencies in a Danish control cohort or in American and European control populations. However, the mean age of onset was significantly lower in HSP patients with intermediate-length CAG/CAA repeats in ATXN2 compared to patients with normal length repeats. Based on these results we conclude that ATXN2 is most likely not a risk factor of HSP, whereas it might serve as a modulator of age of onset. Copyright © 2012 Elsevier B.V. All

Shoulder Muscular Demand During Lever-Activated Vs Pushrim Wheelchair Propulsion in Persons With Spinal Cord Injury

PubMed Central

Requejo, Philip Santos; Lee, Sharon E; Mulroy, Sara J; Haubert, Lisa Lighthall; Bontrager, Ernest L; Gronley, JoAnne K; Perry, Jacquelin

2008-01-01

Background/Objective: The high demand on the upper limbs during manual wheelchair (WC) use contributes to a high prevalence of shoulder pathology in people with spinal cord injury (SCI). Lever-activated (LEVER) WCs have been presented as a less demanding alternative mode of manual WC propulsion. The objective of this study was to evaluate the shoulder muscle electromyographic activity and propulsion characteristics in manual WC users with SCI propelling a standard pushrim (ST) and LEVER WC design. Methods: Twenty men with complete injuries (ASIA A or B) and tetraplegia (C6, n = 5; C7, n = 7) or paraplegia (n = 8) secondary to SCI propelled ST and LEVER WCs at 3 propulsion conditions on a stationary ergometer: self-selected free, self-selected fast, and simulated graded resistance. Average velocity, cycle distance, and cadence; median and peak electromyographic intensity; and duration of electromyography of anterior deltoid, pectoralis major, supraspinatus, and infraspinatus muscles were compared between LEVER and ST WC propulsion. Results: Significant decreases in pectoralis major and supraspinatus activity were recorded during LEVER compared with ST WC propulsion. However, anterior deltoid and infraspinatus intensities tended to increase during LEVER WC propulsion. Participants with tetraplegia had similar or greater anterior deltoid, pectoralis major, and infraspinatus activity for both ST and LEVER WC propulsion compared with the men with paraplegia. Conclusions: Use of the LEVER WC reduced and shifted the shoulder muscular demands in individuals with paraplegia and tetraplegia. Further studies are needed to determine the impact of LEVER WC propulsion on long-term shoulder function. PMID:19086715

Assessing the Rationale and Effectiveness of Frozen Plasma Transfusions: An Evidence-based Review.

PubMed

Tinmouth, Alan

2016-06-01

Frozen plasma is a commonly used blood product. The primary indications for frozen plasma are the treatment and prevention of bleeding in patients with prolonged coagulation tests. However, there is a lack of well-conducted clinical trials to determine the appropriate indications for frozen plasma. The rationale and evidence for frozen plasma transfusions are reviewed, including the evidence or lack of evidence supporting common indications. Targeting indications in which frozen plasma transfusions are clearly not beneficial as supported by the current evidence provides an opportunity to improve the current use of frozen plasma and reduce adverse transfusion events. Copyright © 2016 Elsevier Inc. All rights reserved.

The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease☆

PubMed Central

Dale, Philippa R; Cernecka, Hana; Schmidt, Martina; Dowling, Mark R; Charlton, Steven J; Pieper, Michael P; Michel, Martin C

2014-01-01

Muscarinic receptor antagonists and β-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and β-adrenoceptors are physiological antagonists for smooth muscle tone in airways and bladder. Muscarinic agonism may attenuate β-adrenoceptor-mediated relaxation more than other contractile stimuli. Chronic treatment with one drug class may regulate expression of the target receptor but also that of the opposing receptor. Prejunctional β2-adrenoceptors can enhance neuronal acetylcholine release. Moreover, at least in the airways, muscarinic receptors and β-adrenoceptors are expressed in different locations, indicating that only a combined modulation of both systems may cause dilatation along the entire bronchial tree. While all of these factors contribute to a rationale for a combination of muscarinic receptor antagonists and β-adrenoceptor agonists, the full value of such combination as compared to monotherapy can only be determined in clinical studies. PMID:24682092

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

PubMed Central

2016-01-01

Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported. PMID:27896275

Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-involved Diabetic Macular Edema

PubMed Central

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M.; Browning, David J.; Chalam, KV; Davis, Matthew; Ferris, Frederick L; Glassman, Adam; Maturi, Raj; Stockdale, Cynthia R.; Topping, Trexler

2011-01-01

Objective Describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design Discussion of treatment protocol for DME. Participants Subjects with vision loss from DME involving the center of the macula. Methods The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser in eyes with vision loss from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes, compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. In order to share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures Clinical guidelines based on a DRCR.net protocol. Results The treatment protocol required real time feedback from a web-based data entry system for intravitreal injections, focal/grid laser, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month, or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center

Public Risk Criteria and Rationale for Commercial Launch and Reentry

NASA Astrophysics Data System (ADS)

Wilde, P. D.

2012-01-01

This paper summarizes the rationale for risk criteria intended to protect the public during commercial spaceflight, including launch, reentry, and suborbital missions. The recommended approach includes: (1) safety goals to guide periodic updates of the quantitative collective risk limits if warranted based on the quantity of launch and reentry missions; the demonstrated safety record and benefits provided; technological capabilities and maturity of the industry; and contemporary attitudes about the risks from commercial space transportation; (2) separate limits on the risks from each type of mission with explicit definitions of the extent of launch and reentry missions; and (3) quantitative risk limits consistent with the safety goals. For current conditions, the author's recommends (a) maximum of 1E-6 probability of casualty per-mission (b) a maximum of 100E-6 expected casualties per-mission, and (c) equal per-mission risk limits for orbital and suborbital launches, as well as controlled and uncontrolled reentries.

The Definition, Rationale, and Effects of Thresholding in OCT Angiography.

PubMed

Cole, Emily D; Moult, Eric M; Dang, Sabin; Choi, WooJhon; Ploner, Stefan B; Lee, ByungKun; Louzada, Ricardo; Novais, Eduardo; Schottenhamml, Julia; Husvogt, Lennart; Maier, Andreas; Fujimoto, James G; Waheed, Nadia K; Duker, Jay S

2017-01-01

To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images.

Analysis and evaluation of the rationales for single-sex schooling.

PubMed

Bigler, Rebecca S; Hayes, Amy Roberson; Liben, Lynn S

2014-01-01

Amendments passed as part of the No Child Left Behind Act in 2006 made some forms of single-sex (SS) public education legal in the United States. Proponents offer a host of arguments in favor of such schooling. This chapter identifies and evaluates five broad rationales for SS schooling. We conclude that empirical evidence fails to support proponents' claims but nonetheless suggests ways in which to improve coeducation. Specifically, we (a) show that the purported benefits of SS schooling arise from factors confounded with, but not causally linked to, single-sex composition; (b) challenge claims that biological sex is an effective marker of differences relevant to instruction; (c) argue that sexism on the part of teachers and peers persists in SS contexts; and (d) critique the notion that gender per se "disappears" in SS contexts. We also address societal implications of the use of sex-segregated education and conclude that factors found to be beneficial for students should be implemented within coeducational schools.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

A Rationale for Evaluation and Selection of Antioxidants for Protection of Ration Items of Different Types.

DTIC Science & Technology

1982-06-18

phenolic acids or the glycosides of flavonoids . Figure 7 shows some natural monohydric phenols which are antioxidants , like the abundant tocopherols...34 AD-A117 47b ARMY NATICK RESEARCH AND DEVELOPMENT LABS MA F/G 6/8 A RATIONALE FOR EVALUATION AND SELECTION OF ANTIOXIDANTS FOR PR--ETC(U) JUN 82 W L...scientists have searched for effective antioxidants and means of rating this effectiveness (1-4). For the first forty years fats and oils were the lipids

Utilization management in radiology, part 1: rationale, history, and current status.

PubMed

Duszak, Richard; Berlin, Jonathan W

2012-10-01

Previous growth in the utilization of medical imaging has led to numerous efforts to reduce associated spending. Although these have historically been directed toward unit cost reductions, recent interest has emerged by various stakeholders in curbing inappropriate utilization. Radiology benefits managers have widespread market penetration and have been promoted largely by the payer community as effective mechanisms to curb increases in imaging volume. The provider community has tended to favor real-time order entry decision support systems. These have demonstrated comparable effectiveness to radiology benefits managers in early projects but currently have only limited market penetration. In this first of a two-part series, the rationale for the development of utilization management programs will be discussed and their history and current status reviewed. Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.

A Framework for Measuring the Progress in Exoskeleton Skills in People with Complete Spinal Cord Injury

PubMed Central

van Dijsseldonk, Rosanne B.; Rijken, Hennie; van Nes, Ilse J. W.; van de Meent, Henk; Keijsers, Noel L. W.

2017-01-01

For safe application of exoskeletons in people with spinal cord injury at home or in the community, it is required to have completed an exoskeleton training in which users learn to perform basic and advanced skills. So far, a framework to test exoskeleton skills is lacking. The aim of this study was to develop and test the hierarchy and reliability of a framework for measuring the progress in the ability to perform basic and advanced skills. Twelve participants with paraplegia were given twenty-four training sessions in 8 weeks with the Rewalk-exoskeleton. During the 2nd, 4th, and 6th training week the Intermediate-skills-test was performed consisting of 27 skills, measured in an hierarchical order of difficulty, until two skills were not achieved. When participants could walk independently, the Final-skills-test, consisting of 20 skills, was performed in the last training session. Each skill was performed at least two times with a maximum of three attempts. As a reliability measure the consistency was used, which was the number of skills performed the same in the first two attempts relative to the total number. Ten participants completed the training program. Their number of achieved intermediate skills was significantly different between the measurements XF2(2) = 12.36, p = 0.001. Post-hoc analysis revealed a significant increase in the median achieved intermediate skills from 4 [1–7] at the first to 10.5 [5–26] at the third Intermediate-skills-test. The rate of participants who achieved the intermediate skills decreased and the coefficient of reproducibility was 0.98. Eight participants met the criteria to perform the Final-skills-test. Their median number of successfully performed final skills was 16.5 [13–20] and 17 [14–19] skills in the first and second time. The overall consistency of >70% was achieved in the Intermediate-skills-test (73%) and the Final-skills-test (81%). Eight out of twelve participants experienced skin damage during the training

A Framework for Measuring the Progress in Exoskeleton Skills in People with Complete Spinal Cord Injury.

PubMed

van Dijsseldonk, Rosanne B; Rijken, Hennie; van Nes, Ilse J W; van de Meent, Henk; Keijsers, Noel L W

2017-01-01

For safe application of exoskeletons in people with spinal cord injury at home or in the community, it is required to have completed an exoskeleton training in which users learn to perform basic and advanced skills. So far, a framework to test exoskeleton skills is lacking. The aim of this study was to develop and test the hierarchy and reliability of a framework for measuring the progress in the ability to perform basic and advanced skills. Twelve participants with paraplegia were given twenty-four training sessions in 8 weeks with the Rewalk-exoskeleton. During the 2nd, 4th, and 6th training week the Intermediate-skills-test was performed consisting of 27 skills, measured in an hierarchical order of difficulty, until two skills were not achieved. When participants could walk independently, the Final-skills-test, consisting of 20 skills, was performed in the last training session. Each skill was performed at least two times with a maximum of three attempts. As a reliability measure the consistency was used, which was the number of skills performed the same in the first two attempts relative to the total number. Ten participants completed the training program. Their number of achieved intermediate skills was significantly different between the measurements X F 2 (2) = 12.36, p = 0.001. Post-hoc analysis revealed a significant increase in the median achieved intermediate skills from 4 [1-7] at the first to 10.5 [5-26] at the third Intermediate-skills-test. The rate of participants who achieved the intermediate skills decreased and the coefficient of reproducibility was 0.98. Eight participants met the criteria to perform the Final-skills-test. Their median number of successfully performed final skills was 16.5 [13-20] and 17 [14-19] skills in the first and second time. The overall consistency of >70% was achieved in the Intermediate-skills-test (73%) and the Final-skills-test (81%). Eight out of twelve participants experienced skin damage during the training, in

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress

PubMed Central

Antic, Nick A.; Heeley, Emma; Anderson, Craig S.; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R. Doug

2015-01-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical Trials Registration Number: NCT00738179. Australia New Zealand Clinical Trials Registry Number: ACTRN12608000409370. Citation: Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale, ethics, design, and progress. SLEEP 2015;38(8):1247–1257. PMID:25669180

Rationales of a Shift towards Knowledge Economy in Jordan from the Viewpoint of Educational Experts and Relationship with Some Variables

ERIC Educational Resources Information Center

Al Zboon, Mohammad Saleem; Al Ahmad, Suliman Diab Ali; Al Zboon, Saleem Odeh

2009-01-01

The purpose of the present study was to identify rationales underlying a shift towards knowledge economy in education as perceived by the educational experts in Jordan and relationship with some variables. The random stratum sample (n = 90) consisted of educational experts representing faculty members in the Jordanian universities and top leaders…

The analysis and rationale behind the upgrading of existing standard definition thermal imagers to high definition

NASA Astrophysics Data System (ADS)

Goss, Tristan M.

2016-05-01

With 640x512 pixel format IR detector arrays having been on the market for the past decade, Standard Definition (SD) thermal imaging sensors have been developed and deployed across the world. Now with 1280x1024 pixel format IR detector arrays becoming readily available designers of thermal imager systems face new challenges as pixel sizes reduce and the demand and applications for High Definition (HD) thermal imaging sensors increases. In many instances the upgrading of existing under-sampled SD thermal imaging sensors into more optimally sampled or oversampled HD thermal imaging sensors provides a more cost effective and reduced time to market option than to design and develop a completely new sensor. This paper presents the analysis and rationale behind the selection of the best suited HD pixel format MWIR detector for the upgrade of an existing SD thermal imaging sensor to a higher performing HD thermal imaging sensor. Several commercially available and "soon to be" commercially available HD small pixel IR detector options are included as part of the analysis and are considered for this upgrade. The impact the proposed detectors have on the sensor's overall sensitivity, noise and resolution is analyzed, and the improved range performance is predicted. Furthermore with reduced dark currents due to the smaller pixel sizes, the candidate HD MWIR detectors are operated at higher temperatures when compared to their SD predecessors. Therefore, as an additional constraint and as a design goal, the feasibility of achieving upgraded performance without any increase in the size, weight and power consumption of the thermal imager is discussed herein.

