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Sample records for complete paraplegia rationale

  1. Complete paraplegia resulting from surfer's myelopathy.

    PubMed

    Takakura, Tomokazu; Yokoyama, Osamu; Sakuma, Fujiko; Itoh, Ryousuke; Romero, Ray R

    2013-09-01

    Three patients with diagnoses of surfer's myelopathy (24-31 yrs old; two men, one woman) were admitted to our rehabilitation hospital. All three patients were novice surfers and had a typical clinical course of onset: rapid progression of paraplegia after back pain while taking surfing lessons. Despite months of rehabilitation at our hospital, in all three patients, complete paraplegia (T9-T12) and bladder-bowel dysfunction remained. Our case profiles suggest that the neurologic outcome of surfer's myelopathy is potentially catastrophic, as has been suggested in previous reports. Surfer's myelopathy has been estimated to be an ischemic thoracic myelopathy. From our case profiles and review of the literature, not only the prolonged prone hyperextended posture of paddling but also the repetitive mechanical stress caused by flexion-extension of the spinal column may be related to its pathogenesis. To prevent surfer's myelopathy and to avoid progressive deterioration of neurologic function, increased education and awareness are essential.

  2. Acute spontaneous spinal subdural haematoma presenting as paraplegia and complete recovery with non-operative treatment

    PubMed Central

    Al, Behçet; Yildirim, Cuma; Zengin, Suat; Genc, Sinan; Erkutlu, Ibrahim; Mete, Ahmet

    2009-01-01

    Spontaneous spinal subdural haematoma (SSDH) with no underlying pathology is a very rare condition. Only 20 cases have been previously reported. It can be caused by abnormalities of coagulation, blood dyscrasia, or trauma, underlying neoplasm, and arteriovenous malformation. It occurs most commonly in the thoracic spine and presents with sudden back pain radiating to the arms, legs or trunk, and varying degrees of motor, sensory, and autonomic disturbances. Although the main approach to management is surgical decompression, conservative management is used as well. We report the case of a 57-year-old man who presented with sudden severe low back pain followed by rapid onset of complete paraplegia. Magnetic resonance imaging (MRI) revealed an anterior subdural haematoma from T9 to L1 with cord compression. Corticosteroid treatment was administered. The patient showed substantial clinical improvement after 7 days of bed rest and an intense rehabilitation programme. An MRI scan and a computed tomography angiogram did not reveal any underlying pathology to account for the subdural haematoma. PMID:22065983

  3. Complete Immediate Paraplegia Reversal after Performing Aorto-Lumbar Bypass on the Patient who Underwent Aortoiliac Reconstruction.

    PubMed

    Banzic, Igor; Sladojevic, Milos; Ilic, Nikola; Koncar, Igor; Davidovic, Lazar; Brankovic, Milos

    2016-08-01

    Although both internal iliac arteries were saved during operation, the patient developed paraplegia immediately after aortoiliac reconstruction due to the spinal cord ischemia. We report a successfully treated immediate postoperative paraplegia by performing second operation and creating bypass from the bifurcated Dacron graft to the previously detected nonpaired huge lumbar artery.

  4. Feasibility for developing cardiovascular exercise recommendations for persons with motor-complete paraplegia based on manual wheelchair propulsion; A protocol and preliminary data

    PubMed Central

    Lynch, Meaghan; Liem, Brian; Jacobs, Geneva; Hwang, Peter; Hornby, Thomas George; Rydberg, Leslie; Roth, Elliot

    2016-01-01

    Background The Center for Disease Control, American Heart Association, and American College of Sports Medicine recommendations for duration and intensity of exercise are based on the amount of energy expenditure required to maintain cardiovascular health in able body individuals; 1000 Kilocalories (Kcals) per week of energy expenditure has been demonstrated to achieve this effect. Manual wheelchair propulsion (MWP) represents a practical and accessible form of exercise for individuals with paraplegia. Objective To describe a method to determine the duration of MWP required to expend 1000 Kcals, when performed by individuals with paraplegia due to motor-complete spinal cord injury (SCI). Study Design Cross-sectional study. Setting Rehabilitation Research Laboratory. Participants Sixteen adults with motor complete T3-T12 paraplegia (body mass index < 35, duration of paraplegia > 3 months). Interventions Not applicable. Main Outcome Measures Indirect calorimetry during MWP was measured in order to calculate caloric expenditure per minute. These data were used to calculate the number of minutes of MWP required to expend 1000 Kcal in one week. Results During MWP, participants expended 3.3 ± 1.0 Kcal/minute. Based on this figure, 1000 Kcal of energy expenditure in one week would require 303 minutes of MWP per week, or 43.3 minutes per day, 7 days per week. Conclusions Our data suggest that it is feasible to create a practical and accessible exercise recommendation based on manual wheelchair propulsion for individuals with paraplegia due to motor-complete SCI. Larger studies are needed in order to develop accurate exercise recommendations for persons with SCI. PMID:25582138

  5. Hysterical paraplegia.

    PubMed Central

    Baker, J H; Silver, J R

    1987-01-01

    Between 1944 and 1984 20 patients were admitted to a spinal injuries centre with a diagnosis of traumatic paraplegia. They subsequently walked out and the diagnosis was revised to hysterical paraplegia. A further 23 patients with incomplete traumatic injuries, who also walked from the centre, have been compared with them as controls. The features that enabled a diagnosis of hysterical paraplegia to be arrived at were: They were predominantly paraplegic, There was a high incidence of previous psychiatric illness and employment in the Health Service or allied professions, Many were actively seeking compensation. The physical findings were a disproportionate motor paralysis, non anatomical sensory loss, the presence of downgoing plantar responses, normal tone and reflexes. They made a rapid total recovery. In contrast, the control traumatic cases showed an incomplete recovery and a persistent residual neurological deficit. Investigations apart from plain radiographs of the spinal column were not warranted, and the diagnosis should be possible on clinical grounds alone. PMID:3585346

  6. Genetics Home Reference: spastic paraplegia type 8

    MedlinePlus

    ... Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the nerves and muscles controlling ... the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia. Like all hereditary spastic paraplegias, ...

  7. Genetics Home Reference: spastic paraplegia type 2

    MedlinePlus

    ... Conditions spastic paraplegia type 2 spastic paraplegia type 2 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Spastic paraplegia type 2 is part of a group of genetic disorders ...

  8. Genetics Home Reference: spastic paraplegia type 4

    MedlinePlus

    ... Home Health Conditions spastic paraplegia type 4 spastic paraplegia type 4 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Spastic paraplegia type 4 is part of a group of ...

  9. Living with Paraplegia: Tensions and Contradictions

    ERIC Educational Resources Information Center

    O'Connor, Deborah L.; Young, Jenny M.; Saul, Megan Johnston

    2004-01-01

    Although it is well established that paraplegia results in dramatic lifestyle changes, little is understood about living in the community with paraplegia, especially from the perspective of the person with paraplegia. To develop insight into this experience, in-depth, personal interviews were conducted with seven individuals with paraplegia who…

  10. Late neurological recovery of paraplegia after endovascular repair of an infected thoracic aortic aneurysm.

    PubMed

    Mees, Barend M E; Bastos Gonçalves, Frederico; Koudstaal, Peter J; Verhagen, Hence J M

    2013-02-01

    Spinal cord ischemia is a potentially devastating complication after thoracic endovascular aorta repair (TEVAR). Patients with spinal cord ischemia after TEVAR often develop paraplegia, which is considered irreversible, and have significant increased postoperative morbidity and mortality. We report the case of a patient with unusual late complete neurologic recovery of acute-onset paraplegia after TEVAR for an infected thoracic aortic aneurysm.

  11. Spontaneous acute hemorrhage of intraspinal canal cellular schwannoma with paraplegia: A case report.

    PubMed

    Zhang, Heng-Zhu; Li, Yuping; Han, Yang; Wang, Xiaodong; She, Lei; Yan, Zhengcun; Dong, Lun

    2015-06-01

    Cellular schwannoma, an unusual histological subtype of schwannoma, is a benign hypercellular variant of a peripheral nerve sheath tumor. We report a 48-year-old woman with sudden onset of paraplegia. The complete surgical resection was achieved. This is the first report about intraspinal canal cellular schwannoma following spontaneous acute hemorrhage and paraplegia.

  12. 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

  13. Genetics Home Reference: spastic paraplegia type 31

    MedlinePlus

    ... dominant MalaCards: spastic paraplegia 31 National Health Service (UK) Orphanet: Autosomal dominant spastic paraplegia type 31 Orphanet: ... and Advocacy Resources (5 links) Contact a Family (UK) National Organization for Rare Disorders (NORD): Hereditary Spastic ...

  14. Pott's spine and paraplegia.

    PubMed

    Gautam, M P; Karki, P; Rijal, S; Singh, R

    2005-01-01

    Spinal tuberculosis is usually secondary to lung or abdominal involvement and may also be the first manifestation of tuberculosis. Spinal tuberculosis (often called Pott's disease) is by definition, an advanced disease, requiring meticulous assessment and aggressive systemic therapy. Physicians should keep the diagnosis in mind, especially in a patient from a group with a high rate of tuberculosis infection. This review aims on updating the knowledge on spinal tuberculosis and its management. Skeletal involvement has been reported to occur in approximately 10% of all patents with extrapulmonary tuberculosis, and half of these patients develop infection within the spinal column. Symptoms of spinal tuberculosis are back pain, weakness, weight loss, fever, fatigue, and malaise. It is much more prone to develop neurological manifestation, paraplegia of varying degree. The palpation of spinous process in routine clinical examination is the most rewarding clinical method and is an invaluable measure for early recognition. Diagnosis of spinal tuberculosis is made on the basis of typical clinical presentation along with systemic constitutional manifestation and the evidence of past exposure to tuberculosis or concomitant visceral tuberculosis. Magnetic resonance imaging can define the extent of abscess formation and spinal cord compression. The diagnosis is confirmed through percutaneous or open biopsy of the spinal lesion. Surgery is necessary as an adjunct to antibiotic therapy if the vertebral infection produces an abscess, vertebral collapse, or neurologic compression. Some patents need aggressive supportive care owing to tuberculous meningitis or encephalopathy. Moreover, the importance of immediate commencement of appropriate treatment and its continuation for adequate duration along with the proper counseling of the patient and family members should not be underestimated for successful and desired outcome.

  15. Posterior-only vertebral column resection for revision surgery in post-laminectomy rotokyphoscoliosis associated with late-onset paraplegia

    PubMed Central

    Tao, Youping; Wu, Jigong; Ma, Huasong

    2017-01-01

    Abstract Rationale: Severe post-laminectomy spinal deformity associated with late-onset paraplegia is a complex and rare disorder. Little is known about revision surgery in post-laminectomy rotokyphoscoliosis associated with late-onset paraplegia treated by the single stage posterior-only vertebral column resection (VCR) procedure. Patient concerns and diagnoses: The patient was a 14-year-old male diagnosed as post-laminectomy rotokyphoscoliosis associated with late-onset paraplegia. He underwent posterior total laminectomy through the thoracic spine for intramedullary spinal cord tumors at the age of 3 years in another hospital. He then developed kyphosis deformity 1 year after laminectomy, and underwent posterior spinal fusion without instrumentation at 9 years of age. However, the deformity gradually progressed over the years. Seven months before admission to our hospital, he developed a significant progression of neurological deficits, including weakness of strength and sensation in lower extremities bilaterally, with no bladder or bowel dysfunction. There was no improvement of spinal cord function with conservative measures, and he required a wheelchair for movement. Interventions: The patient underwent posterior-only VCR by single stage with the purposes of spinal cord decompression and spinal deformity correction. Outcomes: Postoperatively, he was transferred to the intensive care unit (ICU) and required positive pressure ventilation support to improve his respiratory condition. The child experienced cerebrospinal fluid leak (CSF) which resulted in an unplanned return to the operating room. The neurological function improved from preoperative Frankel C to Frankel D within 12 months of surgery, and recovered completely to Frankel E by 18 months. At the 24 month follow-up, the good neurological function was maintained; pulmonary function tests (PFTs) revealed improved forced vital capacity (FVC) and forced expiratory volume for 1 second (FEV1). The patient

  16. 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.

  17. Hybrid Treatment of Acute Abdominal Aortic Thrombosis Presenting with Paraplegia.

    PubMed

    Azzarone, Matteo; De Troia, Alessandro; Iazzolino, Luigi; Nabulsi, Bilal; Tecchio, Tiziano

    2016-05-01

    Acute thrombotic or embolic occlusion of the abdominal aorta is a rare vascular emergency associated with high morbidity and mortality rates. Classically, the clinical presentation is a severe peripheral ischemia with bilateral leg pain as the predominant feature. Aortic occlusion presenting as an isolated acute onset of paraplegia due to spinal cord ischemia is very rare and requires improved awareness to prevent adverse outcomes associated with delayed diagnosis. We report the case of a 54-year-old man who presented with sudden paraplegia due to the thrombotic occlusion of the infrarenal aorta involving the first segment of the common iliac arteries on both sides; emergent transperitoneal aorto iliac thrombectomy combined with the endovascular iliac kissing-stent technique were performed achieving perioperative complete regression of the symptoms.

  18. Fluorosis... causing paraplegia... mutilating life...

    PubMed

    Ahsan, Tasnim; Jabeen, Rakhshanda; Hashim, Saba; Bano, Zeenat; Ghafoor, Subheen

    2016-02-01

    Fluorosis is thought to be rare in Pakistan but endemic in various parts of the world, especially in India and China. In Pakistan only a few cases have been reported from Thar, Sibbi and Manga Mandi, with probability of fluorosis on MRI findings, supported by high drinking waterfluoride content. Neurological manifestations of skeletal fluorosis may vary from radiculo-myelopathy to neuropathy. A case of 26 years old female from Thul, Sindh, who presented with paraplegia, is reported here. Her MRI showed extensive classical degenerative changes throughout the spine, consistent with fluorosis, leading to cord compression at multiple levels. No such case with confirmed fluorosis has been previously reported from Pakistan.

  19. Hypokalemic Paraplegia in Pregnancy

    PubMed Central

    TV, Srividya; Gopal, N

    2014-01-01

    Hypokalemic myopathy may range from numbness/weakness to complete paralysis. The aetiology may be congenital or acquired. It is characterized by acute muscular weakness with low levels of potassium (<3.5 meq/L). We present a case of 26-year-old multigravida at 36 weeks of gestation with gestational hypertension on treatment, who came with acute onset of pain, numbness and weakness of both legs which worsened following betamethasone injection. She was diagnosed to have Hypokalemic paralysis with potassium levels of 2.1 meq/L. The medical profile remitted promptly on intravenous potassium replacement. Pregnancy was continued till 37 weeks with oral potassium supplements, antihypertensives and regular monitoring of serum potassium levels. The pregnancy was terminated after 37 weeks in view of gestational hypertension. Postpartum period was uneventful, patient was discharged after two weeks when potassium levels and BP returned to normal. PMID:25121034

  20. [Paraplegia due to adhesive arachnoiditis. A case report].

    PubMed

    Rodríguez Luna, José Guadalupe; Sandoval Sánchez, Víctor; Benavides Rodríguez, David; Olivares Camacho, Jorge L; Taboada, Jesús B

    2009-01-01

    Various conditions of the spinal column occur at the lumbar level and new therapeutic surgical techniques have been applied to reduce the length of hospital stay, contribute to a quick return of patients to their activities of daily living, and reduce the postoperative limitations. However, a silent complication, adhesive arachnoiditis, has been reported with a frequency of 6-16% in cases undergoing lumbar surgery or with a history of revision surgery, and thus a second complication may occur, paraplegia, since the common symptom of arachnoiditis is persistent low back pain. The case of a 40-year-old patient is presented herein, who underwent lumbar spine surgery for herniated discs, and developed adhesive arachnoiditis involving the cauda equina, which was diagnosed with MRI. He had irreversible paraplegia with diffuse involvement of the cauda equina despite the mechanical lavage and surgical debridement performed due to the persistence of serous fluid discharge from the wound. The interbody implant placed during the first surgery was removed and the treatment was completed with posterior stabilization reinstrumentation; the patient had persistent neurologic impairment. There are few reports in the world literature of paraplegia due to non-infectious adhesive arachnoiditis. The remaining reports of paraplegia have been in patients with spinal infection, such as HIV-TB, mycosis, brucellosis or meningeal hemorrhage. It is not easy for patients to understand the very likely irreversible neurologic lesion of his complication. However, it is important for the spine surgeon to bear in mind the occurrence and frequency of adhesive arachnoiditis which could lead to irreversible neurologic deficit in patients undergoing lumbar spine surgery.

  1. Genetics Home Reference: spastic paraplegia type 11

    MedlinePlus

    ... the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and ... with this type of spastic paraplegia, the tissue connecting the left and right halves of the brain ( ...

  2. Double incontinence as a first symptom of saddle embolism of the aorta leads to sudden paraplegia.

    PubMed

    Sabzi, Feridoun; Faraji, Reza

    2015-11-01

    An aortic saddle embolus causing cauda equine syndrome followed by paraplegia is an exceedingly rare phenomenon in post-operative period in coronary artery bypass grafting. In non-CABG cases, reported documentation of neurological recovery from this event is even rarer. A 57-year-old male 8 days after uneventful OPCAP presented with severe lower extremity pain and sudden fecal and urinary incontinence, followed by the absence of pulsations in the lower limbs and paraplegia, during 20-minute period. He underwent immediate bilateral transfemoral embolectomy. The postoperative period was uneventful. The paraplegia recovered immediately after embolectomy and recovery from anesthesia. An angiography has been made to verify that a high origin of the great radicular artery above T12 level may be responsible for better recovery of paraplegia when its ostium obstructed by a saddle embolus relieved using embolectomy. Early surgical intervention in restoring the blood flow into the great radicular artery may prevent severe histological changes hitherto responsible for non-recovery from paraplegia in the earlier reports. Three unique characteristics of this article are as follows: 1) Occurrence of this complication in the post-operative period in off-pump CABG surgery; 2) Commencing of emboli with bizarre symptoms of double incontinence; 3) Combination of cauda equine syndrome and complete paralysis.

  3. Cholesterol crystal embolism and delayed-onset paraplegia after thoracoabdominal aneurysm repair.

    PubMed

    Nasr, Bahaa; Schneider, Fabrice; Marques da Fonseca, Pedro; Gouny, Pierre

    2014-07-01

    Postoperative paraplegia caused by ischemic injury of the spinal cord is the most disabling complication of thoracoabdominal surgery. We described the case of a 75-year-old patient who underwent a thoracoabdominal aneurysm repair (type IV aneurysm according to Crawford classification). The aorta clamping was done at the T11 level without specific medullary protection. The first postoperative week was uneventful. On the postoperative day 8, renal failure and livedo of the left lower limb occurred together with complete hypotonic paraplegia and severe sepsis. Exploratory laparotomy revealed a gangrenous cholecystitis, and skin biopsies showed cholesterol crystals embolisms in the hypodermis small arteries. The patient died on the postoperative day 28 from a multiorgan failure. In this case, paraplegia was due to cholesterol crystal embolism, which migrated secondarily after aortic clamping.

  4. The mouse rumpshaker mutation of the proteolipid protein in human X-linked recessive spastic paraplegia

    SciTech Connect

    Kobayashi, H.; Hoffman, E.P.; Matise, T.C.

    1994-09-01

    X-linked recessive spastic paraplegia is a rare neurodegenerative disorder characterized by slowly progressive weakness and spasticity of the lower extremities. We have recently genetically analyzed the original X-linked recessive spastic paraplegia family reported by Johnston and McKusick in 1962. We employed a fluorescent multiplex CA repeat strategy using a 22 locus, 10 cM framework map of the human X chromosome and localized the gene within a 36 cM region of Xq2l.3-q24 which includes the PLP locus. Saugier-Veber et al. recently reported a point mutation (His139Tyr) in exon 3B of the PLP gene in an X-linked recessive spastic paraplegia family (SPG2). This family shows no optic atrophy, in contrast to the family we have studied. This data showed that SPG2 and Pelizaeus-Merzbacher disease were allelic disorders. We investigated the PLP gene as a candidate gene for the original X-linked recessive spastic paraplegia family using SSCP and direct sequencing methods. We found a point mutation (T to C) in exon 4 of affected males which alters the amino-acid (Ile to Thr) at residue 186. This change was absent in the unaffected males of the family and in 40 unrelated control females (80 X chromosomes). Surprisingly, this mutation is identical to the mutation previously identified in the rumpshaker mouse model. The complete homology between both the mouse and human PLP sequence, and the mouse rumpshaker mutation and human spastic paraplegia mutation in our family, permit direct parallels to be drawn with regards to pathophysiology. Our data indicates that the well-documented and striking clinical differences between Pelizaeus-Merzbacher disease and X-linked recessive spastic paraplegia is due to the specific effect of different mutations of the human PLP gene on oligodendrocyte differentiation and development and on later myelin production and maintenance.

  5. Painless aortic dissection presenting as paraplegia.

    PubMed

    Colak, Necmettin; Nazli, Yunus; Alpay, Mehmet Fatih; Akkaya, Ismail Olgun; Cakir, Omer

    2012-01-01

    Acute dissection of the aorta can be life-threatening. As a presenting manifestation of aortic dissection, neurologic complications such as paraplegia are rare. Herein, we report the case of a 51-year-old man who presented with sudden-onset paraplegia and ischemia of the legs, with no chest or back pain. His medical history included coronary artery bypass grafting. Physical examination revealed pulseless lower extremities, and computed tomography showed aortic dissection from the ascending aorta to the common iliac arteries bilaterally. A lumbar catheter was inserted for cerebrospinal fluid drainage, and axillary arterial cannulation was established. With the use of cardiopulmonary bypass, the aortic dissection was corrected, and the previous coronary artery grafts were reattached. The surgery restored spinal and lower-extremity perfusion, and the patient walked unaided from the hospital upon his discharge 5 days later. Although acute aortic dissection presenting as paraplegia is rare, it should be considered in patients who have pulseless femoral arteries bilaterally and sudden-onset paraplegia, despite no pain in the chest or back. Prompt diagnosis and intervention can prevent morbidity and death.

  6. Leptospirosis presenting as a flaccid paraplegia.

    PubMed Central

    Mumford, C.; Dudley, N.; Terry, H.

    1990-01-01

    A fatal case of leptospirosis in a 64 year old farm worker is described. The dramatic neurological presentation with a rapidly evolving flaccid paraplegia associated with biochemical evidence of renal and hepatic dysfunction is discussed. Attention is drawn to the wide range of neurological symptoms reported in leptospirosis, and to the possibility that this infectious disease may present neurologically. PMID:2362889

  7. Rehabilitation for patients with paraplegia and lower extremity amputation.

    PubMed

    Wang, Fangyong; Hong, Yi

    2015-10-01

    [Purpose] To study the characteristics and treatment strategy for patients with paraplegia and lower extremity amputation. [Subjects] Six cases were selected from among the patients admitted to the China Rehabilitation Research Center from 1991 to 2014. The criteria for the six cases were spinal cord injury with amputation immediately or in a short time (1 week) after the trauma. [Methods] General information, clinical diagnosis, treatment, rehabilitation and other data were analyzed. [Results] All the six cases were injured by high energy or complex energy accidents: two cases by falls after high voltage electric shock, one by an oil pipeline explosion, one by the impact of a falling tower crane and received high energy traffic accident injuries (one was hit by a train, and the other was hit by a truck at high speed). All the six cases had thoracic and lumbar vertebral injuries and complete paraplegia. Amputation stump infection occurred in four cases. After comprehensive rehabilitation treatment, patients' functional independence measure (FIM) scores improved significantly, but American Spinal Injury Association (ASIA) scores and ASIA Impairment Scale (AIS) grades showed no significant improvement. [Conclusion] When formulating the clinical treatment and rehabilitation for spinal cord injury with amputation patients, simultaneous consideration of the characteristics of the spinal cord injury and amputation is needed to develop an individualized strategy. For spinal cord injury with limb amputation patients, prostheses should allow the improvement of patients' self-care ability.

  8. Rehabilitation for patients with paraplegia and lower extremity amputation

    PubMed Central

    Wang, Fangyong; Hong, Yi

    2015-01-01

    [Purpose] To study the characteristics and treatment strategy for patients with paraplegia and lower extremity amputation. [Subjects] Six cases were selected from among the patients admitted to the China Rehabilitation Research Center from 1991 to 2014. The criteria for the six cases were spinal cord injury with amputation immediately or in a short time (1 week) after the trauma. [Methods] General information, clinical diagnosis, treatment, rehabilitation and other data were analyzed. [Results] All the six cases were injured by high energy or complex energy accidents: two cases by falls after high voltage electric shock, one by an oil pipeline explosion, one by the impact of a falling tower crane and received high energy traffic accident injuries (one was hit by a train, and the other was hit by a truck at high speed). All the six cases had thoracic and lumbar vertebral injuries and complete paraplegia. Amputation stump infection occurred in four cases. After comprehensive rehabilitation treatment, patients’ functional independence measure (FIM) scores improved significantly, but American Spinal Injury Association (ASIA) scores and ASIA Impairment Scale (AIS) grades showed no significant improvement. [Conclusion] When formulating the clinical treatment and rehabilitation for spinal cord injury with amputation patients, simultaneous consideration of the characteristics of the spinal cord injury and amputation is needed to develop an individualized strategy. For spinal cord injury with limb amputation patients, prostheses should allow the improvement of patients’ self-care ability. PMID:26644641

  9. Paraplegia After Thoracic Epidural Steroid Injection.

    PubMed

    Loomba, Vivek; Kaveeshvar, Hirsh; Dwivedi, Samvid

    2016-09-01

    Epidural steroid injections are a common procedure performed by pain physicians. The American Society of Regional Anesthesia along with several other groups recently provided guidelines for performing epidural injections in the setting of anticoagulants. We present a case of a patient who developed an epidural hematoma and subsequent paraplegia despite strict adherence to these guidelines. Although new guidelines serve to direct practice, risks of devastating neurologic complications remain as evidenced by our case.

  10. Paraplegia caused by giant intradural herniation of a lumbar disk after combined spinal-epidural anesthesia in total hip arthroplasty.

    PubMed

    Sawai, Toshiyuki; Nakahira, Junko; Minami, Toshiaki

    2016-08-01

    Total paraplegia after epidural or spinal anesthesia is extremely rare. We herein report a case of total paraplegia caused by a giant intradural herniation of a lumbar disk at the L3-L4 level after total hip arthroplasty for coxarthrosis. The patient had no preoperative neurologic abnormalities. Intraoperative anesthetic management involved combined spinal-epidural anesthesia at the L3-L4 level with continuous intravenous propofol administration. Postoperatively, the patient complained of numbness and total paraplegia of the lower extremities. Magnetic resonance imaging showed a giant herniation of a lumbar disk compressing the spinal cord at the L3-L4 level. The intradural herniation was surgically treated, and the patient's symptoms completely resolved.

  11. Walking dreams in congenital and acquired paraplegia.

    PubMed

    Saurat, Marie-Thérèse; Agbakou, Maité; Attigui, Patricia; Golmard, Jean-Louis; Arnulf, Isabelle

    2011-12-01

    To test if dreams contain remote or never-experienced motor skills, we collected during 6 weeks dream reports from 15 paraplegics and 15 healthy subjects. In 9/10 subjects with spinal cord injury and in 5/5 with congenital paraplegia, voluntary leg movements were reported during dream, including feelings of walking (46%), running (8.6%), dancing (8%), standing up (6.3%), bicycling (6.3%), and practicing sports (skiing, playing basketball, swimming). Paraplegia patients experienced walking dreams (38.2%) just as often as controls (28.7%). There was no correlation between the frequency of walking dreams and the duration of paraplegia. In contrast, patients were rarely paraplegic in dreams. Subjects who had never walked or stopped walking 4-64 years prior to this study still experience walking in their dreams, suggesting that a cerebral walking program, either genetic or more probably developed via mirror neurons (activated when observing others performing an action) is reactivated during sleep.

  12. Paraplegia by acute cervical disc protrusion after lumbar spine surgery.

    PubMed

    Chen, Sheng-Huan; Hui, Yu-Ling; Yu, Chong-Ming; Niu, Chi-Chien; Lui, Ping-Wing

    2005-04-01

    Non-traumatic paraplegia caused by herniation of the cervical intervertebral disc is an uncommon postoperative complication. A patient with claudication and radiculopathy was scheduled for lumbar laminectomy due to spinal stenosis. Postoperatively, numbness below T6 was found in his both legs of the patient. MRI showed a protruded intervertebral disc between C6 and C7. Despite urgent disectomy, the patient's lower extremities remained paralyzed without significant improvement for 3 months. Loss of muscle support during general anesthesia, excessive neck extension during endotracheal intubation and positioning, as well as bucking and agitation are believed as triggering factors for the protrusion of the cervical disc. We suggest that a complete history taking and physical examination be accomplished in patients scheduled for lumbar spine surgery in order to exclude coexisting cervical spine disorders. In addition, skillful endotracheal intubation and careful neck positioning are mandatory for patients receiving surgery in the prone position.

  13. Evaluation of activity monitors in manual wheelchair users with paraplegia

    PubMed Central

    Hiremath, Shivayogi V.; Ding, Dan

    2011-01-01

    Objective The aim of this study was to evaluate the performance of SenseWear® (SW) and RT3 activity monitors (AMs) in estimating energy expenditure (EE) in manual wheelchair users (MWUs) with paraplegia for a variety of physical activities. Methods Twenty-four subjects completed four activities including resting, wheelchair propulsion, arm-ergometry exercise, and deskwork. The criterion EE was measured by a K4b2 portable metabolic cart. The EE estimated by the SW and RT3 were compared with the criterion EE by the absolute differences and absolute percentage errors. Intraclass correlations and the Bland and Altman plots were also used to assess the agreements between the two AMs and the metabolic cart. Correlations between the criterion EE and the estimated EE and sensors data from the AMs were evaluated. Results The EE estimation errors for the AMs varied from 24.4 to 125.8% for the SW and from 22.0 to 52.8% for the RT3. The intraclass correlation coefficients (ICCs) between the criterion EE and the EE estimated by the two AMs for each activity and all activities as a whole were considered poor with all the ICCs smaller than 0.75. Except for deskwork, the EE from the SW was more correlated to the criterion EE than the EE from the RT3. Conclusion The results indicate that neither of the AMs is an appropriate tool for quantifying physical activity in MWUs with paraplegia. However, the accuracy of EE estimation could be potentially improved by building new regression models based on wheelchair-related activities. PMID:21528634

  14. [Japan Spastic Paraplegia Research Consortium (JASPAC)].

    PubMed

    Takiyama, Yoshihisa

    2014-10-01

    Japan Spastic Paraplegia Research Consortium (JASPAC), a nationwide clinical and genetic survey of patients with hereditary spastic paraplegia (HSP), was started in 2006 as a project of the Research Committee for Ataxic Diseases of the Ministry of Health, Labor, and Welfare, Japan. To date (April 4, 2014), 448 indexed patients with HSP have been registered from 46 prefectures in Japan. We are now performing molecular testing of the HSP patients using Sanger sequencing (SPG4, SPG11, SPG31, and ARSACS), comparative genomic hybridization (CGH) array (SPG1, 2, 3A, 4, 5, 6, 7, 8, 10, 11, 13, 15, 17, 20, 21, 31, 33, 39, 42, ABCD1, alsin, and ARSACS), and resequencing microarray (SPG1, 2, 3A, 4, 5, 6, 7, 8, 10, 11, 13, 17, 20, 21, 31, 33, and ABCD1). In 206 Japanese families with autosomal dominant HSP, SPG4 was the most common form, accounting for 38%, followed by SPG3A (5%), SPG31 (5%), SPG10 (2%), and SPG8 (1%). In 88 patients with autosomal recessive HSP, although SPG11 was the most common form, accounting for 6%, most showed significant genetic heterogeneity. The results of molecular testing will be applicable to patients in terms of improved positive diagnosis, follow-up, and genetic counseling. JASPAC will contribute to elucidating the molecular mechanisms underlying HSP, and will facilitate the development of better treatments for HSP.

  15. Acute Paraplegia as a Presentation of Aortic Saddle Embolism

    PubMed Central

    Guishard, Kim

    2016-01-01

    Background. Acute onset paraplegia has a myriad of causes most often of a nonvascular origin. Vascular etiologies are infrequent causes and most often associated with postsurgical complications. Objective. To describe the occurrence and possible mechanism for aortic saddle embolism as a rare cause of acute paraplegia. Case Report. Described is a case of a 46-year-old female who presented with the sudden onset of nontraumatic low back pain with rapidly progressive paraplegia which was subsequently determined to be of vascular origin. PMID:27822396

  16. Management of acute spontaneous thoracic spinal epidural hematoma causing paraplegia.

    PubMed

    Alić, Fahrudin; Bečulić, Hakija; Jusić, Aldin; Skomorac, Rasim; Moranjkić, Mirza; Hrvat, Lejla; Tandir, Lejla

    2017-02-01

    Aim To emphasize the importance of early recognition, diagnostic processing and emergent surgical treatment of spontaneous spinal epidural hematoma (SSEH). Methods A 39-year-old female presented with sudden onset of severe pain between the shoulder blades followed by paraparesis and alerted sensibility in the lower extremities. An hour later she developed paraplegia with sensory deficits below ThIV level, absence of patellar reflex, ankle jerk reflex and sphincter dysfunction. Results Magnetic resonance imaging (MRI) demonstrated acute extensive epidural mass of thoracic spinal segments (ThI-ThIII). The patient underwent emergent decompressive laminectomy ThI-ThIII with epidural hematoma evacuation within 24 hours of symptoms onset. After the surgical treatment, because of suspicion on spinal arteriovenous malformation, complete diagnostic evaluation with spinal angiography was done and no form of vascular malformation was found. Idiopathic SSEH was diagnosed. Two months later the patient reached complete neurological improvement. Conclusion The SSEH is a rare condition that should be kept in mind in patients presenting with neurological deficit and a sudden onset of back pain like it was in our case. For early diagnosis, immediate MRI is essential. Prompt surgical decompression such as laminectomy is an absolute surgical indication widely accepted for patients with progressive neurological deficit. The SSEH should be considered as one of the important differential diagnoses in patients who have developed acute myelopathy.

  17. Spinal Arteriovenous Fistula with Progressive Paraplegia after Spinal Anaesthesia

    PubMed Central

    Argyrakis, Nikolaos; Matis, Georgios K.; Mpata-Tshibemba, Stephanie

    2014-01-01

    A case of an iatrogenic spinal arteriovenous fistula with progressive paraplegia in a young woman is reported. The fistula was eventually created after repetitive lumbar punctures performed in the process of spinal anaesthesia. Her symptoms were progressed to paraplegia over a period of 2 years. The digital subtraction angiography demonstrated a single-hole fistula, involving the anterior spinal artery and vein. The lesion was occluded by embolization with immediate improvement. The potential mechanism is discussed. PMID:24653807

  18. [Hereditary spastic paraplegia: up to date].

    PubMed

    Takiyama, Yoshihisa

    2014-01-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterized by progressive spasticity and weakness of the lower limbs. HSP genetic loci are designated SPG1-72 in order of their discovery. In 206 Japanese families with autosomal dominant HSP, SPG4 was the most common form, accounting for 38%, followed by SPG3A (5%), SPG31 (5%), SPG10 (2%), and SPG8 (1%). We have identified novel mutations in the C12orf65 gene and the LYST gene in several Japanese families with autosomal recessive HSP. JASPAC will facilitate gene discovery and mechanistic understanding of HSP. The future challenge will be the establishment of treatment of HSP.

  19. Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage.

    PubMed

    Tsai, Yi-Da; Hsu, Chin-Wang; Hsu, Chia-Ching; Liao, Wen-I; Chen, Sy-Jou

    2016-03-01

    Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease.

  20. A stimulation-driven exoskeleton for walking after paraplegia.

    PubMed

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

    2016-08-01

    An untethered version of a stimulation-driven exoskeleton was evaluated for its ability to restore walking after paralysis from spinal cord injury. The hybrid neuroprosthesis (HNP) combined a passive variable-constraint exoskeleton for stability and support with functional neuromuscular stimulation (FNS) to contract the paralyzed muscles to drive limb movement. This self-contained HNP was operated by an onboard controller that sampled sensor signals, generated appropriate commands to both the exoskeletal constraints and integrated stimulator, and transmitted data wirelessly via Bluetooth to an off-board computer for real-time monitoring and recording for offline analysis. The subject selected the desired function (i.e. standing up, stepping, or sitting down) by means of a wireless finger switch that communicated with the onboard controller. Within the stepping function, a gait event detector supervisory controller transitioned between the different phases of gait such as double stance, swing, and weight acceptance based on signals from sensors incorporated into the exoskeleton. The different states of the control system governed the locking and unlocking of the exoskeletal hip and knee joints as well as the stimulation patterns activating hip and knee flexor or extensor muscles at the appropriate times and intensities to enable stepping. This study was one of our first successful implementations of the self-contained "muscle-first" HNP and successfully restored gait to an individual with motor complete mid-thoracic paraplegia.

  1. Successful surgical treatment of descending aorta interruption in a 29-year-old woman with acute paraplegia and subarachnoid hemorrhage: a case report.

    PubMed

    Bai, Shutang; Wang, Zhiheng; Zhang, Liang; Fu, Hongdu; Zhuang, Huanwei; Cao, Xianjun; Liang, Liming; Yang, Yanqi

    2015-06-06

    Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit.

  2. Paraplegia Due to Spinal Cord Infarction After Coronary Artery Bypass Graft Surgery.

    PubMed

    Sevuk, Utkan; Kaya, Sedat; Ayaz, Firat; Aktas, Ulas

    2016-01-01

    Paraplegia is an extremely rare complication after coronary artery bypass grafting (CABG) and the underlying mechanisms remain poorly understood. We report a patient who developed paraplegia after CABG and review the literature on spinal cord ischemia following CABG surgery.

  3. Paraplegia caused by cerebral contusions in the bilateral precentral gyri

    PubMed Central

    Matsumura, Hideaki; Fujimori, Hiroyuki; Sato, Naoaki; Matsumura, Akira

    2016-01-01

    Background: Paraplegia is mainly caused by spinal cord disease and rarely occurs due to head trauma. In this report, we describe a case of paraplegia caused by cerebral contusions in the bilateral precentral gyri. Case Description: A 72-year-old man was admitted to our hospital with mildly impaired consciousness and severe pure motor paralysis in both legs. He was healthy until the morning of the day, but his wife found him injured in front of his house upon returning home. He had a subcutaneous hematoma in his occipital region, and seemed to have slipped by accident. Computed tomography of the brain and magnetic resonance imaging (MRI) of his spinal cord revealed no apparent cause of the paraplegia, although an MRI of his brain clearly revealed cerebral contusions in the bilateral precentral gyri. The cerebral contusion was diagnosed as the cause of pure motor paralysis of lower extremities. He received rehabilitation, and manual muscle testing of his legs revealed improvements. In the subacute phase, the precentral gyrus lesion disappeared on MRI. Conclusion: We must emphasize that cerebral contusion can be a differential diagnosis for paraplegia. In the acute phase, fluid-attenuated inversion recovery (FLAIR) MRI coronal and sagittal images are useful for identifying precentral gyri contusions. Paraplegia caused by a cerebral contusion may be misdiagnosed as a spinal concussion due to the disappearance of the precentral gyrus lesion on FLAIR MRI in the subacute phase. PMID:27904755

  4. Genetic and phenotypic characterization of complex hereditary spastic paraplegia

    PubMed Central

    Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A.; Haridy, Nourelhoda A.; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P.; Korlipara, L.V. Prasad; Singleton, Andrew B.; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.

    2016-01-01

    The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next

  5. Spinal cord ischemia resulting in paraplegia following extrapleural pneumonectomy.

    PubMed

    Ural, Kelly; Jakob, Kyle; Lato, Scott; Gilly, George; Landreneau, Rodney

    2014-08-01

    A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Paraplegia after aortic and superior mesenteric artery stenting for occlusive disease.

    PubMed

    Hans, Sachinder S; Ngo, William; McAllister, Michael

    2014-02-01

    Paraplegia after endovascular therapy for aortic and visceral artery occlusive disease is an extremely uncommon occurrence. Two cases of paraplegia after placement of an aortic covered stent for infrarenal aortic stenosis and a superior mesenteric artery stent for chronic visceral ischemia are presented. In both patients, embolization of the arterial supply to the spinal cord was the presumed cause. One patient had a slight recovery after intense physical therapy and rehabilitation. The second patient did not have any recovery from her paraplegia.

  11. [Anesthetic management of a patient with hereditary spastic paraplegia].

    PubMed

    Kunisawa, Takayuki; Takahata, Osamu; Takayama, Koji; Sengoku, Kazufumi; Suzuki, Akihiro; Iwasaki, Hiroshi

    2002-01-01

    We experienced the anesthetic management of a 39 year-old-male with hereditary spastic paraplegia (HSP) associated with pain due to pes cavus. He underwent orthomorphia ostectomy and tenodesis. Preoperative neurological examination revealed that he had slight dementia, symptoms of the pyramidal tract, lower limb bathyhypesthesia, and neurogenic bladder in addition to spastic paraplegia, and he was diagnosed as having combined type of HSP. Spinocerebellar degeneration is often accompanied with this type of HSP. To avoid the use of muscle relaxants and narcotics, we tried to induce anesthesia with inhalation of nitrous oxide (N2O), oxygen and sevoflurane (sevo). A laryngeal mask (LM) was inserted at the expiratory concentration of sevo 3.5%. Anesthesia was maintained by N2O, oxygen and sevo (2-3%) under spontaneous respiration. The patient recovered from anesthesia after the end of surgery, and the LM was removed smoothly. The patient's respiratory condition was stable, and no problems were found in the postoperative period.

  12. Aortoiliac occlusive disease presenting as sudden onset paraplegia.

    PubMed

    Lai, Chien-Hung; Wang, Cheng-Hsien; Wu, Shih-Yun; Shih, Hong-Mo

    2014-07-01

    Thromboembolism and atherosclerotic stenosis both can cause arterial occlusion. Aortoiliac occlusive disease involving bifurcation of the aortoiliac artery induces symptoms of ischemia such as claudication and pain of buttocks and thighs, decreased bilateral femoral pulses, and impotence. Here, we describe a 58-year-old woman with a past history of atrial fibrillation and lacuna stroke with minimal right side weakness. She presented to our emergency department with sudden onset bilateral pain in the legs and paraplegia. A comprehensive examination revealed paresthesia and decreasing bilateral distal pulses. Computed tomographic imaging showed filling defects over the low abdominal aorta just above the bifurcation of the common iliac artery and bilateral femoral arteries. Acute aortic embolic occlusion was suspected. Her symptoms were resolved after emergent thrombectomy for acute limb ischemia. Physicians need to be aware of aortoiliac embolic occlusive disease which may present as acute paraplegia.

  13. Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia

    PubMed Central

    Koht, Jeanette; Pihlstrøm, Lasse; Rengmark, Aina H.; Henriksen, Sandra P.; Tallaksen, Chantal M. E.; Toft, Mathias

    2017-01-01

    Hereditary ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early and late-onset hereditary ataxia and spastic paraplegia probands, in whom extensive previous investigations had failed to identify the genetic cause of disease. Pathogenic and likely-pathogenic variants were identified in 20 probands (19%) and variants of uncertain significance in ten probands (10%). Together these accounted for 30 probands (29%) and involved 18 different genes. Among several interesting findings, dominantly inherited KIF1A variants, p.(Val8Met) and p.(Ile27Thr) segregated in two independent families, both presenting with a pure spastic paraplegia phenotype. Two homozygous missense variants, p.(Gly4230Ser) and p.(Leu4221Val) were found in SACS in one consanguineous family, presenting with spastic ataxia and isolated cerebellar atrophy. The average disease duration in probands with pathogenic and likely-pathogenic variants was 31 years, ranging from 4 to 51 years. In conclusion, this study confirmed and expanded the clinical phenotypes associated with known disease genes. The results demonstrate that gene panel sequencing and similar sequencing approaches can serve as efficient diagnostic tools for different heterogeneous disorders. Early use of such strategies may help to reduce both costs and time of the diagnostic process. PMID:28362824

  14. 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

  15. A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia.

    PubMed

    Miura, Shiroh; Morikawa, Takuya; Fujioka, Ryuta; Kosaka, Kengo; Yamada, Kohei; Hattori, Gohsuke; Motomura, Manabu; Taniwaki, Takayuki; Shibata, Hiroki

    2016-08-01

    Spastic paraplegia (SPG) type 28 is an autosomal recessive SPG caused by mutations in the DDHD1 gene. We examined a Japanese 54-years-old male patient with autosomal recessive SPG. His parents were consanguineous. He needed a wheelchair for transfer due to spastic paraplegia. There was a history of operations for bilateral hallux valgus, thoracic ossification of the yellow ligament, bilateral carpal tunnel syndrome, bilateral ankle contracture, and lumbar spinal canal stenosis. He noticed gait disturbance at age 14. He used a cane for walking in his 40s. On neurological examination, he showed hyperreflexia, spasticity, and weakness in the lower extremities and bilateral Babinski reflexes. Urinary dysfunctions and impaired vibration sense in the lower limbs were observed. By exome sequencing analysis using Agilent SureSelect and Illumina MiSeq, we identified 17,248 homozygous nucleotide variants in the patient. Through the examination of 48 candidate genes known to be responsible for autosomal recessive SPG, we identified a novel homozygous 4-bp deletion, c.914_917delGTAA, p.Ser305Ilefs*2 in exon2 of the DDHD1 gene encoding phosphatidic acid-preferring phospholipase A1 (PA-PLA1). The mutation is expected to cause a frameshift generating a premature stop codon 3-bp downstream from the deletion. In consequence, the DDHD domain that is known to be critical for PLA1 activity is completely depleted in the mutated DDHD1 protein, predicted to be a functionally null mutation of the DDHD1 gene. By Sanger sequencing, we confirmed that both parents are heterozygous for the mutation. This variation was not detected in 474 Japanese control subjects as well as the data of the 1,000G Project. We conclude that the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population.

  16. [Urinary infection in patients with the condition of paraplegia].

    PubMed

    Ramić, Ibrahim

    2004-01-01

    The data were retrospectivelly analyzed conserning the frequency of uroinnfect in person with the paraplegia condition at the institute for physiatry and rehabilitation--the Center for paraplegia of the Clinical center of University in Sarajevo. The analysis was involved 71 (10%) of the patients chosen by the method of the casual choice. Males 57 (80.28%), females 14 (19.71%) of the examimnees. Urolitiazation was found in 22 (30.98%), without urolitization was 49 (69.01%) of patients. The sterile urinoculture were found in only 4 (5.63%) of the patients. The greatest number of the patients 34 (47.88%) he had three and more bacteria in urinoculture. Per two bacterias had 18 (25.35%), with the a one bacteria was 15 (21.12%) of patients. That the degree of the education and enabling of the activities of every day life (AEL) has no essential influence on the seizures of uroinfect shows the result of the research of Barther index where we found 59 (83.09%) of the examinees independent in movement. What are social consequences of this condition when the complications by uroinfect and urocaliculosys can be seen by the hospitalization number at the Institute for the rehabilitation where 29 (40.84%) of the examinees was hospitalized more than three times, 12 (16.90%) three times, 16 (22.90%) and only 14 (19.71%) once. It is considered that the persons with the paraplegia condition if they have no the acute becoming works should perform at least the essential control examinations every six months.

  17. Simulated paraplegia: an occasional problem for the neurosurgeon.

    PubMed Central

    Maurice-Williams, R S; Marsh, H

    1985-01-01

    Fourteen cases of simulated paraplegia and tetraplegia encountered amongst 4,800 neurosurgical admissions are described. The classification of such cases is difficult. Use of the term "hysteria" depends on whether the behaviour is judged to be conscious or not, but this can rarely be decided. In most of the patients the paralysis was of relatively short duration and recovered rapidly with simple methods of treatment which permitted this to occur without loss of face, but such cases presenting as acute neurological emergencies represent only one relatively simple form of pretended or "hysterical" illness. Many of these patients are probably never seen by psychiatrists. PMID:4031935

  18. Hereditary spastic paraplegia due to a novel mutation of the REEP1 gene

    PubMed Central

    Richard, Sébastien; Lavie, Julie; Banneau, Guillaume; Voirand, Nathalie; Lavandier, Karine; Debouverie, Marc

    2017-01-01

    Abstract Rationale: Hereditary spastic paraplegia (HSP) is a heterogeneous group of diseases little known in clinical practice due to its low prevalence, slow progression, and difficult diagnosis. This results in an underestimation of HSP leading to belated diagnosis and management. In depth diagnosis is based on clinical presentation and identification of genomic mutations. We describe the clinical presentation and pathogeny of HSP through a report of a case due to a novel mutation of the REEP1 gene (SPG31). Patient concerns: A 64-year-old woman presented gait disturbances due to spasticity of the lower limbs progressing since her third decade. Previous investigations failed to find any cause. Interventions: DNA analysis was performed to search for HSP causing mutations. Diagnoses: A novel heterozygote mutation (c.595 + 1G>A) of the REEP1 gene, within the splice site of intron 6, was discovered. This nucleotide change causes exon 6 skipping leading to frame shift and a truncated transcript identified by complementary DNA sequencing of reverse transcription polymerase chain reaction products. Outcomes: REEP1 is a known protein predominantly located in the upper motor neurons. Mutation of REEP1 primary affects the longest axons explaining predominance of pyramidal syndrome on lower limbs. Lessons: Slow progressive pyramidal syndrome of the lower limbs should elicit a diagnosis of HSP. We describe a novel mutation of the REEP1 gene causing HSP. Pathogeny is based on resulting abnormal REEP1 protein which is involved in the development of longest axons constituting the corticospinal tracts. PMID:28099355

  19. DOE LLW classification rationale

    SciTech Connect

    Flores, A.Y.

    1991-09-16

    This report was about the rationale which the US Department of Energy had with low-level radioactive waste (LLW) classification. It is based on the Nuclear Regulatory Commission`s classification system. DOE site operators met to review the qualifications and characteristics of the classification systems. They evaluated performance objectives, developed waste classification tables, and compiled dose limits on the waste. A goal of the LLW classification system was to allow each disposal site the freedom to develop limits to radionuclide inventories and concentrations according to its own site-specific characteristics. This goal was achieved with the adoption of a performance objectives system based on a performance assessment, with site-specific environmental conditions and engineered disposal systems.

  20. DOE LLW classification rationale

    SciTech Connect

    Flores, A.Y.

    1991-09-16

    This report was about the rationale which the US Department of Energy had with low-level radioactive waste (LLW) classification. It is based on the Nuclear Regulatory Commission's classification system. DOE site operators met to review the qualifications and characteristics of the classification systems. They evaluated performance objectives, developed waste classification tables, and compiled dose limits on the waste. A goal of the LLW classification system was to allow each disposal site the freedom to develop limits to radionuclide inventories and concentrations according to its own site-specific characteristics. This goal was achieved with the adoption of a performance objectives system based on a performance assessment, with site-specific environmental conditions and engineered disposal systems.

  1. Behcet's disease presenting with sudden-onset paraplegia due to anterior spinal artery involvement: 1-year follow-up of rehabilitation in conjunction with medication.

    PubMed

    Duman, Iltekin; Guzelkucuk, Umut; Tezel, Kutay; Aydemir, Koray; Yılmaz, Bilge

    2013-06-01

    A 26-year-old male patient with sudden-onset paraplegia was presented. Clinical and imaging evaluation revealed isolated spinal cord lesions at thoracal levels and anterior spinal arterial involvement. Diagnosis of Behcet's disease was established with associating clinical findings with medical history. Vigorous medication and rehabilitation program were performed. Through the 1-year rehabilitation period in conjunction with medication, strength and functions improved gradually. A satisfactory functional gain as a rehabilitative goal in independence in activities of daily living and long-distance ambulation achieved around 4 months. The patient reached full independence after 1-year. As conclusion, Behcet's disease can present with sudden-onset paraplegia. In case of no evident etiology for paraplegia in young male, neuro-Behcet's disease also should be kept in mind. Contrary to assumption, early aggressive treatment and continuous rehabilitation in conjunction with medication might provide good prognosis with excellent clinical outcome in spinal cord involvement. Satisfactory functional recovery should be expected only after 3-4 months, and complete independence can be achieved after 1 year.

  2. [A Case of Postoperative Paraplegia Caused by Idiopathic Spinal Cord Infarction following Hepatectomy under Both General and Epidural Anesthesia].

    PubMed

    Koga, Yukari; Hiraki, Teruyuki; Ushijima, Kazuo

    2015-04-01

    A 73-year-old woman (height : 155 cm, weight : 55 kg) was scheduled to undergo a laparotomic hepatectomy and radiofrequency ablation for hepatocellular carcinoma. Her medical history did not include any relevant conditions such as cardiovascular or neurological disorders. A thoracic epidural catheter was introduced at T8-9 before the induction of anesthesia with intravenous propofol. General anesthesia was maintained with the inhalation of oxygen, air, and desflurane, and the continuous infusion of remifentanil. Several intraoperative episodes of mild hypotension occurred, each of which was successfully treated with intravenous ephedrine, but otherwise her anesthetic course was uneventful, and she recovered from the anesthesia smoothly. Her postoperative pain was well controlled with continuous epidural infusion of levobupivacaine and fentanyl, and she could walk by herself on postoperative day (POD) 1. However, she suffered weakness in her lower extremities on POD2 and subsequently fell into complete paraplegia with sensory loss below the T4 level on POD3. A magnetic resonance imaging scan taken on POD4 showed an idiopathic spinal cord infarction (SCI) involving levels T1 through T4, although no epidural abnormalities, e.g., hematomas, were detected. Immediate treatment with methylprednisolone, ozagrel, and edaravone failed to resolve her symptoms. We suggest that it is of great importance to consider SCI as a differential diagnosis as soon as possible in cases of unanticipated postoperative paraplegia.

  3. Paraplegia following cervical epidural catheterization using loss of resistance technique with air: a case report.

    PubMed

    Chae, Yun Jeong; Han, Kyung Ream; Park, Hyung Bae; Kim, Chan; Nam, Si Gweon

    2016-02-01

    We report a case of paraplegia without neurologic deficit of upper extremities following cervical epidural catheterization using air during the loss of resistance technique. A 41-year-old woman diagnosed with complex regional pain syndrome had upper and lower extremity pain. A thoracic epidural lead was inserted for a trial spinal cord stimulation for treating lower extremity pain and cervical epidural catheterization was performed for treating upper extremity pain. Rapidly progressive paraplegia developed six hours after cervical epidural catheterization. Spine CT revealed air entrapment in multiple thoracic intervertebral foraminal spaces and surrounding epidural space without obvious spinal cord compression before the decompressive operation, which disappeared one day after the decompressive operation. Her paraplegia symptoms were normalized immediately after the operation. The presumed cause of paraplegia was transient interruption of blood supply to the spinal cord through the segmental radiculomedullary arteries feeding the spinal cord at the thoracic level of the intervertebral foramen caused by the air.

  4. Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

    PubMed

    Ylikallio, Emil; Kim, Doyoun; Isohanni, Pirjo; Auranen, Mari; Kim, Eunjoon; Lönnqvist, Tuula; Tyynismaa, Henna

    2015-10-01

    Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor protein, have been described to cause variable neurological manifestations. Recessive missense variants have led to spastic paraplegia, and recessive truncations to sensory and autonomic neuropathy. De novo missense variants cause developmental delay or intellectual disability, cerebellar atrophy and variable spasticity. We describe a family with father-to-son transmission of de novo variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia. Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested that it impairs the stable binding of ATP to the KIF1A protein. Our study reports the first dominantly inherited KIF1A variant and expands the spectrum of phenotypes caused by heterozygous KIF1A motor domain variants to include pure spastic paraplegia. We conclude that KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern.

  5. Unusual presentation of aortic dissection: post-coital acute paraplegia with renal failure.

    PubMed

    Galabada, Dinith P; Nazar, Abdul L M

    2014-09-01

    We report the case of a 45-year-old chronic smoker who presented with acute paraplegia occurring during coitus and subsequently developed acute renal failure (ARF) requiring dialysis. He had absent peripheral pulses in the lower limbs with evidence of acute ischemia. Doppler study showed dissecting aneurysm of thoracic aorta, thrombotic occlusion of the distal aorta from L1 level up to bifurcation and occlusion of the right renal artery by a thrombus that was confirmed by magnetic resonance imaging of the spine. He was not subjected to any vascular intervention as his lower limbs were not salvageable due to delay in the diagnosis. Post-coital aortic dissection and aortic dissection presenting with acute paraplegia and ARF are very rare. This is probably the first case report with post-coital acute aortic dissection presenting with paraplegia and ARF. This case emphasizes the importance of a careful examination of peripheral pulses in patients presenting with ARF and paraplegia.

  6. Successful staged operation for acute type A aortic dissection with paraplegia.

    PubMed

    Ando, Takashi; Abe, Hiroyuki; Nagata, Tokuichiro; Makuuchi, Haruo

    2013-06-01

    A 75-year-old man presented with both paraplegia and acute occlusion of the abdominal aorta at onset. Extraanatomical bypass was performed following spinal drainage. After 3 days, the ascending aorta replaced under cardiopulmonary bypass using the extraanatomical bypass graft for arterial cannulation. The abdominal aorta was replaced after 6 months. A staged operation is one of the options for acute aortic dissection with paraplegia and acute occlusion of the abdominal aorta.

  7. Spontaneous spinal epidural hematoma presenting as paraplegia after cardiac surgery.

    PubMed

    Kin, Hajime; Mukaida, Masayuki; Koizumi, Junichi; Kamada, Takeshi; Mitsunaga, Yoshino; Iwase, Tomoyuki; Ikai, Akio; Okabayashi, Hitoshi

    2016-03-01

    An 86-year-old woman was scheduled to undergo aortic valve replacement and coronary artery bypass graft. On postoperative day 3, she developed sudden-onset neck pain followed by weakness in the right arm. Her symptoms worsened with time, and she developed paraplegia. At 60 h after the first complaint, spontaneous spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was diagnosed from a magnetic resonance image of the cervical region. We decided on conservative therapy because operative recovery was impossible. Delayed diagnosis led to grievous results in the present case. When neurological abnormalities follow neck or back pain after open heart surgery, SSEH must be considered in the differential diagnosis. Further, if it is suspected, early cervical computed tomography/magnetic resonance imaging and surgery should be considered.

  8. Clinical and genetic study of hereditary spastic paraplegia in Canada

    PubMed Central

    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.

    2016-01-01

    Objective: 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. Methods: 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). Results: 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). Conclusions: 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. PMID:27957547

  9. A preliminary assessment of legged mobility provided by a lower limb exoskeleton for persons with paraplegia.

    PubMed

    Farris, Ryan J; Quintero, Hugo A; Murray, Spencer A; Ha, Kevin H; Hartigan, Clare; Goldfarb, Michael

    2014-05-01

    This paper presents an assessment of a lower limb exoskeleton for providing legged mobility to people with paraplegia. In particular, the paper presents a single-subject case study comparing legged locomotion using the exoskeleton to locomotion using knee-ankle-foot orthoses (KAFOs) on a subject with a T10 motor and sensory complete injury. The assessment utilizes three assessment instruments to characterize legged mobility, which are the timed up-and-go test, the Ten-Meter Walk Test (10 MWT), and the Six-Minute Walk Test (6 MWT), which collectively assess the subject's ability to stand, walk, turn, and sit. The exertion associated with each assessment instrument was assessed using the Physiological Cost Index. Results indicate that the subject was able to perform the respective assessment instruments 25%, 70%, and 80% faster with the exoskeleton relative to the KAFOs for the timed up-and-go test, the 10 MWT, and the 6 MWT, respectively. Measurements of exertion indicate that the exoskeleton requires 1.6, 5.2, and 3.2 times less exertion than the KAFOs for each respective assessment instrument. The results indicate that the enhancement in speed and reduction in exertion are more significant during walking than during gait transitions.

  10. 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

  11. Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding Partners

    PubMed Central

    Zhao, Jiali; Hedera, Peter

    2015-01-01

    Hereditary spastic paraplegia (HSP) is one of the most heterogeneous neurodegenerative diseases with more than 50 identified genes causing a relatively stereotypical phenotypic presentation. Recent studies of HSP pathogenesis have suggested the existence of shared biochemical pathways that are crucial for axonal maintenance and degeneration. We explored possible interactions of several proteins associated with this condition. Here we report interactions of endogenous and overexpressed strumpellin with another HSP-associated protein, spartin. This biochemical interaction does not appear to be a part of the Wiskott–Aldrich syndrome protein and Scar homologue (WASH) complex because spartin is not co-immunoprecipitated with WASH1 protein. The spartin–strumpellin association does not require the presence of the microtubule interacting and trafficking domain of spartin. Over-expression of mutant forms of strumpellin with the introduced HSP-causing mutations does not alter the colocalization of these two proteins. Knockdown of strumpellin in cultured cortical rat neurons interferes with development of neuronal branching and results in reduced expression of endogenous spartin. Proteosomal inhibition stabilized the levels of spartin and WASH1 proteins, supporting increased spartin degradation in the absence of strumpellin. PMID:25987849

  12. Rationales for Teaching World Musics.

    ERIC Educational Resources Information Center

    Fung, C. Victor

    1995-01-01

    Asserts that since the middle of the 20th century the inclusion of world musics in music education programs has become increasingly important. Presents three rationales for teaching world music in the United States. Discusses two assumptions and implications for music educators regarding world music. (CFR)

  13. [Thoraco-abdominal aortic replacement in chronic phase in a patient with temporary paraplegia after Stanford B acute dissection].

    PubMed

    Takahashi, Goro; Hata, Masaki; Tabayashi, Koichi

    2013-07-01

    A 42-year-old man underwent was performed with thoraco-abdominal aneurysm replacement accompaniedy with reconstruction of abdominal branches and intercostal arteries. Eighteen months before, he had suffered from Stanford already been cured with paraplegia on being type B acute aortic dissection combined with paraplegia. When paraplegia had been occurred, cerebrospinal fluid drainage was had been performed promptly, and 4 days later, neurologic deficit was disappeared in 1 day. During the thoraco-abdominal aortic operation, cerebrospinal fluid drainage was performed done again. After the operation, paraplegia did was not occurred and he did not feel somewhat wrong with his legs. He was discharged from hospital on foot by himself. This case showed the efficacy of cerebral spinal fluid drainage for not only both with the prevention but also and treatment of paraplegia.

  14. Endemic Burkitt Lymphoma: Long-term Outcome in 87 Patients Who Presented With Paraplegia in Cameroon.

    PubMed

    Hesseling, P B; Mbah, G; Kouya, F; Kimbi, C; Nfor, P; Kaah, J; Kuruvilla, R; Best, A; Wharin, P

    2015-01-01

    The reported long-term outcome of endemic Burkitt lymphoma (eBL) patients who present with paraplegia is largely unknown. Records of BL patients treated with comparable short-interval cyclophosphamide chemotherapy schedules between 2004 and 2014 at three Baptist mission hospitals in Cameroon were reviewed. Survivors were followed up and examined at home or in hospital. Eighty-seven of 948 (9.2%) patients had paraplegia at diagnosis. The survival rate in eBL patients with paraplegia at diagnosis was 33% (n = 29) after follow-up of between 2 and 96 (median 40) months. Seven patients (24%) had neurological sequelae and needed rehabilitation. There was no relationship between the duration of symptoms (<2, 2-4, >4 weeks) and the survival rate or the risk to have neurological sequelae. The survival rate and risk for sequelae were similar in patients with confirmed St. Jude stage III and IV diseases.

  15. Coagulopathy associated with sac reperfusion for reversing paraplegia after endovascular repair of type II thoracoabdominal aneurysm.

    PubMed

    Lioupis, Christos; Katsanos, Konstantinos; Clough, Rachel; Matharu, Nick; Modarai, Bijan; Carrell, Tom; Taylor, Peter

    2013-11-01

    Sac perfusion may be helpful in preventing or reversing spinal cord injury after endovascular repair of thoracoabdominal aneurysms and it has been used as an adjunct to the standard physiologic measures of sustained hypertension and cerebrospinal fluid drainage. Coagulopathy as a result of endoleak after endovascular aneurysm repair has been reported, and very rare cases of treatment after repair of these endoleaks have been described. We report a 73-year-old man who had endovascular repair of a type II thoracoabdominal aneurysm with a branched stent graft. Sac reperfusion was initiated to manage postoperative paraplegia. The paraplegia partially resolved but severe hemorrhagic complications developed that were attributed to sac perfusion-related hyperfibrinolysis. Discontinuation of sac perfusion resolved the coagulopathy but resulted in paraplegia.

  16. Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene.

    PubMed

    Bayrakli, Fatih; Poyrazoglu, Hatice Gamze; Yuksel, Sirin; Yakicier, Cengiz; Erguner, Bekir; Sagiroglu, Mahmut Samil; Yuceturk, Betul; Ozer, Bugra; Doganay, Selim; Tanrikulu, Bahattin; Seker, Askin; Akbulut, Fatih; Ozen, Ali; Per, Huseyin; Kumandas, Sefer; Altuner Torun, Yasemin; Bayri, Yasar; Sakar, Mustafa; Dagcinar, Adnan; Ziyal, Ibrahim

    2015-12-01

    We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

  17. Novel medical bathing with traditional Chinese herb formula alleviates paraplegia spasticity.

    PubMed

    Liu, Xin; Meng, Qingxi; Yu, Dapeng; Zhao, Xiwu; Zhao, Tingbao

    2014-06-01

    Paraplegia spasm is a kind of chronic disease which lacks effective treatment; the patients have to endure long-term pain, which is a tough problem for nursing practice. Lots of potential candidate medicines are under investigation, and a new Chinese herb formula is introduced in the current study. In the present study, we chose six different well-known Chinese herbs to form a formula, and boiled them into the water with an optimized ratio to make bath water; 80 paraplegic patients received this medicinal bath, and 80 patients received perfume water bath as placebo group. Compared with placebo control patients, the herb-treated patients have significant reduction in paraplegia spasm, visual analogue scale score, clinician global impression and sleep disorder. This novel six-combined formula traditional medicine could be beneficial for alleviating paraplegia spasm, but the underlying action mechanism deserves further study.