Children's toothbrushing frequency: the influence of parents' rationale for brushing, habits and family routines.

PubMed

Trubey, Rob J; Moore, Simon C; Chestnutt, Ivor G

2015-01-01

To assess the relationship between parental and family factors and children's toothbrushing frequency at different times of day. A cross-sectional questionnaire survey of predominantly low-socio-economic status parents of children aged 3-6 years (n = 296) in South Wales, UK. Data were collected on the child's weekly toothbrushing frequency (morning and evening), the parents' rationale for brushing their child's teeth in the morning and evening, the strength of a parent's habit for brushing a child's teeth in the morning and evening, and the extent to which the family's daily routines were stable from day to day. Socio-demographic details were also collected. Reported weekly brushing frequency was significantly (p < 0.001) higher in the morning (mean ± SD: 6.57 ± 1.37) than the evening (mean ± SD: 5.99 ± 2.15). Parents had significantly (p < 0.001) more interest in the cosmetic benefits of toothbrushing in the morning compared to the evening. Multivariate analysis showed that an increasing focus on the cosmetic benefits of toothbrushing was associated with significantly (p < 0.05) less weekly brushing in the evening. The extent to which brushing a child's teeth was 'habitual' was significantly (p < 0.001) associated with weekly toothbrushing frequency at both times of day. Parents' rationale for brushing their children's teeth can vary at both an individual level and at different times of day. Understanding these variations is important in designing interventions to improve brushing frequency for at-risk children. The results also demonstrate habituation as being an important factor in understanding toothbrushing frequency. Further research is required to understand the mechanisms involved in habit formation and maintenance with children's oral hygiene behaviour.

Interruption of spinal cord microglial signaling by alpha-2 agonist dexmedetomidine in a murine model of delayed paraplegia.

PubMed

Bell, Marshall T; Agoston, Viktor A; Freeman, Kirsten A; Puskas, Ferenc; Herson, Paco S; Mares, Joshua; Fullerton, David A; Reece, T Brett

2014-04-01

Despite investigation into preventable pharmacologic adjuncts, paraplegia continues to complicate thoracoabdominal aortic interventions. The alpha 2a adrenergic receptor agonist, dexmedetomidine, has been shown to preserve neurologic function and neuronal viability in a murine model of spinal cord ischemia reperfusion, although the mechanism remains elusive. We hypothesize that dexmedetomidine will blunt postischemic inflammation in vivo following thoracic aortic occlusion with in vitro demonstration of microglial inhibition following lipopolysaccharide (LPS) stimulation. Adult male C57BL/6 mice underwent 4 minutes of aortic occlusion. Mice received 25 μg/kg intraperitoneal dexmedetomidine (n = 8) or 0.9% normal saline (n = 7) at reperfusion and 12-hour intervals postoperatively until 48 hours. Additionally, sham mice (n = 3), which had aortic arch exposed with no occlusion, were included for comparison. Functional scoring was done at 6 hours following surgery and 12-hour intervals until 60 hours when spinal cords were removed and examined for neuronal viability and cytokine production. Additional analysis of microglia activation was done in 12 hours following surgery. Age- and sex-matched mice had spinal cord removed for microglial isolation culture. Cells were grown to confluence and stimulated with toll-like receptor-4 agonist LPS 100 ng/mL in presence of dexmedetomidine or vehicle control for 24 hours. Microglia and media were then removed for analysis of protein expression. Dexmedetomidine treatment at reperfusion significantly preserved neurologic function with mice in treatment group having a Basso Score of 6.3 in comparison to 2.3 in ischemic control group. Treatment was associated with a significant reduction in microglia activation and in interleukin-6 production. Microglial cells in isolation when stimulated with LPS had an increased production of proinflammatory cytokines and markers of activation. Treatment with dexmedetomidine significantly

Large Deployable Reflector Science and Technology Workshop. Volume 2: Scientific Rationale and Technology Requirements

NASA Technical Reports Server (NTRS)

Hollenbach, D. (Editor)

1983-01-01

The scientific rationale for the large deployable reflector (LDR) and the overall technological requirements are discussed. The main scientific objectives include studies of the origins of planets, stars and galaxies, and of the ultimate fate of the universe. The envisioned studies require a telescope with a diameter of at least 20 m, diffraction-limited to wavelengths as short as 30-50 micron. In addition, light-bucket operation with 1 arcsec spatial resolution in the 2-4 microns wavelength region would be useful in studies of high-redshifted galaxies. Such a telescope would provide a large increase in spectroscopic sensitivity and spatial resolving power compared with existing or planned infrared telescopes.

Understanding Water Storage Practices of Urban Residents of an Endemic Dengue Area in Colombia: Perceptions, Rationale and Socio-Demographic Characteristics.

PubMed

García-Betancourt, Tatiana; Higuera-Mendieta, Diana Rocío; González-Uribe, Catalina; Cortés, Sebastian; Quintero, Juliana

2015-01-01

The main preventive measure against dengue virus transmission is often based on actions to control Ae. Aegypti reproduction by targeting water containers of clean and stagnant water. Household water storage has received special attention in prevention strategies but the evidence about the rationale of this human practice is limited. The objective was to identify and describe water storage practices among residents of an urban area in Colombia (Girardot) and its association with reported perceptions, rationales and socio-demographic characteristics with a mixed methods approach. Knowledge, attitudes and practices and entomological surveys from 1,721 households and 26 semi-structured interviews were conducted among residents of Girardot and technicians of the local vector borne disease program. A multivariate analysis was performed to identify associations between a water storage practice and socio-demographic characteristics, and knowledge, attitudes and practices about dengue and immature forms of the vector, which were then triangulated with qualitative information. Water storage is a cultural practice in Girardot. There are two main reasons for storage: The scarcity concern based on a long history of shortages of water in the region and the perception of high prices in water rates, contrary to what was reported by the local water company. The practice of water storage was associated with being a housewife (Inverse OR: 2.6, 95% CI 1.5 -4.3). The use of stored water depends on the type of container used, while water stored in alberca (Intra household cement basins) is mainly used for domestic cleaning chores, water in plastic containers is used for cooking. It is essential to understand social practices that can increase or reduce the number of breeding sites of Ae. Aegypti. Identification of individuals who store water and the rationale of such storage allow a better understanding of the social dynamics that lead to water accumulation.

Understanding Water Storage Practices of Urban Residents of an Endemic Dengue Area in Colombia: Perceptions, Rationale and Socio-Demographic Characteristics

PubMed Central

González-Uribe, Catalina; Cortés, Sebastian; Quintero, Juliana

2015-01-01

Introduction The main preventive measure against dengue virus transmission is often based on actions to control Ae. Aegypti reproduction by targeting water containers of clean and stagnant water. Household water storage has received special attention in prevention strategies but the evidence about the rationale of this human practice is limited. The objective was to identify and describe water storage practices among residents of an urban area in Colombia (Girardot) and its association with reported perceptions, rationales and socio-demographic characteristics with a mixed methods approach. Methods Knowledge, attitudes and practices and entomological surveys from 1,721 households and 26 semi-structured interviews were conducted among residents of Girardot and technicians of the local vector borne disease program. A multivariate analysis was performed to identify associations between a water storage practice and socio-demographic characteristics, and knowledge, attitudes and practices about dengue and immature forms of the vector, which were then triangulated with qualitative information. Results Water storage is a cultural practice in Girardot. There are two main reasons for storage: The scarcity concern based on a long history of shortages of water in the region and the perception of high prices in water rates, contrary to what was reported by the local water company. The practice of water storage was associated with being a housewife (Inverse OR: 2.6, 95% CI 1.5 -4.3). The use of stored water depends on the type of container used, while water stored in alberca (Intra household cement basins) is mainly used for domestic cleaning chores, water in plastic containers is used for cooking. Conclusions It is essential to understand social practices that can increase or reduce the number of breeding sites of Ae. Aegypti. Identification of individuals who store water and the rationale of such storage allow a better understanding of the social dynamics that lead to water

Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study

PubMed Central

Kunin-Batson, Alicia S.; Lu, Xiaomin; Balsamo, Lyn; Graber, Kelsey; Devidas, Meenakshi; Hunger, Stephen P.; Carroll, William L.; Winick, Naomi J.; Mattano, Leonard A.; Maloney, Kelly W.; Kadan-Lottick, Nina S.

2016-01-01

Background The months immediately following completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after completion of treatment were examined. Methods Participants included 160 children (ages 2-9 years) with standard-risk ALL enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of children's emotional-behavioral functioning, and measures of coping and family functioning at ∼1, 6, and 12 months after diagnosis, and again 3 months following completion of chemotherapy. Results Three months off-therapy, 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, significantly higher than the expected 15% in the general population (p=0.028 and 0.001, respectively). Patients with elevated anxiety one-month post-diagnosis were at greater risk for off–therapy anxiety (OR=4.1; 95% CI, 1.31-12.73, p=0.022), and those with elevated depressive symptoms 6-months post-diagnosis were at greater risk for off-therapy depression (OR=7.88, 95% CI, 2.61-23.81, p=0.0002). In adjusted longitudinal analyses, unhealthy family functioning (p=0.008), and less reliance on social support coping (p=0.009) were associated with risk for emotional distress. Children from Spanish-speaking families (p=0.05) were also at greater risk for distress. Conclusions A significant proportion of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening, and psychosocial interventions to support family functioning and coping skills. PMID:27028090

Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

PubMed

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M; Browning, David J; Chalam, K V; Davis, Matthew; Ferris, Frederick L; Glassman, Adam R; Maturi, Raj K; Stockdale, Cynthia R; Topping, Trexler M

2011-12-01

To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Discussion of treatment protocol for DME. Subjects with vision loss resulting from DME involving the center of the macula. The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Clinical guidelines based on a DRCR.net protocol. The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may

Acceptance and Commitment Therapy with Older Adults: Rationale and Considerations

PubMed Central

Petkus, Andrew J; M.A; Wetherell, Julie Loebach

2015-01-01

Older adults are the fastest growing segment of the population. With these changing demographics, mental health professionals will be seeing more older clients. Additionally, older adults are an underserved population in that most older adults in need of mental health services do not receive treatment. Thus, it is essential that treatments for mental and behavioral health problems are empirically supported with older adults and that mental health professionals are aware of the special needs of older adult populations. Acceptance and Commitment Therapy (ACT) is an emerging approach to the treatment of distress. The purpose of this article is to provide a rationale for using ACT with older adults based on gerontological theory and research. We also review research on ACT-related processes in later life. We present a case example of an older man with depression and anxiety whom we treated with ACT. Finally, we describe treatment recommendations and important adaptations that need to be considered when using ACT with older adults and discuss important areas for future research. PMID:26997859

Cognitive Defusion versus Thought Distraction: A Clinical Rationale, Training, and Experiential Exercise in Altering Psychological Impacts of Negative Self-Referential Thoughts

ERIC Educational Resources Information Center

Masuda, Akihiko; Feinstein, Amanda B.; Wendell, Johanna W.; Sheehan, Shawn T.

2010-01-01

Using two modes of intervention delivery, the present study compared the effects of a cognitive defusion strategy with a thought distraction strategy on the emotional discomfort and believability of negative self-referential thoughts. One mode of intervention delivery consisted of a clinical rationale and training (i.e., Partial condition). The…

What is the biochemical and physiological rationale for using cold-water immersion in sports recovery? A systematic review.

PubMed

Bleakley, Chris M; Davison, Gareth W

2010-02-01

Cold-water immersion (CWI) is a popular recovery intervention after exercise. The scientific rationale is not clear, and there are no clear guidelines for its use. The aim of this review was to study the physiological and biochemical effect of short periods of CWI. A computer-based literature search, citation tracking and related articles searches were undertaken. Primary research studies using healthy human participants, immersed in cold water (<15 degrees C), for 5 min durations or less were included. Data were extracted on body temperature, cardiovascular, respiratory and biochemical response. 16 studies were included. Sample size was restricted, and there was a large degree of study heterogeneity. CWI was associated with an increase in heart rate, blood pressure, respiratory minute volume and metabolism. Decreases in end tidal carbon dioxide partial pressure and a decrease in cerebral blood flow were also reported. There was evidence of increases in peripheral catecholamine concentration, oxidative stress and a possible increase in free-radical-species formation. The magnitude of these responses may be attenuated with acclimatisation. CWI induces significant physiological and biochemical changes to the body. Much of this evidence is derived from full body immersions using resting healthy participants. The physiological and biochemical rationale for using short periods of CWI in sports recovery still remains unclear.

A microhydrodynamic rationale for selection of bead size in preparation of drug nanosuspensions via wet stirred media milling.

PubMed

Li, Meng; Alvarez, Paulina; Bilgili, Ecevit

2017-05-30

Although wet stirred media milling has proven to be a robust process for producing nanoparticle suspensions of poorly water-soluble drugs and thereby enhancing their bioavailability, selection of bead size has been largely empirical, lacking fundamental rationale. This study aims to establish such rationale by investigating the impact of bead size at various stirrer speeds on the drug breakage kinetics via a microhydrodynamic model. To this end, stable suspensions of griseofulvin, a model BCS Class II drug, were prepared using hydroxypropyl cellulose and sodium dodecyl sulfate. The suspensions were milled at four different stirrer speeds (1000-4000rpm) using various sizes (50-1500μm) of zirconia beads. Laser diffraction, SEM, and XRPD were used for characterization. Our results suggest that there is an optimal bead size that achieves fastest breakage at each stirrer speed and that it shifts to a smaller size at higher speed. Calculated microhydrodynamic parameters reveal two counteracting effects of bead size: more bead-bead collisions with less energy/force upon a decrease in bead size. The optimal bead size exhibits a negative power-law correlation with either specific energy consumption or the microhydrodynamic parameters. Overall, this study rationalizes the use of smaller beads for more energetic wet media milling. Copyright © 2017 Elsevier B.V. All rights reserved.