  18. Acute Paraplegia After Lumbar Steroid Injection in Patients With Spinal Dural Arteriovenous Fistulas: Case Reports

    PubMed Central

    2016-01-01

    Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal vascular malformations. However, SDAVFs are still underdiagnosed entities because their clinical symptoms are usually non-specific, as they include low back pain or radiating pain to the limb. There have been several reports of acute paraplegia after lumbar epidural steroid injections in patients with SDAVFs. We present 4 patients with SDAVFs who received lumbar steroid injection. Among the 4 cases, acute paraplegia developed in 2 cases that received a larger volume of injectate than the other cases. Thus, we are suggesting that the volume of injectate may be a contributing factor for acute paraplegia after lumbar steroid injection in patients with SDAVFs. PMID:27847727

  19. A Rationale for College Student Services Program

    ERIC Educational Resources Information Center

    Teeter, Ruskin

    1974-01-01

    Article points to need for new rationale for student personnel administration. Such a rationale could assist administrators in answering such questions as derive from the abandonment of the doctrine of in loco parentis. (Author/EK)

  20. 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.

  1. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) .

    PubMed

    Bauer, Peter; Leshinsky-Silver, Esther; Blumkin, Lubov; Schlipf, Nina; Schröder, Christopher; Schicks, Julia; Lev, Dorit; Riess, Olaf; Lerman-Sagie, Tally; Schöls, Ludger

    2012-02-01

    We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

  2. 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…

  3. A pregnant woman with metastatic papillary thyroid carcinoma and paraplegia: Multiple considerations involved in the management.

    PubMed

    Basu, Sandip; Kand, Purushottam

    2011-01-01

    undertaken 48h after the administration of (131)I scan dose. Both the diagnostic and post (131)I treatment scan demonstrated multiple foci of (131)I uptake in the skeleton, lungs and liver. Following discharge from the isolation ward, adequate separation from the infant was ensured and the childcare was undertaken by relatives. The patient had a remarkable improvement clinically. During the next 3-½ years she was treated 2 more times with (131)I with cumulative doses of about 25.9GBq. The last post-treatment scan is depicted in. She has been presently ambulatory with complete resolution of paraplegia and a significantly better quality of life without any requirement of support, despite the presence of extensive skeletal disease. A recent review entitled "Approach to the pregnant patient with thyroid cancer", addresses this topic as a separate category. Similar emphasis has also been given by other authors while dealing with these patients. In our experience, patients with PTC metastatic lesions in the vertebrae show better response compared to those with large flat bone metastases likely related to the small size of the former. In conclusion, a teamwork of surgeons, obstetricians, nuclear medicine physicians as well as the strong support by the relatives, was necessary to favorably treat this patient with metastatic PTC, paraplegia and pregnancy.

  4. Blood irradiation: Rationale and technique

    SciTech Connect

    Lewis, M.C. )

    1990-01-01

    Upon request by the local American Red Cross, the Savannah Regional Center for Cancer Care irradiates whole blood or blood components to prevent post-transfusion graft-versus-host reaction in patients who have severely depressed immune systems. The rationale for blood irradiation, the total absorbed dose, the type of patients who require irradiated blood, and the regulations that apply to irradiated blood are presented. A method of irradiating blood using a linear accelerator is described.

  5. 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

  6. 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"…

  7. Prevalence of Oxidative Stress and Metabolic Syndrome in Adults with Paraplegia and Tetraplegia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To investigate the extent of oxidative stress and metabolic syndrome (MetS) in people with spinal cord injuries (SCI) and to identify the major factors associated with oxidative stress and MetS in this population. Methods: 24 subjects with paraplegia (PARA), 26 subjects with tetraplegia ...

  8. Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia

    PubMed Central

    Coutelier, Marie; Goizet, Cyril; Durr, Alexandra; Habarou, Florence; Morais, Sara; Dionne-Laporte, Alexandre; Tao, Feifei; Konop, Juliette; Stoll, Marion; Charles, Perrine; Jacoupy, Maxime; Matusiak, Raphaël; Alonso, Isabel; Tallaksen, Chantal; Mairey, Mathilde; Kennerson, Marina; Gaussen, Marion; Schule, Rebecca; Janin, Maxime; Morice-Picard, Fanny; Durand, Christelle M.; Depienne, Christel; Calvas, Patrick; Coutinho, Paula; Saudubray, Jean-Marie; Rouleau, Guy; Brice, Alexis; Nicholson, Garth; Darios, Frédéric; Loureiro, José L.; Zuchner, Stephan; Ottolenghi, Chris; Mochel, Fanny

    2015-01-01

    Hereditary spastic paraplegias are heterogeneous neurological disorders characterized by a pyramidal syndrome with symptoms predominantly affecting the lower limbs. Some limited pyramidal involvement also occurs in patients with an autosomal recessive neurocutaneous syndrome due to ALDH18A1 mutations. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), an enzyme that catalyses the first and common step of proline and ornithine biosynthesis from glutamate. Through exome sequencing and candidate gene screening, we report two families with autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment, without any cutaneous abnormality. More interestingly, we also identified monoallelic ALDH18A1 mutations segregating in three independent families with autosomal dominant pure or complex hereditary spastic paraplegia, as well as in two sporadic patients. Low levels of plasma ornithine, citrulline, arginine and proline in four individuals from two families suggested P5CS deficiency. Glutamine loading tests in two fibroblast cultures from two related affected subjects confirmed a metabolic block at the level of P5CS in vivo. Besides expanding the clinical spectrum of ALDH18A1-related pathology, we describe mutations segregating in an autosomal dominant pattern. The latter are associated with a potential trait biomarker; we therefore suggest including amino acid chromatography in the clinico-genetic work-up of hereditary spastic paraplegia, particularly in dominant cases, as the associated phenotype is not distinct from other causative genes. PMID:26026163

  9. Tetraplegia or paraplegia with brachial diparesis? What is the most appropriate designation for the motor deficit in patients with lower cervical spinal cord injury?

    PubMed

    Figueiredo, Nicandro; Figueiredo, Iara Eberhard; Resnick, Daniel

    2013-02-01

    The authors seek to clarify the nomenclature used to describe cervical spinal cord injuries, particularly the use of the terms "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia" when applied to patients with lower cervical cord injuries. A review of the origin of the terms and nomenclature used currently to describe the neurological status of patients with SCI in the literature was performed. The terms "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia" have been used very often to describe patients with complete lower cervical SCI despite the fact that the clinical scenario is all the same for most of these patients. Most of these patients have total loss of the motor voluntary movements of their lower trunk and inferior limbs, and partial impairment of movement of their superior limbs, preserving many motor functions of the proximal muscles of their arms (superior limbs). A potentially better descriptive term may be "paraplegia with brachial diparesis". In using the most appropriate terminology, the patients with lower cervical SCI currently referred as presenting with "tetraplegia", "quadriplegia", "quadriparesis", "tetraparesis", "incomplete quadriplegia" or "incomplete tetraplegia", might be better described as having "paraplegia with brachial diparesis".

  10. SDI: its nature and rationale

    SciTech Connect

    Nitze, P.H.

    1985-01-01

    Because of fixed preconceptions or erroneous assumptions, this is an attempt by Mr. Nitze, mostly, to clarify the background and rationale for SDI. After discussing briefly the three factors that led to the President's decision in early 1983 to launch SDI, he emphasizes that SDI is a research program that is investigating the feasibility of new defense technologies, both earth- and space-based. Further, he emphasizes what SDI is not: (1) a deployment program, but research only; (2) an attempt of the US to obtain superiority; and (3) designed to produce a regime that would replace deterrence, but rather to shift its means.

  11. X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg.

    PubMed Central

    Zatz, M; Penha-Serrano, C; Otto, P A

    1976-01-01

    A family with 24 males affected by an X-linked type of spastic paraplegia is reported. Twelve affected members were personally examined showing the pure form of the disease. Half of the affected males had many descendants, all normal. Linkage studies strongly suggest that this X-linked form of spastic paraplegia and Xg loci are not at a measurable distance on the X chromosome. PMID:1084423

  12. Confirmation of locus heterogeneity in the pure form of familial spastic paraplegia

    SciTech Connect

    Speer, M.C.; Gaskell, P.C.; Robinson, L.C.

    1995-08-14

    Familial spastic paraplegia (FSP), characterized by progressive spasticity of the lower extremities, is in its {open_quotes}pure{close_quotes} form generally of autosomal dominant inheritance pattern. Hazen et al. reported tight linkage of a large FSP family to the highly polymorphic microsatellite marker D14S269 with z ({sub {theta}}) = 8.49 at {sub {theta}} = 0.00. They further demonstrated evidence for locus heterogeneity when they showed that 2 FSP families were unlinked to this region. We have subsequently studied 4 FSP families (3 American, one British) and excluded the disease locus in these families for approximately 30 cM on either side of D14S269, thereby confirming evidence for locus heterogeneity within the spastic paraplegia diagnostic classification. 28 refs., 2 figs., 4 tabs.

  13. An Approach for the Cooperative Control of FES With a Powered Exoskeleton During Level Walking for Persons With Paraplegia.

    PubMed

    Ha, Kevin H; Murray, Spencer A; Goldfarb, Michael

    2016-04-01

    This paper describes a hybrid system that combines a powered lower limb exoskeleton with functional electrical stimulation (FES) for gait restoration in persons with paraplegia. The general control structure consists of two control loops: a motor control loop, which utilizes joint angle feedback control to control the output of the joint motor to track the desired joint trajectories, and a muscle control loop, which utilizes joint torque profiles from previous steps to shape the muscle stimulation profile for the subsequent step in order to minimize the motor torque contribution required for joint angle trajectory tracking. The implementation described here incorporates stimulation of the hamstrings and quadriceps muscles, such that the hip joints are actuated by the combination of hip motors and the hamstrings, and the knee joints are actuated by the combination of knee motors and the quadriceps. In order to demonstrate efficacy, the control approach was implemented on three paraplegic subjects with motor complete spinal cord injuries ranging from levels T6 to T10. Experimental data indicates that the cooperative control system provided consistent and repeatable gait motions and reduced the torque and power output required from the hip and knee motors of the exoskeleton compared to walking without FES.

  14. 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)

  15. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia.

    PubMed

    Wu, Y; Satkunendrarajah, K; Fehlings, M G

    2014-04-18

    The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia-reperfusion injury to the spinal cord. Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14±4.85 compared with 1.86±1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4h post-injury, a clinically relevant therapeutic time window.

  16. [Incomplete paraplegia after delayed diagnostics of motor function deficits. Severe malpractice?].

    PubMed

    Regauer, M; Neu, J

    2013-03-01

    A 72-year-old female patient was transferred to a rehabilitation centre after surgical stabilization of a subtrochanteric femoral fracture. However, adequate mobilization was not possible there and 5 days after transfer deficits in the motor function of both lower extremities were documented for the first time and an initial paraplegia was diagnosed the following day by a neurologist. Magnetic resonance imaging (MRI) revealed the suspicion of an unstable fracture of the seventh thoracic vertebral body 8 days after the initial symptoms, which was confirmed by computed tomography after another 3 days. Surgical decompression and stabilization were performed at a department for neurosurgery 4 days later but incomplete paraplegia persisted permanently. The patient complained about insufficient diagnostic measures at the rehabilitation centre. The expert opinion concluded that it would have been mandatory to investigate the matter of the newly occurring neurological symptoms immediately but this had only been performed after undue delay, which had to be interpreted as a case of medical malpractice. The expert pointed out that it was not possible to provide clear evidence that emergent diagnosis and surgery would have enabled a significantly better outcome.The arbitration board ascertained a lack of examination and argued that prompt and adequate diagnostic measures would have revealed the relevant pathological finding and thus surgery would have been performed immediately. According to the reversal of evidence in favor of the patient it could be assumed that no permanent neurological damage existed when the first neurological symptoms occurred and that emergent surgery at least had the potential to prevent permanent paraplegia. This opinion of the arbitration board is supported by numerous references in the literature.

  17. Successful reversal of immediate paraplegia associated with repair of acute Type A aortic dissection using cerebrospinal fluid drainage.

    PubMed

    Shimura, Shinichiro; Cho, Yasunori; Aki, Akira; Ueda, Toshihiko

    2013-12-01

    We present a case of a 49-year old man who suffered from immediate paraplegia upon awakening from anaesthesia after surgery for acute aortic dissection Type A. A catheter was promptly inserted into the spinal canal for cerebrospinal fluid drainage, and the cerebrospinal fluid pressure was maintained <10 cmH2O. Although magnetic resonance imaging showed extensive spinal cord ischaemia, the patient gradually recovered from the paraplegia and was able to walk by himself after rehabilitation. In some cases, cerebrospinal fluid drainage can be effective for the treatment of immediate postoperative spinal cord damage.

  18. Spastic paraplegia, optic atrophy, microcephaly with normal intelligence, and XY sex reversal: a new autosomal recessive syndrome?

    PubMed Central

    Teebi, A S; Miller, S; Ostrer, H; Eydoux, P; Colomb-Brockmann, C; Oudjhane, K; Watters, G

    1998-01-01

    Two female sibs of first cousin Iranian parents were found to have the syndrome of spastic paraplegia, optic atrophy with poor vision, microcephaly, and normal cognitive development. Karyotype analysis showed a normal female constitution in one and a male constitution (46,XY) in the other. The XY female showed normal female external genitalia, normal uterus and tubes, and streak gonads. SRY gene sequencing was normal. We conclude that the present family probably represents a new autosomal recessive trait of pleiotropic effects including XY sex reversal and adds further evidence for the heterogeneity of spastic paraplegia syndromes as well as sex reversal syndromes. Images PMID:9733035

  19. 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

  20. Mutations in the Novel Mitochondrial Protein REEP1 Cause Hereditary Spastic Paraplegia Type 31

    PubMed Central

    Züchner, Stephan; Wang, Gaofeng; Tran-Viet, Khanh-Nhat; Nance, Martha A.; Gaskell, Perry C.; Vance, Jeffery M.; Ashley-Koch, Allison E.; Pericak-Vance, Margaret A.

    2006-01-01

    Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. For the novel SPG31 locus on chromosome 2p12, we identified six different mutations in the receptor expression–enhancing protein 1 gene (REEP1). REEP1 mutations occurred in 6.5% of the patients with HSP in our sample, making it the third-most common HSP gene. We show that REEP1 is widely expressed and localizes to mitochondria, which underlines the importance of mitochondrial function in neurodegenerative disease. PMID:16826527

  1. REEPing the benefits of an animal model of hereditary spastic paraplegia.

    PubMed

    Deutch, Ariel Y; Hedera, Peter; Colbran, Roger J

    2013-10-01

    The hereditary spastic paraplegias (HSPs) are characterized by spasticity of the leg muscles due to axonal degeneration of corticospinal neurons. Beetz et al. report that the core motor phenotype and axonal pathology of HSPs are recapitulated in mice lacking the HSP-associated gene Reep1. REEP1 is shown to regulate ER structure in motor cortex neurons. The Reep1 knockout mouse should be a very useful model in which to study the mechanisms of progressive axon loss in HSPs and other disorders.

  2. REEPing the benefits of an animal model of hereditary spastic paraplegia

    PubMed Central

    Deutch, Ariel Y.; Hedera, Peter; Colbran, Roger J.

    2013-01-01

    The hereditary spastic paraplegias (HSPs) are characterized by spasticity of the leg muscles due to axonal degeneration of corticospinal neurons. Beetz et al. report that the core motor phenotype and axonal pathology of HSPs are recapitulated in mice lacking the HSP-associated gene Reep1. REEP1 is shown to regulate ER structure in motor cortex neurons. The Reep1 knockout mouse should be a very useful model in which to study the mechanisms of progressive axon loss in HSPs and other disorders. PMID:24051371

  3. Paraplegia and quadriplegia: special considerations during pregnancy and labor and delivery.

    PubMed

    Greenspoon, J S; Paul, R H

    1986-10-01

    Patients with spinal cord injury resulting in paraplegia or quadriplegia increasingly desire to bear children. Management by a health care team attentive to the special problems that may complicate pregnancy offers the best chance for a successful pregnancy outcome. Life-threatening autonomic hyperreflexia may occur in patients with lesions above the T5-6 level. Precautions should be taken to avoid an unsupervised delivery. Vaginal delivery is appropriate unless there is an obstetric indication for cesarean section. Surveillance for urinary tract infection, anemia, and skin ulcers is advisable.

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

    PubMed Central

    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. PMID:28377856

  5. TFG associated hereditary spastic paraplegia: an addition to the phenotypic spectrum.

    PubMed

    Tariq, Huma; Naz, Sadaf

    2017-01-25

    Hereditary spastic paraplegias (HSPs) constitute movement disorders with extreme lower limb spasticity caused by axonopathies of the upper motor neurons. We describe two siblings affected with a recessive form of movement disorder. Whole-exome sequencing revealed a homozygous missense mutation c.64 C>T (p.Arg22Trp) in TFG as cause of the disorder. Comparison of the phenotype of the patients of this study, with that reported previously, revealed differences in the severity of the disorder as well as new clinical findings. These include presence of clonus, undeveloped speech, and sleep disturbances. Our findings extend the phenotypic spectrum associated with the TFG mutations in HSP.

  6. Powered Lower-Limb Exoskeletons to Restore Gait for Individuals with Paraplegia – a Review

    PubMed Central

    Chang, Sarah R.; Kobetic, Rudi; Audu, Musa L.; Quinn, Roger D.; Triolo, Ronald J.

    2016-01-01

    Individuals with paraplegia due to spinal cord injury rank restoration of walking high on the list of priorities to improving their quality of life. Powered lower-limb exoskeleton technology provides the ability to restore standing up, sitting down, and walking movements for individuals with paraplegia. The robotic exoskeletons generally have electrical motors located at the hip and knee joint centers, which move the wearers' lower limbs through the appropriate range of motion for gait according to control systems using either trajectory control or impedance control. Users of exoskeletons are able to walk at average gait speeds of 0.26 m/s and distances ranging between 121-171 m. However, the achieved gait speeds and distances fall short of those required for full community ambulation (0.8 m/s and at least 230 m), restricting use of the devices to limited community use with stand-by assist or supervised rehabilitation settings. Improvement in the gait speed and distance may be achievable by combining a specially designed powered exoskeleton with neuromuscular stimulation technologies resulting in a hybrid system that fully engages the user and achieves the necessary requirements to ambulate in the community environment with benefits of muscle contraction. PMID:28004009

  7. Powered Lower-Limb Exoskeletons to Restore Gait for Individuals with Paraplegia - a Review.

    PubMed

    Chang, Sarah R; Kobetic, Rudi; Audu, Musa L; Quinn, Roger D; Triolo, Ronald J

    2015-01-01

    Individuals with paraplegia due to spinal cord injury rank restoration of walking high on the list of priorities to improving their quality of life. Powered lower-limb exoskeleton technology provides the ability to restore standing up, sitting down, and walking movements for individuals with paraplegia. The robotic exoskeletons generally have electrical motors located at the hip and knee joint centers, which move the wearers' lower limbs through the appropriate range of motion for gait according to control systems using either trajectory control or impedance control. Users of exoskeletons are able to walk at average gait speeds of 0.26 m/s and distances ranging between 121-171 m. However, the achieved gait speeds and distances fall short of those required for full community ambulation (0.8 m/s and at least 230 m), restricting use of the devices to limited community use with stand-by assist or supervised rehabilitation settings. Improvement in the gait speed and distance may be achievable by combining a specially designed powered exoskeleton with neuromuscular stimulation technologies resulting in a hybrid system that fully engages the user and achieves the necessary requirements to ambulate in the community environment with benefits of muscle contraction.

  8. 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.

  9. Bladder and rectal incontinence without paraplegia or paraparesis after endovascular aneurysm repair.

    PubMed

    Nishioka, Naritomo; Kurimoto, Yoshihiko; Maruyama, Ryushi; Ujihira, Kosuke; Iba, Yutaka; Hatta, Eiichiro; Yamada, Akira; Nakanishi, Katsuhiko

    2016-12-01

    Spinal cord ischemia is a well-known potential complication of endovascular aneurysm repair (EVAR), and it is usually manifested by paraplegia or paraparesis. We describe a case in which spinal cord ischemia after EVAR presented by isolated bladder and rectal incontinence without other neurological deficits. A 63-year-old woman presented with intermittent claudication secondary to an infrarenal abdominal aortic aneurysm (AAA), and a left common iliac artery obstruction, for which she underwent EVAR using an aorto-uniiliac (AUI) device and ilio-femoral artery bypass. On postoperative day 3, she developed urinary and fecal incontinence without signs of paraplegia or paraparesis. Magnetic resonance imaging (MRI) showed a hyper-intense signal in the spinal cord. She received hyperbaric oxygen (HBO) therapy and was discharged after 18 days when her urinary and fecal incontinence were almost resolved. This report suggests that spinal cord ischemia after EVAR for aortoiliac occlusive disease might present as bladder and rectal incontinence without other neurological manifestations.

  10. Effect of increased load on scapular kinematics during manual wheelchair propulsion in individuals with paraplegia and tetraplegia.

    PubMed

    Raina, Shashank; McNitt-Gray, Jill L; Mulroy, Sara; Requejo, Philip S

    2012-04-01

    Repetitive loading of the upper extremity musculature during activities like wheelchair propulsion can lead to fatigue of surrounding musculature causing irregular segment kinematics. The goal of this study was to determine the effect of increase in load on the kinematics of the scapula in users with paraplegia and tetraplegia. Data were collected on 18 participants (11 with paraplegia and 7 with tetraplegia) using an electromagnetic motion tracking system (100Hz) and force sensing pushrim (200Hz). The participants propelled under no load and loaded conditions at their customary propulsion velocity. On average a 60N increase in force was elicited with the experimental protocol. Users with tetraplegia showed significant increases (p<.05) in the rate of change of scapular angles in the upward/downward rotation and the retraction/protraction direction under the loaded conditions, whereas users with paraplegia only showed difference in the retraction/protraction rotation direction. Overall both user populations moved towards position of increased downward rotation, anterior tilt and protraction with increase in load hence increasing the risk of impingement. This experiment adds depth to our understanding of dynamic scapular kinematics during wheelchair propulsion under different loading conditions and differences in scapular control between users with paraplegia and tetraplegia.

  11. 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…

  12. A Pilot Study To Assess the Relationships among Coping, Self-Efficacy and Functional Improvement in Men with Paraplegia.

    ERIC Educational Resources Information Center

    Lou, M. F.; And Others

    1997-01-01

    A study of four men with paraplegia admitted to a rehabilitation ward investigated the relationship between levels of coping, self-efficacy, and improvement in rehabilitation performance. The subjects using more coping strategies had more rehabilitation improvement after the first month and those using problem-oriented coping strategies showed…

  13. 33 CFR 279.9 - Objective rationale.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Management actions on existing projects, including leasing and licensing, will also be directed towards the... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment... as a guide for the preparation of detailed development plans and management actions to achieve...

  14. 33 CFR 279.9 - Objective rationale.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Management actions on existing projects, including leasing and licensing, will also be directed towards the... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment... as a guide for the preparation of detailed development plans and management actions to achieve...

  15. 33 CFR 279.9 - Objective rationale.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... Management actions on existing projects, including leasing and licensing, will also be directed towards the... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment... as a guide for the preparation of detailed development plans and management actions to achieve...

  16. 33 CFR 279.9 - Objective rationale.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Management actions on existing projects, including leasing and licensing, will also be directed towards the... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment... as a guide for the preparation of detailed development plans and management actions to achieve...

  17. 33 CFR 279.9 - Objective rationale.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Management actions on existing projects, including leasing and licensing, will also be directed towards the... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment... as a guide for the preparation of detailed development plans and management actions to achieve...

  18. Twelve Major Concept Categories and Their Rationale.

    ERIC Educational Resources Information Center

    Howlett, George

    Twelve concepts utilized by Project I-C-E (Instruction-Curriculum-Environment) for integrating science, social studies, and language arts with environmental studies are elaborated in this booklet. The rationale for each concept is put forth together with a more detailed explanation of the concept. Topics considered include: energy, ecosystems,…

  19. An Expanding Rationale for Cooperative Education.

    ERIC Educational Resources Information Center

    Abitia, Fred

    1985-01-01

    The author discusses cooperative education: how it is viewed by private enterprise and where it fits into higher education's framework. The cooperative education program at California Polytechnic State University is examined: faculty responsibility, rationale for the program's existence, and reasons for the program's importance. (CT)

  20. 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.

  1. Rationale for the Perceptual Analysis Kindergarten Test.

    ERIC Educational Resources Information Center

    Pender, Robert M.

    The Perceptual Analysis Kindergarten Test is based on the rationale or thesis that learning is hierarchical. The test is used to help determine the level of the child in the hierarchy so that a remedial program can be devised to bring the child up to the level where he can develop the associative conceptualization required to be able to learn in…

  2. School Choice and Educational Opportunity: Rationales, Outcomes and Racial Disparities

    ERIC Educational Resources Information Center

    Ben-Porath, Sigal

    2012-01-01

    This article examines the rationales for school choice, and the significance of choice mechanisms for racial disparities in educational opportunities and outcomes. It identifies tensions between liberty-based rationales and equality-based rationales, and surveys research findings on the outcomes of school choice policies, especially with regard to…

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

    SciTech Connect

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T.; Sharp, G.B.; Lange, B.M.; Varvil, T.; Otterud, B.; Leppert, M.

    1995-01-01

    Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.

  4. Mobile spinal enterogenous cyst resulting in intermittent paraplegia in a child: case report.

    PubMed

    Kojima, Satoko; Yoshimura, Junichi; Takao, Tetsuro; Tamura, Tetsuro; Nishiyama, Kenichi; Maruyama, Shigeru; Suda, Masashi; Fujii, Yukihiko

    2016-10-01

    The authors report the case of a mobile spinal enterogenous cyst in a 2-year-old boy, who was admitted to the hospital several times for intermittent paraplegia. Magnetic resonance imaging and CT revealed an isolated cyst in the lumbar spinal canal. The symptoms were caused by transient myelopathy of the conus medullaris and radiculopathy of the cauda equina due to the changing size and location of the cyst. The cyst was surgically extirpated, after which the symptoms resolved. The histopathological diagnosis was enterogenous cyst. The clinical history of intraspinal enterogenous cyst is usually progressive. Mobility and changes in size are rare pathophysiological findings. The authors speculate that the cyst wall did not adhere to the surrounding structures and had ruptured and quickly reformed. Enterogenous cyst should be considered in the differential diagnosis of spinal intradural cysts in children with radiculomyelopathy.

  5. Disseminated mycobacteriosis manifesting as paraplegia in two Parma wallabies (Macropus parma) naturally exposed to Mycobacterium avium.

    PubMed

    Robveille, Cynthia; Albaric, Olivier; Gaide, Nicolas; Abadie, Jérome

    2015-11-01

    Two captive female Parma wallabies (Macropus parma) died after a history of flaccid paraplegia. On postmortem examination, granulomatous and suppurative osteomyelitis involving the left ischium and the lumbosacral region, with meningeal extension at the cauda equina, and caseonecrotic mastitis were the most significant changes. Multiple small nodules in the liver and spleen, and an enlargement of some lymph nodes with central caseous necrosis were also observed. Microscopically, a disseminated granulomatous inflammation with numerous multinucleate giant cells was seen. Numerous acid-fast bacilli were detected in macrophages, in multinucleated giant cells, and free in the central necrosis and suppurative exudate. After culture, polymerase chain reaction assays were carried out to detect the 65-kDa heat shock protein (Hsp65) and insertion sequences (IS)1245 and IS900. The causative agent was identified as Mycobacterium avium subsp. avium.

  6. A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia

    PubMed Central

    Helbig, Katherine L.; Hedrich, Ulrike B.S.; Shinde, Deepali N.; Krey, Ilona; Teichmann, Anne‐Christin; Hentschel, Julia; Schubert, Julian; Chamberlin, Adam C.; Huether, Robert; Lu, Hsiao‐Mei; Alcaraz, Wendy A.; Tang, Sha; Jungbluth, Chelsy; Dugan, Sarah L.; Vainionpää, Leena; Karle, Kathrin N.; Synofzik, Matthis; Schöls, Ludger; Schüle, Rebecca; Lehesjoki, Anna‐Elina; Helbig, Ingo; Lerche, Holger

    2016-01-01

    The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage‐gated K+‐channel, KV1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow‐up analysis of > 2,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two‐electrode voltage‐clamp recordings of Xenopus laevis oocytes expressing mutant KV1.2 channels showed loss of function with a dominant‐negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. Ann Neurol 2016 PMID:27543892

  7. Mapping of a complicated familial spastic paraplegia to locus SPG4 on chromosome 2p.

    PubMed Central

    Heinzlef, O; Paternotte, C; Mahieux, F; Prud'homme, J F; Dien, J; Madigand, M; Pouget, J; Weissenbach, J; Roullet, E; Hazan, J

    1998-01-01

    Autosomal dominant familial spastic paraplegia (AD-FSP) is a degenerative disorder of the central motor system characterised by progressive spasticity of the lower limbs. AD-FSP has been divided into pure and complicated forms. Pure AD-FSP is genetically heterogeneous; three loci have been mapped to chromosomes 14q (SPG3), 2p (SPG4), and 15q (SPG6), whereas no loci responsible for complicated forms have been identified to date. Here we report linkage to the SPG4 locus in a three generation family with AD-FSP complicated by dementia and epilepsy. Assuming that both forms of AD-FSP are caused by mutations involving the same FSP gene, analysis of recombination events in this family positions the SPG4 gene within a 0 cM interval flanked by loci D2S2255 and D2S2347. PMID:9507385

  8. Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement.

    PubMed

    Hotchkiss, Leslie; Donkervoort, Sandra; Leach, Meganne E; Mohassel, Payam; Bharucha-Goebel, Diana X; Bradley, Nathaniel; Nguyen, David; Hu, Ying; Gurgel-Giannetti, Juliana; Bönnemann, Carsten G

    2016-08-01

    Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A.

  9. 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

  10. Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia

    PubMed Central

    Gan-Or, Ziv; Bouslam, Naima; Birouk, Nazha; Lissouba, Alexandra; Chambers, Daniel B.; Vérièpe, Julie; Androschuck, Alaura; Laurent, Sandra B.; Rochefort, Daniel; Spiegelman, Dan; Dionne-Laporte, Alexandre; Szuto, Anna; Liao, Meijiang; Figlewicz, Denise A.; Bouhouche, Ahmed; Benomar, Ali; Yahyaoui, Mohamed; Ouazzani, Reda; Yoon, Grace; Dupré, Nicolas; Suchowersky, Oksana; Bolduc, Francois V.; Parker, J. Alex; Dion, Patrick A.; Drapeau, Pierre; Rouleau, Guy A.; Bencheikh, Bouchra Ouled Amar

    2016-01-01

    Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms. PMID:27153400

  11. The Extended Posterior Circumferential Decompression Technique in the Management of Tubercular Spondylitis with and without Paraplegia

    PubMed Central

    Rathinavelu, Barani; Krishnan, Venkatesh; Amritanand, Rohit; Sundararaj, Gabriel David

    2014-01-01

    Study Design Retrospective clinical series. Purpose To study the clinical, functional and radiological results of patients with tuberculous spondylitis with and without paraplegia, treated surgically using the "Extended Posterior Circumferential Decompression (EPCD)" technique. Overview of Literature With the increasing possibility of addressing all three columns by a single approach, posterior and posterolateral approaches are gaining acceptance. A single exposure for cases with neurological deficit and kyphotic deformity requiring circumferential decompression, anterior column reconstruction and posterior instrumentation is helpful. Methods Forty-one patients with dorsal/dorsolumbar/lumbar tubercular spondylitis who were operated using the EPCD approach between 2006 to 2009 were included. Postoperatively, patients were started on nine-month anti-tuberculous treatment. They were serially followed up to thirty-six months and both clinical measures (including pain, neurological status and ambulatory status) and radiological measures (including kyphotic angle correction, loss of correction and healing status) were used for assessment. Results Disease-healing with bony fusion (interbody fusion) was seen in 97.5% of cases. Average deformity (kyphosis) correction was 54.6% in dorsal spine and 207.3% in lumbar spine. Corresponding loss of correction was 3.6 degrees in dorsal spine and 1.9 degrees in the lumbar spine. Neurological recovery in Frankel B and C paraplegia was 85.7% and 62.5%, respectively. Conclusions The EPCD approach permits all the advantages of a single or dual session anterior and posterior surgery, with significant benefits in terms of decreased operative time, reduced hospital stay and better kyphotic angle correction. PMID:25558312

  12. 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.

  13. Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study

    PubMed Central

    Martinuzzi, Andrea; Montanaro, Domenico; Vavla, Marinela; Paparella, Gabriella; Bonanni, Paolo; Musumeci, Olimpia; Brighina, Erika; Hlavata, Hana; Rossi, Giuseppe; Aghakhanyan, Gayane; Martino, Nicola; Baratto, Alessandra; D’Angelo, Maria Grazia; Peruch, Francesca; Fantin, Marianna; Arnoldi, Alessia; Citterio, Andrea; Vantaggiato, Chiara; Rizzo, Vincenzo; Toscano, Antonio; Bresolin, Nereo; Bassi, Maria Teresa

    2016-01-01

    Background Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (“pure” forms). The involvement of other components of the central nervous system or of other systems is described in the “complicate” forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. Methods We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Results Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The “complicated” forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. Conclusion We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel

  14. Progressive paraplegia caused by recurrence of mantle-cell lymphoma with atypical spinal magnetic resonance imaging features.

    PubMed

    Yamane, Hiromichi; Ochi, Nobuaki; Yamagishi, Tomoko; Takigawa, Nagio; Maeda, Yoshinobu

    2015-01-01

    We describe a case of paraplegia, which had progressed rapidly in a 60-year-old Japanese man with mantle-cell lymphoma. (MCL). He admitted to our hospital due to lumbago and progressive muscle weakness of bilateral lower thighs lasting for 1. month, while he had the history of the systemic chemotherapy for MCL since 10 months. Magnetic resonance imaging. (MRI) revealed a wide-spreading intradural tumor situated in the spinal canal from L1 to L5 with an intervertebral slipped disk as the only site of recurrence. Laminectomy followed by salvage chemotherapy led disappearance of lumbago and paraplegia of the bilateral lower extremities. Although wide-spreading tumor formation in spinal canal without other involvement sites is very rare in MCL, physicians should be aware of such patterns of central nervous system. (CNS) relapse for the early diagnosis and adequate selection of treatment modality.

  15. Disturbed Mental Imagery of Affected Body-Parts in Patients with Hysterical Conversion Paraplegia Correlates with Pathological Limbic Activity

    PubMed Central

    Saj, Arnaud; Raz, Noa; Levin, Netta; Ben-Hur, Tamir; Arzy, Shahar

    2014-01-01

    Patients with conversion disorder generally suffer from a severe neurological deficit which cannot be attributed to a structural neurological damage. In two patients with acute conversion paraplegia, investigation with functional magnetic resonance imaging (fMRI) showed that the insular cortex, a limbic-related cortex involved in body-representation and subjective emotional experience, was activated not only during attempt to move the paralytic body-parts, but also during mental imagery of their movements. In addition, mental rotation of affected body-parts was found to be disturbed, as compared to unaffected body parts or external objects. fMRI during mental rotation of the paralytic body-part showed an activation of another limbic related region, the anterior cingulate cortex. These data suggest that conversion paraplegia is associated with pathological activity in limbic structures involved in body representation and a deficit in mental processing of the affected body-parts. PMID:24961768

  16. Illuminating Rationale and Uses for Light Therapy

    PubMed Central

    Shirani, Afshin; St. Louis, Erik K.

    2009-01-01

    Light therapy is increasingly applied in a variety of sleep medicine and psychiatric conditions including circadian rhythm sleep disorders, seasonal affective disorder, and dementia. This article reviews the neural underpinnings of circadian neurobiology crucial for understanding the influence of light therapy on brain function, common mood and sleep disorders in which light therapy may be effectively used, and applications of light therapy in clinical practice. Citation: Shirani A; St. Louis EK. Illuminating rationale and uses for light therapy. J Clin Sleep Med 2009;5(2):155-163. PMID:19968050

  17. 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.

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

    PubMed

    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; Durr, Alexandra

    2012-10-01

    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

  19. 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.

  20. A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts neurofilament transport

    PubMed Central

    2010-01-01

    Background Hereditary spastic paraplegias are a group of neurological disorders characterized by progressive distal degeneration of the longest ascending and descending axons in the spinal cord, leading to lower limb spasticity and weakness. One of the dominantly inherited forms of this disease (spastic gait type 10, or SPG10) is caused by point mutations in kinesin-1A (also known as KIF5A), which is thought to be an anterograde motor for neurofilaments. Results We investigated the effect of an SPG10 mutation in kinesin-1A (N256S-kinesin-1A) on neurofilament transport in cultured mouse cortical neurons using live-cell fluorescent imaging. N256S-kinesin-1A decreased both anterograde and retrograde neurofilament transport flux by decreasing the frequency of anterograde and retrograde movements. Anterograde velocity was not affected, whereas retrograde velocity actually increased. Conclusions These data reveal subtle complexities to the functional interdependence of the anterograde and retrograde neurofilament motors and they also raise the possibility that anterograde and retrograde neurofilament transport may be disrupted in patients with SPG10. PMID:21087519

  1. Severe adhesive arachnoiditis resulting in progressive paraplegia following obstetric spinal anaesthesia: a case report and review.

    PubMed

    Killeen, T; Kamat, A; Walsh, D; Parker, A; Aliashkevich, A

    2012-12-01

    A 27-year-old woman developed severe adhesive arachnoiditis after an obstetric spinal anaesthetic with bupivacaine and fentanyl, complicated by back pain and headache. No other precipitating cause could be identified. She presented one week postpartum with communicating hydrocephalus and syringomyelia and underwent ventriculoperitoneal shunting and foramen magnum decompression. Two months later, she developed rapid, progressive paraplegia and sphincter dysfunction. Attempted treatments included exploratory laminectomy, external drainage of the syrinx and intravenous steroids, but these were unsuccessful and the patient remains significantly disabled 21 months later. We discuss the pathophysiology of adhesive arachnoiditis following central neuraxial anaesthesia and possible causative factors, including contamination of the injectate, intrathecal blood and local anaesthetic neurotoxicity, with reference to other published cases. In the absence of more conclusive data, practitioners of central neuraxial anaesthesia can only continue to ensure meticulous, aseptic, atraumatic technique and avoid all potential sources of contamination. It seems appropriate to discuss with patients the possibility of delayed, permanent neurological deficit while taking informed consent.

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

    SciTech Connect

    Dube, M.P.; Kibar, Z.; Rouleau, G.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. 19 refs., 1 fig., 1 tab.

  3. Autosomal dominant familial spastic paraplegia; Linkage analysis and evidence for linkage to chromosome 2p

    SciTech Connect

    Figlewicz, D.A.; Dube, M.P.; Rouleau, G.A.

    1994-09-01

    Familial spastic paraplegia (FSP) is a degenerative disorder of the motor system characterized by progressive weakness and spasticity of the lower limbs. Little is known about the pathophysiology of this disorder. FSP can be inherited as an autosomal dominant (AD), autosomal recessive, or X-linked trait. We have undertaken linkage analysis for a group of 36 AD FSP families from which we have collected blood samples from 427 individuals, including 148 affected individuals. Typing of polymorphic markers has allowed us to exclude more than 50% of the genome. Recently, linkage for AD FSP to a locus on chromosome 14q was reported. Our AD FSP kindreds were tested for linkage to markers spanning the 20 cM region between D14S69 and D14S66; however, we were not able to establish linkage for any of our families to chromosome 14. Lod scores suggestive of linkage for some AD FSP kindreds have been obtained for markers on chromosome 2p. We have tested seven polymorphic markers spanning the region between D2S405 and D2S177. Our highest aggregate lod score, including all families tested, was obtained at the locus D2S352: 2.4 at 20 cM. Results from HOMOG analysis for linkage heterogeneity will be reported.

  4. Optimal control of FES-assisted standing up in paraplegia using genetic algorithms.

    PubMed

    Davoodi, R; Andrews, B J

    1999-11-01

    A practical system for Functional Electrical Stimulation (FES) assisted standing up in paraplegia should involve only a minimum of manual set up and tuning. An improved tuning method, using a genetic algorithm (GA) is proposed and demonstrated using computer simulation. Specifically, the GA adjusts the parameters of fuzzy logic (FL) and gain-scheduling proportional integral derivative (GS-PID) controllers that electrically stimulate the hip and knee musculature during the sit-stand maneuver. These new GA designed controllers were found to be effective in coordinating volitional and FES control according to formulated criteria. The latter was based on the deviations from a desired trajectory of the knee and hip joints and the magnitude of the voluntary upper body forces. The magnitude of the average arm forces were slightly higher when compared with the open-loop maximal stimulation of the hip and knee musculature; however, the terminal knee velocities were significantly reduced to less than 10 degrees /s. For practical implementation, the number of trials required to optimize the FL and GS-PID controllers can be reduced by a proposed pre-training procedure using a computer model scaled to the individual. The GA designed controllers remain near optimal provided the model-subject mismatch is small.

  5. PMCA4 (ATP2B4) Mutation in Familial Spastic Paraplegia

    PubMed Central

    Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2014-01-01

    Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP. PMID:25119969

  6. PMCA4 (ATP2B4) mutation in familial spastic paraplegia.

    PubMed

    Li, Miaoxin; Ho, Philip Wing-Lok; Pang, Shirley Yin-Yu; Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2014-01-01

    Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP.

  7. Revisiting genotype-phenotype overlap in neurogenetics: triplet-repeat expansions mimicking spastic paraplegias.

    PubMed

    Bettencourt, Conceição; Quintáns, Beatriz; Ros, Raquel; Ampuero, Israel; Yáñez, Zuleima; Pascual, Samuel Ignacio; de Yébenes, Justo García; Sobrido, María-Jesús

    2012-09-01

    Hereditary spastic paraplegias (HSPs) constitute a heterogeneous group of neurological disorders, characterized primarily by progressive spasticity and weakness of the lower limbs. HSPs are caused by mutations in multiple genes (at least 48 loci and 28 causative genes). The clinical spectrum of HSPs is wide and important differences have been reported between patients with distinct mutations in the same gene, or even between different family members bearing the same mutation. Many patients with HSP present clinical deficits related to the involvement of neuronal systems other than corticospinal tracts, namely, peripheral nerves, sensory, or cerebellar pathways. These cases may be difficult to differentiate from other neurological diseases (e.g., hereditary ataxias), also genetically and clinically heterogeneous. As an illustration of how overlapping this genotype-phenotype relationship is, and the difficulties that it brings upon the development of neurogenetic algorithms and databases, we review the main clinical and genetic features of HSPs, and summarize reports on cases of triplet-repeat spinocerebellar ataxias that can mimic HSP phenotypes. This complex scenario makes the necessity of high-quality, curated mutation databases even more urgent, in order to develop adequate diagnostic guidelines, correct interpretation of genetic testing, and appropriate genetic counseling.

  8. 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

    2015-01-01

    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 more than 50 % of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, while 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

  9. Towards Parameters and Protocols to Recommend FES-Cycling in Cases of Paraplegia: A Preliminary Report

    PubMed Central

    Guimarães, Juliana Araujo; da Fonseca, Lucas Oliveira; dos Santos-Couto-Paz, Clarissa Cardoso; Bó, Antônio Padilha Lanari; Fattal, Charles; Azevedo-Coste, Christine; Fachin-Martins, Emerson

    2016-01-01

    Functional Electrical Stimulation assisted cycling (FES-Cycling) is increasingly becoming an alternative option recommended to people with spinal cord injury struggling with paraplegia and interested in practicing sports. In order to propose preconditions to guide FES-Cycling recommendation, we aimed to investigate some features and their potential relationships with responsiveness to Neuromuscular Electrical Stimulation (NMES). Fourteen volunteers attended a public recruitment forum to be assessed about their responsiveness through the 16-sessions of NMES. Volunteers were separated in two groups (responsive and non-responsive to NMES) which were investigated in the light of some personal, clinical, structural and functional features. Fifty seven percent of the initial sample responded to electrical stimulation with a visual contraction. This responsive group was predominantly composed by subjects presenting traumatic spinal cord injuries above T12 vertebral level. Only two subjects became responsive at the 3rd and 16th sessions. Among the observed features, the etiology and level of injuries seems to be more associated to responsiveness. Our observations seem to indicate that subjects with traumatic spinal cord injury above T12 level were the best potential candidates for FES-cycling. PMID:27990239

  10. Coexistence of Factor VII Deficiency and Hereditary Spastic Paraplegia in Two Siblings

    PubMed Central

    De la Corte-Rodriguez, Hortensia; Alvarez-Roman, M. Teresa; Hernandez-Moreno, Ana L.

    2016-01-01

    We present the case of two patients aged 12 years and 7 years who were referred to our hospital for factor VII deficiency inherited in an autosomal recessive pattern, who had suffered from previous multiple joint haemarthroses. They presented with fine motor symptoms and difficulty in walking. During physical examination we observed neurological symptoms (general hypotonia, muscular hypotrophy, exaggerated tendon reflexes, pes cavus, and spastic gait). Given that the symptoms were not justified by the deficiency of coagulation factor VII and on suspicion of hereditary spastic paraplegia (HSP), tests were carried out. Findings from the tests confirmed the diagnosis of HSP (axonal degeneration of the central motor pathway and pyramidal tracts), further complicated by mixed neuropathy. This disease was also inherited in an autosomal recessive pattern with no direct genetic association with factor VII deficiency. Neurological symptoms had gone unnoticed due to a history of multiple joint haemarthrosis; musculoskeletal examination led to a satisfactory differential diagnosis. Haematological prophylaxis was commenced with rFVIIa at 30 mcg/kg, three days per week. A rehabilitation programme was prescribed so that the patient could remain independent for as long as possible, based on orthosis, physiotherapy, and occupational therapy. Response to treatment is currently satisfactory and no new bleeding has presented. As far as we are aware, the coexistence of these two diseases (factor VII deficiency and HSP) has not been previously reported in the literature. PMID:28018685

  11. 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

  12. Total knee arthroplasty in patient with paraplegia after spinal cord injury.

    PubMed

    Zietek, P; Dobiecki, K

    2015-01-01

    The clinical management of paraplegic patients is more complex than in able-bodied subjects. Spinal cord injury (SCI) affects younger, active people more often than the elderly during high-energy fall or traffic accidents. In order to return to work after suffering an SCI, patients need to regain their functional independence, especially their ability to drive. The literature lacks strong evidence addressing the surgical solutions in severe knee arthrosis in paralyzed patients after SCI. We present a favourable outcome of total knee arthroplasty (TKA) of a stiff knee in extension in a man with T12 grade C paraplegia after SCI. We describe an effective rehabilitation protocol after knee arthroplasty in patient with damage to the spinal cord. Several factors should be taken into account before performing surgery: 1. ability of regaining some of spinal cord locomotor function through intensive gait rehabilitation in SCI patients, 2. presence of muscle imbalance and knee contractures combined with a risk of bone fracture resulting from intensive postoperative rehabilitation, 3. the impaired microvasculature of the skin and subcutaneous tissues and increased risk of occlusion occurrence of the capillaries and small vessels of the leg, 4. higher prevalence of secondary infections via urinary entry sites in patients after SCI, 5. patient's strong determination and willingness to undergo the arthroplasty procedure. TKA might be considered in selected paralyzed patients after SCI, especially in those with severe arthrosis as well as significant knee contractures. Our study reveals the advantage of performing TKA in improving functional state in patients with cord injury.

  13. 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

  14. Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia

    PubMed Central

    Pirozzi, Marinella; Quattrini, Angelo; Andolfi, Gennaro; Dina, Giorgia; Malaguti, Maria Chiara; Auricchio, Alberto; Rugarli, Elena I.

    2006-01-01

    Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus–mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves. PMID:16357941

  15. Complete prewetting

    NASA Astrophysics Data System (ADS)

    Yatsyshin, P.; Parry, A. O.; Kalliadasis, S.

    2016-07-01

    We study continuous interfacial transitions, analagous to two-dimensional complete wetting, associated with the first-order prewetting line, which can occur on steps, patterned walls, grooves and wedges, and which are sensitive to both the range of the intermolecular forces and interfacial fluctuation effects. These transitions compete with wetting, filling and condensation producing very rich phase diagrams even for relatively simple prototypical geometries. Using microscopic classical density functional theory to model systems with realistic Lennard-Jones fluid-fluid and fluid-substrate intermolecular potentials, we compute mean-field fluid density profiles, adsorption isotherms and phase diagrams for a variety of confining geometries.

  16. Oral pulsatile delivery: rationale and chronopharmaceutical formulations.

    PubMed

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Loreti, Giulia; Gazzaniga, Andrea

    2010-10-15

    Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies.

  17. Education and the Rationale of Cost-Benefit Analysis

    ERIC Educational Resources Information Center

    Gilead, Tal

    2014-01-01

    It is increasingly maintained that cost-benefit analysis (CBA) should play a greater role in educational policy-making. This article critically examines the rationale guiding CBA and its compatibility to educational settings. Drawing on philosophical discussions, it argues that the rationale guiding CBA has some fundamental limitations that render…

  18. A Rationale for Special Education in Catholic Schools

    ERIC Educational Resources Information Center

    Long, Thomas J.; Schuttloffel, Merylann J.

    2006-01-01

    Debates about inclusive education for students with special needs challenge Catholic educators to develop a rationale consistent with Catholic theology and Church teaching. Guided by the rationale, arguments are made for the role Catholic schools, seminaries, and Catholic higher education should contribute to realize an inclusive Church.…

  19. 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…

  20. "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…

  1. 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.

  2. 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

  3. Linkage of the late onset autosomal dominant familial spastic paraplegia (DFSPII) to chromosome 2p markers

    SciTech Connect

    Hentati, A.; Wasserman, B.; Siddique, T.

    1994-09-01

    Pure familial spastic paraplegias (FSP) is a neurodegenerative disease characterized by spasticity of lower limbs. FSP in inherited as an autosomal dominant (DFSP) or an autosomal recessive (RFSP) trait. DFSP has been classified into early onset (DFSPI) and late onset (DFSPII) based on the mean age of onset in families. A locus for RFSP has been mapped to chromosome 8, while a locus for DFSPI has been mapped to chromosome 14q. Genetic locus heterogeneity was observed in both of these forms. The location of DFSPII locus (or loci) is unknown. We collected DNA samples from 81 individuals including 26 affecteds from three DFSPII families (9998, 840, 581). The mean age of onset of systems was 26.5, 42.5, and 35.2 years, respectively. We first tested 156 DNA markers distributed throughout the human 22 autosomes with family 9998 and positive lod scores were obtained with chromosome 2p markers D2S174 (Z({theta})=2.93 at {theta}=0.00), D2S146 (Z({theta})=1.03 at {theta}=0.00) and D2S177 (Z({theta})=1.04 at {theta}=0.00). Analysis of the 2 additional families confirmed the linkage with a peak lod score of Z({theta})=4.62 at {theta}=0.105 with D2S174. The multipoint linkage analysis using the map D2S175-10cM-D2S174-14cM-D2DS177 suggested that the DFSPII locus most likely maps between D2S174 and D2S177 with Z({theta})=6.11. There was no evidence in our data supporting genetic locus heterogeneity for the DFSPII.

  4. Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia.

    PubMed

    Garaci, Francesco; Toschi, Nicola; Lanzafame, Simona; Meschini, Alessandro; Bertini, Enrico; Simonetti, Giovanni; Santorelli, Filippo Maria; Guerrisi, Maria; Floris, Roberto

    2014-04-01

    The aim of this study was to identify potential diagnostic markers of Hereditary Spastic Paraplegia (HSP). We investigated the white matter features of spastic gait (SPG)11- and SPG4-linked HSP, using diffusion tensor imaging performed with a 3-Tesla (3T) scanner. We examined four patients with SPG11 mutations, three with SPG4 mutations, and 26 healthy controls. We obtained maps of fractional anisotropy (FA) and mean diffusivity (MD), which we analyzed through both region of interest -based approach and tract-based spatial statistics (TBSS). Compared with healthy controls, SPG11 patients presented increased MD and decreased FA in the semioval centers, frontal and peritrigonal white matter, posterior limb of the internal capsule, and throughout the corpus callosum. Similar alterations were seen in the SPG4 patients at the levels of the semioval centers, the posterior limb of the internal capsule, the left cerebral pedicle, the genu and trunk of the corpus callosum, and the peritrigonal white matter on the left. No MD or FA alterations were observed in the cerebellar white matter. In a direct comparison, white matter alterations were more pronounced and widespread in HSP-SPG11 than in HSP-SPG4 patients. Joint TBSS analysis of all three groups confirmed significant widespread alterations of FA and MD values in the supratentorial white matter. This noninvasive study documented the presence of altered diffusivity in white matter in both forms of HSP, which could represent an important diagnostic marker of HSP. The association of reduced FA and increased MD in this patient population supports the interpretation of HPG as a neurodegenerative disorder.

  5. Identification and Expression Analysis of Spastin Gene Mutations in Hereditary Spastic Paraplegia

    PubMed Central

    Svenson, Ingrid K.; Ashley-Koch, Allison E.; Gaskell, P. Craig; Riney, Travis J.; Cumming, W. J. Ken; Kingston, Helen M.; Hogan, Edward L.; Boustany, Rose-Mary N.; Vance, Jeffery M.; Nance, Martha A.; Pericak-Vance, Margaret A.; Marchuk, Douglas A.

    2001-01-01

    Pure hereditary spastic paraplegia (SPG) type 4 is the most common form of autosomal dominant hereditary SPG, a neurodegenerative disease characterized primarily by hyperreflexia and progressive spasticity of the lower limbs. It is caused by mutations in the gene encoding spastin, a member of the AAA family of ATPases. We have screened the spastin gene for mutations in 15 families consistent with linkage to the spastin gene locus, SPG4, and have identified 11 mutations, 10 of which are novel. Five of the mutations identified are in noninvariant splice-junction sequences. Reverse transcription–PCR analysis of mRNA from patients shows that each of these five mutations results in aberrant splicing. One mutation was found to be “leaky,” or partially penetrant; that is, the mutant allele produced both mutant (skipped exon) and wild-type (full-length) transcripts. This phenomenon was reproduced in in vitro splicing experiments, with a minigene splicing-vector construct only in the context of the endogenous splice junctions flanking the splice junctions of the skipped exon. In the absence of endogenous splice junctions, only mutant transcript was detected. The existence of at least one leaky mutation suggests that relatively small differences in the level of wild-type spastin expression can have significant functional consequences. This may account, at least in part, for the wide ranges in age at onset, symptom severity, and rate of symptom progression that have been reported to occur both among and within families with SPG linked to SPG4. In addition, these results suggest caution in the interpretation of data solely obtained with minigene constructs to study the effects of sequence variation on splicing. The lack of full genomic sequence context in these constructs can mask important functional consequences of the mutation. PMID:11309678

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

    SciTech Connect

    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 American 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.

  7. 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

  8. Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice

    PubMed Central

    Nielsen, Marit N.; Hansen, Jakob; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; West, Mark; Corydon, Thomas J.; Gregersen, Niels; Bross, Peter

    2010-01-01

    The mitochondrial Hsp60 chaperonin plays an important role in sustaining cellular viability. Its dysfunction is related to inherited forms of the human diseases spastic paraplegia and hypomyelinating leukodystrophy. However, it is unknown whether the requirement for Hsp60 is neuron specific or whether a complete loss of the protein will impair mammalian development and postnatal survival. In this study, we describe the generation and characterization of a mutant mouse line bearing an inactivating gene-trap insertion in the Hspd1 gene encoding Hsp60. We found that heterozygous mice were born at the expected ratio compared to wild-type mice and displayed no obvious phenotype deficits. Using quantitative reverse transcription PCR, we found significantly decreased levels of the Hspd1 transcript in all of the tissues examined, demonstrating that the inactivation of the Hspd1 gene is efficient. By Western blot analysis, we found that the amount of Hsp60 protein, compared to either cytosolic tubulin or mitochondrial voltage-dependent anion-selective channel protein 1/porin, was decreased as well. The expression of the nearby Hspe1 gene, which encodes the Hsp10 co-chaperonin, was concomitantly down regulated in the liver, and the protein levels in all tissues except the brain were reduced. Homozygous Hspd1 mutant embryos, however, died shortly after implantation (day 6.5 to 7.5 of gestation, Theiler stages 9–10). Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice, while reducing the amount of Hsp60 by inactivation of one allele of the gene is compatible with survival to term as well as postnatal life. PMID:20393889

  9. Complete Makeover

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    Released July 23, 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth.

    Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms.

    We finish our look at Mars's dynamic atmosphere with an image of the surface that has been completely modified by the wind. Even the small ridges that remain have been ground down to a cliff-face with a 'tail' of eroded material. The crosshatching shows that the wind regime has remained mainly E/W to ENE/WSW.

    Image information: VIS instrument. Latitude 8.9, Longitude 221 East (139 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip

  10. Opening Minds in Canada: Background and Rationale

    PubMed Central

    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

    2014-01-01

    Objective: To summarize the background and rationale of the approach taken by the Mental Health Commission of Canada’s Opening Minds (OM) Anti-Stigma Initiative. Method: 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. Results: 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. Conclusions: 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. PMID:25565705

  11. 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

  12. 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.

  13. Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia.

    PubMed

    Lu, Xingjiao; Cen, Zhidong; Xie, Fei; Ouyang, Zhiyuan; Zhang, Baorong; Zhao, Guohua; Luo, Wei

    2014-12-15

    Hereditary spastic paraplegia (HSP or SPG) is a group of genetically and clinically heterogeneous neurodegenerative disorders. At least 52 different gene loci have been identified so far, involving autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), and maternal inheritance. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes are responsible for about 50% of pure AD-HSP patients. In this study, SPAST and ATL1 mutations were screened in 36 unrelated HSP patients (17 probands with AD family history and 19 sporadic HSP patients) by direct sequencing and multiplex ligation dependent probe amplification (MLPA). We identified 3 micro-mutations and 2 exon deletions in SPAST gene and 2 micro-mutations in ATL1 gene. Four of five micro-mutations were novel and del. ex. 13-15 in SPAST was not reported previously. In this cohort of Chinese patients with spastic paraplegia, SPAST and ATL1 mutations were found in 5 of 17 HSP probands with AD family history and in 2 of 19 sporadic HSP patients. Four novel micro-mutations and one novel exon deletion were identified, which broadened the mutational spectrum of the genes.

  14. Characterization of Alu and recombination-associated motifs mediating a large homozygous SPG7 gene rearrangement causing hereditary spastic paraplegia.

    PubMed

    López, Eva; Casasnovas, Carlos; Giménez, Javier; Matilla-Dueñas, Antoni; Sánchez, Ivelisse; Volpini, Víctor

    2015-04-01

    Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal recessive hereditary spastic paraplegia (AR-HSP). Although over 77 different mutations have been identified in SPG7 patients, only 9 gross deletions have been reported with only a few of them being fully characterized. Here, we present a detailed description of a large homozygous intragenic SPG7 gene rearrangement involving a 5144-base pair (bp) genomic loss (c. 1450-446_1779 + 746 delinsAAAGTGCT) encompassing exons 11 to 13, identified in a Spanish AR-HSP family. Analysis of the deletion junction sequences revealed that the 5' breakpoint of this SPG7 gene deletion was located within highly homologous Alu sequences where the 3' breakpoint appears to be flanked by the core crossover hotspot instigator (chi)-like sequence (GCTGG). Furthermore, an 8-bp (AAAGTTGCT) conserved sequence at the breakpoint junction was identified, suggesting that the most likely mechanism for the occurrence of this rearrangement is by Alu microhomology and chi-like recombination-associated motif-mediated multiple exon deletion. Our results are consistent with non-allelic homologous recombination and non-homologous end joining in deletion mutagenesis for the generation of rearrangements. This study provides more evidence associating repeated elements as a genetic mechanism underlying neurodegenerative disorders, highlighting their importance in human diseases.

  15. Comparison of Blood Lactate Elimination in Individuals With Paraplegia and Able-Bodied Individuals During Active Recovery From Exhaustive Exercise

    PubMed Central

    Leicht, Christof; Perret, Claudio

    2008-01-01

    Background/Objective: The aim of the present study was to compare blood lactate elimination between individuals with paraplegia (P) and able-bodied (AB) individuals after strenuous arm exercise. Methods: Eight P and 8 AB men (matched for age, height, and weight) participated in this study. Average weekly arm-training volume for P participants (eg, hand bike, wheelchair basketball) and AB participants (eg, swimming, rowing, cross-country skiing) was 4.1 ± 1.6 vs 2.8 ± 0.8 h. A maximal-arm-cranking intensity-graded exercise test to volitional exhaustion was performed by all test participants. Immediately after the exercise test, the participants performed arm cranking for another 30 minutes at a workload of one third of the maximally achieved power output. During this active recovery, mixed-capillary blood samples were taken for lactate analysis. Results: The lactate accumulation constant was significantly higher for P individuals, whereas the lactate elimination constant showed no significant difference between the two groups. Conclusions: Individuals with paraplegia seem to have no disadvantages in lactate elimination after exhaustive arm exercise compared with able-bodied individuals. PMID:18533413

  16. Paraplegia increased cardiac NGF content, sympathetic tonus, and the susceptibility to ischemia-induced ventricular tachycardia in conscious rats

    PubMed Central

    Lujan, Heidi L.; Chen, Ying; DiCarlo, Stephen E.

    2009-01-01

    Midthoracic spinal cord injury is associated with ventricular arrhythmias that are mediated, in part, by enhanced cardiac sympathetic activity. Furthermore, it is well known that sympathetic neurons have a lifelong requirement for nerve growth factor (NGF). NGF is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, we tested the hypothesis that paraplegia is associated with an increased cardiac NGF content, sympathetic tonus, and susceptibility to ischemia-induced ventricular tachyarrhythmias. Intact and paraplegic (6–9 wk posttransection, T5 spinal cord transection) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, and a snare was placed around the left main coronary artery. Following recovery, the susceptibility to ventricular arrhythmias (coronary artery occlusion) was determined in intact and paraplegic rats. In additional groups of matched intact and paraplegic rats, cardiac nerve growth factor content (ELISA) and cardiac sympathetic tonus were determined. Paraplegia, compared with intact, increased cardiac nerve growth factor content (2,146 ± 286 vs. 180 ± 36 pg/ml, P < 0.05) and cardiac sympathetic tonus (154 ± 4 vs. 68 ± 4 beats/min, P < 0.05) and decreased the ventricular arrhythmia threshold (3.6 ± 0.2 vs. 4.9 ± 0.2 min, P < 0.05). Thus altered autonomic behavior increases the susceptibility to ventricular arrhythmias in paraplegic rats. PMID:19286942

  17. 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.

  18. Non-traumatic acute paraplegia associated with a CT-guided needle biopsy in a silicotic nodule: A case report

    PubMed Central

    XU, LIYING; DING, XUN; LIAO, MEIYAN

    2016-01-01

    The present study reports the case of an adult patient with non-traumatic acute paraplegia following a computed tomography (CT)-guided automated cutting needle biopsy (ACNB). Multiple nodules and masses were revealed on performing chest radiography and CT on a 45-year-old man. In order to make a pathological diagnosis, a CT-guided biopsy using an automatic cutting needle was performed. However, 10 min after the biopsy, a weakness of the lower extremities occurred, and the patient collapsed to the ground, albeit with clear consciousness. Spinal magnetic resonance imaging (MRI) performed subsequently revealed no abnormal findings in the spinal cord. An MRI performed 24 h later, however, revealed swelling of the thoracic spinal cord and a high-signal-intensity lesion in T2-weighted images at the level of T7, T8 and T9. The patient subsequently received hyperbaric oxygen therapy for a few days, and rehabilitative treatment over the course of a few weeks. At 6 months following the biopsy, the patient was unable to walk, although the patient could stand for 10 min and defecate independently. Currently, the patient remains active in daily life, in spite of confinement to a wheelchair. The present case study was reported to raise the awareness of the possibility of spinal cord ischemia and acute paraplegia following a CT-guided ACNB of the lungs. The mechanism underlying spinal cord ischemia remains to be fully elucidated, although is thought to be multifactorial, involving air embolism. PMID:26998303

  19. Rationale for tilted implants: FEA considerations and clinical reports

    PubMed Central

    DE VICO, G.; BONINO, M.; SPINELLI, D.; SCHIAVETTI, R.; SANNINO, G.; POZZI, A.; OTTRIA, L.