Rationale for the Use of CAD/CAM Technology in Implant Prosthodontics

PubMed Central

Abduo, Jaafar; Lyons, Karl

2013-01-01

Despite the predictable longevity of implant prosthesis, there is an ongoing interest to continue to improve implant prosthodontic treatment and outcomes. One of the developments is the application of computer-aided design and computer-aided manufacturing (CAD/CAM) to produce implant abutments and frameworks from metal or ceramic materials. The aim of this narrative review is to critically evaluate the rationale of CAD/CAM utilization for implant prosthodontics. To date, CAD/CAM allows simplified production of precise and durable implant components. The precision of fit has been proven in several laboratory experiments and has been attributed to the design of implants. Milling also facilitates component fabrication from durable and aesthetic materials. With further development, it is expected that the CAD/CAM protocol will be further simplified. Although compelling clinical evidence supporting the superiority of CAD/CAM implant restorations is still lacking, it is envisioned that CAD/CAM may become the main stream for implant component fabrication. PMID:23690778

The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis.

PubMed

Veale, Douglas J; McGonagle, Dennis; McInnes, Iain B; Krueger, James G; Ritchlin, Christopher T; Elewaut, Dirk; Kanik, Keith S; Hendrikx, Thijs; Berstein, Gabriel; Hodge, Jennifer; Telliez, Jean-Baptiste

2018-04-03

The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.

Active Learning with Rationales for Identifying Operationally Significant Anomalies in Aviation

NASA Technical Reports Server (NTRS)

Sharma, Manali; Das, Kamalika; Bilgic, Mustafa; Matthews, Bryan; Nielsen, David Lynn; Oza, Nikunj C.

2016-01-01

A major focus of the commercial aviation community is discovery of unknown safety events in flight operations data. Data-driven unsupervised anomaly detection methods are better at capturing unknown safety events compared to rule-based methods which only look for known violations. However, not all statistical anomalies that are discovered by these unsupervised anomaly detection methods are operationally significant (e.g., represent a safety concern). Subject Matter Experts (SMEs) have to spend significant time reviewing these statistical anomalies individually to identify a few operationally significant ones. In this paper we propose an active learning algorithm that incorporates SME feedback in the form of rationales to build a classifier that can distinguish between uninteresting and operationally significant anomalies. Experimental evaluation on real aviation data shows that our approach improves detection of operationally significant events by as much as 75% compared to the state-of-the-art. The learnt classifier also generalizes well to additional validation data sets.

Tomorrow's Teachers--Selecting the Best: An Exploration of the Quality Rationale behind Academic and Experiential Selection Criteria for Initial Teacher Education Programmes

ERIC Educational Resources Information Center

Heinz, Manuela

2013-01-01

Using Ireland as an example, this paper explores the rationale behind various selection criteria currently used to select suitable candidates for initial teacher education courses. It investigates and discusses patterns of association between second-level student teachers' background characteristics on entry to their teacher education programme…

[Computerized monitoring for integrated cervical screening. Rationale, methods and indicators of participation].

PubMed

Bucchi, L; Pierri, C; Caprara, L; Cortecchia, S; De Lillo, M; Bondi, A

2003-02-01

This paper presents a computerised system for the monitoring of integrated cervical screening, i.e. the integration of spontaneous Pap smear practice into organised screening. The general characteristics of the system are described, including background and rationale (integrated cervical screening in European countries, impact of integration on monitoring, decentralised organization of screening and levels of monitoring), general methods (definitions, sections, software description, and setting of application), and indicators of participation (distribution by time interval since previous Pap smear, distribution by screening sector--organised screening centres vs public and private clinical settings--, distribution by time interval between the last two Pap smears, and movement of women between the two screening sectors). Also, the paper reports the results of the application of these indicators in the general database of the Pathology Department of Imola Health District in northern Italy.

NITRIC OXIDE FOR THE ADJUNCTIVE TREATMENT OF SEVERE MALARIA: HYPOTHESIS AND RATIONALE

PubMed Central

Hawkes, Michael; Opoka, Robert Opika; Namasopo, Sophie; Miller, Christopher; Conroy, Andrea L.; Serghides, Lena; Kim, Hani; Thampi, Nisha; Liles, W. Conrad; John, Chandy C.; Kain, Kevin C.

2011-01-01

We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor L-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215). PMID:21745716

Ambulatory and Non-Ambulatory Benefits of Lower Limb Exoskeleton Use, with and without FES, in Clinical and Community Settings

DTIC Science & Technology

2016-10-01

15. SUBJECT TERMS spinal cord injury, paraplegia, exoskeleton, physical medicine and rehabilitation, rehabilitation research, legged mobility...2. KEYWORDS • spinal cord injury • paraplegia • exoskeleton • physical medicine and rehabilitation • rehabilitation research • legged mobility...study protocol notebooks and record books have been assembled with session-by-session instructions and data entry. o Electronic data entry forms have

Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

PubMed

Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

2008-09-01

A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

An investigation of pre-activity cardiovascular screening procedures in health/fitness facilities--part II: rationale for low adherence with national standards.

PubMed

Springer, Judy B; Eickhoff-Shemek, JoAnn M; Zuberbuehler, Ernest J

2009-01-01

The purpose of this study was to explore the rationale provided by program directors and general managers of health/fitness facilities for low adherence to nationally accepted standards related to pre-activity cardiovascular screening procedures (PACSPs) for members and clients of personal trainers. Qualitative interviews were conducted with the directors/managers in a Midwest region representing 76 facilities who indicated they did not conduct PACSPs for members and clients of personal trainers. Analysis of the rationale provided revealed 6 major clusters: (1) Purpose or need for screening; (2) time and staffing; (3) barrier to participation; (4) personal responsibility for health and actions; (5) legal issues; and (6) company or franchise policy that categorized the reasons for low adherence to PACSPs. These findings highlight the need to increase awareness of the relevance of PACSPs among health/fitness managers, staff members, and current exercise science students as well as engage those in risk management for informed dialogue for consistent application of the standard of care. Copyright 2009 Wiley Periodicals, Inc.

Not just another multi-professional course! Part 1. Rationale for a transformative curriculum.

PubMed

Duncan, Madeleine; Alperstein, Melanie; Mayers, Pat; Olckers, Lorna; Gibbs, Trevor

2006-02-01

Undergraduate inter- and multi-professional education has traditionally aimed to develop health professionals who are able to collaborate effectively in comprehensive healthcare delivery. The respective professions learn from and about each other through comparisons of roles, responsibilities, powers, duties and perspectives in order to promote integrated service. Described here is the educational rationale of a multi-professional course with a difference; one that injects value to undergraduate health professional education through the development of critical cross-field knowledge, skills and attitudes that unite rather than differentiate professions. The aim of this course, offered at the Faculty of Health Sciences, University of Cape Town, is to lay an integrated, pan-professional foundation for the advancement of collective commitment to and understanding of national health and social development objectives such as primary health care, human rights and professionalism. Pan-professional refers to curriculum content that is core and of critical relevance to all participating professions. What is learned, how it is learned, how learning is facilitated and how it is applied, has been co-constructed by a multi-professional design team representing a range of health professions (audiology, medicine, occupational therapy, nursing, physiotherapy and speech therapy) and academic disciplines (anthropology, sociology, psychology, history, African studies and social development, information technology and language literacy). Education specialists facilitate the ongoing design process ensuring that the structure and content of the curriculum complies with contemporary adult learning principles and national higher education imperatives. Designing the original curriculum required the deconstruction of intra-professional and disciplinary canons of knowledge and ways of 'doing things' in order to identify and develop shared interpretations of critical epistemology and axiology

Design and Rationale for a Parent-Led Intervention to Increase Fruit and Vegetable Intake in Young Childhood Cancer Survivors (Reboot): Protocol for a Pilot Study

PubMed Central

Cohen, Jennifer; Wakefield, Claire; Grech, Allison; Garnett, Sarah; Gohil, Paayal; Cohn, Richard

2018-01-01

Background Poor dietary habits are common among childhood cancer survivors, despite increasing their risk of cardio metabolic complications after cancer treatment. Here, we describe the design and rationale for a pilot telephone-based, parent-led intervention aimed at increasing fruit and vegetable intake in young cancer survivors (Reboot). Objective This pilot study aims to assess the feasibility and acceptability of delivering evidence-based telephone support to parents of childhood cancer survivors. A secondary aim includes assessing the effect of Reboot on improving childhood cancer survivors’ dietary quality by increasing child fruit and vegetable intake and variety and its contribution to overall nutrient intake. Methods We aim to recruit parents of 15 young cancer survivors aged 2 to 12 years who have completed cancer treatment less than five years ago. The intervention comprises of 4 weekly 45-minute telephone sessions led by a health professional and one booster session 6 weeks later. Sessions address the effects of cancer treatment on children’s diets, recommended fruit and vegetable intake for children, and evidence-based strategies to promote the consumption of fruit and vegetables as well as to manage fussy eating. Results Reboot is based on an existing, evidence-based parent nutrition intervention and modified for childhood cancer survivors following extensive collaboration with experts in the field. Primary outcomes of feasibility and acceptability will be measured by the number of participants who complete all five sessions, average session length (minutes), length between sessions (days) and parent Likert ratings of the usefulness and impact of the intervention collected after the booster session. Of the 15 participants we aim to recruit, 3 have completed the intervention, 1 declined to participate, 11 are actively completing the intervention and 2 participants are providing written consent. The remaining 3 participants will be recruited via

Lorcaserin plus lifestyle modification for weight loss maintenance: Rationale and design for a randomized controlled trial.

PubMed

Tronieri, Jena Shaw; Alfaris, Nasreen; Chao, Ariana M; Pearl, Rebecca L; Alamuddin, Naji; Bakizada, Zayna M; Berkowitz, Robert I; Wadden, Thomas A

2017-08-01

Few studies have examined the efficacy of recently approved medications for chronic weight management in facilitating the maintenance of lost weight. This paper provides an overview of the design and rationale for a trial investigating whether lorcaserin, when combined with behavioral weight loss maintenance sessions (WLM), will facilitate the maintenance of losses of ≥5% of initial weight. In this two-phase trial, participants with obesity will enroll in a 14-week run-in diet program consisting of weekly group lifestyle modification sessions and a 1000-1200kcal/d meal replacement diet. Participants who complete this weight induction phase and lose at least 5% of initial weight will then be randomized to 52weeks of WLM plus lorcaserin or WLM plus placebo. We hypothesize that at 52weeks post randomization, participants assigned to WLM plus lorcaserin will achieve significantly better maintenance of the prior 5% weight loss. We will recruit 182 adults with obesity to participate in the diet run-in, 136 of whom (75%) are expected to become eligible for the randomized controlled trial. Co-primary outcomes include the percentage of participants who maintain a loss of at least 5% of initial weight at week 52 and change in weight (kg) from randomization to week 52. This two-phase design will allow us to determine the potential efficacy of chronic weight management using lorcaserin for maintaining initial losses of at least 5% body weight, induced by the use of a structured meal-replacement diet. This combined approach holds promise of achieving larger long-term weight losses. NCT02388568 on ClinicalTrials.gov. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating the Rationale for Affirmative Action in College Admissions: Direct and Indirect Relationships between Campus Diversity and Gains in Understanding Diverse Groups

ERIC Educational Resources Information Center

Pike, Gary R.; Kuh, George D.; Gonyea, Robert M.

2007-01-01

Affirmative action in college admissions is based on the premise that a diverse student body contributes to interactions among students from different backgrounds, which are in turn positively related to desirable outcomes of college. This study evaluates the merits of this rationale for affirmative action by examining the direct and indirect…

The Impact of a Course on Nature of Science Pedagogical Views and Rationales: Comparing Preservice Teachers in Their First versus Second Experience

ERIC Educational Resources Information Center

Kruse, Jerrid W.; Easter, Jaclyn M.; Edgerly, Hallie S.; Seebach, Colin; Patel, Neal

2017-01-01

This study explored changes in preservice teachers' (PSTs) nature of science pedagogical (NOSP) views and nature of science (NOS) rationales using pre- and post-course written responses as well as interview data. Through systematic analysis, themes were generated and compared to the NOS literature. Comparisons between pre- and post-course data…

Development of a Publicly Available, Comprehensive Database of Fiber and Health Outcomes: Rationale and Methods

PubMed Central

Livingston, Kara A.; Chung, Mei; Sawicki, Caleigh M.; Lyle, Barbara J.; Wang, Ding Ding; Roberts, Susan B.; McKeown, Nicola M.

2016-01-01

Background Dietary fiber is a broad category of compounds historically defined as partially or completely indigestible plant-based carbohydrates and lignin with, more recently, the additional criteria that fibers incorporated into foods as additives should demonstrate functional human health outcomes to receive a fiber classification. Thousands of research studies have been published examining fibers and health outcomes. Objectives (1) Develop a database listing studies testing fiber and physiological health outcomes identified by experts at the Ninth Vahouny Conference; (2) Use evidence mapping methodology to summarize this body of literature. This paper summarizes the rationale, methodology, and resulting database. The database will help both scientists and policy-makers to evaluate evidence linking specific fibers with physiological health outcomes, and identify missing information. Methods To build this database, we conducted a systematic literature search for human intervention studies published in English from 1946 to May 2015. Our search strategy included a broad definition of fiber search terms, as well as search terms for nine physiological health outcomes identified at the Ninth Vahouny Fiber Symposium. Abstracts were screened using a priori defined eligibility criteria and a low threshold for inclusion to minimize the likelihood of rejecting articles of interest. Publications then were reviewed in full text, applying additional a priori defined exclusion criteria. The database was built and published on the Systematic Review Data Repository (SRDR™), a web-based, publicly available application. Conclusions A fiber database was created. This resource will reduce the unnecessary replication of effort in conducting systematic reviews by serving as both a central database archiving PICO (population, intervention, comparator, outcome) data on published studies and as a searchable tool through which this data can be extracted and updated. PMID:27348733

Complete to Compete: Common College Completion Metrics. Technical Guide

ERIC Educational Resources Information Center

Reyna, Ryan; Reindl, Travis; Witham, Keith; Stanley, Jeff

2010-01-01

Improved college completion rates are critical to the future of the United States, and states must have better data to understand the nature of the challenges they confront or target areas for policy change. The 2010-2011 National Governors Association (NGA) Chair's initiative, "Complete to Compete", recommends that all states collect data from…

Maxillary advancement for mandibular prognathism: indications and rationale.