    2011-01-01

    SUMMARY The prevalence of the elderly population, as well as life expectancy, increased in the final decades of the 20th century, as described in the World Health Organization 2004 Annual Report. The edentulous condition therefore has a negative impact on the oral health–related quality of life. Patients wearing complete dentures for many years infact, and especially in the mandible, are often unsatisfied because of the instability of the prosthesis during speaking and eating. To date dental implant treatment is well documented as a predictable treatment for partial or complete edentulism. On the other hand the rehabilitation of atrophied edentulous arches with endosseous implants (> 10 mm) in the posterior regions is often associated with anatomic problems such as bone resorption, poor bone quality, mandibular canal, and the presence of maxillary sinuses. Different procedures have been proposed to overcome these anatomic limitations. The use of tilted implants parallel to the anterior wall of the maxillary sinus or the mental foramen/inferior alveolar nerve has been proposed as a conservative solution for the treatment of the atrophic edentulous maxilla. Aim of this study was to describe, through a detailed literature review, the clinical and biomechanical rationale for tilting implants and to evaluate the long-term prognosis of immediately loaded full fixed prostheses for the treatment of edentulous patients (#35) with extreme bone atrophy rehabilited with both axial (#70) and tilted (#70) implants from 2008 to 2010. The results of the present study would suggest that this new surgical technique may reduce patient morbidity and extend the indications for immediate loading full fixed rehabilitations. This improves the predictability of treatment goal, allows for a better risk management, and provides more individual information for the patient. These are the most important aspects of this technology, which may contribute to establish higher-quality standards in

  20. The Healthy Communities Study: Its Rationale, Aims, and Approach.

    PubMed

    Arteaga, S Sonia; Loria, Catherine M; Crawford, Patricia B; Fawcett, Stephen B; Fishbein, Howard A; Gregoriou, Maria; John, Lisa V; Kelley, Melinda; Pate, Russell R; Ritchie, Lorrene D; Strauss, Warren J

    2015-10-01

    Communities across the U.S. are implementing programs and policies designed to address the epidemic of childhood obesity. These programs vary widely in their approaches, including the intensity level, duration, funding, target population, and implementation techniques. However, no previous studies have examined these variations and determined how such aspects of community programs and policies are related to childhood obesity outcomes. The Healthy Communities Study is an observational study that is assessing the associations between characteristics of community programs and policies and BMI, nutrition, and physical activity in children. The Healthy Communities Study was funded in 2010, field data collection and medical record abstraction will be completed in 2015, and data cleaning and analyses will be completed by mid-year 2016. One-hundred and thirty communities (defined as a high school catchment area) and approximately 5,000 children in kindergarten through eighth grade and their parents have been recruited from public elementary and middle schools across the country. The study is examining quantitative and qualitative information obtained from community-based initiatives; measures of community characteristics (e.g., school environment); and child and parent measures, including children's physical activity levels and dietary practices and children's and parents' BMI. The Healthy Communities Study employs a complex study design that includes a diverse sample of communities across the country and combines current/cross-sectional and retrospective data (abstracted from children's medical records). This paper describes the rationale for the Healthy Communities Study, the study aims and logic model, and a brief overview of the study design.

  1. Treatment rationale of fractured posterior teeth.

    PubMed

    Silvestri, A R; Singh, I

    1978-11-01

    The four types of fractures most frequently encountered in posterior teeth--obliquely directed complete fractures, vertically directed complete fractures, obliquely directed incomplete fractures, and vertically directed incomplete fractures--have been described. A detailed treatment approach for each type has been presented.

  2. 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

  3. Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.

    PubMed

    Finsterer, Josef; Löscher, Wolfgang; Quasthoff, Stefan; Wanschitz, Julia; Auer-Grumbach, Michaela; Stevanin, Giovanni

    2012-07-15

    Hereditary spastic paraplegia (SPG) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterised by progressive spasticity and weakness of the lower-limbs (pure SPG) and, majoritorian, additional more extensive neurological or non-neurological manifestations (complex or complicated SPG). Pure SPG is characterised by progressive spasticity and weakness of the lower-limbs, and occasionally sensory disturbances or bladder dysfunction. Complex SPGs additionally include cognitive impairment, dementia, epilepsy, extrapyramidal disturbances, cerebellar involvement, retinopathy, optic atrophy, deafness, polyneuropathy, or skin lesions in the absence of coexisting disorders. Nineteen SPGs follow an autosomal-dominant (AD-SPG), 27 an autosomal-recessive (AR-SPG), 5 X-linked (XL-SPG), and one a maternal trait of inheritance. SPGs are due to mutations in genes encoding for proteins involved in the maintenance of corticospinal tract neurons. Among the AD-SPGs, 40-45% of patients carry mutations in the SPAST-gene (SPG4) and 10% in the ATL1-gene (SPG3), while the other 9 genes are more rarely involved (NIPA1 (SPG6), KIAA0196 (SPG8), KIF5A (SPG10), RNT2 (SPG12), SPGD1 (SPG13), BSCL2 (SPG17), REEP1 (SPG31), ZFYVE27 (SPG33, debated), and SLC33A1 (SPG42, debated)). Among the AR-SPGs, ~20% of the patients carry mutations in the KIAA1840 (SPG11) gene whereas the 15 other genes are rarely mutated and account for SPGs in single families yet (CYP7B1 (SPG5), SPG7 (SPG7), ZFYVE26 (SPG15), ERLIN2 (SPG18), SPG20 (SPG20), ACP33 (SPG21), KIF1A (SPG30), FA2H (SPG35), NTE (SPG39), GJA12/GJC2 (SPG44), KIAA0415 (SPG48) and 4 genes encoding for the AP4-complex (SPG47)). Among the XL-SPGs, 3 causative genes have been identified (L1CAM (SPG1), PLP1 (SPG2), and SLC16A2 (SPG22)). The diagnosis of SPGs is based on clinical, instrumental and genetic investigations. Treatment is exclusively symptomatic.

  4. 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

  5. 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

  6. 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.

  7. Rationale-Augmented Convolutional Neural Networks for Text Classification

    PubMed Central

    Zhang, Ye; Marshall, Iain; Wallace, Byron C.

    2016-01-01

    We present a new Convolutional Neural Network (CNN) model for text classification that jointly exploits labels on documents and their constituent sentences. Specifically, we consider scenarios in which annotators explicitly mark sentences (or snippets) that support their overall document categorization, i.e., they provide rationales. Our model exploits such supervision via a hierarchical approach in which each document is represented by a linear combination of the vector representations of its component sentences. We propose a sentence-level convolutional model that estimates the probability that a given sentence is a rationale, and we then scale the contribution of each sentence to the aggregate document representation in proportion to these estimates. Experiments on five classification datasets that have document labels and associated rationales demonstrate that our approach consistently outperforms strong baselines. Moreover, our model naturally provides explanations for its predictions. PMID:28191551

  8. [The medical rationale category and a new epistemology in health].

    PubMed

    do Nascimento, Marilene Cabral; de Barros, Nelson Filice; Nogueira, Maria Inês; Luz, Madel Therezinha

    2013-12-01

    This article is an analytical report on the 20-year trajectory of the 'medical rationale' category that emerged in the early 1990s in the area of Social and Human Sciences in Health in the field of Public Health. Its objective was to study complex and therapeutic medical systems and traditional, complementary and alternative medicines. Based on a critical review of the literature, it presents some aspects of the cultural, political, institutional and social context of its emergence, as well as its main contributions and developments on a theoretical level and on social policies and practices in health. The southern epistemology concept of Boaventura de Sousa Santos is used to reflect upon the contribution of the 'medical rationale' category to the critique of the post-modern scientific rationale and to the creation of a new epistemology in health.

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

    SciTech Connect

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

    1995-05-22

    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 previous 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.

  10. Africa South of the Sahara, Rationale and Introduction: An Experimental Program of Study for Secondary School Social Studies Students. Teaching Guide.

    ERIC Educational Resources Information Center

    Carnegie-Mellon Univ., Pittsburgh, PA. Project Africa.

    The articulation of a rationale for Project Africa's instructional program, the collection of materials for improving inquiry-oriented instruction at the secondary level about Africa south of the Sahara, and the preparation of teaching and study guides have been completed. This geographic region, rather than the whole continent, was chosen to…

  11. Angioplasty and Stenting for Atherosclerotic Intracranial Stenosis: Rationale for a Randomized Clinical Trial

    PubMed Central

    Derdeyn, Colin P.; Chimowitz, Marc I.

    2007-01-01

    Synopsis Atherosclerotic disease of the major intracranial arteries is a frequent cause of stroke. In addition, many patients with symptomatic intracranial stenosis are at very high risk for recurrent stroke. A recently completed medical treatment trial, the Warfarin versus Aspirin for Symptomatic Intracranial Stenosis (WASID) trial, showed that aspirin was as effective and safer than warfarin for preventing stroke or vascular death in these patients, and that patients with 70%-99% intracranial stenosis are at particularly high risk of stroke despite antithrombotic therapy and usual management of vascular risk factors. Preliminary studies suggest that angioplasty and stenting may reduce the risk of stroke in patients with severe stenosis of intracranial arteries. However, data for angioplasty and stenting consists of case series: no randomized studies have been completed to date. These data will be reviewed and the rationale for a randomized trial of angioplasty and stenting versus best medical management for patients with symptomatic intracranial stenosis will be discussed. PMID:17826637

  12. Rationale for Antioxidant Supplementation in Sarcopenia

    PubMed Central

    Cerullo, Francesco; Gambassi, Giovanni; Cesari, Matteo

    2012-01-01

    Sarcopenia is an age-related clinical condition characterized by the progressive loss of motor units and wasting of muscle fibers resulting in decreased muscle function. The molecular mechanisms leading to sarcopenia are not completely identified, but the increased oxidative damage occurring in muscle cells during the course of aging represents one of the most accepted underlying pathways. In fact, skeletal muscle is a highly oxygenated tissue and the generation of reactive oxygen species is particularly enhanced in both contracting and at rest conditions. It has been suggested that oral antioxidant supplementation may contribute at reducing indices of oxidative stress both in animal and human models by reinforcing the natural endogenous defenses. Aim of the present paper is to discuss present evidence related to possible benefits of oral antioxidants in the prevention and treatment of sarcopenia. PMID:22292119

  13. 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…

  14. "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)

  15. 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…

  16. 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…

  17. 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,…

  18. Understanding Readiness: A Rationale (A Rejoinder to Jensen).

    ERIC Educational Resources Information Center

    Ogletree, Earl

    It is only out of a sound theoretical rationale of readiness that practical educational application can derive. The child gradually gains voluntary control of movement throughout the states of locomotive, speech and cognitive development. Thinking is a more subtle form of movement. Voluntary control of movement is an integral part of learning. An…

  19. 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,…

  20. Learner-Controlled Computing: A Description and Rationale.

    ERIC Educational Resources Information Center

    Milner, Stuart

    Learner controlled instruction in which the student controls the computer (e.g., computer programing) instead of it controlling the student (e.g., drill-and-drill-and-practice) is described. The nature of this mode of computer use is explored, and some examples based on case studies conducted by the author are given. A rationale for learner…

  1. A Rationale for Use of "Grendel" in the High School.

    ERIC Educational Resources Information Center

    Burress, Lee

    In providing a rationale for the use of "Grendel" in high school English classes, this paper presents explanatory material demonstrating its appropriateness, beginning with a discussion of "Grendel" as part of a course in major or contemporary works of literature. The second section of the paper illustrates the use of the novel…

  2. 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…

  3. Framing Involvement: Rationale Construction in an Interorganisational Collaboration

    ERIC Educational Resources Information Center

    Siegel, David J.

    2008-01-01

    An analysis of the different rationales articulated and utilized by partners in an interorganizational collaboration is the focus of this paper. The Leadership Education and Development (LEAD) Program in Business is an initiative involving 12 US universities, nearly 40 multinational corporations, a federal government agency, and a non-profit…

  4. 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…

  5. 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…

  6. Meta-case based realization of design rationale management systems

    SciTech Connect

    Paul, G.

    1996-12-31

    System design is an iterative, creative, and cooperative process where informal ideas are transformed into a detailed definition of how a system can be implemented. Design rationale aims at capturing and preserving the why underlying the what, the argument behind the artifact in the design process. Recording deliberations of the design process therefore promises benefits for the overall system engineering life cycle. Providing adequate computer support for design rationale is an interesting issue and a real need for effective application. A design rationale management system (DRMS) supports the capturing, storing and retrieval of interaction rationale in a shared corporate knowledge base and allows organizational learning through long-term and inter-project reuse. The intent of meta-CASE systems is to capture the specification of a required CASE tool and then generate the tool for actual production from the specification. In this paper we identify the requirements for a DRMS and investigate the applicability of meta-CASE tools for the implementation of DRMS`s. Furthermore we describe the experiences gained in the development of two DRMS`s adopting the meta CASE tools MaestroII GED/TCI and Hardy.

  7. 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…

  8. 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…

  9. 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)

  10. Survey of Basic Skills: Grade 3. Rationale and Content.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento. Office of Program Evaluation and Research.

    This publication was developed as a useful tool for school personnel in interpreting California Assessment Program (CAP) test results. The skills measured by the Survey of Basic Skills: Grade 3 (an integral part of the CAP) are described. Rationale for test content specifications, methods of skill assessment, and activities conducted during the…

  11. Survey of Basic Skills: Grade 6. Rationale and Content.

    ERIC Educational Resources Information Center

    Law, Alexander I.

    This document presents more useful statewide testing as a rationale for a revision to the California Assessment Program (CAP). A brief description of the revision procedures, and an illustrative outline of the skills and concepts covered by CAP are included. Approximately 270 districts and counties participated in the test development process to…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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)…

  17. Cannabidiol and epilepsy: Rationale and therapeutic potential.

    PubMed

    Leo, Antonio; Russo, Emilio; Elia, Maurizio

    2016-05-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue. To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy. In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action. However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD. In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis. Likewise, clinical evidence seems to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile. However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising.

  18. 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

  19. The Elementary Science Teaching Rationale (STR): Analysis via a Preservice Teacher Self-Report Instrument

    ERIC Educational Resources Information Center

    Varrella, Gary F.; Veronesi, Peter D.

    2004-01-01

    This paper represents Part I of a two-part study examining preservice teachers' development of a personalized, research-based Science Teaching Rationale (STR). Researchers have historically documented the application of the "rationale paper" (Clough, 1992; Veronesi, 1998) using qualitative methodologies. Since the rationale paper continues to…

  20. 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…

  1. Transcriptional and post-transcriptional regulation of SPAST, the gene most frequently mutated in hereditary spastic paraplegia.

    PubMed

    Henson, Brian J; Zhu, Wan; Hardaway, Kelsey; Wetzel, Jaime L; Stefan, Mihaela; Albers, Kathryn M; Nicholls, Robert D

    2012-01-01

    Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70-80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3'-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP.

  2. Endogenous spar tin, mutated in hereditary spastic paraplegia, has a complex subcellular localization suggesting diverse roles in neurons

    SciTech Connect

    Robay, Dimitri; Patel, Heema; Simpson, Michael A.; Brown, Nigel A.; Crosby, Andrew H. . E-mail: acrosby@sgul.ac.uk

    2006-09-10

    Mutation of spartin (SPG20) underlies a complicated form of hereditary spastic paraplegia, a disorder principally defined by the degeneration of upper motor neurons. Using a polyclonal antibody against spartin to gain insight into the function of the endogenous molecule, we show that the endogenous molecule is present in two main isoforms of 85 kDa and 100 kDa, and 75 kDa and 85 kDa in human and murine, respectively, with restricted subcellular localization. Immunohistochemical studies on human and mouse embryo sections and in vitro cell studies indicate that spartin is likely to possess both nuclear and cytoplasmic functions. The nuclear expression of spartin closely mirrors that of the snRNP (small nuclear ribonucleoprotein) marker {alpha}-Sm, a component of the spliceosome. Spartin is also enriched at the centrosome within mitotic structures. Notably we show that spartin protein undergoes dynamic positional changes in differentiating human SH-SY5Y cells. In undifferentiated non-neuronal cells, spartin displays a nuclear and diffuse cytosolic profile, whereas spartin transiently accumulates in the trans-Golgi network and subsequently decorates discrete puncta along neurites in terminally differentiated neuroblastic cells. Investigation of these spartin-positive vesicles reveals that a large proportion colocalizes with the synaptic vesicle marker synaptotagmin. Spartin is also enriched in synaptic-like structures and in synaptic vesicle-enriched fraction.

  3. PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion

    PubMed Central

    Ho, Philip Wing-Lok; Pang, Shirley Yin-Yu; Li, Miaoxin; Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2015-01-01

    Background Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. Recently, we described a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP. Further to this finding, here we describe the functional effect of this mutation. Methods As PMCA4 removes cytosolic calcium, we measured transient changes and the time-dependent decay of cytosolic calcium level as visualized by using fura-2 fluorescent dye with confocal microscopy in human SH-SY5Y neuroblastoma cells overexpressing either wild-type or R268Q mutant PMCA4. Results Overexpressing both wild-type and R268Q PMCA4 significantly reduced maximum calcium surge after KCl-induced depolarization as compared with vector control cells. However, cells overexpressing mutant PMCA4 protein demonstrated significantly higher level of calcium surge when compared with wild-type. Furthermore, the steady-state cytosolic calcium concentration in these mutant cells remained markedly higher than the wild-type after SERCA inhibition by thapsigargin. Conclusion Our result showed that p.R268Q mutation in PMCA4 resulted in functional changes in calcium homeostasis in human neuronal cells. This suggests that calcium dysregulation may be associated with the pathogenesis of FSP. PMID:25798335

  4. Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis.

    PubMed

    Kaji, Seiji; Kawarai, Toshitaka; Miyamoto, Ryosuke; Nodera, Hiroyuki; Pedace, Lucia; Orlacchio, Antonio; Izumi, Yuishin; Takahashi, Ryosuke; Kaji, Ryuji

    2016-05-15

    Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS.

  5. 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.

  6. Defense Acquistion: Rationale for Imposing Domestic Source Restrictions.

    DTIC Science & Technology

    2007-11-02

    retained the restriction for polyacrylonitrile-based carbon fiber, periscope tube forgings, bull gear ring forgings, and ship propulsion shaft...forgings 1984 Protect sensitive data Ship propulsion shaft forgings 1984 Unsettled conditions among suppliers In its reviews of industrial base... Ship Propulsion Shafts 14 14 15 16 17 Appendix III Rationale for 10 U.S.C. 2534-Imposed Restrictions Buses Chemical Weapons Antidote

  7. Structural-Engineering Rationales of Gold Nanoparticles for Cancer Theranostics.

    PubMed

    Chen, Wenwen; Zhang, Shaohua; Yu, Yangyang; Zhang, Huisheng; He, Qianjun

    2016-10-01

    Personalized theranostics of cancer is increasingly desired, and can be realized by virtue of multifunctional nanomaterials with possible high performances. Gold nanoparticles (GNPs) are a type of especially promising candidate for cancer theranostics, because their synthesis and modification are facile, their structures and physicochemical properties are flexibly controlled, and they are also biocompatible. Especially, the localized surface plasmon resonance and multivalent coordination effects on the surface endow them with NIR light-triggered photothermal imaging and therapy, controlled drug release, and targeted drug delivery. Although the structure, properties, and theranostic application of GNPs are considerably plentiful, no expert review systematically explains the relationships among their structure, property. and application and induces the engineering rationales of GNPs for cancer theranostics. Hence, there are no clear rules to guide the facile construction of optimal GNP structures aiming at a specific theranostic application. A series of structural-engineering rationales of GNPs for cancer theranostics is proposed through digging out the deep relationships between the structure and properties of GNPs. These rationales will be inspiring for guiding the engineering of specific and advanced GNPs for personalized cancer theranostics.

  8. A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

    PubMed Central

    Słabicki, Mikołaj; Theis, Mirko; Krastev, Dragomir B.; Samsonov, Sergey; Mundwiller, Emeline; Junqueira, Magno; Paszkowski-Rogacz, Maciej; Teyra, Joan; Heninger, Anne-Kristin; Poser, Ina; Prieur, Fabienne; Truchetto, Jérémy; Confavreux, Christian; Marelli, Cécilia; Durr, Alexandra; Camdessanche, Jean Philippe; Brice, Alexis; Shevchenko, Andrej; Pisabarro, M. Teresa; Stevanin, Giovanni; Buchholz, Frank

    2010-01-01

    DNA repair is essential to maintain genome integrity, and genes with roles in DNA repair are frequently mutated in a variety of human diseases. Repair via homologous recombination typically restores the original DNA sequence without introducing mutations, and a number of genes that are required for homologous recombination DNA double-strand break repair (HR-DSBR) have been identified. However, a systematic analysis of this important DNA repair pathway in mammalian cells has not been reported. Here, we describe a genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen for genes involved in DNA double strand break repair. We report 61 genes that influenced the frequency of HR-DSBR and characterize in detail one of the genes that decreased the frequency of HR-DSBR. We show that the gene KIAA0415 encodes a putative helicase that interacts with SPG11 and SPG15, two proteins mutated in hereditary spastic paraplegia (HSP). We identify mutations in HSP patients, discovering KIAA0415/SPG48 as a novel HSP-associated gene, and show that a KIAA0415/SPG48 mutant cell line is more sensitive to DNA damaging drugs. We present the first genome-scale survey of HR-DSBR in mammalian cells providing a dataset that should accelerate the discovery of novel genes with roles in DNA repair and associated medical conditions. The discovery that proteins forming a novel protein complex are required for efficient HR-DSBR and are mutated in patients suffering from HSP suggests a link between HSP and DNA repair. PMID:20613862

  9. Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene–disease associations and unanticipated rare disorders

    PubMed Central

    van de Warrenburg, Bart P; Schouten, Meyke I; de Bot, Susanne T; Vermeer, Sascha; Meijer, Rowdy; Pennings, Maartje; Gilissen, Christian; Willemsen, Michèl AAP; Scheffer, Hans; Kamsteeg, Erik-Jan

    2016-01-01

    Cerebellar ataxia (CA) and hereditary spastic paraplegia (HSP) are two of the most prevalent motor disorders with extensive locus and allelic heterogeneity. We implemented clinical exome sequencing, followed by filtering data for a ‘movement disorders' gene panel, as a generic test to increase variant detection in 76 patients with these disorders. Segregation analysis or phenotypic re-evaluation was utilized to substantiate findings. Disease-causing variants were identified in 9 of 28 CA patients, and 8 of 48 HSP patients. In addition, possibly disease-causing variants were identified in 1 and 8 of the remaining CA and HSP patients, respectively. In 10 patients with CA, the total disease-causing or possibly disease-causing variants were detected in 8 different genes, whereas 16 HSP patients had such variants in 12 different genes. In the majority of cases, the identified variants were compatible with the patient phenotype. Interestingly, in some patients variants were identified in genes hitherto related to other movement disorders, such as TH variants in two siblings with HSP. In addition, rare disorders were uncovered, for example, a second case of HSP caused by a VCP variant. For some patients, exome sequencing results had implications for treatment, exemplified by the favorable L-DOPA treatment in a patient with HSP due to ATP13A2 variants (Parkinson type 9). Thus, clinical exome sequencing in this cohort of CA and HSP patients suggests broadening of disease spectra, revealed novel gene–disease associations, and uncovered unanticipated rare disorders. In addition, clinical exome sequencing results have shown their value in guiding practical patient management. PMID:27165006

  10. 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.

  11. 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.

  12. Acute paraplegia in a patient with spinal tophi: a case report.

    PubMed

    Wang, L C; Hung, Y C; Lee, E J; Chen, H H

    2001-03-01

    A 28-year-old man with a 5-year history of gouty arthritis suffered from an acute episode of lower back pain. He visited a rehabilitative clinic and received physical therapy following his examination. Weakness and numbness of both lower legs developed rapidly after physical therapy. He was sent to our hospital with complete paralysis of both lower limbs and complete sensory loss below the umbilicus 3 hours after the physical therapy. No peripheral tophi were found. Myelography showed an extrinsic compression of the dura sac at T10. Emergency decompressive laminectomy of T9 to T11 was performed. During the surgery, caseous material was found deposited in the ligamentum flavum and the left T9 to T10 facet joint, with indentation of the dura sac. The pathologic diagnosis was spinal tophi. After surgery, the patient's neurologic function recovered rapidly. It was suspected that inappropriate physical therapy might have aggravated acute inflammation of spinal gout and resulted in a rapid deterioration of neurologic function. Though gout is a chronic medical disease, an acute attack of spinal gout may be disastrous and requires emergency neurosurgical intervention.

  13. 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.

  14. 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.

  15. Critique of rationale for transmutation of nuclear waste

    SciTech Connect

    Smith, C.F.; Cohen, J.J.

    1980-07-01

    It has been suggested that nuclear transmutation could be used in the elimination or reduction of hazards from radioactive wastes. The rationale for this suggestion is the subject of this paper. The objectives of partitioning-transmutation are described. The benefits are evaluated. The author concludes that transmutation would appear at best to offer the opportunity of reducing an already low risk. This would not seem to be justifiable considering the cost. If non-radiological risks are considered, there is a negative total benefit. (DC)

  16. “I Can’t Walk!” Acute Thrombosis of Descending Aorta Causing Paraplegia

    PubMed Central

    Mitchell, Matthew L.; Yucebey, Elif; Weaver, Mitchell R.; Jaehne, A. Kathrin; Rivers, Emanuel P.

    2013-01-01

    A 50-year-old man presented to the emergency department (ED) with acute, bilateral lower extremity weakness and loss of sensation, as well as absent pulses bilaterally. Computed tomography angiography showed complete occlusion of the aorta below the inferior mesenteric artery, extending to the iliac bifurcations. Echocardiographic findings showed severe systolic dysfunction (ejection fraction of 15%) and cryptic cardiogenic shock in spite of stable vital signs. Prior to early operative intervention, an early goal-oriented hemodynamic strategy of shock management resulted in the resolution of motor and sensory deficits.After definitive surgical intervention, the patient was discharged neurologically intact. Acute aortic occlusion is frequently accompanied by myocardial dysfunction, which can be from mild to severe. The most severe form can even occur with normal vital signs or occult cardiogenic shock. Early detection and goal-directed preoperative hemodynamic optimization, along with surgical intervention in the ED, is required to optimize outcomes. PMID:24106532

  17. Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region variant and known pathogenic variant in SPG11

    PubMed Central

    Chan, Anne Yin-Yan; Au, Wing Chi; Shen, Yun; Chan, Ting Fung

    2016-01-01

    Hereditary spastic paraplegias (HSPs) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of HSP subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with HSP symptoms, including bilateral lower limb weakness, unsteady gait, cognitive decline, dysarthria, and slurring of speech since the age of 14. Subsequent whole-genome sequencing revealed that the patients are compound heterozygous for variants in the SPG11 gene, including the paternally inherited c.6856C>T (p.Arg2286*) variant and the novel maternally inherited c.2316+5G>A splice-donor region variant. Variants in SPG11 are the common cause of autosomal recessive spastic paraplegia type 11. According to the ClinVar database, there are already 101 reported pathogenic variants in SPG11 that are associated with HSPs. To our knowledge, this is the first report of SPG11 variants in our local population. The novel splice variant identified in this study enriches the catalog of SPG11 variants, potentially leading to better genetic diagnosis of HSPs. PMID:27900367

  18. Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia

    PubMed Central

    2010-01-01

    Background Hereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes would account for about 50% of the ADHSP cases. Methods We defined the SPAST and ATL1 mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype). Results We found 50 SPAST mutations (including two large deletions) in 54 patients and 7 ATL1 mutations in 11 patients. A total of 33 of the SPAST and 3 of the ATL1 were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the SPAST mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF. Conclusions In a large cohort of Spanish patients with spastic paraplegia, SPAST and ATL1 mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations. PMID:20932283

  19. 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…

  20. An implantable neuroprosthesis for standing and walking in paraplegia: 5-year patient follow-up

    NASA Astrophysics Data System (ADS)

    Guiraud, David; Stieglitz, Thomas; Koch, Klaus Peter; Divoux, Jean-Louis; Rabischong, Pierre

    2006-12-01

    We present the results of a 5-year patient follow-up after implantation of an original neuroprosthesis. The system is able to stimulate both epimysial and neural electrodes in such a way that the complete flexor-extensor chain of the lower limb can be activated without using the withdrawal reflex. We demonstrate that standing and assisted walking are possible, and the results have remained stable for 5 years. Nevertheless, some problems were noted, particularly regarding the muscle response on the epimysial channels. Analysis of the electrical behaviour and thresholds indicated that the surgical phase is crucial because of the sensitivity of the functional responses to electrode placement. Neural stimulation proved to be more efficient and more stable over time. This mode requires less energy and provides more selective stimulation. This FES system can be improved to enable balanced standing and less fatiguing gait, but this will require feedback on event detection to trigger transitions between stimulation sequences, as well as feedback to the patient about the state of his lower limbs.

  1. 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.

  2. Congenital complete heart block.

    PubMed Central

    Agarwala, B.; Sheikh, Z.; Cibils, L. A.

    1996-01-01

    Congenital complete heart block in utero has become diagnosed more frequently with the clinical use of fetal echocardiography. The fetus with complete heart block may remain asymptomatic or may develop congestive heart failure. Congenital complete heart block is more frequently seen in infants of mothers with systemic lupus erythematosus, both clinically manifested and subclinical systemic lupus erythematosus with positive antibodies (SS-A and SS-B antibodies). At birth, the neonate with complete heart block may remain asymptomatic and may not require a pacemaker to increase the heart rate. The indications for a pacemaker in neonates with complete heart block have been discussed. Both in-utero and neonatal management of congenital complete heart block are discussed to manage congestive heart failure in a fetus. Four patients with congenital complete heart block are presented covering a broad spectrum of clinical presentation, diagnosis, and management both in the fetal and neonatal period. Images Figure 1 PMID:8961692

  3. Physical Activity and Quality of Life among Adults with Paraplegia in Odisha, India

    PubMed Central

    Ganesh, Shankar; Mishra, Chittaranjan

    2016-01-01

    Objectives: The complete rehabilitation of patients with spinal cord injuries (SCI) comprises both physical and psychosocial factors. This study therefore aimed to assess physical activity and quality of life (QOL) among paraplegic patients with SCI in Odisha, India. Methods: This cross-sectional prospective study was conducted between March 2010 and December 2013. All paraplegic patients treated at the Swami Vivekanand National Institute of Rehabilitation Training & Research in Odisha, India, during the study period who met the inclusion criteria were invited to participate in the study (n = 364). Structured face-to-face interviews were held with participants and QOL and physical activity were assessed using the abbreviated World Health Organization QOL instrument and the Physical Activity Scale for Individuals with Physical Disabilities, respectively. Results: A total of 84 people participated in the study (response rate: 23.1%). The mean age was 32.54 ± 10.75 years and 90.5% of the participants were male. Participants had a low mean metabolic equivalent score (18.18 ± 10.68 hours/day). Additionally, low mean scores were noted for the physical health, psychological well-being, social relationships and environment QOL domains (49.76 ± 18.74, 48.57 ± 17.04, 57.88 ± 17.04 and 49.85 ± 17.77, respectively). There was a strong positive association between levels of physical activity and all QOL domains (P <0.050). Physical activity and employment status were significant predictors of all QOL domains (P <0.001). Conclusion: Low physical activity levels and QOL were noted among the paraplegic subjects. Interventions promoting physical activity and employment may help to improve QOL among this patient group. PMID:26909214

  4. Pegylated liposomal doxorubicin and immunomodulatory drug combinations in multiple myeloma: rationale and clinical experience.

    PubMed

    Chanan-Khan, Asher Alban; Lee, Kelvin

    2007-04-01

    The availability of new agents for multiple myeloma (MM) provides an opportunity to further improve response rates through the development of new combination regimens. Such new agents include pegylated liposomal doxorubicin (PLD) and the immunomodulatory drugs thalidomide and lenalidomide, all of which have demonstrated efficacy and safety in the treatment of newly diagnosed and relapsed/refractory MM. Based on their complementary mechanisms of action and nonoverlapping toxicity profiles, PLD and the immunomodulatory drugs might provide incremental benefits when used in combined treatment regimens. Thus, they have been evaluated in clinical studies that combine PLD/vincristine/dexamethasone and thalidomide (DVd-T) or PLD/vincristine/dexamethasone and lenalidomide (DVd-R) as well as in a study combining bortezomib with PLD and thalidomide. Results of all these studies have included high overall response rates, with improved rates of complete/near complete response compared with similar regimens that do not include chemotherapy (ie, immunomodulatory drugs plus dexamethasone). This article provides the clinical rationale for the use of PLD in combination with immunomodulatory drugs to treat patients with MM and summarizes the clinical experience with these combinations to date. Notably, the early phase I/II study results have been sufficiently encouraging to warrant further investigation in additional large-scale, phase II/III studies. Future clinical trials should focus on determining the optimal dose and schedule for each of these agents when used in combination and whether the addition of other new agents provides an additional response benefit.

  5. 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

  6. The new polio eradication end game: rationale and supporting evidence.

    PubMed

    Sutter, Roland W; Platt, Lauren; Mach, Ondrej; Jafari, Hamid; Aylward, R Bruce

    2014-11-01

    Polio eradication requires the removal of all polioviruses from human populations, whether wild poliovirus or those emanating from the oral poliovirus vaccine (OPV). The Polio Eradication & Endgame Strategic Plan 2013-2018 provides a framework for interruption of wild poliovirus transmission in remaining endemic foci and lays out a plan for the new polio end game, which includes the withdrawal of Sabin strains, starting with type 2, and the introduction of inactivated poliovirus vaccine, for risk mitigation purposes. This report summarizes the rationale and evidence that supports the policy decision to switch from trivalent OPV to bivalent OPV and to introduce 1 dose of inactivated poliovirus vaccine into routine immunization schedules, and it describes the proposed implementation of this policy in countries using trivalent OPV.