PubMed

Rosen, H M

1991-05-01

The surgical correction of mandibular prognathism has traditionally involved posterior repositioning of the mandibular body. This treatment approach corrects the skeletal disproportion at the expense of reducing facial skeletal volume and can unpredictably result in inadequately supported soft tissues with loss of skeletal definition. In an effort to avoid these sequelae of mandibular reduction, 18 patients diagnosed as having mandibular prognathism were treated with maxillary advancement surgery at the Le Fort I level. Mean patient SNB angle was 85.2 degrees, as compared with a normal 79 +/- 3 degrees. Maxillae were documented to be in normal position relative to both cranial base and Frankfort horizontal. The mean maxillary advancement was 6.9 mm, with a range of 4.5 to 8.8 mm. All patients required genioplasty to reduce vertical chin height and/or to laterally shift the chin. At the time of follow-up (mean 16.2 months), all patients retained cephalometric data suggestive of enlarged mandibles and excessive anterior facial divergence. However, maxillomandibular harmony and facial convexity had been restored without sacrificing skeletal volume. Treatment results demonstrated these faces to be skeletally well proportioned despite lower face protrusion that was beyond "normal." Postoperative appearances were characterized by a well-supported soft-tissue envelope and a highlighted skeletal foundation, creating angular, well-defined lower faces. These findings support the credibility of maxillary advancement as the procedure of choice in selected individuals with mandibular prognathism. Indications and an aesthetic rationale for this surgical approach are presented.

Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study.

PubMed

Kunin-Batson, Alicia S; Lu, Xiaomin; Balsamo, Lyn; Graber, Kelsey; Devidas, Meenakshi; Hunger, Stephen P; Carroll, William L; Winick, Naomi J; Mattano, Leonard A; Maloney, Kelly W; Kadan-Lottick, Nina S

2016-05-15

The months immediately after the completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after the completion of treatment were examined. Participants included 160 children aged 2 to 9 years with standard-risk ALL who were enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of their children's emotional-behavioral functioning and measures of coping and family functioning at approximately 1 month, 6 months, and 12 months after diagnosis and again 3 months after the completion of chemotherapy. At 3 months off therapy, approximately 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, which are significantly higher than the expected 15% in the general population (P = .028 and .001, respectively). Patients with elevated anxiety 1 month after diagnosis were at greater risk of off-therapy anxiety (odds ratio, 4.1; 95% confidence interval, 1.31-12.73 [P = .022]) and those with elevated depressive symptoms 6 months after diagnosis were at greater risk of off-therapy depression (odds ratio, 7.88; 95% confidence interval, 2.61-23.81 [P = .0002]). In adjusted longitudinal analyses, unhealthy family functioning (P = .008) and less reliance on social support coping (P = .009) were found to be associated with risk of emotional distress. Children from Spanish-speaking families (P = .05) also were found to be at a greater risk of distress. A significant percentage of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening and psychosocial interventions to support family functioning and coping skills. Cancer 2016;122:1608-17. © 2015 American Cancer Society. © 2016 American Cancer Society.

The Examination of Secondary Education Chemistry Curricula Published between 1957-2007 in Terms of the Dimensions of Rationale, Goals, and Subject-Matter

ERIC Educational Resources Information Center

Pekdag, Bulent; Erol, Hilal

2013-01-01

Fifteen secondary education chemistry curricula published from 1957 until 2007 were examined based on the dimensions of rationale, goals, and subject matter. An examination of documents in the scope of qualitative research was carried out in the study. The goals included in the examined chemistry curricula were analyzed according to the cognitive,…

Rationale and Description of Right Ventricle-Protective Ventilation in ARDS.

PubMed

Paternot, Alexis; Repessé, Xavier; Vieillard-Baron, Antoine

2016-10-01

Pulmonary vascular dysfunction is associated with ARDS and leads to increased right-ventricular afterload and eventually right-ventricular failure, also called acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on outcome in patients with ARDS has grown in recent years. Right-ventricular function in these patients should be closely monitored, and this is helped by the widespread use of echocardiography in intensive care units. Because mechanical ventilation may worsen right-ventricular failure, the interaction between the lungs and the right ventricle appears to be a key factor in the ventilation strategy. In this review, a rationale for a right ventricle-protective ventilation approach is provided, and such a strategy is described, including the reduction of lung stress (ie, the limitation of plateau pressure and driving pressure), the reduction of PaCO2 , and the improvement of oxygenation. Prone positioning seems to be a crucial part of this strategy by protecting both the lungs and the right ventricle, resulting in increased survival of patients with ARDS. Further studies are required to validate the positive impact on prognosis of right ventricle-protective mechanical ventilation. Copyright © 2016 by Daedalus Enterprises.

The Living Donor Lost Wages Trial: Study Rationale and Protocol.

PubMed

Rodrigue, James R; Fleishman, Aaron; Carroll, Michaela; Evenson, Amy R; Pavlakis, Martha; Mandelbrot, Didier A; Baliga, Prabhakar; Howard, David H; Schold, Jesse D

2018-03-01

This paper describes the background, rationale, and design of an NIH-funded, single-center study to test the impact of offering reimbursement for donor lost wages incurred during the post-nephrectomy recovery period on the live donor kidney transplant (LDKT) rate in newly evaluated kidney transplant candidates, to examine whether offering reimbursement for donor lost wages reduces racial disparity in LDKT rates, and to determine whether higher reimbursement amounts lead to higher LDKT rates. LDKT is the optimal treatment for renal failure. However, living kidney donation has declined in the past decade, particularly among men, younger adults, blacks, and low-income adults. There is evidence that donation-related costs may deter both transplant candidates and potential donors from considering LDKT. Lost wages is a major source of financial loss for some living donors and, unlike travel and lodging expenses, is not reimbursed by financial assistance programs. The study addresses the transplant community's call to reduce the financial burden of living donation and examine its impact on LDKT rates. Findings have the potential to influence policy, clinical practice, LDKT access, and income-related and racial disparities in LDKT and living donation.

Deconstructing the Brain Disconnection–Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death

PubMed Central

Moschella, Melissa

2016-01-01

This article explains the problems with Alan Shewmon’s critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death. PMID:27095749

An electronic rationale for observed initiation rates in ruthenium-mediated olefin metathesis: charge donation in phosphine and N-heterocyclic carbene ligands.

PubMed

Getty, Kendra; Delgado-Jaime, Mario Ulises; Kennepohl, Pierre

2007-12-26

Ru K-edge XAS data indicate that second generation ruthenium-based olefin metathesis precatalysts (L = N-heterocyclic carbene) possess a more electron-deficient metal center than in the corresponding first generation species (L = tricyclohexylphosphine). This surprising effect is also observed from DFT calculations and provides a simple rationale for the slow phosphine dissociation kinetics previously noted for second-generation metathesis precatalysts.

Rationale and operational plan to upgrade the U.S. gravity database

USGS Publications Warehouse

Hildenbrand, Thomas G.; Briesacher, Allen; Flanagan, Guy; Hinze, William J.; Hittelman, A.M.; Keller, Gordon R.; Kucks, R.P.; Plouff, Donald; Roest, Walter; Seeley, John; Stith, David A.; Webring, Mike

2002-01-01

A concerted effort is underway to prepare a substantially upgraded digital gravity anomaly database for the United States and to make this data set and associated usage tools available on the internet. This joint effort, spearheaded by the geophysics groups at the National Imagery and Mapping Agency (NIMA), University of Texas at El Paso (UTEP), U.S. Geological Survey (USGS), and National Oceanic and Atmospheric Administration (NOAA), is an outgrowth of the new geoscientific community initiative called Geoinformatics (www.geoinformaticsnetwork.org). This dominantly geospatial initiative reflects the realization by Earth scientists that existing information systems and techniques are inadequate to address the many complex scientific and societal issues. Currently, inadequate standardization and chaotic distribution of geoscience data, inadequate accompanying documentation, and the lack of easy-to-use access tools and computer codes for analysis are major obstacles for scientists, government agencies, and educators. An example of the type of activities envisioned, within the context of Geoinformatics, is the construction, maintenance, and growth of a public domain gravity database and development of the software tools needed to access, implement, and expand it. This product is far more than a high quality database; it is a complete data system for a specific type of geophysical measurement that includes, for example, tools to manipulate the data and tutorials to understand and properly utilize the data. On August 9, 2002, twenty-one scientists from the federal, private and academic sectors met at a workshop to discuss the rationale for upgrading both the United States and North American gravity databases (including offshore regions) and, more importantly, to begin developing an operational plan to effectively create a new gravity data system. We encourage anyone interested in contributing data or participating in this effort to contact G.R. Keller or T.G. Hildenbrand

How Primary Care Providers Talk to Patients about Genome Sequencing Results: Risk, Rationale, and Recommendation.

PubMed

Vassy, Jason L; Davis, J Kelly; Kirby, Christine; Richardson, Ian J; Green, Robert C; McGuire, Amy L; Ubel, Peter A

2018-06-01

Genomics will play an increasingly prominent role in clinical medicine. To describe how primary care physicians (PCPs) discuss and make clinical recommendations about genome sequencing results. Qualitative analysis. PCPs and their generally healthy patients undergoing genome sequencing. Patients received clinical genome reports that included four categories of results: monogenic disease risk variants (if present), carrier status, five pharmacogenetics results, and polygenic risk estimates for eight cardiometabolic traits. Patients' office visits with their PCPs were audio-recorded, and summative content analysis was used to describe how PCPs discussed genomic results. For each genomic result discussed in 48 PCP-patient visits, we identified a "take-home" message (recommendation), categorized as continuing current management, further treatment, further evaluation, behavior change, remembering for future care, or sharing with family members. We analyzed how PCPs came to each recommendation by identifying 1) how they described the risk or importance of the given result and 2) the rationale they gave for translating that risk into a specific recommendation. Quantitative analysis showed that continuing current management was the most commonly coded recommendation across results overall (492/749, 66%) and for each individual result type except monogenic disease risk results. Pharmacogenetics was the most common result type to prompt a recommendation to remember for future care (94/119, 79%); carrier status was the most common type prompting a recommendation to share with family members (45/54, 83%); and polygenic results were the most common type prompting a behavior change recommendation (55/58, 95%). One-fifth of recommendation codes associated with monogenic results were for further evaluation (6/24, 25%). Rationales for these recommendations included patient context, family context, and scientific/clinical limitations of sequencing. PCPs distinguish substantive

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

PubMed

Keeney, Tamra; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Heinemann, Allen W; Charlifue, Susan; Fyffe, Denise C; Marino, Ralph J; Morse, Leslie R; Worobey, Lynn A; Tate, Denise; Rosenblum, David; Zafonte, Ross; Tulsky, David; Jette, Alan M

2018-03-31

To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). Multisite longitudinal (12-mo follow-up) study. Nine SCI Model Systems programs. Adults (N=165) with SCI enrolled in the SCI Model Systems database. Not applicable. SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Complementary and alternative medicine for autism spectrum disorders: rationale, safety and efficacy.

PubMed

Whitehouse, Andrew J O

2013-09-01

Complementary and alternative medicine is widely used for children with autism spectrum disorder, despite uncertainty regarding efficacy. This review describes complementary and alternative practices commonly used among this population, the rationale for the use of each practice, as well as the side-effect profile and evidence for efficacy. The existing evidence base indicates that melatonin can be recommended as a treatment for sleeping disturbances associated with autism spectrum disorder, while secretin can be rejected as an efficacious treatment for broader autistic symptoms. There is insufficient evidence to draw conclusions on the efficacy of modified diets, hyperbaric oxygen therapy, immune therapy, and vitamin and fatty acid supplementation. There is a clear need for methodologically rigorous studies to provide evidence-based guidance to families and clinicians regarding complementary and alternative practices for individuals with autism spectrum disorders. © 2013 The Author. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Navy Shipbuilding: Need to Document Rationale for the Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added Incentives

DTIC Science & Technology

2017-03-01

NAVY SHIPBUILDING Need to Document Rationale for the Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added...Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added Incentives What GAO Found Over 80 percent of the Navy’s shipbuilding...mackinm@gao.gov. Why GAO Did This Study DOD encourages the use of FPI contracts because they allow for equitable sharing of costs savings and risk

Perioperative ketorolac in high risk breast cancer patients. Rationale, feasibility and methodology of a prospective randomized placebo-controlled trial.

PubMed

Forget, Patrice; Berlière, Martine; van Maanen, Aline; Duhoux, Francois P; Machiels, Jean-Pascal; Coulie, Pierre G; Bouche, Gauthier; De Kock, Marc

2013-10-01

Ketorolac, a NSAID routinely used during surgery proposed to have anticancer effects, is a promising way to improve postoperative oncological outcome. This effect may be particularly prominent in patients with elevated preoperative inflammatory scores, like the neutrophil:lymphocyte ratio. In this paper, we describe the rationale, the preliminary analyses in our patients, the feasibility and the methodology of a prospective randomized trial called "Ketorolac in Breast Cancer trial" (KBCt) (NCT01806259). Copyright © 2013 Elsevier Ltd. All rights reserved.