  7. Procoagulant therapeutics in liver disease: a critique and clinical rationale.

    PubMed

    Shah, Neeral L; Intagliata, Nicolas M; Northup, Patrick G; Argo, Curtis K; Caldwell, Stephen H

    2014-11-01

    The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis. These opposing outcomes, which have multiple contributing factors, can pose diagnostic and therapeutic dilemmas for physicians. With the high rate of haemorrhagic complications in patients with cirrhosis, we examine the various procoagulants available for use in this population. In this Review, we describe the clinical and current rationale for using each of the currently available procoagulants-vitamin K, fresh frozen plasma (FFP), cryoprecipitate, platelets, recombinant factor VIIa (rFVIIa), antifibrinolytics, prothrombin concentrate complexes (PCC), desmopressin and red blood cells. By examining the evidence and use of these agents in liver disease, we provide a framework for targeted, goal-directed therapy with procoagulants.

  8. Rationale of arthroscopic surgery of the temporomandibular joint.

    PubMed

    Murakami, KenIchiro

    2013-01-01

    Arthroscopic surgery has been widely used for treatment of temporomandibular joint (TMJ) internal derangements and diseases for the last 40 years. Although 626 articles have been hit by Pubmed search in terms of "TMJ arthroscopic surgery", this review article is described based on distinguished publishing works and on my experiences with TMJ arthroscopic surgery and related research with an aim to analyse the rationale of arthroscopic surgeries of the temporomandibular joint. With arthrocentesis emerging as an alternative, less invasive, treatment for internal derangement with closed lock, the primary indication of arthroscopic surgery seems to be somewhat limited. However, the value of endoscopic inspection and surgery has its position for both patient and physician with its long-term reliable results.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Latino College Completion: Maine

    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…

  16. 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…

  17. Latino College Completion: California

    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…

  18. Latino College Completion: Ohio

    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…

  19. Latino College Completion: Massachusetts

    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…

  20. Latino College Completion: Florida

    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…

  1. Latino College Completion: Iowa

    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…

  2. 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…

  3. Latino College Completion: Mississippi

    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…

  4. Latino College Completion: Maryland

    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…

  5. Latino College Completion: Montana

    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…

  6. Latino College Completion: Nevada

    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…

  7. 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

  8. Rationales and Norms for Teacher Dress Codes: A Review of Employee Handbooks

    ERIC Educational Resources Information Center

    Freeburg, Beth W.; Workman, Jane E.; Arnett, Sally E.; Robinson, Joyce R.

    2011-01-01

    The research question was "What dress norms and related rationales are found in teacher dress policies?" Data were 102 school employee handbooks. Eighty-two handbooks (80.4%) provided one or more rationale, most frequently being "To project a positive image in the community" (n = 56). Dress norms, categorized as broad and itemized, were determined…

  9. 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…

  10. Preservice Teachers Defining "Self-as-Teacher": The Elementary Science Teaching Rationale

    ERIC Educational Resources Information Center

    Varrella, Gary F.; Veronesi, Peter D.

    2004-01-01

    This study reviews allied literature and specific teacher educator behaviors that promote preservice teachers' development of a personalized, research-based elementary science teaching rationale (STR). Declaring absolutes is not the goal of the rationale. Rather, the goal is to initiate, among preservice teachers, the lifelong professional…

  11. A Psychological Rationale in Support of the Alcoholics Anonymous' Concept of Fellowship.

    ERIC Educational Resources Information Center

    Machell, David F.

    This article creates a strong theoretical rationale in support of the concept of fellowship, the cornerstone healing influence of Alcoholic Anonymous (AA). It reviews the literature which supports the Alcoholic Anonymous' concept of fellowship or client perceived belongingness. It provides a strong rationale for the establishment of new…

  12. Cultural Rationales Guiding Medication Adherence Among African American with HIV/AIDS

    PubMed Central

    Neufeld, Stewart; Berry, Rico; Luborsky, Mark

    2011-01-01

    Abstract To date, only modest gains have been achieved in explaining adherence to medical regimens, limiting effective interventions. This is a particularly important issue for African Americans who are disproportionately affected by the HIV epidemic. Few studies have focused on intragroup variation among African Americans in adherence to ART. The aim of this study was to identify and describe the cultural rationales guiding African American patients' formulation and evaluation of adherence. Rationales are key features of purposeful human action. In-depth interviews with 80 seropositive African Americans were tape recorded, transcribed, and analyzed. Participant CD4, viral load and medical histories were collected at each data point. Analysis of four waves of panel data identified three types of adherence rationales: Authoritative Knowledge Rationale (AKR; n=29, 36.3%), Following Doctors' Orders Rationale (DOR; n=24, 30.0%) and Individualized Adherence Rationale (IAR; n=27, 33.8%). Differences in mean reported adherence between the rationale groups did not achieve statistical significance. However, the fraction reporting low adherence (<70%), although not different by rationale group at the first interview (T1), was significantly higher for the IAR group by the fourth interview (T4). Objective clinical markers (CD4 and viral load) improved over time (from T1 to T4) for AKR and DOR groups, but remained unchanged for the IAR group, yet self-reported adherence declined for all groups over the course of the four interviews. PMID:21777141

  13. Autosomal dominant familial spastic paraplegia: Reduction of the FSPI candidate region on chromosome 14q to 7 cM and locus heterogeneity

    SciTech Connect

    Gispert, S.; Santos, N.; Auburger, G.; Damen, R.; Voit, T.; Schulz, J.; Klockgether, T.; Orozco, G.; Kreuz, F.; Weissenbach, J.

    1995-01-01

    Three large pedigrees of Germany descent with autosomal dominant {open_quotes}pure{close_quotes} familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigree D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. 11 refs., 2 figs., 2 tabs.

  14. 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 Central

    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

    Background: 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. Materials and Methods: 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. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/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. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs. PMID:27110548

  15. Hereditary Spastic Paraplegia

    MedlinePlus

    ... by other symptoms. These additional symptoms include impaired vision due to cataracts and problems with the optic nerve and retina of the eye, ataxia (lack of muscle coordination), epilepsy, cognitive impairment, peripheral neuropathy, and deafness. The diagnosis of HSP ...

  16. 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.

  17. The National Neurosurgery Quality and Outcomes Database Qualified Clinical Data Registry: 2015 measure specifications and rationale.

    PubMed

    Parker, Scott L; McGirt, Matthew J; Bekelis, Kimon; Holland, Christopher M; Davies, Jason; Devin, Clinton J; Atkins, Tyler; Knightly, Jack; Groman, Rachel; Zyung, Irene; Asher, Anthony L

    2015-12-01

    Meaningful quality measurement and public reporting have the potential to facilitate targeted outcome improvement, practice-based learning, shared decision making, and effective resource utilization. Recent developments in national quality reporting programs, such as the Centers for Medicare & Medicaid Services Qualified Clinical Data Registry (QCDR) reporting option, have enhanced the ability of specialty groups to develop relevant quality measures of the care they deliver. QCDRs will complete the collection and submission of Physician Quality Reporting System (PQRS) quality measures data on behalf of individual eligible professionals. The National Neurosurgery Quality and Outcomes Database (N(2)QOD) offers 21 non-PQRS measures, initially focused on spine procedures, which are the first specialty-specific measures for neurosurgery. Securing QCDR status for N(2)QOD is a tremendously important accomplishment for our specialty. This program will ensure that data collected through our registries and used for PQRS is meaningful for neurosurgeons, related spine care practitioners, their patients, and other stakeholders. The 2015 N(2)QOD QCDR is further evidence of neurosurgery's commitment to substantively advancing the health care quality paradigm. The following manuscript outlines the measures now approved for use in the 2015 N(2)QOD QCDR. Measure specifications (measure type and descriptions, related measures, if any, as well as relevant National Quality Strategy domain[s]) along with rationale are provided for each measure.

  18. Cardiovascular genetic medicine: evolving concepts, rationale, and implementation.

    PubMed

    Hershberger, Ray E

    2008-06-01

    Cardiovascular genetic medicine is devoted to the identification and understanding of cardiac conditions resulting from genetic and genomic mechanisms and to the development and validation of diagnostic and treatment algorithms and guidelines. Cardiovascular genetic medicine clinics now provide expert cardiovascular subspecialty care, genetic counseling and clinical genetic testing, and will eventually provide disease-specific gene or genetic therapies. Currently, the most tractable diagnoses for cardiovascular genetic medicine are the single-gene disorders: the cardiomyopathies, the channelopathies, and others. The recent explosion of genetic knowledge within the single-gene disorders and consequent rapid proliferation of genetic testing enables far greater numbers of individuals to directly benefit from this progress. A compelling rationale exists for this approach: cardiovascular single-gene diseases commonly present with life-threatening events (e.g., sudden cardiac death, heart failure, stroke, etc.), but identification, evaluation, and treatment of individuals with presymptomatic genetic risk has the promise to prevent or ameliorate cardiovascular morbidity and mortality. Cardiovascular genetic medicine programs also anchor training and research, thereby enabling the next generation of academic specialists in cardiovascular genetic medicine to continue to improve cardiovascular health.

  19. Early pharmacological treatment of autism: a rationale for developmental treatment

    PubMed Central

    Bethea, Terrence C.; Sikich, Linmarie

    2007-01-01

    Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks. PMID:17276749

  20. Optimal Lipid Modification: The Rationale for Combination Therapy

    PubMed Central

    Backes, James M; Gibson, Cheryl A; Howard, Patricia A

    2005-01-01

    Background An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence. Objective To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Method Literature was obtained from MEDLINE (1966 – June 2005) and references from selected articles. Results A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising. Conclusion Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy. PMID:17315604

  1. 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.

  2. Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation

    PubMed Central

    Boison, Detlev; Stewart, Kerry-Ann

    2009-01-01

    Epilepsy is a common seizure disorder affecting approximately 70 million people worldwide. Current pharmacotherapy is neuron-centered, frequently accompanied by intolerable side-effects, and fails to be effective in about one third of patients. Therefore, new therapeutic concepts are needed. Recent research suggests an astrocytic basis of epilepsy, presenting the possibility of novel therapeutic targets. In particular, dysfunction of the astrocyte-controlled, endogenous, adenosine-based seizure control system of the brain is implicated in seizure generation. Thus, astrogliosis – a pathological hallmark of the epileptic brain – is associated with upregulation of the adenosine-removing enzyme adenosine kinase (ADK), resulting in focal adenosine deficiency. Both astrogliotic upregulation of ADK in epilepsy and transgenic overexpression of ADK are associated with seizures, and inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. These findings link adenosine deficiency with seizures and predict that adenosine augmentation therapies (AATs) will likely be effective in preventing seizures. Given the widespread systemic and central side effects of systemically administered AATs, focal AATs (i.e., limited to the astrogliotic lesion) are a necessity. This Commentary will discuss the pharmacological rationale for the development of focal AATs. Additionally, several AAT strategies will be discussed: (1) adenosine released from silk-based brain implants; (2) adenosine released from locally implanted encapsulated cells; (3) adenosine released from stem cell-derived brain implants; and (4) adenosine augmenting gene therapies. Finally, new developments and therapeutic challenges in using focal AATs for epilepsy therapy will critically be evaluated. PMID:19682439

  3. Rattling the plate--reasons and rationales for early weaning.

    PubMed

    Anderson, A S; Guthrie, C A; Alder, E M; Forsyth, S; Howie, P W; Williams, F L

    2001-08-01

    To identify a range of attitudes and beliefs which influence the timing of introduction to solid food, five focus group discussions were undertaken within a maternity hospital setting. These sessions explored early feeding behaviour, stimuli to changing feeding habits and subsequent responses in 22 primiparous and seven multiparous mothers (mean age 27.0+/-4.8 years) with babies aged 8-18 weeks (mean age 13.0+/-4.2 weeks). One-third of the participants had introduced solid food to their infants (mean age of introduction 11.6 weeks, range 2-16 weeks). Mothers believed that the introduction of solids was baby led and initiated by some physical characteristic or behavioural action of the infant. All mothers were aware of current recommendations to avoid the introduction of solid food until 4 months. Few knew why this should be and concepts of long-term ill health were difficult to conceptualize. The conflict between rigid feeding guidelines and flexible advice from supportive health professionals created confusion over the importance of good weaning practices. The current findings highlight issues relevant to the introduction of solid food, and provide a foundation for further research which can identify the relative importance of these factors and provide a rationale for the design of contemporary intervention strategies.

  4. 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

  5. Beyond FASFA Completion

    ERIC Educational Resources Information Center

    Castleman, Ben; Page, Lindsay

    2015-01-01

    The Free Application for Federal Student Aid (FAFSA)--which students must complete to qualify for most federal, state, and institutional financial aid--is a gateway to college through which many students must pass, particularly those from low- to moderate-income households (King, 2004; Kofoed, 2013). Yet given the complexity of the…

  6. Making College Completion Personal

    ERIC Educational Resources Information Center

    Thomas, Heather

    2011-01-01

    There are countless justifications for why young adults, faced with so many distractions, do not complete their educations. Many students fail to finish college because of a lack of information and understanding about healthy relationships and sex education. The author's own struggles and eventual successes as a student and mother compelled her to…

  7. College Completion Tool Kit

    ERIC Educational Resources Information Center

    US Department of Education, 2011

    2011-01-01

    In March, 2009, President Obama proposed the American Graduation Initiative, which established the goal that by 2020 the United States will regain its position as the nation with the highest percentage of its population holding post-secondary degrees and credentials. The College Completion Toolkit provides information that governors and other…

  8. Completing a Simple Circuit.

    ERIC Educational Resources Information Center

    Slater, Timothy F.; Adams, Jeffrey P.; Brown, Thomas R.

    2000-01-01

    Students have problems successfully arranging an electric circuit to make the bulb produce light. Investigates the percentage of students able to complete a circuit with a given apparatus, and the effects of prior experience on student success. Recommends hands-on activities at the elementary and secondary school levels. (Contains 14 references.)…

  9. Implementing the World Mental Health Survey Initiative in Portugal – rationale, design and fieldwork procedures

    PubMed Central

    2013-01-01

    Background The World Mental Health Survey Initiative was designed to evaluate the prevalence, the correlates, the impact and the treatment patterns of mental disorders. This paper describes the rationale and the methodological details regarding the implementation of the survey in Portugal, a country that still lacks representative epidemiological data about psychiatric disorders. Methods The World Mental Health Survey is a cross-sectional study with a representative sample of the Portuguese population, aged 18 or older, based on official census information. The WMH-Composite International Diagnostic Interview, adapted to the Portuguese language by a group of bilingual experts, was used to evaluate the mental health status, disorder severity, impairment, use of services and treatment. Interviews were administered face-to-face at respondent’s dwellings, which were selected from a nationally representative multi-stage clustered area probability sample of households. The survey was administered using computer-assisted personal interview methods by trained lay interviewers. Data quality was strictly controlled in order to ensure the reliability and validity of the collected information. Results A total of 3,849 people completed the main survey, with 2,060 completing the long interview, with a response rate of 57.3%. Data cleaning was conducted in collaboration with the WMHSI Data Analysis Coordination Centre at the Department of Health Care Policy, Harvard Medical School. Collected information will provide lifetime and 12-month mental disorders diagnoses, according to the International Classification of Diseases and to the Diagnostic and Statistical Manual of Mental Disorders. Conclusions The findings of this study could have a major influence in mental health care policy planning efforts over the next years, specially in a country that still has a significant level of unmet needs regarding mental health services organization, delivery of care and epidemiological

  10. A review of therapies for diabetic macular oedema and rationale for combination therapy

    PubMed Central

    Amoaku, W M K; Saker, S; Stewart, E A

    2015-01-01

    Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5–9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO. A comprehensive review of clinical trials related to DMO and their outcomes was completed. Where phase III randomised

  11. An introductory course in computation molecular biology: rationale, history, observations, and course description.

    PubMed

    Johns, S J; Thompson, S M; Dunker, A K

    1996-01-01

    A course called "Molecular Biology Computer Techniques" was implemented in 1987 and has been evolving ever since. Currently the semester-long three credit course consists of thirty hours of lecture (three hours/week for the first ten weeks of the semester) and a minimum of 45 hours of laboratory instruction (three hours/week). The lectures survey both bioinformatics and structure based methods. The laboratory has two tracks, one that can be described loosely as "sequence analysis" and the other as "molecular modelling." Most students choose one of the two laboratory tracks, although a small number have done both, either simultaneously or in successive years. For each student, the goal of the course is the completion of a student-initiated research project. The culmination of the course is the presentation of the completed projects at a "Poster Session Final." During this final, which is conducted like a poster session at a typical biological science meeting, students are examined, not only by the instructors in the course, but also by a diverse cross-section of the university community at large, including non-scientists (who are specially invited to attend). Questioning by non-scientists provides opportunity for the students to improve their communication skills with the lay public. In this manuscript we discuss our views regarding the rationale for the development of formal courses in computational molecular biology, relate our experiences in the development of our course, and describe the course as it stood the last time it was taught, which was in the Fall of 1994.

  12. Image Zoom Completion.

    PubMed

    Hidane, Moncef; El Gheche, Mireille; Aujol, Jean-Francois; Berthoumieu, Yannick; Deledalle, Charles-Alban

    2016-08-01

    We consider the problem of recovering a high-resolution image from a pair consisting of a complete low-resolution image and a high-resolution but incomplete one. We refer to this task as the image zoom completion problem. After discussing possible contexts in which this setting may arise, we introduce a nonlocal regularization strategy, giving full details concerning the numerical optimization of the corresponding energy and discussing its benefits and shortcomings. We also derive two total variation-based algorithms and evaluate the performance of the proposed methods on a set of natural and textured images. We compare the results and get with those obtained with two recent state-of-the-art single-image super-resolution algorithms.

  13. The Community College Penalty and Bachelor's Degree Completion: Fact or Fiction? Policy Research: IERC 2013-1

    ERIC Educational Resources Information Center

    Lichtenberger, Eric J.; Dietrich, Cecile

    2013-01-01

    Rationale: Research examining the relationship between initial community college enrollment and bachelor's completion have shown mixed results with some studies indicating a clear penalty for community college enrollment and other studies showing no penalty, partly due to the point at which the given study began tracking the community college…

  14. Antipsychotic polypharmacy: a Japanese survey of prescribers' attitudes and rationales.

    PubMed

    Kishimoto, Taishiro; Watanabe, Koichiro; Uchida, Hiroyuki; Mimura, Masaru; Kane, John M; Correll, Christoph U

    2013-10-30

    While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ≤50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r(2)=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP.

  15. 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

  16. The Counselor in a Nuclear World: A Rationale for Awareness and Action.

    ERIC Educational Resources Information Center

    Gearhart, Jo Anne

    1984-01-01

    Explores a rationale for counselors' responses to the threat of nuclear annihilation and suggests some action possibilities. Includes a response by Milton Schwebel emphasizing professional roles, and by Albert Ellis emphasizing the dangers of religous zealotism. (Author/JAC)

  17. 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

  18. SRS SWPF Construction Completion

    SciTech Connect

    Craig, Jack; Sheppard, Frank; Marks, Pam

    2016-08-04

    Now that construction is complete, DOE and construction contractor Parsons, are focusing on testing the Savannah River Site’s Salt Waste Processing Facility (SWPF) systems and training the workforce to operate the plant in preparation for the start of operations. Once in operation, the SWPF will significantly increase processing rates at SRS tank farms in an effort to empty the site’s high-level radioactive waste tanks.

  19. SRS SWPF Construction Completion

    ScienceCinema

    Craig, Jack; Sheppard, Frank; Marks, Pam

    2016-08-17

    Now that construction is complete, DOE and construction contractor Parsons, are focusing on testing the Savannah River Site’s Salt Waste Processing Facility (SWPF) systems and training the workforce to operate the plant in preparation for the start of operations. Once in operation, the SWPF will significantly increase processing rates at SRS tank farms in an effort to empty the site’s high-level radioactive waste tanks.

  20. 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.

  1. Complete thoracic ectopia cordis.

    PubMed

    Alphonso, N; Venugopal, P S; Deshpande, R; Anderson, D

    2003-03-01

    Thoracic ectopia cordis is a rare congenital defect with very few reported survivors after surgical correction. We report a case of complete thoracic ectopia cordis with double outlet right ventricle. The diagnosis was established antenatally and a repair was undertaken soon after birth. The child remained stable and was extubated on the fifth post-operative day. Forty-eight hours later the child succumbed to an unexplained respiratory arrest. Also presented is a review of the different surgical strategies for this unusual condition.

  2. Complete Androgen Insensitivity Syndrome.

    PubMed

    Hashmi, Asra; Hanif, Farha; Hanif, Shumaila Muhammad; Abdullah, Farhan Essa; Shamim, Muhammad Shahid

    2008-07-01

    The incidence of Complete Androgen Insensitivity Syndrome (CAIS) is about 1 in 20,000. People with CAIS are normal appearing females, despite the presence of testes and a 46, XY chromosome constitution. We came across a case in which a 17 years old girl presented with the complaint of inguinal hernia and amenorrhea. Subsequent investigations were done revealing absence of female internal genitalia and the presence of abdominal mass, possibly testes. Syndrome has been linked to mutations in AR, the gene for the human Androgen Receptor, located at Xq11-12 leading to the insensitivity of the receptor to testosterone. Gonadectomy was performed and life long Hormone replacement therapy was advised.

  3. Insert tree completion system

    SciTech Connect

    Brands, K.W.; Ball, I.G.; Cegielski, E.J.; Gresham, J.S.; Saunders, D.N.

    1982-09-01

    This paper outlines the overall project for development and installation of a low-profile, caisson-installed subsea Christmas tree. After various design studies and laboratory and field tests of key components, a system for installation inside a 30-in. conductor was ordered in July 1978 from Cameron Iron Works Inc. The system is designed to have all critical-pressure-containing components below the mudline and, with the reduced profile (height) above seabed, provides for improved safety of satellite underwater wells from damage by anchors, trawl boards, and even icebergs. In addition to the innovative nature of the tree design, the completion includes improved 3 1/2-in. through flowline (TFL) pumpdown completion equipment with deep set safety valves and a dual detachable packer head for simplified workover capability. The all-hydraulic control system incorporates a new design of sequencing valve for both Christmas tree control and remote flowline connection. A semisubmersible drilling rig was used to initiate the first end flowline connection at the wellhead for subsequent tie-in to the prelaid, surface-towed, all-welded subsea pipeline bundle.

  4. In utero Repair of Myelomeningocele: Rationale, Initial Clinical Experience and a Randomized Controlled Prospective Clinical Trial

    PubMed Central

    Danzer, Enrico; Flake, Alan W.

    2008-01-01

    Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities, including paraplegia, hydrocephalus, Arnold-Chiari II malformation, incontinence, sexual dysfunction, skeletal deformations, and mental impairment. MMC was the first nonlethal anomaly to be treated by fetal surgery. Studies in animals provide compelling evidence that the primary cause of the neurological deficit associated with MMC is not simply incomplete neurulation but rather chronic mechanical injury and amniotic-fluid-induced chemical trauma that progressively damage the exposed neural tissue during gestation. Initial results suggest that the surgical repair of MMC before 25 weeks of gestation may preserve neurological function, reverse the hindbrain herniation of the Arnold-Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. As it is currently unknown whether fetal surgery for MMC is truly beneficial compared to standard postnatal care, a randomized, controlled clinical trial has been initiated within the United States. PMID:22479081

  5. Gene therapy in Parkinson's disease: rationale and current status.

    PubMed

    Feng, Li Rebekah; Maguire-Zeiss, Kathleen A

    2010-03-01

    utilizes rAAV2 to deliver glutamic acid decarboxylase to the subthalamic nucleus, converting a subset of excitatory neurons to GABA-producing cells. In contrast, the final clinical trial is aimed at protecting the degenerating nigrostriatum by striatal delivery of rAAV2 harbouring the neuroprotective gene, neurturin. Based on preclinical studies, this gene therapeutic approach is posited to slow disease progression by enhancing neuronal survival. In addition, we discuss the outcome of each clinical trial and discuss the potential rationale for the marginal yet incremental clinical advancements that have thus far been realized for Parkinson's disease gene therapy.

  6. Beyond complete positivity

    NASA Astrophysics Data System (ADS)

    Dominy, Jason M.; Lidar, Daniel A.

    2016-04-01

    We provide a general and consistent formulation for linear subsystem quantum dynamical maps, developed from a minimal set of postulates, primary among which is a relaxation of the usual, restrictive assumption of uncorrelated initial system-bath states. We describe the space of possibilities admitted by this formulation, namely that, far from being limited to only completely positive (CP) maps, essentially any C-linear, Hermiticity-preserving, trace-preserving map can arise as a legitimate subsystem dynamical map from a joint unitary evolution of a system coupled to a bath. The price paid for this added generality is a trade-off between the set of admissible initial states and the allowed set of joint system-bath unitary evolutions. As an application, we present a simple example of a non-CP map constructed as a subsystem dynamical map that violates some fundamental inequalities in quantum information theory, such as the quantum data processing inequality.

  7. Completely bootstrapped tokamak

    SciTech Connect

    Weening, R.H. ); Boozer, A.H. )

    1992-01-01

    Numerical simulations of the evolution of large-scale magnetic fields have been developed using a mean-field Ohm's law. The Ohm's law is coupled to a {Delta}{prime} stabilty analysis and a magnetic island growth equation in order to simulate the behavior of tokamak plasmas that are subject to tearing modes. In one set of calculations, the magnetohydrodynamic (MHD)-stable regime of the tokamak is examined via the construction of an {ital l}{sub {ital i}} -{ital q}{sub {ital a}} diagram. The results confirm previous calculations that show that tearing modes introduce a stability boundary into the {ital l}{sub {ital i}} -{ital q}{sub {ital a}} space. In another series of simulations, the interaction between tearing modes and the bootstrap current is investigated. The results indicate that a completely bootstrapped tokamak may be possible, even in the absence of any externally applied loop voltage or current drive.

  8. 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

    2017-03-23

    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.

  9. 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

  10. 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.

  11. 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

  12. Developing a Web-Based Weight Management Program for Childhood Cancer Survivors: Rationale and Methods

    PubMed Central

    Meagher, Susan; Scheurer, Michael; Folta, Sara; Finnan, Emily; Criss, Kerry; Economos, Christina; Dreyer, ZoAnn; Kelly, Michael

    2016-01-01

    Background Due to advances in the field of oncology, survival rates for children with cancer have improved significantly. However, these childhood cancer survivors are at a higher risk for obesity and cardiovascular diseases and for developing these conditions at an earlier age. Objective In this paper, we describe the rationale, conceptual framework, development process, novel components, and delivery plan of a behavioral intervention program for preventing unhealthy weight gain in survivors of childhood acute lymphoblastic leukemia (ALL). Methods A Web-based program, the Healthy Eating and Active Living (HEAL) program, was designed by a multidisciplinary team of researchers who first identified behaviors that are appropriate targets for weight management in childhood ALL survivors and subsequently developed the intervention components, following core behavioral change strategies grounded in social cognitive and self-determination theories. Results The Web-based HEAL curriculum has 12 weekly self-guided sessions to increase parents’ awareness of the potential impact of cancer treatment on weight and lifestyle habits and the importance of weight management in survivors’ long-term health. It empowers parents with knowledge and skills on parenting, nutrition, and physical activity to help them facilitate healthy eating and active living soon after the child completes intensive cancer treatment. Based on social cognitive theory, the program is designed to increase behavioral skills (goal-setting, self-monitoring, and problem-solving) and self-efficacy and to provide positive reinforcement to sustain behavioral change. Conclusions Lifestyle interventions are a priority for preventing the early onset of obesity and cardiovascular risk factors in childhood cancer survivors. Intervention programs need to meet survivors’ targeted behavioral needs, address specific barriers, and capture a sensitive window for behavioral change. In addition, they should be convenient

  13. Cervical spine fracture in a patient with ankylosing spondylitis causing a C2-T9 spinal epidural hematoma- Treatment resulted in a rapid and complete recovery from tetraplegia: Case report and literature review.

    PubMed

    Wong, Albert Sii Hieng; Yu, Denis Hee Youg

    2015-01-01

    Full recovery from tetraplegia is uncommon in cervical spine injury. This has not being reported for cervical spine fracture in a patient with ankylosing spondylitis causing spinal epidural hematoma. We report on a case of cervical spine fracture in a patient with ankylosing spondylitis who came with tetraplegia. He underwent a two stage fixation and fusion. He had a complete recovery. Two hours after the operation he regained full strength in all the limbs while in the Intensive Care Unit. He went back to full employment. There are only two other reports in the literature where patients with ankylosing spondylitis and extradural hematoma who underwent treatment within 12 h and recovered completely from tetraparesis and paraplegia respectively. Patient with ankylosing spondylitis has a higher incidence of spinal fracture and extradural hematoma. Good outcome can be achieved by early diagnosis and treatment. This can ensure not only a stable spine, but also a rapid and complete recovery in a tetraplegic patient.

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

    PubMed Central

    2016-01-01

    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. PMID:28119845

  15. A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother.

    PubMed

    Aulitzky, Anna; Friedrich, Katrin; Gläser, Dieter; Gastl, Regina; Kubisch, Christian; Ludolph, Albert C; Volk, Alexander E

    2014-12-15

    Hereditary spastic paraplegias (HSPs) represent a clinically and genetically heterogeneous group of diseases. Major symptoms comprise progressive bilateral leg stiffness, spasticity at rest and diffuse muscle weakness. Complex forms are characterized by additional symptoms like dementia, cerebellar dysfunction or seizures. Autosomal dominant, autosomal recessive, X-linked recessive and possibly mitochondrial inheritance have been described in familial HSP. The most frequently mutated gene in familial cases of uncomplicated autosomal dominant HSP is SPAST, however de novo mutations in SPAST are rarely found. Here, we report on the clinical and genetic findings in a family with three children afflicted by complex HSP and their unaffected parents. Although autosomal dominant inheritance seemed unlikely in this family, genetic testing revealed a novel SPAST mutation, c.1837G>C (p.Asp613His), in a heterozygous state in all affected individuals and somatic mosaicism of this mutation in the unaffected mother. Our study thus expands the knowledge on SPAST-associated HSP and emphasizes that de novo mutations and somatic mosaicism should be taken into consideration in HSP families presenting with a family history not suggestive for an autosomal dominant inheritance pattern.

  16. Phenomenological Analysis of Rationale for School Transfer Credit Policies

    ERIC Educational Resources Information Center

    Melton, Amye M.

    2012-01-01

    Students face challenges when attempting to transfer college credits; sometimes, the process results in having to retake classes already completed at another institution. A qualitative phenomenological study, grounded in an advocacy/participatory worldview, was used to explore how leaders of higher learning institutions determined reasons academic…

  17. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment.

    PubMed

    Klitgaard, Henrik; Matagne, Alain; Nicolas, Jean-Marie; Gillard, Michel; Lamberty, Yves; De Ryck, Marc; Kaminski, Rafal M; Leclercq, Karine; Niespodziany, Isabelle; Wolff, Christian; Wood, Martyn; Hannestad, Jonas; Kervyn, Sophie; Kenda, Benoit

    2016-04-01

    Despite availability of effective antiepileptic drugs (AEDs), many patients with epilepsy continue to experience refractory seizures and adverse events. Achievement of better seizure control and fewer side effects is key to improving quality of life. This review describes the rationale for the discovery and preclinical profile of brivaracetam (BRV), currently under regulatory review as adjunctive therapy for adults with partial-onset seizures. The discovery of BRV was triggered by the novel mechanism of action and atypical properties of levetiracetam (LEV) in preclinical seizure and epilepsy models. LEV is associated with several mechanisms that may contribute to its antiepileptic properties and adverse effect profile. Early findings observed a moderate affinity for a unique brain-specific LEV binding site (LBS) that correlated with anticonvulsant effects in animal models of epilepsy. This provided a promising molecular target and rationale for identifying selective, high-affinity ligands for LBS with potential for improved antiepileptic properties. The later discovery that synaptic vesicle protein 2A (SV2A) was the molecular correlate of LBS confirmed the novelty of the target. A drug discovery program resulted in the identification of anticonvulsants, comprising two distinct families of high-affinity SV2A ligands possessing different pharmacologic properties. Among these, BRV differed significantly from LEV by its selective, high affinity and differential interaction with SV2A as well as a higher lipophilicity, correlating with more potent and complete seizure suppression, as well as a more rapid brain penetration in preclinical models. Initial studies in animal models also revealed BRV had a greater antiepileptogenic potential than LEV. These properties of BRV highlight its promising potential as an AED that might provide broad-spectrum efficacy, associated with a promising tolerability profile and a fast onset of action. BRV represents the first selective SV2A

  18. Rationale for Seismic Measurements on Mars by a Single Station

    NASA Technical Reports Server (NTRS)

    Lognonne, P.; Banerdt, W. B.

    2003-01-01

    We present here some of the scientific objectives which can be achieved by a single seismic station on Mars, equipped with a 3 axis VBB seismometer and a 3 axis Short Period Seismometer. We assume that this station is also equipped with meteorological sensors, including infra-sound and pressure, in order to perform a complete meteorological noise correction. The science objectives are listed in order of increasing difficulty.

  19. 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

  20. Care of rats with complete high-thoracic spinal cord injury.

    PubMed

    Ramsey, John B G; Ramer, Leanne M; Inskip, Jessica A; Alan, Nima; Ramer, Matt S; Krassioukov, Andrei V

    2010-09-01

    The complications of spinal cord injury (SCI) increase in number and severity with the level of injury. A recent survey of SCI researchers reveals that animal models of high SCI are essential. Despite this consensus, most laboratories continue to work with mid- or low-thoracic SCI. The available data on cervical SCI in animals characterize incomplete injuries; for example, nearly all studies published in 2009 examine discrete, tract-specific lesions that are not clinically-relevant. A primary barrier to developing animal models of severe, higher SCI is the challenge of animal care, a critical determinant of experimental outcome. Currently, many of these practices vary substantially between laboratories, and are passed down anecdotally within institutions. The care of animals with SCI is complex, and becomes much more challenging as the lesion level ascends. In our experience, the care of animals with high-thoracic (T3) SCI is much more demanding than the care of animals with low-thoracic SCI, even though both injuries result in paraplegia. We have developed an animal care regimen for rats with complete high-thoracic SCI. Our practices have been refined over the past 7 years, in collaboration with animal care centre staff and veterinarians. During this time, we have cared for more than 300 rats with T3 complete transection SCI, with experimental end-points of up to 3 months. Here we provide details of our animal care procedures, including acclimatization, housing, diet, antibiotic prophylaxis, surgical procedures, post-operative monitoring, and prevention of complications. In our laboratory, this comprehensive approach consistently produces good outcomes following T3 complete transection SCI: using body weight as an objective indicator of animal health, we have found that our rats typically return to pre-operative weights within 10 days of T3 complete SCI. It is our hope that the information provided here will improve care of experimental animals, and facilitate

  1. 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.

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

    PubMed Central

    Moffet, Howard H

    2006-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:16824230

  3. 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.

  4. Mission statement rationales and organizational alignment in the not-for-profit health care sector.

    PubMed

    Bart, C K; Tabone, J C

    1998-01-01

    This article presents the findings from a research study conducted on the use of mission statements in not-for-profit health care organizations. In particular, the study sought to determine if a relationship exists between the initial "rationales" that led to the creation of a mission statement and hospital performance. The findings suggest that some of the rationales for developing mission statements are indeed more important than others and that organizational alignment with the mission statement is of key importance to both the mission's and the hospital's success.

  5. Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13).

    PubMed

    Hansen, J; Corydon, T J; Palmfeldt, J; Dürr, A; Fontaine, B; Nielsen, M N; Christensen, J H; Gregersen, N; Bross, P

    2008-05-02

    The mitochondrial chaperonin heat shock protein 60 (Hsp60) assists the folding of a subset of proteins localized in mitochondria and is an essential component of the mitochondrial protein quality control system. Mutations in the HSPD1 gene that encodes Hsp60 have been identified in patients with an autosomal dominant form of hereditary spastic paraplegia (SPG13), a late-onset neurodegenerative disorder characterized by a progressive paraparesis of the lower limbs. The disease-associated Hsp60-(p.Val98Ile) protein, encoded by the c.292G>A HSPD1 allele, has reduced chaperonin activity, but how its expression affects mitochondrial functions has not been investigated. We have studied mitochondrial function and expression of genes encoding mitochondrial chaperones and proteases in a human lymphoblastoid cell line and fibroblast cells from a patient who is heterozygous for the c.292G>A HSPD1 allele. We found that both the c.292G>A RNA transcript and the corresponding Hsp60-(p.Val98Ile) protein were present at comparable levels to their wild-type counterparts in SPG13 patient cells. Compared with control cells, we found no significant cellular or mitochondrial dysfunctions in SPG13 patient cells by assessing the mitochondrial membrane potential, cell viability, and sensitivity toward oxidative stress. However, a decreased expression of the mitochondrial protein quality control proteases Lon and ClpP, both at the RNA and protein level, was demonstrated in SPG13 patient cells. We propose that decreased levels of mitochondrial proteases Lon and ClpP may allow Hsp60 substrate proteins to go through more folding attempts instead of being prematurely degraded, thereby supporting productive folding in cells with reduced Hsp60 chaperonin activity. In conclusion, our studies with SPG13 patient cells expressing the functionally impaired mutant Hsp60 chaperonin suggest that reduction of the degradative activity of the protein quality control system may represent a previously

  6. Experiencing Functional Electrical Stimulation Roots on Education, and Clinical Developments in Paraplegia and Tetraplegia With Technological Innovation.

    PubMed

    Varoto, Renato; Cliquet, Alberto

    2015-10-01

    Cybernetics-based concepts can allow for complete independence for paralyzed individuals, including sensory motor recovery. Spinal cord injuries are responsible for a huge stress on health and a financial burden to society. This article focuses on novel procedures such as functional diagnosis for paraplegics and tetraplegics, cybertherapies toward lessening comorbidities such as cardiovascular diseases, osteoporosis, etc., and the production of new technology for upper and lower limb control. Functional electrical stimulation reflects a unique opportunity for bipedal gait to be achieved by paraplegics and tetraplegics. Education and training of undergraduates and postgraduates in engineering and life sciences have also been a major aim of this work.

  7. Rattlesnake Bites in Southern California and Rationale for Recommended Treatment

    PubMed Central

    Wingert, Willis A.; Chan, Linda

    1988-01-01

    Rattlesnake bite is most common in young men who often are intoxicated and have purposely handled a venomous snake. The incidence of bites is highest in the spring and early summer months, and they most often occur in the afternoon. The hands and feet only are involved in 95% of all bites. First-aid therapy should be limited to splinting the extremity and transporting the victim to a medical facility. Definitive therapy is administering antivenin (Crotalidae) polyvalent intravenously in adequate initial doses and repeating every two hours until the venom is completely neutralized. Serum sickness usually follows all doses of more than five vials but is readily controlled by giving corticosteroids. Bites are avoided by protecting the hands and feet, not handling venomous snakes, and using utmost caution while in the snakes' habitat. PMID:3277335

  8. Jordan tobacco dependence treatment guidelines: rationale and development.

    PubMed

    Ayub, H; Obeidat, N; Leischow, S; Glynn, T; Hawari, F

    2016-02-01

    Jordan, a high tobacco-burden country, has been working to expand its tobacco dependence treatment services and has completed development of its first customized treatment guidelines. Our paper presents the development process for these guidelines. A group of national and international experts was formed and a national situation analysis for tobacco dependence treatment practices and a detailed review of international evidence were conducted. The guidelines were then drafted and reviewed by national, regional and international experts and were official endorsed by the Jordanian Ministry of Health before being launched. The guidelines comprise concise descriptions and practical supplementary flowcharts covering the major elements of general tobacco dependence treatment. These are the first comprehensive Arabic-language guidelines, including a section focusing on waterpipe use, and we believe they are a reliable and useful resource for neighbouring countries seeking to develop similar guidelines.

  9. 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…

  10. 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,…

  11. Rationale and Methodology for a National Study of Higher Education Science and Engineering Learning Communities

    ERIC Educational Resources Information Center

    Coll, Richard K.

    2008-01-01

    This paper reports on a major national study of higher education science and engineering learning communities in New Zealand. The scope of the research project along with a description of the methodology and method used in the study together with rationale for the study and research approach adopted are provided here. Details of the theoretical…

  12. 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…

  13. 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…

  14. 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…

  15. Standards-Based Grading Practices among Practicing Music Educators: Prevalence and Rationale

    ERIC Educational Resources Information Center

    St. Pierre, Nathan A.; Wuttke, Brian C.

    2017-01-01

    This study sought to describe the prevalence of Standards-based grading (SBG) among practicing music teachers and report the rationale teachers provided for or against its use. Participants were music educators (N = 96) responsible for grading students. Most participants (52.08%, n = 50) indicated that they were not familiar with SBG. Many…

  16. 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…

  17. Slow-to-Recover Brain-Injured Patients: Rationale for Treatment.

    ERIC Educational Resources Information Center

    Ansell, Barbara J.

    1991-01-01

    This article addresses the theoretical rationale for treatment of slow-to-recover (STR) head-injury survivors with sensory stimulation programs. Evidence from four areas (sensory deprivation, enriched environments, nervous system plasticity, and sensitive periods of neurodevelopment) suggests that sensory stimulation programs are potentially…

  18. Introduction to Psychology and Leadership. Leadership Course; Phase I, Sequencing Rationale.

    ERIC Educational Resources Information Center

    Westinghouse Learning Corp., Annapolis, MD.

    The rationale for determining the content sequence of the leadership course developed for the United States Naval Academy by Westinghouse Learning Corporation (the final report appears under EM 010 418, EM 010 419, and EM 010 484) is discussed. Each of several theoretical bases for sequencing is discussed and sample applications of the rationale…

  19. 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…

  20. Rationale and Content for English-Language Arts. Survey of Academic Skills: Grade 12. Preliminary Edition.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    As a preliminary version of the rationale and content for the English-language arts portion of the "Survey of Academic Skills: Grade 12," this booklet describes elements of the new reading and editing tests to be used to complement a direct writing assessment in this part of the 1987-88 California Assessment Program (CAP). After a brief…

  1. The Rationale for Canadian Studies in Schools of the United States.

    ERIC Educational Resources Information Center

    Miles, Edward J.

    A rationale for the study of Canada by Americans is advocated in this paper. Among the justifications for the study are: our common geographical environment; our need to comparatively understand the cultural, economic, political, and social differences and similarities of the two countries; the part Canada can play in serving as a laboratory for…

  2. 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…

  3. A Rationale for the Development of an Extracurricular Employability Award at a British University

    ERIC Educational Resources Information Center

    Watson, Rose

    2011-01-01

    This article examines the rationale behind the development of employability awards in universities in the UK. Whilst recognising the value of the embedding of employability skills within the formal curriculum, the benefits of extracurricular activity are examined and it is argued that there is a case for the development of a wider range of…

  4. 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…

  5. Why These Data?: Rationales for Data Selection in Doctoral Student Presentations

    ERIC Educational Resources Information Center

    Sunderland, Jane

    2004-01-01

    Doctoral students' research presentations were investigated for the way in which the students articulated their rationales for data selection for their research projects. Rather than look for genre-related characteristics, though still working within the area of academic discourse (spoken), the objective of this study was to identify a set of…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. Implementing AAC with Children with Profound and Multiple Learning Disabilities: A Study in Rationale Underpinning Intervention

    ERIC Educational Resources Information Center

    Harding, Celia; Lindsay, Gemma; O'Brien, Aoife; Dipper, Lucy; Wright, Julie

    2011-01-01

    There is a developing research base to support the rationale underpinning augmentative and alternative communication (AAC) for people with learning disabilities. However, there is a paucity of research examining the process involved in implementing AAC support for people who have profound disabilities. This paper seeks to explore the processes…

  11. Wetlands Evaluation Technique (WET). Volume 1: Literature Review and Evaluation Rationale.

    DTIC Science & Technology

    1991-10-01

    Vegetation Class/Subclass (Primary) Ranking: Riverine wetlands dominated by aquatic bryophytes (mosses and liverworts) are most likely to discharge ground...water. Rationale: Because many bryophytes prefer water rich in carbon dioxide, they sometimes proliferate near springs (Hynes 1970/*R). Confidence in

  12. 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…

  13. Interagency Collaborative Arrangements and Activities: Types, Rationales, Considerations (Interagency Paper, Number 5, June 2011)

    DTIC Science & Technology

    2011-06-01

    Rebellion or Insurrection in 1794 . In this precedent-setting case, President George Washington, accompanied by Secretary of the Treasury Alexander...or unsuccessful; and operating under different rationales and restrictions. An early example was the federal government’s response to the Whiskey

  14. 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…

  15. 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.…

  16. Comprehensive Health Education Standards (Including Physical Activity Standards). Comprehensive Health Rationale.

    ERIC Educational Resources Information Center

    Arizona State Dept. of Education, Phoenix.

    Arizona's comprehensive health education standards begins with a health rationale for each standard, then details the seven standards: (1) students comprehend concepts related to health promotion and disease prevention; (2) students demonstrate the ability to access accurate health information; (3) students demonstrate the ability to practice…

  17. A Psychological Rationale in Support of the Alcoholics Anonymous' Concept of Fellowship.

    ERIC Educational Resources Information Center

    Machell, David F.

    1992-01-01

    Develops a theoretical rationale in support of the concept of "fellowship," the healing cornerstone of Alcoholics Anonymous (AA). Reviews supporting literature from the areas of personality theory, group psychotherapy, alcoholism psychopathology, and alcoholism psychological treatment. Suggests a common premise and common ground of…

  18. 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)

  19. 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…

  20. 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)

  1. 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

  2. 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

  3. A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.

    PubMed

    Blumkin, Lubov; Lerman-Sagie, Tally; Lev, Dorit; Yosovich, Keren; Leshinsky-Silver, Esther

    2011-06-15

    The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition.

  4. 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…

  5. Latino College Completion: North Dakota

    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…

  6. Latino College Completion: South Dakota

    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…

  7. Latino College Completion: New Jersey

    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…

  8. Latino College Completion: New Mexico

    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…

  9. Latino College Completion: Rhode Island

    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…

  10. High School Completion Longitudinal Study

    ERIC Educational Resources Information Center

    Alberta Education, 2009

    2009-01-01

    While Alberta enjoys proven high, world-class results in student achievement, raising high school completion rates is one of the top priorities in improving the provincial education system. The 2011-12 targeted high school completion rate is 82% five years after entering Grade 10--a 2.5% increase from the current average rate of 79.5%. The purpose…

  11. Ethnic variations in observance and rationale for postpartum sexual abstinence in Malawi.

    PubMed

    Zulu, E M

    2001-11-01

    Using quantitative and qualitative data from three culturally heterogeneous ethnic groups in Malawi, I show that differences in postpartum sexual abstinence are closely associated with community-specific rationales for the practice, particularly differences in the definition and timing of child-strengthening rituals that couples are required to perform before resuming intercourse. Contrary to conventional wisdom, the primary rationale for abstinence in the study areas is not linked to child spacing. Among Tumbukas in the north, most women perform the ritual immediately after resuming menstruation. Among the other ethnic groups, the rituals can be performed at any time after the end of postpartum bleeding. The study underscores the utility of the complementary micro-level approach in understanding reproductive behavior in sub-Saharan Africa.

  12. 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.

  13. The MeTeOR trial (Meniscal Tear in Osteoarthritis Research): rationale and design features.

    PubMed

    Katz, Jeffrey N; Chaisson, Christine E; Cole, Brian; Guermazi, Ali; Hunter, David J; Jones, Morgan; Levy, Bruce A; Mandl, Lisa A; Martin, Scott; Marx, Robert G; Safran-Norton, Clare; Roemer, Frank W; Skoniecki, Debra; Solomon, Daniel H; Spindler, Kurt P; Wright, John; Wright, Rick W; Losina, Elena

    2012-11-01

    This paper presents the rationale and design features of the MeTeOR Trial (Meniscal Tear in Osteoarthritis Research; Clinical Trials.gov NCT00597012). MeTeOR is an NIH-funded seven-center prospective randomized controlled trial (RCT) designed to establish the efficacy of arthroscopic partial meniscectomy combined with a standardized physical therapy program as compared with a standardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change (OA). The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges. The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features, with particular attention to those that present clinical and methodologic challenges.

  14. A rationale for the symmetries by base substitutions of degeneracy in the genetic code.

    PubMed

    Jestin, Jean-Luc

    2010-01-01

    The first symmetry by base substitutions of degeneracy in the genetic code was described by Rumer (1966) and the other symmetries were identified later by Jestin (2006) and Jestin and Soulé (2007). Here, a rationale accounting for these symmetries is reported. The number of non-synonymous substitutions over the replicated coding sequence is written as a function of the substitution matrix, whose elements are the number of substitutions from any codon to any other codon. The p-adic distance used as a similarity measure and applied to this matrix is shown to be biologically relevant. The rationale indicates that symmetries by base substitutions of degeneracy in the genetic code are symmetries of the measures of the number of non-synonymous substitutions for sets of synonymous codons.

  15. Utility-Interconnected Photovoltaic Systems: Evaluating the Rationale for the Utility-Accessible External Disconnect Switch

    SciTech Connect

    Coddington, M.; Margolis, R.M.; Aabakken, J.

    2008-01-01

    The utility-accessible alternating current (AC) external disconnect switch (EDS) for distributed generators, including photovoltaic (PV) systems, is a hardware feature that allows a utility?s employees to manually disconnect a customer-owned generator from the electricity grid. This paper examines the utility-accessible EDS debate in the context of utility-interactive PV systems for residential and small commercial installations. It also evaluates the rationale for EDS requirements.

  16. 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.

  17. [Biological review of completed suicide].

    PubMed

    Otsuka, Ikuo; Sora, Ichiro; Hishimoto, Akitoyo

    2016-06-01

    Family, twin and adoption studies have revealed genetic factors involved in suicide, while the accumulation of stress and mental illnesses are major contributing factors of suicide. Since higher lethality of suicidal behavior is considered to increase familial liability to suicidal behavior, we believe biological research of completed suicide is most important for a better understanding of the pathophysiology in suicide. Dysregulated hypothalamic-pituitary-adrenal axis has gained a special interest in the neurobiology of suicide, mostly because of the findings using a dexamethasone suppression test (DST), in which DST non-suppressors show a nearly 10-fold higher risk of completed suicide than DST suppressors in a depressed cohort. Other data mainly from postmortem brain studies indicate abnormalities of the noradrenergic-locus coeruleus system, serotonergic system, endogenous opioid system, brain-derived neurotrophic factor, inflammatory cytokines and omega-3 fatty acid in completed suicide. However, genetic research of complete suicide is behind other mental problems because it is extremely difficult to obtain tissue samples of completed suicide. Under the difficult situation, we now retain over 800 blood samples of suicide completers thanks to bereaved families' cooperation. We are actively working on the research of suicide, for instance, by performing a GWAS using 500 samples of suicide completers.

  18. Reregulation of the Swedish pharmacy sector-A qualitative content analysis of the political rationale.

    PubMed

    Wisell, Kristin; Winblad, Ulrika; Sporrong, Sofia Kälvemark

    2015-05-01

    In 2009, a reregulation of the Swedish pharmacy sector took place, and a fundamental change in ownership and structure followed. The reregulation provides an opportunity to reveal the politicians' views on pharmacies. The aim of this study was to explore and analyze the political arguments for the reregulation of the Swedish pharmacy sector in 2009. The method used was a qualitative content analysis of written political documents regarding the reregulation. The primary rationales for the reregulation were better availability, efficiency, price pressure, and safe usage of medicines. During the preparatory work, the rationales of diversity on the market and entrepreneurship were added, while the original rationales of efficiency, price pressure, and better usage of medicines were abandoned. The reform can be seen as a typical New Public Management reform influenced by the notion that private actors are better equipped to perform public activities. The results point to that the reform was done almost solely in order to introduce private ownership in the pharmacy sector, and was not initiated in order to solve any general problems, or to enhance patient outcomes of medicine use.

  19. An essay on Bergman completeness

    NASA Astrophysics Data System (ADS)

    Chen, Bo-Yong

    2013-10-01

    We give first of all a new criterion for Bergman completeness in terms of the pluricomplex Green function. Among several applications, we prove in particular that every Stein subvariety in a complex manifold admits a Bergman complete Stein neighborhood basis, which improves a theorem of Siu. Secondly, we give for hyperbolic Riemann surfaces a sufficient condition for when the Bergman and Poincaré metrics are quasi-isometric. A consequence is an equivalent characterization of uniformly perfect planar domains in terms of growth rates of the Bergman kernel and metric. Finally, we provide a noncompact Bergman complete pseudoconvex manifold without nonconstant negative plurisubharmonic functions.

  20. Genotype imputation via matrix completion

    PubMed Central

    Chi, Eric C.; Zhou, Hua; Chen, Gary K.; Del Vecchyo, Diego Ortega; Lange, Kenneth

    2013-01-01

    Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people. We describe an efficient genotype imputation method based on matrix completion. Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project. Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly. Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency. PMID:23233546

  1. Successful Completion of the Top-off Upgrade of the Advanced Light Source

    SciTech Connect

    Steier, C.; Bailey, B.; Baptiste, K.; Barry, W.; Biocca, A.; Byrne, W.; Casey, P.; Chin, M.; Donahue, R.; Duarte, R.; Fahmie, M.; Gath, B.; Jacobson, S.; Julian, J.; Jung, J. Y.; Kritscher, M.; Kwiatkowski, S.; Marks, S.; McKean, P.; Mueller, R.

    2010-06-23

    An upgrade of the Advanced Light Source (ALS) to enable top-off operation has been completed during the last four years. The final work centered around radiation safety aspects, culminating in a systematic proof that top-off operation is equally safe as decaying beam operation. Commissioning and transition to full user operations happened in late 2008 and early 2009. Top-off operation at the ALS provides a very large increase in time-averaged brightness (by about a factor of 10) as well as improvements in beam stability. The following sections provide an overview of the radiation safety rationale, commissioning results, as well as experience in user operations.

  2. JWST Primary Mirror Installation Complete

    NASA Video Gallery

    Completing the assembly of the primary mirror, which took place at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, is a significant milestone and the culmination of over a decade of desi...

  3. Is complete seizure control imperative?

    PubMed

    Andermann, Frederick

    2002-01-01

    Is complete control imperative? The answer depends on whether complete control is indeed possible, on the possibility of achieving modifications of lifestyle, and on the type of epilepsy, with particular reference to the presence of progressive dysfunction. This may be seen in patients with temporal lobe or other forms of focal epilepsy, in the epileptic encephalopathies such as West and Lennox Gastaut Syndromes and even in some patients with idiopathic generalized epilepsy. Progressive memory changes and global cognitive problems are examples. Progressive language deterioration, secondary epileptogenesis and phenomena analogous to kindling are also important issues. How long treatment should be continued depends on many factors, not least the preference of the patient and of the family. Weighing the benefits of complete control versus the side effects and risks of medication or surgery is crucial. There are obvious benefits to complete control; it is imperative if these benefits are greater than the cost.

  4. Tight informationally complete quantum measurements

    NASA Astrophysics Data System (ADS)

    Scott, A. J.

    2006-10-01

    We introduce a class of informationally complete positive-operator-valued measures which are, in analogy with a tight frame, 'as close as possible' to orthonormal bases for the space of quantum states. These measures are distinguished by an exceptionally simple state-reconstruction formula which allows 'painless' quantum state tomography. Complete sets of mutually unbiased bases and symmetric informationally complete positive-operator-valued measures are both members of this class, the latter being the unique minimal rank-one members. Recast as ensembles of pure quantum states, the rank-one members are in fact equivalent to weighted 2-designs in complex projective space. These measures are shown to be optimal for quantum cloning and linear quantum state tomography.

  5. Complete nitrification by Nitrospira bacteria

    PubMed Central

    Daims, Holger; Lebedeva, Elena V.; Pjevac, Petra; Han, Ping; Herbold, Craig; Albertsen, Mads; Jehmlich, Nico; Palatinszky, Marton; Vierheilig, Julia; Bulaev, Alexandr; Kirkegaard, Rasmus H.; von Bergen, Martin; Rattei, Thomas; Bendinger, Bernd; Nielsen, Per H.; Wagner, Michael

    2016-01-01

    Nitrification, the oxidation of ammonia via nitrite to nitrate, has always been considered as a two-step process catalyzed by chemolithoautotrophic microorganisms oxidizing either ammonia or nitrite. No known nitrifier carries out both steps, although complete nitrification should be energetically advantageous. This functional separation has puzzled microbiologists for a century. Here we report on the discovery and cultivation of a completely nitrifying bacterium from the genus Nitrospira, a globally distributed group of nitrite oxidizers. The genome of this chemolithoautotrophic organism encodes both the pathways for ammonia and nitrite oxidation, which are concomitantly expressed during growth by ammonia oxidation to nitrate. Genes affiliated with the phylogenetically distinct ammonia monooxygenase and hydroxylamine dehydrogenase genes of Nitrospira are present in many environments and were retrieved on Nitrospira-contigs in new metagenomes from engineered systems. These findings fundamentally change our picture of nitrification and point to completely nitrifying Nitrospira as key components of nitrogen-cycling microbial communities. PMID:26610024

  6. Program Costs and Student Completion

    ERIC Educational Resources Information Center

    Manning, Terri M.; Crosta, Peter M.

    2014-01-01

    Community colleges are under pressure to increase completion rates, prepare students for the workplace, and contain costs. Colleges need to know the financial implications of what are often perceived as routine decisions: course scheduling, program offerings, and the provision of support services. This chapter presents a methodology for estimating…

  7. Complete feeds-intensive systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most commercially cultivated fish are raised in high-density culture systems where the assumption is that the contribution of natural foods to the nutrition of the fish is insignificant. Thus, intensively cultured fish must be fed a nutritionally complete feed. A short section on the concept and im...

  8. Indiana College Completion. 2014 Report

    ERIC Educational Resources Information Center

    Indiana Commission for Higher Education, 2014

    2014-01-01

    The Indiana Commission for Higher Education is committed to providing a clearer and more comprehensive picture of college completion in order to inform and advance Indiana's collective efforts to boost education attainment. In partnership with Indiana public colleges and the National Student Clearinghouse, the Commission has collected completion…

  9. Completing College: Rethinking Institutional Action

    ERIC Educational Resources Information Center

    Tinto, Vincent

    2012-01-01

    Even as the number of students attending college has more than doubled in the past forty years, it is still the case that nearly half of all college students in the United States will not complete their degree within six years. It is clear that much remains to be done toward improving student success. For more than twenty years, Vincent Tinto's…

  10. A-3 steel work completed

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Stennis Space Center engineers celebrated a key milestone in construction of the A-3 Test Stand on April 9 - completion of structural steel work. Workers with Lafayette (La.) Steel Erector Inc. placed the last structural steel beam atop the stand during a noon ceremony attended by more than 100 workers and guests.

  11. Review of "A Complete Education"

    ERIC Educational Resources Information Center

    Warren, Beth

    2010-01-01

    The research summary, "A Complete Education," presents the Obama administration's proposal for ensuring that all students have a comprehensive education. The key areas include: strengthening instruction in literacy and in science, technology, engineering, and mathematics (STEM); increasing access to instruction in a broader range of subject…

  12. Addressing problems in complete dentures.

    PubMed

    LaBarre, Eugene; Giusti, Lola; Pitigoi-Aron, Gabriela

    2007-10-01

    The authors have compiled a set of solutions to the most common issues influencing the success of complete denture cases. A brief review and discussion of occlusal vertical dimension is presented, followed by a troubleshooting guide to problems such as inadequate retention and stability, discomfort, and other problems affecting treatment outcome.

  13. Shannon Information in Complete Genomes

    NASA Astrophysics Data System (ADS)

    Hsieh, Li-Ching; Chang, Chang-Heng; Lee, Hoong-Chien

    2004-03-01

    Genomes are books of life and necessarily carry a huge amount of information. This study was first motivated by the question: "How much information do complete genomes have?" As an answer we measured a particular type of Shannon information in all prokaryotes and eukaryotes whose complete genomes have been sequenced and are available in publically assessible database. The Shannon information in complete genome sequences follow an extremely simple pattern. With the exception of one eukaryote the Shannon information in all (more than 200) complete sequences belong to a single universality class given by a simple geometric recursion formula. The data are interpreted in terms of models for genome growth and inferred to suggest that the ancestors of present day genomes began to grow, mainly by stochastic, selectively neutral, duplications and short mutations, most likely when they were not more than 300 nt long. This notion of selective neutralism independently corroborates Kimura's neutral theory of evolution which was based on the investigation of polymorphisms of genes.

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

    PubMed Central

    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

    Purpose 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. Methods 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. Results 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%. Conclusion 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. PMID:26844121

  15. Racial and Ethnic Disparities in Functioning at Discharge and Follow-Up Among Patients With Motor Complete Spinal Cord Injury

    PubMed Central

    Fyffe, Denise C.; Deutsch, Anne; Botticello, Amanda L.; Kirshblum, Steven; Ottenbacher, Kenneth J.

    2015-01-01

    Objective To examine racial and ethnic differences in self-care and mobility outcomes for persons with a motor complete, traumatic spinal cord injury (SCI) at discharge and 1-year follow-up. Design Retrospective cohort study. Setting Sixteen rehabilitation centers contributing to the Spinal Cord Injury Model Systems (SCIMS) database. Participants Adults with traumatic, motor complete SCI (N=1766; American Spinal Injury Association Impairment Scale grade A or B) enrolled in the SCIMS between 2000 and 2011. Selected cases had complete self-reported data on race and ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic) and motor FIM scores assessed at inpatient rehabilitation admission, discharge, and 1-year follow-up. Interventions Not applicable. Main Outcome Measures Functional outcomes were measured by FIM self-care and mobility scores on a 1 to 7 FIM scale, at discharge and 1-year follow-up. Results Multiple regression models stratified by neurologic category and adjusted for sociodemographic and injury characteristics assessed racial and ethnic group differences in FIM self-care and mobility change scores at discharge and 1-year follow-up. At discharge, non-Hispanic black participants with tetraplegia and paraplegia had significantly poorer gains in FIM self-care and mobility scores relative to non-Hispanic white and Hispanic participants. At 1-year follow-up, similar FIM self-care and mobility change scores were found across racial and ethnic groups within each neurologic category. Conclusions Non-Hispanic white and Hispanic participants had comparatively more improvement in self-care and mobility during inpatient rehabilitation compared with non-Hispanic black participants. At 1-year follow-up, no differences in self-care and mobility outcomes were observed across racial and ethnic groups. Additional research is needed to identify potential modifiable factors that may contribute to racially and ethnically different patterns of functional outcomes

  16. The Ontario Prehospital Advanced Life Support (OPALS) Study: rationale and methodology for cardiac arrest patients.

    PubMed

    Stiell, I G; Wells, G A; Spaite, D W; Lyver, M B; Munkley, D P; Field, B J; Dagnone, E; Maloney, J P; Jones, G R; Luinstra, L G; Jermyn, B D; Ward, R; DeMaio, V J

    1998-08-01

    The Ontario Prehospital Advanced Life Support Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period. The study will evaluate the incremental benefit of rapid defibrillation and prehospital Advanced Cardiac Life Support measures for cardiac arrest survival and the benefit of Advanced Life Support for patients with traumatic injuries and other critically ill prehospital patients. This article describes the OPALS study with regard to the rationale and methodology for cardiac arrest patients.

  17. 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.

  18. Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals.

    PubMed

    Ferrero, Maria Elena

    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.

  19. 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

  20. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control

    PubMed Central

    Werneck, Guilherme Loureiro

    2014-01-01

    The control of zoonotic visceral leishmaniasis is a challenge, particularly in Brazil, where the disease has been gradually spreading across the country over the past 30 years. Strategies employed for decreasing the transmission risk are based on the control of vector populations and reservoirs; since humans are considered unnecessary for the maintenance of transmission. Among the adopted strategies in Brazil, the sacrifice of infected dogs is commonly performed and has been the most controversial measure. In the present study, we provide the rationale for the implementation of different control strategies targeted at reservoir populations and highlight the limitations and concerns associated with each of these strategies. PMID:25372177

  1. Biologic agents as adjunctive therapy for prostate cancer: a rationale for use with androgen deprivation.

    PubMed

    Nelson, Eric C; Cambio, Angelo J; Yang, Joy C; Lara, Primo N; Evans, Christopher P

    2007-02-01

    The prevalence of prostate cancer emphasizes the need for improved therapeutic options, particularly for metastatic disease. Current treatment includes medical or surgical castration, which initially induces apoptosis of prostate cancer cells, but ultimately an androgen-independent subpopulation emerges. In addition to a transient therapeutic effect, androgen-deprivation therapy (ADT) can initiate biochemical events that may contribute to the development of and progression to an androgen-independent state. This transition involves multiple signal transduction pathways that are accompanied by many biochemical changes resulting from ADT. These molecular events themselves are therapeutic targets and serve as a rationale for adjunctive treatment at the time of ADT.

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

    SciTech Connect

    Houde, Sebastien; Spurlock, C. Anna

    2016-04-01

    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.

  3. Pediatric therapeutic apheresis: rationale and indications for plasmapheresis, cytapheresis, extracorporeal photopheresis, and LDL apheresis.

    PubMed

    Kim, Yeowon A; Sloan, Steven R

    2013-12-01

    Apheresis refers to the removal of a component of the blood and is performed using a group of medical technologies in which peripheral blood is processed by an instrument that separates the various components. The selected component is isolated while the remainder is returned to the patient. The rationale behind therapeutic apheresis is to remove the pathogenic components from the circulation. Apheresis is also used for peripheral hematopoietic progenitor cell collection. The procedure can be safely performed in most children with modifications to account for smaller pediatric blood volumes.