The Rationale for Probiotics in Female Urogenital Healthcare

PubMed Central

Reid, Gregor; Burton, Jeremy; Devillard, Estelle

2004-01-01

Urogenital infections are a major reason that women visit their family physician and are referred to gastroenterology, gynecology, urology, and infectious disease specialists. The association between abnormal vaginal microbiota and increased risk for sexually transmitted infections, bladder and vaginal infections per se, and a higher rate of preterm labor indicate the need to better understand and manage urogenital health. The concept of probiotics arose from the realization that humans are inhabited with microbes from birth and that these organisms play a role in preventing disease. Defined as “live microorganisms, which when administered in adequate amounts confer a health benefit on the host,” probiotic strains have already been shown to effectively prevent diarrhea and to hold potential in preventing and treating tonsillitis, caries, renal calculi, and respiratory infections. This review provides a rationale for the use of probiotics in maintaining female vaginal and bladder health and as a treatment option for recurrent bacterial vaginosis, urinary tract infection, yeast vaginitis, and sexually transmitted infections. We consider only probiotic strains that fulfill the United Nations/World Health Organization Guidelines for Probiotics in being fully characterized and clinically documented through scientific investigations describing known or presumed mechanisms of action. Although medical practitioners as yet are unable to access these probiotic strains, an awareness of recent and ongoing research for probiotics is important, as results are encouraging. The concept of probiotic therapy is familiar to many consumers and although it has historically lacked credibility in the medical community, perceptions are changing. PMID:15208560

Buffalo complete streets.

DOT National Transportation Integrated Search

2013-01-01

Buffalo, NY formally adopted a local Complete Streets ordinance in 2008; however, implementation has yet : to become institutionalized. Buffalos Complete Streets Coalition, a multi-sector partnership was convened : to implement a Summit and Neighb...

Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets.

PubMed

O'Connor, A; Anthony, R; Bergamasco, L; Coetzee, J F; Dzikamunhenga, R S; Johnson, A K; Karriker, L A; Marchant-Forde, J N; Martineau, G P; Millman, S T; Pajor, E A; Rutherford, K; Sprague, M; Sutherland, M A; von Borell, E; Webb, S R

2016-04-01

Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.

Accuracy of Digitally Fabricated Wax Denture Bases and Conventional Completed Complete Dentures.

PubMed

Stawarczyk, Bogna; Lümkemann, Nina; Eichberger, Marlis; Wimmer, Timea

2017-12-19

The purpose of this investigation was to analyze the accuracy of digitally fabricated wax trial dentures and conventionally finalized complete dentures in comparison to a surface tessellation language (STL)-dataset. A generated data set for the denture bases and the tooth sockets was used, converted into STL-format, and saved as reference. Five mandibular and 5 maxillary denture bases were milled from wax blanks and denture teeth were waxed into their tooth sockets. Each complete denture was checked on fit, waxed onto the dental cast, and digitized using an optical laboratory scanning device. The complete dentures were completed conventionally using the injection method, finished, and scanned. The resulting STL-datasets were exported into the three-dimensional (3D) software GOM Inspect. Each of the 5 mandibular and 5 maxillary complete dentures was aligned with the STL- and the wax trial denture dataset. Alignment was performed based on a best-fit algorithm. A three-dimensional analysis of the spatial divergences in x -, y - and z -axes was performed by the 3D software and visualized in a color-coded illustration. The mean positive and negative deviations between the datasets were calculated automatically. In a direct comparison between maxillary wax trial dentures and complete dentures, complete dentures showed higher deviations from the STL-dataset than the wax trial dentures. The deviations occurred in the area of the teeth as well as in the distal area of the denture bases. In contrast, the highest deviations in both the mandibular wax trial dentures and the mandibular complete dentures were observed in the distal area. The complete dentures showed higher deviations on the occlusal surfaces of the teeth compared to the wax dentures. Computer-aided design/computer-aided manufacturing (CAD/CAM)-fabricated wax dentures exhibited fewer deviations from the STL-reference than the complete dentures. The deviations were significantly greater in the vicinity of the

Reproducibility and effect of posture on impulse oscillation parameters in persons with spinal cord injury

PubMed Central

Cirnigliaro, Christopher M.; Lesser, Marvin; Moyer, Jeremy; Kirshblum, Steven C.; Bauman, William A.; Spungen, Ann M.

2012-01-01

Background The impulse oscillation system (IOS) offers significant value in the assessment of airway dynamics in persons with spinal cord injury (SCI) because of minimal patient effort but measurement reproducibility in SCI is unknown. Objective To evaluate between-day reproducibility and the effect of posture on airway resistance [respiratory resistances at 5 Hz (R5) and 20 Hz (R20)] in subjects with tetraplegia, paraplegia and able-bodied controls. Methods Ten subjects with tetraplegia, 10 subjects with paraplegia and 11 able-bodied individuals were evaluated using IOS. Three 30 second trials were obtained in each while in the seated and supine position on Day 1, and repeated on Day 2. Results The within-day coefficient of variation (CV%) for R5 and R20 were comparable in the 3 study groups in the seated and supine positions. Compared to controls, the between-day CV% for the combined data was higher in subjects with tetraplegia and paraplegia for R5 seated, and was higher in subjects with tetraplegia for R5 supine. Conclusions IOS has applicability to the study of within-day respiratory resistance in SCI. However, performing longer-term studies in subjects with tetraplegia and paraplegia may be problematic because of the greater variability for R5 when compared to able-bodied individuals. PMID:22330188

Role and rationale for extended periarterial sympathectomy in the management of severe Raynaud syndrome: techniques and results.

PubMed

Merritt, Wyndell H

2015-02-01

There is no consensus regarding etiology or best surgical technique for severe Raynaud syndrome in patients with connective tissue disease. Observations after 30 years' experience in more than 100 cases led to the conclusion that an extended periarterial sympathectomy (with or without vein-graft reconstruction) and adjunctive use of Botox topically will offer benefits that exceed palliation and reduce recurrent ulcerations. In this article the rationale for this approach is reviewed, techniques and results are outlined, and a hypothesis for the mechanism of Raynaud attacks is offered. Copyright © 2015 Elsevier Inc. All rights reserved.

[Experimental rationale for the parameters of a rapid method for oxidase activity determination].

PubMed

Butorina, N N

2010-01-01

Experimental rationale is provided for the parameters of a rapid (1-2-min) test to concurrently determine the oxidase activity of all bacteria grown on the membrane filter after water filtration. Oxidase reagents that are the aqueous solutions of tetramethyl-p-phenylenediamine dihydrochloride and demethyl-p-phenylenediamine dihydrochloride have been first ascertained to exert no effect on the viability and enzymatic activity of bacteria after one-hour contact. An algorithm has been improved for the rapid oxidase activity test: the allowable time for bacteria to contact oxidase reagents and procedures for minimizing the effect on bacterial biochemical activity following the contact. An accelerated method based on lactose medium with tergitol 7 and Endo agar has been devised to determine coliform bacteria, by applying the rapid oxidase test: the time of a final response is 18-24 hours. The method has been included into GOST 52426-2005.

Study rationale and design of OPTIMISE, a randomised controlled trial on the effect of benchmarking on quality of care in type 2 diabetes mellitus.

PubMed

Nobels, Frank; Debacker, Noëmi; Brotons, Carlos; Elisaf, Moses; Hermans, Michel P; Michel, Georges; Muls, Erik

2011-09-22

To investigate the effect of physician- and patient-specific feedback with benchmarking on the quality of care in adults with type 2 diabetes mellitus (T2DM). Study centres in six European countries were randomised to either a benchmarking or control group. Physicians in both groups received feedback on modifiable outcome indicators (glycated haemoglobin [HbA1c], glycaemia, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein [LDL]-cholesterol and triglycerides) for each patient at 0, 4, 8 and 12 months, based on the four times yearly control visits recommended by international guidelines. The benchmarking group also received comparative results on three critical quality indicators of vascular risk (HbA1c, LDL-cholesterol and systolic blood pressure [SBP]), checked against the results of their colleagues from the same country, and versus pre-set targets. After 12 months of follow up, the percentage of patients achieving the pre-determined targets for the three critical quality indicators will be assessed in the two groups. Recruitment was completed in December 2008 with 3994 evaluable patients. This paper discusses the study rationale and design of OPTIMISE, a randomised controlled study, that will help assess whether benchmarking is a useful clinical tool for improving outcomes in T2DM in primary care. NCT00681850.

Design and Rationale for a Parent-Led Intervention to Increase Fruit and Vegetable Intake in Young Childhood Cancer Survivors (Reboot): Protocol for a Pilot Study.

PubMed

Touyz, Lauren; Cohen, Jennifer; Wakefield, Claire; Grech, Allison; Garnett, Sarah; Gohil, Paayal; Cohn, Richard

2018-05-16

Poor dietary habits are common among childhood cancer survivors, despite increasing their risk of cardio metabolic complications after cancer treatment. Here, we describe the design and rationale for a pilot telephone-based, parent-led intervention aimed at increasing fruit and vegetable intake in young cancer survivors (Reboot). This pilot study aims to assess the feasibility and acceptability of delivering evidence-based telephone support to parents of childhood cancer survivors. A secondary aim includes assessing the effect of Reboot on improving childhood cancer survivors' dietary quality by increasing child fruit and vegetable intake and variety and its contribution to overall nutrient intake. We aim to recruit parents of 15 young cancer survivors aged 2 to 12 years who have completed cancer treatment less than five years ago. The intervention comprises of 4 weekly 45-minute telephone sessions led by a health professional and one booster session 6 weeks later. Sessions address the effects of cancer treatment on children's diets, recommended fruit and vegetable intake for children, and evidence-based strategies to promote the consumption of fruit and vegetables as well as to manage fussy eating. Reboot is based on an existing, evidence-based parent nutrition intervention and modified for childhood cancer survivors following extensive collaboration with experts in the field. Primary outcomes of feasibility and acceptability will be measured by the number of participants who complete all five sessions, average session length (minutes), length between sessions (days) and parent Likert ratings of the usefulness and impact of the intervention collected after the booster session. Of the 15 participants we aim to recruit, 3 have completed the intervention, 1 declined to participate, 11 are actively completing the intervention and 2 participants are providing written consent. The remaining 3 participants will be recruited via telephone follow-up calls. The intervention

Rationale for a natural products approach to herbicide discovery.

PubMed

Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

2012-04-01

Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry. Published 2012 by John Wiley & Sons, Ltd.

Evaluation of the physical activity scale for individuals with physical disabilities in people with spinal cord injury.

PubMed

de Groot, S; van der Woude, L H V; Niezen, A; Smit, C A J; Post, M W M

2010-07-01

Cross-sectional study. To evaluate the physical activity scale for individuals with physical disabilities (PASIPD) in people with spinal cord injury (SCI). Eight Dutch rehabilitation centers with a specialized SCI unit. The PASIPD was examined by comparing group scores of people with different personal (age, gender and body mass index) and lesion characteristics (level (paraplegia/tetraplegia), completeness, time since injury (TSI)) in 139 persons with SCI 1 year after discharge from in-patient rehabilitation. Relationships between PASIPD scores and measures of activities (wheelchair skills, Utrecht Activity List, mobility range and social behavior subscales of the SIP68) and fitness (peak oxygen uptake, peak power output and muscular strength) were determined. Persons with tetraplegia had significantly lower PASIPD scores than those with paraplegia (P<0.02). Persons with longer TSI had lower PASIPD scores than persons with shorter TSI (P<0.03). PASIPD scores showed moderate correlations with activities (0.36-0.51, P<0.01) and weak-to-moderate correlations with fitness parameters (0.25-0.36, P<0.05). In a fairly homogeneous group of persons with SCI, 1 year after in-patient rehabilitation, the PASIPD showed weak-to-moderate relationships with activity and fitness parameters. There seems to be a limited association between self-reported activity level and fitness in people with SCI.

Motor exam of patients with spinal cord injury: a terminological imbroglio.

PubMed

Figueiredo, Nicandro

2017-07-01

The description of the motor deficit of patients with spinal cord injury (SCI) varies significantly, leading to confusion within the neurological terminology. This paper proposes a concise and easy to use terminology to describe the motor deficit of patients with SCI. A broad review of the origin of the nomenclature used to describe the motor deficit of patients with SCI was performed and discussed. The prefix: "hemi" should be used to describe paralysis of one half of the body; "mono" for one limb; "para" for lower limbs, di" for two symmetrical segments and/or parts in both sides of the body; "tri" for three limbs, or two limbs and one side of the face; and "tetra" for four limbs. The suffix: "plegia" should be used for total paralysis of a limb or part of the body, and "paresis" for partial paralysis. The term "brachial" refers to the upper limbs; and "podal" to the lower limbs. According to the spinal cord origin of the main key muscles for the limbs, patients with complete injury affecting spinal cord segments C1-5 usually presents with "tetraplegia"; C6-T1 presents with "paraplegia and brachial diparesis"; T2-L2 with "paraplegia"; and L3-S1 with "paraparesis".

Amodal Completion in Bonobos

ERIC Educational Resources Information Center

Nagasaka, Yasuo; Brooks, Daniel I.; Wasserman, Edward A.

2010-01-01

We trained two bonobos to discriminate among occluded, complete, and incomplete stimuli. The occluded stimulus comprised a pair of colored shapes, one of which appeared to occlude the other. The complete and incomplete stimuli involved the single shape that appeared to have been partially covered in the occluded stimulus; the complete stimulus…

In vivo animal stroke models: a rationale for rodent and non-human primate models

PubMed Central

Tajiri, Naoki; Dailey, Travis; Metcalf, Christopher; Mosley, Yusef I.; Lau, Tsz; Staples, Meaghan; van Loveren, Harry; Kim, Seung U.; Yamashima, Tetsumori; Yasuhara, Takao; Date, Isao; Kaneko, Yuji; Borlongan, Cesario V.

2013-01-01

On average, every four minutes an individual dies from a stroke, accounting for 1 out of every 18 deaths in the United States. Apporximately 795,000 Americans have a new or recurrent stroke each year, with just over 600,000 of these being first attack [1]. There have been multiple animal models of stroke demonstrating that novel therapeutics can help improve the clinical outcome. However, these results have failed to show the same outcomes when tested in human clinical trials. This review will discuss the current in vivo animal models of stroke, advantages and limitations, and the rationale for employing these animal models to satisfy translational gating items for examination of neuroprotective, as well as neurorestorative strategies in stroke patients. An emphasis in the present discussion of therapeutics development is given to stem cell therapy for stroke. PMID:23682299

GRADE equity guidelines 1: considering health equity in GRADE guideline development: introduction and rationale.

PubMed

Welch, Vivian A; Akl, Elie A; Guyatt, Gordon; Pottie, Kevin; Eslava-Schmalbach, Javier; Ansari, Mohammed T; de Beer, Hans; Briel, Matthias; Dans, Tony; Dans, Inday; Hultcrantz, Monica; Jull, Janet; Katikireddi, Srinivasa Vittal; Meerpohl, Joerg; Morton, Rachael; Mosdol, Annhild; Petkovic, Jennifer; Schünemann, Holger J; Sharaf, Ravi N; Singh, Jasvinder A; Stanev, Roger; Tonia, Thomy; Tristan, Mario; Vitols, Sigurd; Watine, Joseph; Tugwell, Peter

2017-10-01

This article introduces the rationale and methods for explicitly considering health equity in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for development of clinical, public health, and health system guidelines. We searched for guideline methodology articles, conceptual articles about health equity, and examples of guidelines that considered health equity explicitly. We held three meetings with GRADE Working Group members and invited comments from the GRADE Working Group listserve. We developed three articles on incorporating equity considerations into the overall approach to guideline development, rating certainty, and assembling the evidence base and evidence to decision and/or recommendation. Clinical and public health guidelines have a role to play in promoting health equity by explicitly considering equity in the process of guideline development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Rationale for differentiated sanitary protection zones for battery recycling enterprises in modern conditions].

PubMed

Pinigin, M A; Popov, B A; Sabirova, Z F; Budarina, O V; Ul'ianova, A V

2013-01-01

In the paper there is presented the rationale for differentiated sanitary protective zones in the present conditions both of the increase of volumes of production and introduction of various technological solutions on the example of battery recycling enterprise. It is established that the in acting regulations the classification of enterprises recycling of non-ferrous metals, fails to take into account such the hazard risks criteria of the enterprise, as volume of emissions of priority substances, the height of their arrival in the atmosphere, etc., and also does not take into account increased significantly in the current time processing volumes. The results of the performed research allowed to offer new positions in the classification of production of secondary lead from used batteries (I to IV class), depending on the volume of production (from 20 000 to 160 000 tons per year), the amount of emissions of lead (0.2 to 1, 6 tons per year) and release height (15 to 60 m).

The Mediterranean healthy eating, ageing, and lifestyle (MEAL) study: rationale and study design.

PubMed

Grosso, Giuseppe; Marventano, Stefano; D'Urso, Maurizio; Mistretta, Antonio; Galvano, Fabio

2017-08-01

There is accumulating evidence suggesting that Mediterranean lifestyles, including nutrition and sleeping patterns as well as social integration, may play a role in reducing age-related diseases. However, the literature is mostly deficient of evidence provided by Italian Mediterranean islands that more closely adhered to the originally described lifestyles. In this paper, we described the rationale and the study design of the Mediterranean healthy Eating, Ageing, and Lifestyle (MEAL) study, a prospective population-based cohort established in Sicily, southern Italy. The main exposures investigated are classical determinants of health, including demographic, nutritional habits, smoking and physical activity status, as well as eating-related behaviors, sleeping habits, sun exposure, social resources, and perceived stress. Anthropometric measurements will be collected. The main outcomes included depression, quality of life, and, after the follow-up period, also cardiovascular disease and cancer. The MEAL study may provide important data to increase our knowledge regarding the prevalence, incidence, and risk factors of age-related disorders in the Mediterranean region.

Knowledge based system verification and validation as related to automation of space station subsystems: Rationale for a knowledge based system lifecycle

NASA Technical Reports Server (NTRS)

Richardson, Keith; Wong, Carla

1988-01-01

The role of verification and validation (V and V) in software has been to support and strengthen the software lifecycle and to ensure that the resultant code meets the standards of the requirements documents. Knowledge Based System (KBS) V and V should serve the same role, but the KBS lifecycle is ill-defined. The rationale of a simple form of the KBS lifecycle is presented, including accommodation to certain critical KBS differences from software development.

Laparoscopic complete mesocolic excision with central vascular ligation in right colon cancer: A comprehensive review

PubMed Central

Siani, Luca Maria; Garulli, Gianluca

2016-01-01

Aim of the study is to comprehensively review the latest trends in laparoscopic complete mesocolic excision (CME) with central vascular ligation (CVL) for the multimodal management of right colon cancer. Historical and up-to-date anatomo-embryological concepts are analyzed in detail, focusing on the latest studies of the mesenteric organ, its dissection by mesofascial and retrofascial cleavage planes, and questioning the need for a new terminology in colonic resections. The rationale behind Laparoscopic CME with CVL is thoroughly investigated and explained. Attention is paid to the current surgical techniques and the quality of the surgical specimen, yielded through mesocolic, intramesocolic and muscularis propria plane of surgery. We evaluate the impact on long term oncologic outcome in terms of local recurrence, overall and disease-free survival, according to the plane of resection achieved. Conclusions are drawn on the basis of the available evidence, which suggests a pivotal role of laparoscopic CME with CVL in the multimodal management of right sided colonic cancer: performed in the right mesocolic plane of resection, laparoscopic CME with CVL demonstrates better oncologic results when compared to standard non-mesocolic planes of surgery, with all the advantages of laparoscopic techniques, both in faster recovery and better immunological response. The importance of minimally invasive meso-resectional surgery is thus stressed and highlighted as the new frontier for a modern laparoscopic total right mesocolectomy. PMID:26981184

Climate Model Ensemble Methodology: Rationale and Challenges

NASA Astrophysics Data System (ADS)

Vezer, M. A.; Myrvold, W.

2012-12-01

A tractable model of the Earth's atmosphere, or, indeed, any large, complex system, is inevitably unrealistic in a variety of ways. This will have an effect on the model's output. Nonetheless, we want to be able to rely on certain features of the model's output in studies aiming to detect, attribute, and project climate change. For this, we need assurance that these features reflect the target system, and are not artifacts of the unrealistic assumptions that go into the model. One technique for overcoming these limitations is to study ensembles of models which employ different simplifying assumptions and different methods of modelling. One then either takes as reliable certain outputs on which models in the ensemble agree, or takes the average of these outputs as the best estimate. Since the Intergovernmental Panel on Climate Change's Fourth Assessment Report (IPCC AR4) modellers have aimed to improve ensemble analysis by developing techniques to account for dependencies among models, and to ascribe unequal weights to models according to their performance. The goal of this paper is to present as clearly and cogently as possible the rationale for climate model ensemble methodology, the motivation of modellers to account for model dependencies, and their efforts to ascribe unequal weights to models. The method of our analysis is as follows. We will consider a simpler, well-understood case of taking the mean of a number of measurements of some quantity. Contrary to what is sometimes said, it is not a requirement of this practice that the errors of the component measurements be independent; one must, however, compensate for any lack of independence. We will also extend the usual accounts to include cases of unknown systematic error. We draw parallels between this simpler illustration and the more complex example of climate model ensembles, detailing how ensembles can provide more useful information than any of their constituent models. This account emphasizes the

The rationale for attempting to define salt marsh mosquito-breeding areas in Galveston County by remote sensing the associated vegetation

NASA Technical Reports Server (NTRS)

Arp, G. K.

1975-01-01

The rationale for attempting to define salt marsh mosquito breeding areas in Galveston County was discussed, including a botanical survey of the marsh plant communities, their relationship to flooding, and their exposure to salt water. Particular emphasis is given to Distichlis spicata, a widespread marsh grass. Evidence suggests that breeding areas of Aedes sollicitans are associated with Distichlis and that both species respond to similar ecological conditions in the salt marsh. Aspects of the remote sensing of the Distichlis are considered.

40 CFR 72.61 - Completeness.

Code of Federal Regulations, 2010 CFR

2010-07-01

... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will determine whether the Acid Rain permit application is complete within 60... the Acid Rain permit application is complete under paragraph (a) of this section, the Administrator...

40 CFR 72.61 - Completeness.

Code of Federal Regulations, 2014 CFR

2014-07-01

... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will determine whether the Acid Rain permit application is complete within 60... the Acid Rain permit application is complete under paragraph (a) of this section, the Administrator...

40 CFR 72.61 - Completeness.

Code of Federal Regulations, 2013 CFR

2013-07-01

... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will determine whether the Acid Rain permit application is complete within 60... the Acid Rain permit application is complete under paragraph (a) of this section, the Administrator...

40 CFR 72.61 - Completeness.

Code of Federal Regulations, 2011 CFR

2011-07-01

... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will determine whether the Acid Rain permit application is complete within 60... the Acid Rain permit application is complete under paragraph (a) of this section, the Administrator...

40 CFR 72.61 - Completeness.

Code of Federal Regulations, 2012 CFR

2012-07-01

... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will determine whether the Acid Rain permit application is complete within 60... the Acid Rain permit application is complete under paragraph (a) of this section, the Administrator...

Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross-sectional study on effects of time since injury and physical activity level.

PubMed

de Groot, Sonja; van der Scheer, Jan W; Bakkum, Arjan J T; Adriaansen, Jacinthe J E; Smit, Christof A; Dijkstra, Catja; Post, Marcel W M; van der Woude, Lucas H V

2016-01-01

To study the impact of time since injury (TSI) and physical activity (PA) on fitness of persons with spinal cord injury (SCI). Cross-sectional study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and ≥30 years after SCI and divided in an active and inactive group. Fitness [peak power output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. In persons with tetraplegia, no significant relationship was found between TSI and fitness after controlling for confounders, while a higher activity level was related to a higher POpeak in this group. Active people with tetraplegia also showed less decline in POpeak with an increase in TSI compared to inactive people. In persons with paraplegia, after controlling for confounders, it was shown that TSI had a negative effect on POpeak, while PA was not significantly associated with fitness in people with paraplegia. In people with paraplegia, fitness was significantly lower in those with a longer TSI. Persons with a long TSI might need more attention to remain fit and PA might be an important element in that respect as shown by the results of the group with a tetraplegia. Wheelchair-specific fitness seems to diminish over time after paraplegia. An active lifestyle is related to wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term deconditioning is very important.

Rationale and Methods for Archival Sampling and Analysis of Atmospheric Trace Chemical Contaminants On Board Mir and Recommendations for the International Space Station

NASA Technical Reports Server (NTRS)

Perry, J. L.; James, J. T.; Cole, H. E.; Limero, T. F.; Beck, S. W.

1997-01-01

Collection and analysis of spacecraft cabin air samples are necessary to assess the cabin air quality with respect to crew health. Both toxicology and engineering disciplines work together to achieve an acceptably clean cabin atmosphere. Toxicology is concerned with limiting the risk to crew health from chemical sources, setting exposure limits, and analyzing air samples to determine how well these limits are met. Engineering provides the means for minimizing the contribution of the various contaminant generating sources by providing active contamination control equipment on board spacecraft and adhering to a rigorous material selection and control program during the design and construction of the spacecraft. A review of the rationale and objectives for sampling spacecraft cabin atmospheres is provided. The presently-available sampling equipment and methods are reviewed along with the analytical chemistry methods employed to determine trace contaminant concentrations. These methods are compared and assessed with respect to actual cabin air quality monitoring needs. Recommendations are presented with respect to the basic sampling program necessary to ensure an acceptably clean spacecraft cabin atmosphere. Also, rationale and recommendations for expanding the scope of the basic monitoring program are discussed.

Neonatal Immunization: Rationale, Current State, and Future Prospects.

PubMed

Whittaker, Elizabeth; Goldblatt, David; McIntyre, Peter; Levy, Ofer

2018-01-01

Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette-Guérin (BCG), may offer single shot protection, potentially in part via heterologous ("non-specific") beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, Haemophilus influenza type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, in vitro platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to neonatal

Neonatal Immunization: Rationale, Current State, and Future Prospects

PubMed Central

Whittaker, Elizabeth; Goldblatt, David; McIntyre, Peter; Levy, Ofer

2018-01-01

Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette–Guérin (BCG), may offer single shot protection, potentially in part via heterologous (“non-specific”) beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, Haemophilus influenza type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, in vitro platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to

Economic Values for Evaluation of Federal Aviation Administration Investment and Regulatory Programs

DTIC Science & Technology

1989-10-01

Classifications: Critical Spinal Cord Injury Resulting in Quadriplegia $ 2,210,000 Critical Head Injury Resulting in Total Disability $ 2,460,000...34 Table 8 Percentage Utility Loss Associated with Severe Injuries AIS 4 AIS 5 Quadriplegia Paraplegia Quadriplegia Paraplegia Spinal Cord 109% 46% 109... Quadriplegia : d Air Carrier Domestic Pass. 1,719,071 91,522 223,492 23,784 75.4% Int’l Pass. 1,719,071 237,261 225,049 23,915 4.8% Commuter 1,719,071

Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation.

PubMed

Ferris, Robert L; Lenz, Heinz-Josef; Trotta, Anna Maria; García-Foncillas, Jesús; Schulten, Jeltje; Audhuy, François; Merlano, Marco; Milano, Gerard

2018-02-01

Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity-including, but not limited to, ADCC-provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Locating responsibility: the Sphere Humanitarian Charter and its rationale.

PubMed

Darcy, James

2004-06-01

Criticised by some as a technical initiative that neglects core principles, Sphere was seen by its originators precisely as an articulation of principle. The Humanitarian Charter was the main vehicle through which this was expressed, but its relationship to the Minimum Standards has remained a matter of uncertainty. Specifically, it was unclear in the original (1999) edition of Sphere how the concept of rights informed the Minimum Standards. The revised (2004) edition goes some way to clarifying this in the way the standards are framed, yet the link between the standards and the charter remains unclear. The concern with the quality and accountability of humanitarian assistance, which motivated the attempt to establish system-wide standards through the Sphere Project, was accompanied by a desire to establish such actions in a wider framework of legal and political responsibility. In part, this reflects the conditional nature of the undertaking that agencies make when they adopt Sphere. This aspect of the charter has been neglected, but it is fundamental to an understanding of the standards and their application. This paper considers the rationale of the Sphere Humanitarian Charter and the conceptual model that underpins it. It discusses the relationship between the charter and the Minimum Standards, and the sense in which the latter are properly called "rights-based" (explored further in a related paper herein by Young and Taylor). The author was closely involved in the conception and drafting of the charter, and this paper attempts to convey some of the thinking that lay behind it.

Preliminary scientific rationale for a voyage to a thousand astronomical units

NASA Technical Reports Server (NTRS)

Etchegaray, M. I. (Compiler)

1987-01-01

A proposed mission to 1000 astronomical units (TAU) is under study by the Jet Propulsion Laboratory. Launch date for a TAU mission is likely to be well into the first decade of the 21st century. Study of TAU has focused on the technologies required to carry out this ambitious mission and the identification of preliminary scientific rationale for such a deep space flight. A 1-MW nuclear-powered electric propulsion (NEP) system forms the baseline method for achieving the high velocities required. A solar system escape velocity of 106 km/s is needed to propel the TAU vehicle to 1000 AU in 50 years. The NEP system must accelerate the vehicle for about ten years before this velocity is attained because of the extremely low thrust nature of the xenon-fueled ion engines. At the end of the thrusting phase the NEP system is jettisoned to allow the TAU spacecraft and science experiments to coast out to 1000 AU. Another important technology for TAU is advanced optical communication systems, which are envisioned for transmitting science data to Earth. A 1-m optical telescope combined with a 10-W laser transponder can transmit 20 kbps to a 10-m Earth-orbit-based telescope from 1000 AU.

Structure-based rationale for differential recognition of lacto- and neolacto- series glycosphingolipids by the N-terminal domain of human galectin-8

NASA Astrophysics Data System (ADS)

Bohari, Mohammad H.; Yu, Xing; Zick, Yehiel; Blanchard, Helen

2016-12-01

Glycosphingolipids are ubiquitous cell surface molecules undertaking fundamental cellular processes. Lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are the representative core structures for lacto- and neolacto-series glycosphingolipids. These glycolipids are the carriers to the blood group antigen and human natural killer antigens mainly found on blood cells, and are also principal components in human milk, contributing to infant health. The β-galactoside recognising galectins mediate various cellular functions of these glycosphingolipids. We report crystallographic structures of the galectin-8 N-terminal domain (galectin-8N) in complex with LNT and LNnT. We reveal the first example in which the non-reducing end of LNT binds to the primary binding site of a galectin, and provide a structure-based rationale for the significant ten-fold difference in binding affinities of galectin-8N toward LNT compared to LNnT, such a magnitude of difference not being observed for any other galectin. In addition, the LNnT complex showed that the unique Arg59 has ability to adopt a new orientation, and comparison of glycerol- and lactose-bound galectin-8N structures reveals a minimum atomic framework for ligand recognition. Overall, these results enhance our understanding of glycosphingolipids interactions with galectin-8N, and highlight a structure-based rationale for its significantly different affinity for components of biologically relevant glycosphingolipids.

Study rationale and design of OPTIMISE, a randomised controlled trial on the effect of benchmarking on quality of care in type 2 diabetes mellitus

PubMed Central

2011-01-01

Background To investigate the effect of physician- and patient-specific feedback with benchmarking on the quality of care in adults with type 2 diabetes mellitus (T2DM). Methods Study centres in six European countries were randomised to either a benchmarking or control group. Physicians in both groups received feedback on modifiable outcome indicators (glycated haemoglobin [HbA1c], glycaemia, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein [LDL]-cholesterol and triglycerides) for each patient at 0, 4, 8 and 12 months, based on the four times yearly control visits recommended by international guidelines. The benchmarking group also received comparative results on three critical quality indicators of vascular risk (HbA1c, LDL-cholesterol and systolic blood pressure [SBP]), checked against the results of their colleagues from the same country, and versus pre-set targets. After 12 months of follow up, the percentage of patients achieving the pre-determined targets for the three critical quality indicators will be assessed in the two groups. Results Recruitment was completed in December 2008 with 3994 evaluable patients. Conclusions This paper discusses the study rationale and design of OPTIMISE, a randomised controlled study, that will help assess whether benchmarking is a useful clinical tool for improving outcomes in T2DM in primary care. Trial registration NCT00681850 PMID:21939502

Hanford waste-form release and sediment interaction: A status report with rationale and recommendations for additional studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serne, R.J.; Wood, M.I.

1990-05-01

This report documents the currently available geochemical data base for release and retardation for actual Hanford Site materials (wastes and/or sediments). The report also recommends specific laboratory tests and presents the rationale for the recommendations. The purpose of this document is threefold: to summarize currently available information, to provide a strategy for generating additional data, and to provide recommendations on specific data collection methods and tests matrices. This report outlines a data collection approach that relies on feedback from performance analyses to ascertain when adequate data have been collected. The data collection scheme emphasizes laboratory testing based on empiricism. 196more » refs., 4 figs., 36 tabs.« less

A Critical Analysis of the Scientific and Commercial Rationales for the De Novo Synthesis of Horsepox Virus

PubMed Central

2018-01-01

ABSTRACT This article evaluates the scientific and commercial rationales for the synthesis of horsepox virus. I find that the claimed benefits of using horsepox virus as a smallpox vaccine rest on a weak scientific foundation and an even weaker business case that this project will lead to a licensed medical countermeasure. The combination of questionable benefits and known risks of this dual use research raises serious questions about the wisdom of undertaking research that could be used to recreate variola virus. This analysis also raises important questions about the propriety of a private company sponsoring such dual use research without appropriate oversight and highlights an important gap in United States dual use research regulations. PMID:29569633

Collection of real-world data on nivolumab's effectiveness in renal cell carcinoma: rationale for an observational study.

PubMed

Bedke, Jens; Grimm, Marc-Oliver; Grünwald, Viktor

2018-05-01

Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth (women) most frequent cancer in western countries. After one or more lines of VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in patients with metastatic RCC. Nivolumab is the first, and so far, only approved PD-1 immune checkpoint inhibitor to demonstrate a gain in overall survival in RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a prospective, noninterventional cohort study investigating the effectiveness of nivolumab. This systematic collection of real-world effectiveness data will recruit 323 patients with advanced RCC to provide a precise estimate for overall survival over a 5-year follow-up period (Trial registration: NCT02940639).

To Report or Not to Report: Exploring Healthy Volunteers' Rationales for Disclosing Adverse Events in Phase I Drug Trials.

PubMed

McManus, Lisa; Fisher, Jill A

2018-04-25

Phase I trials test the safety and tolerability of investigational drugs and often use healthy volunteers as research participants. Adverse events (AEs) are collected in part through participants' self-reports of any symptoms they experience during the trial. In some cases, experiencing AEs can result in trial participation being terminated. Because of the economic incentives underlying their motivation to participate, there is concern that healthy volunteers routinely fail to report AEs and, thereby, jeopardize the validity of the trial results. We interviewed 131 U.S. healthy volunteers about their experiences with AEs, including their rationales for reporting or failing to report symptoms. We found that participants have three primary rationales for their AE reporting behavior: economic, health-oriented, and data integrity. Participants often make decisions about whether to report AEs on a case-by-case basis evaluating what effects reporting or not reporting might have on the compensation they receive from the trial, the risk to their health, and the results of the particular clinical trial. Participants' interpretations of clinic policies, staff behaviors, and personal or vicarious experiences with reporting AEs also shape reporting decisions. Our findings demonstrate that participants' reporting behavior is more complex than previous portraits of healthy volunteers have suggested. Rather than finding participants who were so focused on the financial compensation that they were willing to subvert trial results, our study indicates that participants are willing in most cases to forgo their full compensation if they believe not reporting their symptoms jeopardizes their own safety or the validity of the research.

Rationale for Using Social Media to Collect Patient-Reported Outcomes in Patients with Celiac Disease.

PubMed

Park, Kt; Harris, Merissa; Khavari, Nasim; Khosla, Chaitan

2014-02-01

Patients with celiac disease (CD) are increasingly interconnected through social media, exchanging patient experiences and health-tracking information between individuals through various web-based platforms. Social media represents potentially unique communication interface between gastroenterologists and active social media users - especially young adults and adolescents with celiac disease-regarding adherence to the strict gluten-free diet, gastrointestinal symptoms, and meaningful discussion about disease management. Yet, various social media platforms may be underutilized for research purposes to collect patient-reported outcomes data. In this commentary, we summarize the scientific rationale and potential for future growth of social media in patient-reported outcomes research, focusing on college freshmen with celiac disease as a case study and provide overview of the methodological approach. Finally, we discuss how social media may impact patient care in the future through increasing mobile technology use.

Integration of mental health into primary care and community health working in Kenya: context, rationale, coverage and sustainability.

PubMed

Jenkins, Rachel; Kiima, David; Okonji, Marx; Njenga, Frank; Kingora, James; Lock, Sarah

2010-03-01

Integration of mental health into primary care is essential to meet population needs yet faces many challenges if such projects are to achieve impact and be sustainable in low income countries alongside other competing priorities. This paper describes the rationale and progress of a collaborative project in Kenya to train primary care and community health workers about mental health and integrate mental health into their routine work, Within a health systems strengthening approach. So far 1877 health workers have been trained. The paper describes the multiple challenges faced by the project, and reviews the mechanisms deployed which have strengthened its impact and sustainability to date.

The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

PubMed Central

Tiano, Luca; Silvestri, Sonia; Orlando, Patrik; Calcabrini, Cinzia; Stocchi, Vilberto

2017-01-01

Sarcopenia represents an increasing public health risk due to the rapid aging of the world's population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS) production and decreased antioxidant (AO) defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed. PMID:29123615

Building confidence in quantitative systems pharmacology models: An engineer's guide to exploring the rationale in model design and development.

PubMed

Timmis, J; Alden, K; Andrews, P; Clark, E; Nellis, A; Naylor, B; Coles, M; Kaye, P

2017-03-01

This tutorial promotes good practice for exploring the rationale of systems pharmacology models. A safety systems engineering inspired notation approach provides much needed rigor and transparency in development and application of models for therapeutic discovery and design of intervention strategies. Structured arguments over a model's development, underpinning biological knowledge, and analyses of model behaviors are constructed to determine the confidence that a model is fit for the purpose for which it will be applied. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

PubMed

Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

2016-04-01

To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

Holonic Rationale and Bio-inspiration on Design of Complex Emergent and Evolvable Systems

NASA Astrophysics Data System (ADS)

Leitao, Paulo

Traditional centralized and rigid control structures are becoming inflexible to face the requirements of reconfigurability, responsiveness and robustness, imposed by customer demands in the current global economy. The Holonic Manufacturing Systems (HMS) paradigm, which was pointed out as a suitable solution to face these requirements, translates the concepts inherited from social organizations and biology to the manufacturing world. It offers an alternative way of designing adaptive systems where the traditional centralized control is replaced by decentralization over distributed and autonomous entities organized in hierarchical structures formed by intermediate stable forms. In spite of its enormous potential, methods regarding the self-adaptation and self-organization of complex systems are still missing. This paper discusses how the insights from biology in connection with new fields of computer science can be useful to enhance the holonic design aiming to achieve more self-adaptive and evolvable systems. Special attention is devoted to the discussion of emergent behavior and self-organization concepts, and the way they can be combined with the holonic rationale.

Company profile: Complete Genomics Inc.

PubMed

Reid, Clifford

2011-02-01

Complete Genomics Inc. is a life sciences company that focuses on complete human genome sequencing. It is taking a completely different approach to DNA sequencing than other companies in the industry. Rather than building a general-purpose platform for sequencing all organisms and all applications, it has focused on a single application - complete human genome sequencing. The company's Complete Genomics Analysis Platform (CGA™ Platform) comprises an integrated package of biochemistry, instrumentation and software that sequences human genomes at the highest quality, lowest cost and largest scale available. Complete Genomics offers a turnkey service that enables customers to outsource their human genome sequencing to the company's genome sequencing center in Mountain View, CA, USA. Customers send in their DNA samples, the company does all the library preparation, DNA sequencing, assembly and variant analysis, and customers receive research-ready data that they can use for biological discovery.

Paraplegia due to adrenomyeloneuropathy.

PubMed

Lamid, S; El Ghatit, A Z

1984-04-01

Only nine cases of adrenomyeloneuropathy have been reported in the literature. It manifested as adrenal insufficiency, spastic paraparesis, loss of bowel, bladder and sexual functions, and peripheral neuropathy. Our paper describes a patient with the diagnosis of adrenomyeloneuropathy who was admitted to our hospital for rehabilitation. Family and neurological history, physical examination and special laboratory studies such as ACTH stimulation test, electrodiagnostic findings, cystometrogram and sexual function evaluation were essential to establish the diagnosis of this disease. His rehabilitation consisted of bowel and bladder training, ambulation with long-leg braces and crutches, wheelchair mobilization and transfers, and independence of all activities of daily living.

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

PubMed Central

FRIEDMANN, PETER D.; KATZ, ELIZABETH C.; RHODES, ANNE G.; TAXMAN, FAYE S.; O'CONNELL, DANIEL J.; FRISMAN, LINDA K.; BURDON, WILLIAM M.; FLETCHER, BENNETT W.; LITT, MARK D.; CLARKE, JENNIFER; MARTIN, STEVEN S.

2009-01-01

This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment counselors to provide role induction counseling, contract for pro-social behavior, and deliver contingent reinforcement of behaviors consistent with treatment objectives. The Step'n Out study will randomize 450 drug-involved parolees to collaborative behavioral management or usual parole. Follow-up at 3-and 9-months will assess primary outcomes of rearrest, crime and drug use. If collaborative behavioral management is effective, its wider adoption could improve the outcomes of community reentry of drug-involved ex-offenders. PMID:19809591

Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries.

PubMed

Etz, Christian D; Homann, Tobias M; Luehr, Maximilian; Kari, Fabian A; Weisz, Donald J; Kleinman, George; Plestis, Konstadinos A; Griepp, Randall B

2008-06-01

Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may

Effects of Mindfulness on Diabetes Mellitus: Rationale and Overview.

PubMed

Medina, Wilson L; Wilson, David; de Salvo, Vera; Vannucchi, Bruna; de Souza, Érika Leonardo; Lucena, Leandro; Sarto, Héctor Morillo; Modrego-Alarcón, Marta; Garcia-Campayo, Javier; Demarzo, Marcelo

2017-01-01

Diabetes mellitus (DM) is an emerging global healthcare problem and its prevalence is increasing at an alarming rate. Despite improvements in both medical and pharmacological therapies, a complex medical condition may demand a diversified approach, such as: drug therapy, healthy diet and exercises, diabetes education programs, adherence to medical treatment and active participation of the patients in their lifestyle changes, such as stress management. The concept of mindfulness is here defined as the awareness that unfolds from the intention to attentively observe the current experience in a non-judgmental and non-evaluative way. This state of awareness can be enhanced through the use of mindfulness-based interventions (MBIs), which have been associated to many physical and psychological health indicators. The aim of this overview is to offer the rationale and potential benefits of mindfulness in the control of DM and its complications. a narrative review of the current and updated literature available on online database and which came up using the terms "mindfulness" and "diabetes mellitus". Mindfulness-based Interventions (MBIs) can be seen as preventive and complementary interventions in DM, particularly for the relief of symptoms related to depression and anxiety in diabetic patients and also in the management of other factors, including mindful eating, physical exercises and treatment adherence. Although many studies only present research protocols, mindfulness seems to have beneficial effects on all aspects of diabetes, including incidence, control and complications. Furthermore, longer term and more carefully controlled trials are necessary in order to draw consistent conclusions on the beneficial role of MBIs on DM. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial - Cell Phone Intervention for You (CITY).

PubMed

Batch, Bryan C; Tyson, Crystal; Bagwell, Jacqueline; Corsino, Leonor; Intille, Stephen; Lin, Pao-Hwa; Lazenka, Tony; Bennett, Gary; Bosworth, Hayden B; Voils, Corrine; Grambow, Steven; Sutton, Aziza; Bordogna, Rachel; Pangborn, Matthew; Schwager, Jenifer; Pilewski, Kate; Caccia, Carla; Burroughs, Jasmine; Svetkey, Laura P

2014-03-01

The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population. To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to 3) a usual care, advice-only control condition. A total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 24 [corrected] months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. ClinicalTrial.gov: NCT01092364. Published by Elsevier Inc.

Aspergillus spondylodiscitis in an immunocompetent paraplegic patient.

PubMed

Schubert, M; Schär, G; Curt, A; Dietz, V

1998-11-01

A case of an immunocompetent 60 year old patient is reported, who suffered extensive thoracic spinal injury and paraplegia after polytrauma. In the course of rehabilitation he developed aspergillus spondylodiscitis in a part of the thoraco-lumbar spine which was primarily uninjured. The diagnostic assessment and therapeutic approach of this rare disorder is elucidated and discussed in the context of paraplegia and polytrauma. Possible mechanisms of inoculation and spreading of the moulds as well as predisposing factors of the disease are discussed in this paper and a review of the recent literature is provided.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studiesmore » on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.« less

Deconstructing the Brain Disconnection-Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death.

PubMed

Moschella, Melissa

2016-06-01

This article explains the problems with Alan Shewmon's critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Changing Rationales for Governing the Child: A Historical Perspective on the Emergence of the Psychological Child in the Context of Preschool--Notes on a Study in Progress.

ERIC Educational Resources Information Center

Hultqvist, Kenneth

1997-01-01

Focuses on the issue of change in preschool discourse and argues that changes are related to the emergence of new rationales for governing the child. Specifically describes a period of transition (1920-1940) in the history of the Swedish preschool when Friedrich Froebel's discourse on the child became replaced by developmental psychology. (SD)

An objective rationale for the choice of regularisation parameter with application to global multiple-frequency S-wave tomography

NASA Astrophysics Data System (ADS)

Zaroli, C.; Sambridge, M.; Lévêque, J.-J.; Debayle, E.; Nolet, G.

2013-06-01

In a linear ill-posed inverse problem, the regularisation parameter (damping) controls the balance between minimising both the residual data misfit and the model norm. Poor knowledge of data uncertainties often makes the selection of damping rather arbitrary. To go beyond that subjectivity, an objective rationale for the choice of damping is presented, which is based on the coherency of delay-time estimates in different frequency bands. Our method is tailored to the problem of global Multiple-Frequency Tomography (MFT), using a data set of 287 078 S-wave delay-times measured in five frequency bands (10, 15, 22, 34, 51 s central periods). Whereas for each ray path the delay-time estimates should vary coherently from one period to the other, the noise most likely is not coherent. Thus, the lack of coherency of the information in different frequency bands is exploited, using an analogy with the cross-validation method, to identify models dominated by noise. In addition, a sharp change of behaviour of the model ℓ∞-norm, as the damping becomes lower than a threshold value, is interpreted as the signature of data noise starting to significantly pollute at least one model component. Models with damping larger than this threshold are diagnosed as being constructed with poor data exploitation. Finally, a preferred model is selected from the remaining range of permitted model solutions. This choice is quasi-objective in terms of model interpretation, as the selected model shows a high degree of similarity with almost all other permitted models (correlation superior to 98% up to spherical harmonic degree 80). The obtained tomographic model is displayed in mid lower-mantle (660-1910 km depth), and is shown to be compatible with three other recent global shear-velocity models. A wider application of the presented rationale should permit us to converge towards more objective seismic imaging of the Earth's mantle.

Design Rationale Behind the Serious Self-Regulation Game Intervention "Balance It": Overweight Prevention Among Secondary Vocational Education Students in The Netherlands.

PubMed

Spook, Jorinde E; Paulussen, Theo; Paulissen, Rosie; Visschedijk, Gillian; Kok, Gerjo; van Empelen, Pepijn

2015-10-01

This article describes the design rationale behind a serious self-regulation game intervention. The aim of the game is to promote healthy dietary intake and physical activity among secondary vocational educational students in The Netherlands (approximately 16-20 years of age). The game "Balance It" was developed according to an intervention mapping (IM) protocol. Following IM, we specified health promotion and usability objectives and linked these objectives to selected behavior change and persuasive methods. Accordingly, these methods were translated into a coherent intervention program. The health behavior change objectives were derived from the determinants of the behavior and from Self-Regulation Theory (e.g., students are asked to set goals, monitor and evaluate their behavior, and create coping plans). Usability objectives were derived from the RE-AIM model (i.e., Reach, Effectiveness, Adoption, Implementation, and Maintenance). Next, behavior change and persuasive techniques were selected (e.g., goal setting and prompting, respectively) that did fit with the targeted change objectives and were translated in the design of a (mobile) serious self-regulation game intervention. Subsequently, three concept and usability tests were performed to improve intervention usability, and an evaluation plan was developed. The aim of this study was to provide a design rationale for game interventions targeting health-related behaviors. We developed a coherent program design in which both health behavior change and usability factors are addressed. The IM protocol can serve as a useful guide for decision making in program development and evaluation.

Latino College Completion: Oregon

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Minnesota

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Virginia

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Pennsylvania

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Connecticut

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Hawaii

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Idaho

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Latino College Completion: Wisconsin

ERIC Educational Resources Information Center

Excelencia in Education (NJ1), 2012

2012-01-01

In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

Coupled plasma filtration adsorption: rationale, technical development and early clinical experience.

PubMed

Ronco, Claudio; Brendolan, Alessandra; d'Intini, Vincenzo; Ricci, Zaccaria; Wratten, Mary Lou; Bellomo, Rinaldo

2003-01-01

The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications. Copyright 2003 S. Karger AG, Basel

[Completion Study Report on Completion Problems in the Ph.D. Program at Chicago (University of).

ERIC Educational Resources Information Center

Cunningham, Phyllis; And Others

Based on adult education students who completed Ph.D. work in the Department of Education, University of Chicago, during 1960-69, this study examined the problems they perceive in completing doctoral study. Eighty-five doctoral graduates submitted usable questionnaires. Data were obtained on completion time as related to such variables as number…

Sleep health education in pediatric community settings: rationale and practical suggestions for incorporating healthy sleep education into pediatric practice.

PubMed

Gruber, Reut; Cassoff, Jamie; Knäuper, Bärbel

2011-06-01

This article offers practical ways to incorporate healthy sleep education into pediatric practice and discusses key questions, barriers, and strategies associated with such efforts. The rationale for incorporating healthy sleep education in pediatric practice settings is presented, and desirable features of sleep education programs that may be implemented in pediatric practice are identified. Potential barriers are reviewed and strategies offered to overcome these barriers, such as developing resources applicable to healthy sleep education and practical information for pediatricians. Key factors regarding effectiveness of such interventional programs and key points relevant to successful healthy sleep education in pediatric practice are highlighted. Copyright © 2011. Published by Elsevier Inc.

Readiness for diabetes prevention and barriers to lifestyle change in women with a history of gestational diabetes mellitus: rationale and study design.

PubMed

Lipscombe, Lorraine L; Banerjee, Ananya Tina; McTavish, Sarah; Mukerji, Geetha; Lowe, Julia; Ray, Joel; Evans, Marilyn; Feig, Denice S

2014-10-01

Women with gestational diabetes mellitus (GDM) have a high risk of future diabetes, which can be prevented with lifestyle modification. Prior diabetes prevention programmes in this population have been limited by lack of adherence. The aim of this study is to evaluate readiness for behaviour change at different time points after GDM diagnosis and identify barriers and facilitators, to inform a lifestyle modification programme specifically designed for this group. The objective of this paper is to present the rationale and methodological design of this study. The ongoing prospective cohort study has recruited a multi-ethnic cohort of 1353 women with GDM from 7 Ontario, Canada hospitals during their pregnancy. A questionnaire was developed to evaluate stage of readiness for behaviour change, and sociodemographic, psychosocial, and clinical predictors of healthy diet and physical activity. Thus far, 960 women (71%) have completed a baseline survey prior to delivery. Prospective postpartum follow-up is ongoing. We are surveying women at 2 time-points after delivery: 3-12 months postpartum, and 13-24 months postpartum. Survey data will be linked to health care administrative databases for long-term follow-up for diabetes. Qualitative interviews were conducted in a subset of women to gain a deeper understanding of barriers and facilitators to lifestyle change. Our study is a fundamental first step in effectively addressing diabetes prevention in women with GDM. Our findings will aid in the design of a diabetes prevention intervention specifically targeted to women with recent GDM, which can then be evaluated in a clinical trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Electronic medication complete communication strategy for opioid prescriptions in the emergency department: Rationale and design for a three-arm provider randomized trial.

PubMed

McCarthy, Danielle M; Courtney, D Mark; Lank, Patrick M; Cameron, Kenzie A; Russell, Andrea M; Curtis, Laura M; Kim, Kwang-Youn A; Walton, Surrey M; Montague, Enid; Lyden, Abbie L; Gravenor, Stephanie J; Wolf, Michael S

2017-08-01

Thousands of people die annually from prescription opioid overdoses; however there are few strategies to ensure patients receive medication risk information at the time of prescribing. To compare the effectiveness of the Emergency Department (ED) Electronic Medication Complete Communication (EMC 2 ) Opioid Strategy (with and without text messaging) to promote safe medication use and improved patient knowledge as compared to usual care. The ED EMC 2 Opioid Strategy consists of 5 automated components to promote safe medication use: 1) physician reminder to counsel, 2) inbox message sent on to the patient's primary care physician, 3) pharmacist message on the prescription to counsel, 4) MedSheet supporting prescription information, and 5) patient-centered Take-Wait-Stop wording of prescription instructions. This strategy will be assessed both with and without the addition of text messages via a three-arm randomized trial. The study will take place at an urban academic ED (annual volume>85,000) in Chicago, IL. Patients being discharged with a new prescription for hydrocodone-acetaminophen will be enrolled and randomized (based on their prescribing physician). The primary outcome of the study is medication safe use as measured by a demonstrated dosing task. Additionally actual safe use, patient knowledge and provider counseling will be measured. Implementation fidelity as well as costs will be reported. The ED EMC 2 Opioid Strategy embeds a risk communication strategy into the electronic health record and promotes medication counseling with minimal workflow disruption. This trial will evaluate the strategy's effectiveness and implementation fidelity as compared to usual care. This trial is registered on clinicaltrials.gov with identifier NCT02431793. Copyright © 2017 Elsevier Inc. All rights reserved.

Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

PubMed Central

Grosmaire, Anne Gaëlle; Battini, Elena

2017-01-01

A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections), modulate neural activity (noninvasive brain stimulation), and enhance motivation (virtual reality) in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them. PMID:29057269

Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase.

PubMed

Berg, Alexander K; Manokaran, Sumathra; Eiler, Daniel; Kooren, Joel; Mallik, Sanku; Srivastava, D K

2008-01-01

Peptide deformylase (PDF) catalyzes the removal of formyl group from the N-terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural-functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)-induced unfolding of the enzyme by monitoring the secondary structural changes via CD spectroscopy. The experimental data revealed that EcPDF is a highly stable enzyme, and it undergoes slow denaturation in the presence of varying concentrations of GdmCl. The most interesting aspect of these studies has been the abrupt reversal of the unfolding pathway at low to moderate concentrations of the denaturant, but not at high concentration. An energetic rationale for such an unprecedented feature in protein chemistry is offered.

Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

PubMed

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

2017-10-27

Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

24 CFR 884.212 - Project completion.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Project completion. 884.212 Section... RENTAL HOUSING PROJECTS Project Development and Operation § 884.212 Project completion. (a) FmHA certifications upon completion. Upon completion of the project, FmHA shall inspect the project and, if determined...

24 CFR 884.212 - Project completion.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Project completion. 884.212 Section... RENTAL HOUSING PROJECTS Project Development and Operation § 884.212 Project completion. (a) FmHA certifications upon completion. Upon completion of the project, FmHA shall inspect the project and, if determined...

24 CFR 884.212 - Project completion.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Project completion. 884.212 Section... RENTAL HOUSING PROJECTS Project Development and Operation § 884.212 Project completion. (a) FmHA certifications upon completion. Upon completion of the project, FmHA shall inspect the project and, if determined...