  4. [Experimental rationale for the use of enterosorbents in acute ethanol intoxication].

    PubMed

    Orbidans, A G; Terekhin, G A; Vladimirskiĭ, E V; Terekhina, N A

    2009-01-01

    The experiment on 83 rats has provided a rationale for the use of enterosorbents in acute ethanol intoxication. Polysorb reduces the halflife of ethanol, recovers physical fitness in the animals with acute poisoning. The enterosorbents polysorb, litovit, and sapropel have been found to have a corrective effect on the level of the major plasma antioxidant ceruloplasmin in acute ethanol intoxication. Enterosorbents are an effective detoxifying agent in this condition. Examining the mechanisms of toxic action of ethanol allows the most expedient treatment policy to be substantiated in acute poisonings.

  5. Theoretical Rationale of Heating Block for Testing Bench of Aerospace Crafts Thermal Protection Elements

    NASA Astrophysics Data System (ADS)

    Petrova, Anna A.; Reznik, Sergey V.

    2016-02-01

    The theoretical rationale for the structural layout of a testing bench with zirconium dioxide heating elements on the basis of modelling radiative-conductive heat transfer are presented. The numerical simulation of radiative-conductive heat transfer for the two-dimensional scaled model of the testing segment with the finite-element analysis software package Ansys 15.0 are performed. The simulation results showed that for the selected layout of the heaters the temperature non-uniformity along the length of the sample over time will not exceed 3 % even at a temperature of 2000 K.

  6. Contour Completion Without Region Segmentation.

    PubMed

    Ming, Yansheng; Li, Hongdong; He, Xuming

    2016-08-01

    Contour completion plays an important role in visual perception, where the goal is to group fragmented low-level edge elements into perceptually coherent and salient contours. Most existing methods for contour completion have focused on pixelwise detection accuracy. In contrast, fewer methods have addressed the global contour closure effect, despite psychological evidences for its importance. This paper proposes a purely contour-based higher order CRF model to achieve contour closure, through local connectedness approximation. This leads to a simplified problem structure, where our higher order inference problem can be transformed into an integer linear program and be solved efficiently. Compared with the methods based on the same bottom-up edge detector, our method achieves a superior contour grouping ability (measured by Rand index), a comparable precision-recall performance, and more visually pleasing results. Our results suggest that contour closure can be effectively achieved in contour domain, in contrast to a popular view that segmentation is essential for this purpose.

  7. Complete EOS for PBX 9502

    SciTech Connect

    Menikoff, Ralph S

    2009-10-08

    PBX 9502 is an insensitive plastic-bonded explosive based on triamino-trinitrobenzene (TATB). A complete equation of state (EOS) is constructed for unreacted PBX 9502 suitable for reactive burn models, i.e., high pressure regime in which material strength is unimportant. The PBX EOS is composed of two parts: a complete EOS for TATB and a porosity model which allows for variations in the initial PBX density. The TATB EOS is based on a cold curve and a thermal model for lattice vibrations. The heat capacity, and hence thermal model, is determined by the vibrational spectrum from Raman scattering. The cold curve is calibrated to diamond anvil cell data for isothermal compression using a two-piece Keane fitting form. Hugoniot data for PBX 9502 is used as a consistency check.

  8. A complete subsea wireline system

    SciTech Connect

    Manzi, B.; Dines, C.; Headworth, C.

    1987-01-01

    At the present time there are around 400 subsea completions worldwide and even the most conservative surveys predict a doubling of this number within the next decade. This paper discusses the evolution and operation of a flexible, self-contained system which makes optimum use of existing technology thereby offering a safe, reliable and economical system for riserless re-entry into any subsea well.

  9. Complete liquefaction methods and apparatus

    SciTech Connect

    Turner, Terry D.; Wilding, Bruce M.

    2013-10-15

    A method and apparatus are described to provide complete gas utilization in the liquefaction operation from a source of gas without return of natural gas to the source thereof from the process and apparatus. The mass flow rate of gas input into the system and apparatus may be substantially equal to the mass flow rate of liquefied product output from the system, such as for storage or use.

  10. Complete normal ordering 1: Foundations

    NASA Astrophysics Data System (ADS)

    Ellis, John; Mavromatos, Nick E.; Skliros, Dimitri P.

    2016-08-01

    We introduce a new prescription for quantising scalar field theories (in generic spacetime dimension and background) perturbatively around a true minimum of the full quantum effective action, which is to 'complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all 'cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of 'complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative interactions, and by using a point splitting 'trick' we extend this result to theories with derivative interactions, such as those appearing as non-linear σ-models in the world-sheet formulation of string theory. We focus here on theories with trivial vacua, generalising the discussion to non-trivial vacua in a follow-up paper.

  11. 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.

  12. 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

  13. Examining reports and policies on cognitive enhancement: approaches, rationale, and recommendations.

    PubMed

    Outram, Simon M; Racine, Eric

    2011-01-01

    The phenomenon of cognitive enhancement is attracting attention in bioethics literature and beyond, in public policy. In response, three bodies--the British Medical Association (BMA); the Commission de l'éthique de la Science et de la technologie (CEST) du Québec; the American Academy of Neurology (AAN)--have produced reports and guidance on this topic. To gain insights into different public policy approaches, rationales, and recommendations on the topic, we analyzed these reports in depth. We found convergence on the definition (with the exception of the CEST) of cognitive enhancement. However, we noted a lack of critical reflection with respect to the underlying rationale for developing these reports, i.e., that cognitive enhancement practices are rampant and represent major social changes. As it currently stands, cognitive enhancement is constituted in a way that challenges the creation of coherent and effective policy recommendations. However, policy makers should not simply wait for definitional consensus and hope that on balance the benefits turn out to be greater than the risks. Some components of cognitive enhancement could be reduced down to clearly identified policy targets to be further examined. Then, if appropriate, policy should be created that is, amongst other criteria, beneficial to the majority of the population.

  14. 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

  15. The rationale of combined radiotherapy and chemotherapy - Joint action of Castor and Pollux.

    PubMed

    Brunner, Thomas B

    2016-08-01

    This article aims to review the rationale behind the combination of radiotherapy and chemotherapy. Theoretical concepts describing the principles of the joint effects of chemoradiotherapy are reviewed. Preclinical and clinical evidence are collected and summarised demonstrating the co-operation between the two modalities which form the mainstay of the treatment of most solid tumours. Initially, the evolution of chemoradiotherapy was mostly empirically driven which is true for both, the early studies and the experimental investigations, rather than relying on scientific rationale. To date, the revised Steel's model proposes five mechanisms, spatial cooperation, cytotoxic enhancement, biological co-operation, temporary modulation and normal tissue protection to describe the interaction between radiotherapy and chemotherapy. Chemoradiotherapy has become the standard modality for most patients with locally advanced solid tumours due to better control of loco-regional disease and prolonged survival. Gradually, molecular prediction of efficacy is integrated such as MGMT status for combining temozolomide with radiotherapy in glioblastoma. As molecular targeted drugs are ready to be taken into triple combinations with chemoradiotherapy it is crucial to have a good understanding of the mechanisms of chemoradiotherapy for the rational development of future combinations.

  16. 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.

  17. Whole-body hyperthermia. Rationale and potential use for cancer treatment.

    PubMed

    Page, R L; Thrall, D E; Dewhirst, M W; Meyer, R E

    1987-01-01

    Whole-body hyperthermia is the controlled elevation of systemic temperature for therapeutic purposes. Historically, this treatment has been used for symptomatic control of many diseases. Recently, the potential therapeutic benefit of whole-body hyperthermia in the management of neoplastic disease has been investigated vigorously. The rationale for improved tumor control is based on heat-induced enhancement of the antineoplastic effects of radiation and chemotherapy. Although the complex biologic interaction of heat and radiation has been studied for many years, chemotherapy combined with hyperthermia has been studied less thoroughly. Despite a lack of adequate long-term laboratory and clinical investigation, use of whole-body hyperthermia with chemotherapy and radiotherapy is a logical and potentially powerful therapeutic strategy for neoplasia. Relevant issues regarding the application of whole-body hyperthermia with more traditional modes of therapy are being studied in preliminary clinical trials involving dogs and humans. Identification of optimal timing and sequencing of adjunctive therapy, proper cytotoxic drug application, methods to further minimize toxicity, and heat-sensitive tumor types will lead to expanded clinical use of whole-body hyperthermia. The historical development, clinical rationale, and application of whole-body hyperthermia for the control of disseminated or refractory neoplasia in humans and dogs is reviewed.

  18. A systematic rationale for defining the significance of aircraft noise impacts.

    PubMed

    Fidell, Sanford; Mestre, Vincent; Schomer, Paul; Horonjeff, Richard; Reid, Tim

    2014-09-01

    Regulatory agencies often define strict, decibel-denominated thresholds of significance of noise impacts to protect some fraction of the residential population from exposure to highly annoying noise. Definitions of the "significance" of aircraft noise impacts and recommendations of land use "compatibility," however, typically lack detailed, systematic rationales. Instead, the definitions are justified by reference to decades-old policies that were adopted without benefit of modern understandings of noise-induced annoyance, by appeals to authority, and by generic citations of non-peer reviewed documents. Although regulatory policy decisions may properly take into consideration political and economic consequences, aspects of them are amenable to logical formalization. In particular, advances in understanding of community reaction to transportation noise now permit a systematic rationale for aircraft noise regulation. The current analyses show how regulatory policy positions can be derived from two parameters: (1) the minimal percentage of the population of a nominally average community to be protected from exposure to highly annoying noise; and (2) the percentage of all communities to which this degree of protection is intended to apply. Together with a reliable dosage-response relationship, these two parameters permit quantitatively justifiable definitions of significant noise impact.

  19. 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.

  20. Is quantum theory predictably complete?

    NASA Astrophysics Data System (ADS)

    Kupczynski, M.

    2009-07-01

    Quantum theory (QT) provides statistical predictions for various physical phenomena. To verify these predictions a considerable amount of data has been accumulated in the 'measurements' performed on the ensembles of identically prepared physical systems or in the repeated 'measurements' on some trapped 'individual physical systems'. The outcomes of these measurements are, in general, some numerical time series registered by some macroscopic instruments. The various empirical probability distributions extracted from these time series were shown to be consistent with the probabilistic predictions of QT. More than 70 years ago the claim was made that QT provided the most complete description of 'individual' physical systems and outcomes of the measurements performed on 'individual' physical systems were obtained in an intrinsically random way. Spin polarization correlation experiments (SPCEs), performed to test the validity of Bell inequalities, clearly demonstrated the existence of strong long-range correlations and confirmed that the beams hitting far away detectors somehow preserve the memory of their common source which would be destroyed if the individual counts of far away detectors were purely random. Since the probabilities describe the random experiments and are not the attributes of the 'individual' physical systems, the claim that QT provides a complete description of 'individual' physical systems seems not only unjustified but also misleading and counter productive. In this paper, we point out that we even do not know whether QT is predictably complete because it has not been tested carefully enough. Namely, it was not proven that the time series of existing experimental data did not contain some stochastic fine structures that could have been averaged out by describing them in terms of the empirical probability distributions. In this paper, we advocate various statistical tests that could be used to search for such fine structures in the data and to

  1. Kinematically complete chemical reaction dynamics

    NASA Astrophysics Data System (ADS)

    Trippel, S.; Stei, M.; Otto, R.; Hlavenka, P.; Mikosch, J.; Eichhorn, C.; Lourderaj, U.; Zhang, J. X.; Hase, W. L.; Weidemüller, M.; Wester, R.

    2009-11-01

    Kinematically complete studies of molecular reactions offer an unprecedented level of insight into the dynamics and the different mechanisms by which chemical reactions occur. We have developed a scheme to study ion-molecule reactions by velocity map imaging at very low collision energies. Results for the elementary nucleophilic substitution (SN2) reaction Cl- + CH3I → ClCH3 + I- are presented and compared to high-level direct dynamics trajectory calculations. Furthermore, an improved design of the crossed-beam imaging spectrometer with full three-dimensional measurement capabilities is discussed and characterization measurements using photoionization of NH3 and photodissociation of CH3I are presented.

  2. Complete Photo-production Experiments

    SciTech Connect

    D'Angelo, A.; Bartalini, O.; Fantini, A.; Schaerf, C.; Vegna, V.; Ardashev, K.; Bade, C.; Hicks, K.; Kizilgul, S.; Lucas, M.; Mahon, J.; Bellini, V.; Blecher, M.; Bocquet, J.-P.; Lleres, A.; Rebreyend, D.; Capogni, M.; Caracappa, A.; Kistner, O. C.; Miceli, L.

    2011-10-24

    The extraction of resonance parameters from meson photo-reaction data is a challenging effort, that would greatly benefit from the availability of several polarization observables, measured for each reaction channel on both proton and neutron targets. In the aim of obtaining such complete experiments, polarized photon beams and targets have been developed at facilities, worldwide. We report on the latest results from the LEGS and GRAAL collaborations, providing single and double polarization measurements on pseudo-scalar meson photo-production from the nucleon.

  3. Global warming: The complete briefing

    SciTech Connect

    Houghton, J.

    1994-12-31

    John Houghton has drawn on the exhaustive efforts of the Intergovernmental Panel on Climate Change (IPCC) to produce a notably compact, impeccably complete and authoritative, meticulously balanced, and lucidly presented guide to the complex yet vital issue of global warming. Its subtitle is not mere hyperbole: this truly is a complete briefing. Certainly, one could not ask for a more authoritative brief: Houghton has led an imposing series of national and international efforts relating to climate, including the most recent scientific assessments of the IPCC. Citing many concrete examples, Houghton begins by convincing that climate truly is important to humankind and that climate is far from constant. He then elucidates the mechanisms that maintain the benign climate of our planet, providing in the process, for example, the most accurate explanation of the natural greenhouse effect that has yet appeared in print. He then treats the individual greenhouse gases responsible for maintaining the earth`s warmth and presents projections of their probable future concentrations as influenced by human activities. Further chapters deal with conclusions drawn from climate models, estimates of the impacts on human activities, and possible policies and actions to mitigate or alleviate the changes and their consequences.

  4. Contour Completion without Region Segmentation.

    PubMed

    Ming, Yansheng; Li, Hongdong; He, Xuming

    2016-05-06

    Contour completion plays an important role in visual perception, where the goal is to group fragmented low-level edge elements into perceptually coherent and salient contours. Most existing methods for contour completion have focused on pixelwise detection accuracy. In contrast, fewer methods have addressed the global contour closure effect, despite of psychological evidences for its importance. This paper proposes a purely contour-based higher-order CRF model to achieve contour closure, through local connectedness approximation. This leads to a simplified problem structure, where our higher-order inference problem can be transformed into an integer linear program (ILP) and be solved efficiently. Compared with methods based on the same bottom-up edge detector, our method achieves a superior contour grouping ability (measured by Rand index), a comparable precision-recall performance, and more visually pleasing results. Our results suggest that contour closure can be effectively achieved in contour domain, in contrast to a popular view that segmentation is essential for this purpose.

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

    PubMed

    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

    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. RESUMO O papel da tuberculose como uma prioridade de saúde pública e a disponibilidade de ferramentas diagnósticas para avaliar o estado

  6. Stability of geodesically complete cosmologies

    NASA Astrophysics Data System (ADS)

    Creminelli, Paolo; Pirtskhalava, David; Santoni, Luca; Trincherini, Enrico

    2016-11-01

    We study the stability of spatially flat FRW solutions which are geodesically complete, i.e. for which one can follow null (graviton) geodesics both in the past and in the future without ever encountering singularities. This is the case of NEC-violating cosmologies such as smooth bounces or solutions which approach Minkowski in the past. We study the EFT of linear perturbations around a solution of this kind, including the possibility of multiple fields and fluids. One generally faces a gradient instability which can be avoided only if the operator (3) R δ N is present and its coefficient changes sign along the evolution. This operator (typical of beyond-Horndeski theories) does not lead to extra degrees of freedom, but cannot arise starting from any theory with second-order equations of motion. The change of sign of this operator prevents to set it to zero with a generalised disformal transformation.

  7. Stability of geodesically complete cosmologies

    SciTech Connect

    Creminelli, Paolo; Pirtskhalava, David; Santoni, Luca; Trincherini, Enrico

    2016-11-22

    We study the stability of spatially flat FRW solutions which are geodesically complete, i.e. for which one can follow null (graviton) geodesics both in the past and in the future without ever encountering singularities. This is the case of NEC-violating cosmologies such as smooth bounces or solutions which approach Minkowski in the past. We study the EFT of linear perturbations around a solution of this kind, including the possibility of multiple fields and fluids. One generally faces a gradient instability which can be avoided only if the operator {sup (3)} RδN is present and its coefficient changes sign along the evolution. This operator (typical of beyond-Horndeski theories) does not lead to extra degrees of freedom, but cannot arise starting from any theory with second-order equations of motion. The change of sign of this operator prevents to set it to zero with a generalised disformal transformation.

  8. Brainstem Monitoring in the Neurocritical Care Unit: A Rationale for Real-Time, Automated Neurophysiological Monitoring.

    PubMed

    Stone, James L; Bailes, Julian E; Hassan, Ahmed N; Sindelar, Brian; Patel, Vimal; Fino, John

    2017-02-01

    Patients with severe traumatic brain injury or large intracranial space-occupying lesions (spontaneous cerebral hemorrhage, infarction, or tumor) commonly present to the neurocritical care unit with an altered mental status. Many experience progressive stupor and coma from mass effects and transtentorial brain herniation compromising the ascending arousal (reticular activating) system. Yet, little progress has been made in the practicality of bedside, noninvasive, real-time, automated, neurophysiological brainstem, or cerebral hemispheric monitoring. In this critical review, we discuss the ascending arousal system, brain herniation, and shortcomings of our current management including the neurological exam, intracranial pressure monitoring, and neuroimaging. We present a rationale for the development of nurse-friendly-continuous, automated, and alarmed-evoked potential monitoring, based upon the clinical and experimental literature, advances in the prognostication of cerebral anoxia, and intraoperative neurophysiological monitoring.

  9. 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.

  10. CURRICULUM MATTERS: Authentic science in schools? - an evidence-based rationale

    NASA Astrophysics Data System (ADS)

    Woolnough, Brian E.

    2000-07-01

    Students can, and should, do open-ended projects in their school science education. This article draws together findings from a series of research investigations into students' research projects in schools. It finds that they are effective in developing core skills in students, especially problem-solving, communication and interpersonal skills; that they improve the attitudes of students towards science and technology and the likelihood that they will enter careers in these areas; and that they allow students to experience and develop one important type of authentic science in schools. It suggests that we now have a rationale for the inclusion of student research projects into the science curriculum and evidence that school science will be enriched and revived by the introduction of such authentic science.

  11. 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

  12. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description.

    PubMed

    Spitzer, R L; Williams, J B; Gibbon, M; First, M B

    1992-08-01

    The history, rationale, and development of the Structured Clinical Interview for DSM-III-R (SCID) is described. The SCID is a semistructured interview for making the major Axis I DSM-III-R diagnoses. It is administered by a clinician and includes an introductory overview followed by nine modules, seven of which represent the major axis I diagnostic classes. Because of its modular construction, it can be adapted for use in studies in which particular diagnoses are not of interest. Using a decision tree approach, the SCID guides the clinician in testing diagnostic hypotheses as the interview is conducted. The output of the SCID is a record of the presence or absence of each of the disorders being considered, for current episode (past month) and for lifetime occurrence.

  13. The epidemiological, clinical, and pathological rationale for the herpes zoster vaccine.

    PubMed

    Schmader, Kenneth; Gnann, John W; Watson, C Peter

    2008-03-01

    Worldwide, herpes zoster (HZ) affects millions of patients (particularly older adults) annually and causes significant suffering due to acute and chronic pain, or postherpetic neuralgia (PHN). The objective of this article is to explain the rationale for the HZ vaccine by summarizing data on the epidemiology of HZ in the immunocompetent host, with a focus on recent incidence and risk factor studies; to review information on the burden of HZ; and to discuss the challenges of lessening the morbidity of the disease. The incidence and severity of HZ and PHN are highest in older adults. Given the central nervous system damage caused by HZ, the difficulty of adequately treating HZ to prevent PHN, and the intractability of PHN, the advent of the HZ vaccine appears to be a crucial innovation for preventing HZ and PHN.

  14. Targeting 20-HETE producing enzymes in cancer – rationale, pharmacology, and clinical potential

    PubMed Central

    Alexanian, Anna; Sorokin, Andrey

    2013-01-01

    Studies demonstrate that lipid mediator 20-Hydroxyeicosatetraenoic acid (20-HETE) synthesis and signaling are associated with the growth of cancer cells in vitro and in vivo. Stable 20-HETE agonists promote the proliferation of cancer cells, whereas selective inhibitors of the 20-HETE-producing enzymes of the Cytochrome (CYP450)4A and CYP4F families can block the proliferation of glioblastoma, prostate, renal cell carcinoma, and breast cancer cell lines. A recent observation that the expression of CYP4A/4F genes was markedly elevated in thyroid, breast, colon, and ovarian cancer further highlights the significance of 20-HETE-producing enzymes in the progression of different types of human cancer. These findings provide the rationale for targeting 20-HETE-producing enzymes in human cancers and set the basis for the development of novel therapeutic strategies for anticancer treatment. PMID:23569388

  15. The prevention of youth violence. The rationale for and characteristics of four evaluation projects.

    PubMed

    Ikeda, R M; Simon, T R; Swahn, M

    2001-01-01

    In response to the magnitude of violence in the United States, a number of violence-prevention programs have been implemented throughout the country. However, relatively few have been rigorously evaluated for effectiveness. To encourage development and evaluation of violence-prevention interventions that focus on young children and their families, the Centers for Disease Control and Prevention (CDC) provided funding to four projects in 1996. This paper briefly describes the rationale for funding these projects, which is based on our understanding of the development of aggressive and violent behavior and on the literature regarding promising approaches to prevent problem behavior in this age group. We provide an overview of the four specific projects funded by the CDC as well as a short discussion of some of the many challenges encountered during their implementation.

  16. [A new neuromuscular transmission monitor (TOF Guard): the rationale behind the method and its clinical usefulness].

    PubMed

    Ueda, N; Masuda, Y; Muteki, T; Tsuda, H; Hiraki, T; Harada, H; Tobata, H

    1994-01-01

    TOF Guard is one of the latest developments in the field of neuromuscular monitoring equipment. This system uses a miniature acceleration transducer (a piezo-electric ceramic wafer is used), simply fastened to the thumb with tape. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. In this study, authors assessed the accuracy of this system in clinical use, comparing with the force transducer method (Myograph 2000). The result showed that there was a very close positive correlation between the values of T1, TOF ratio and posttetanic count simultaneously measured by both methods. The coefficient of correlation was 0.96, and its significance level was P < 0.001. From the clinical view point, it is concluded that TOF Guard is very useful because of its accuracy and because the equipment is easy to handle, compact and of low price as a neuromuscular monitoring system for routine anesthesia.

  17. Distress tolerance treatment for early-lapse smokers: rationale, program description, and preliminary findings.

    PubMed

    Brown, Richard A; Palm, Kathleen M; Strong, David R; Lejuez, Carl W; Kahler, Christopher W; Zvolensky, Michael J; Hayes, Steven C; Wilson, Kelly G; Gifford, Elizabeth V

    2008-05-01

    A significant percentage of individuals attempting smoking cessation lapse within a matter of days, and very few are able to recover to achieve long-term abstinence. This observation suggests that many smokers may have quit-attempt histories characterized exclusively by early lapses to smoking following quit attempts. Recent negative-reinforcement conceptualizations of early lapse to smoking suggest that individuals' reactions to withdrawal and inability to tolerate the experience of these symptoms, rather than withdrawal severity itself, may represent an important treatment target in the development of new behavioral interventions for this subpopulation of smokers. This article presents the theoretical rationale and describes a novel, multicomponent distress-tolerance treatment for early-lapse smokers that incorporates behavioral and pharmacological elements of standard smoking-cessation treatment, whereas drawing distress-tolerance elements from exposure-based and Acceptance and Commitment Therapy-based treatment approaches. Preliminary data from a pilot study (N = 16) are presented, and clinical implications are discussed.

  18. Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure.

    PubMed

    Lopatin, Yuri M; Rosano, Giuseppe M C; Fragasso, Gabriele; Lopaschuk, Gary D; Seferovic, Petar M; Gowdak, Luis Henrique W; Vinereanu, Dragos; Hamid, Magdy Abdel; Jourdain, Patrick; Ponikowski, Piotr

    2016-01-15

    Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

  19. Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy.

    PubMed

    Yuen, Alan W C; Sander, Josemir W

    2014-04-01

    There has been resurgence in the use of dietary treatment, principally the classical ketogenic diet and its variants, for people with epilepsy. These diets generally require significant medical and dietician support. An effective but less restrictive dietary regimen is likely to be more acceptable and more widely used. Calorie-restricted diets appear to produce a range of biochemical and metabolic changes including reduced glucose levels, reduced inflammatory markers, increased sirtuins, increased AMPK signaling, inhibition of mTOR signaling, and increase in autophagy. There are studies in animal seizure models that suggest that these biochemical and metabolic changes may decrease ictogenesis and epileptogenesis. A calorie-restricted diet might be effective in reducing seizures in people with epilepsy. Hence, there is a sufficient rationale to undertake clinical trials to assess the efficacy and safety of calorie-restricted diets in people with epilepsy.

  20. Why Telestroke networks? Rationale, implementation and results of the Stroke Eastern Saxony Network.

    PubMed

    Bodechtel, Ulf; Puetz, Volker

    2013-09-01

    Stroke is the third leading cause of death and the leading cause of acquired long-term disability in Europe and North America. Intravenous (IV) thrombolysis with alteplase and organized inpatient (stroke unit) care have been shown to improve stroke patients' functional outcomes. However, stroke unit care is not area-wide available and thrombolysis rates are low, partly due to limited stroke thrombolysis expertise in smaller community hospitals. Telemedical stroke networks (Telestroke network) with remote video assessment of patients and brain computed tomography (CT) scans by stroke neurologists have been shown to increase IV thrombolysis rates and functional outcomes of patients in smaller community hospitals. Our article summarizes the rationale, clinical, and currently published scientific results of Telestroke networks with special respect to the telemedical Stroke Eastern Saxony Network (SOS-NET), which has been established by the Dresden University Stroke Center (DUSC) in July 2007. From July 2007 to December 2012, 3416 teleconsultations have been performed within the SOS-NET.

  1. Scientific rationale for the development of gene therapy strategies for Parkinson's disease.

    PubMed

    Björklund, Tomas; Kirik, Deniz

    2009-07-01

    The ever-evolving understanding of the neuronal systems involved in Parkinson's disease together with the recent advances in recombinant viral vector technology has led to the development of several gene therapy applications that are now entering into clinical testing phase. To date, four fundamentally different approaches have been pursued utilizing recombinant adeno-associated virus and lentiviruses as vectors for delivery. These strategies aim either to restore the lost brain functions by substitution of enzymes critical for synthesis of neurotransmitters or neurotrophic factors as a means to boost the function of remaining neurons in the diseased brain. In this review we discuss the differences in mechanism of action and describe the scientific rationale behind the currently tested gene therapy approaches for Parkinson's disease in some detail and pinpoint their individual unique strengths and weaknesses.

  2. Prepectoral Implant-Based Breast Reconstruction: Rationale, Indications, and Preliminary Results.

    PubMed

    Sigalove, Steven; Maxwell, G Patrick; Sigalove, Noemi M; Storm-Dickerson, Toni L; Pope, Nicole; Rice, Jami; Gabriel, Allen

    2017-02-01

    Implant-based breast reconstruction is currently performed with placement of the implant in a subpectoral pocket beneath the pectoralis major muscle, by means of the dual-plane approach. Although the safety and breast aesthetics of this approach are well recognized, it is not without concerns. Animation deformities and accompanying patient discomfort, which are direct consequences of muscle elevation, can be severe in some patients. Moving the implant prepectorally may eliminate these concerns. For a successful prepectoral approach, the authors advocate use of their bioengineered breast concept, which was detailed in a previous publication. In this report, the authors discuss the rationale for prepectoral implant reconstruction, its indications/contraindications, and preliminary results from over 350 reconstructions.

  3. Rationale and Considerations for the Internet-Based Delivery of Parent-Child Interaction Therapy.

    PubMed

    Comer, Jonathan S; Furr, Jami M; Cooper-Vince, Christine; Madigan, Ryan J; Chow, Candice; Chan, Priscilla; Idrobo, Fabio; Chase, Rhea M; McNeil, Cheryl B; Eyberg, Sheila M

    2015-08-01

    Given the enormous individual, familial, and societal costs associated with early disruptive behavior disorders, transformative efforts are needed to develop innovative options for overcoming traditional barriers to effective care and for broadening the availability of supported interventions. This paper presents the rationale and key considerations for a promising innovation in the treatment of early-onset disruptive behavior disorders-that is, the development of an Internet-based format for the delivery of Parent-Child Interaction Therapy (PCIT) directly to families in their own homes. Specifically, we consider traditional barriers to effective care, and discuss how technological innovations can overcome problems of treatment availability, accessibility, and acceptability. We then detail our current Internet-delivered PCIT treatment program (I-PCIT), which is currently being evaluated across multiple randomized clinical trials relative to waitlist comparison, and to traditional in-office PCIT. Embedded video clips of children treated with I-PCIT are used to illustrate novel aspects of the treatment.

  4. Resolution of bilateral moyamoya associated collateral vessel aneurysms: Rationale for endovascular versus surgical intervention

    PubMed Central

    Amin-Hanjani, Sepideh; Goodin, Sean; Charbel, Fady T.; Alaraj, Ali

    2014-01-01

    Background: Management of aneurysms associated with deep collateral vessels in moyamoya disease is challenging both from an endovascular and a surgical standpoint. Difficulties with access or localization, and compromise of the collateral circulation with subsequent ischemia are the primary concerns, making direct obliteration potentially unfeasible or risky. Alternatively, superficial temporal artery–middle cerebral artery bypass is another potential strategy for resolution of these aneurysms. Case Description: Presented are the findings and management for a patient with moyamoya disease and bilateral deep collateral vessel aneurysms, successfully treated with endovascular obliteration following a right-sided hemorrhage and subsequently with bypass for an unruptured but growing contralateral aneurysm. Conclusions: A rationale and approach to management is outlined, as derived from review of the current literature and the illustrative case with bilateral collateral vessel aneurysms. PMID:25071939

  5. Organ Donation in the 50+ Age Demographic: Survey Results on Decision Rationale and Information Preferences.

    PubMed

    Tartaglia, Alexander; Dodd-McCue, Diane; Myer, Kevin A; Mullins, Andrew

    2016-09-01

    The rate of organ donation by older potential donors is significantly declining even though recent studies show positive clinical outcomes with organs transplanted from older donors. This study examined the 50+ age demographic to identify the rationale for donation decisions, preferred media methods of donation information delivery, and responsiveness to an age-tailored donation message. Results from 579 surveys, 87% from the 50+ age demographic, found respondents prone to self-select themselves as medically ineligible based on current medication and health status, even though they might be medically suitable donors. Their incentive to pursue additional information on donation is limited except when motivated by personal accounts within their families and communities. In addition, even when computer literate, they continue to favor the printed or spoken word for donation information delivery. The results suggest an opportunity for those working with older adults to develop more personalized, localized donation education programs targeting this age demographic.

  6. 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.

  7. 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.

  8. Scientific rationale behind the development and approval of biosimilar infliximab (CT-P13) in Europe.

    PubMed

    Müller-Ladner, Ulf; Hong, SeungSuh; Oh, Choongseob; Taylor, Peter

    2015-01-01

    Biosimilars are drugs developed to be highly similar to their originator biologic (or 'reference medicinal product') with no clinically meaningful differences in purity, efficacy or safety. Production of biologics and biosimilars is highly complex and sensitive, with any change in manufacturing process having a potential impact on efficacy and safety. This review provides an overview of the manufacturing process for these drugs and considers the implications of any process changes. The scientific rationale underlying the regulatory comparability exercise for process-changed reference medicinal products and biosimilars is also discussed, as is the issue of 'switchability' from a reference medicinal product to its biosimilar. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab, is used as a case study to discuss these issues.

  9. [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).

  10. Completed Suicides and their Previous Attempts

    ERIC Educational Resources Information Center

    Lester, David; Beck, Aaron T.

    1976-01-01

    Investigates the reliability of the findings of Ovenstone and Krietman (some completed suicides have attempted suicide previously, whereas other completed suicides have no such history) with a sample of completed suicides in the United States. (Author/RK)

  11. Stimulation rationale for shale gas wells: a state-of-the-art report

    SciTech Connect

    Young, C.; Barbour, T.; Blanton, T.L.

    1980-12-01

    Despite the large quantities of gas contained in the Devonian Shales, only a small percentage can be produced commercially by current production methods. This limited production derives both from the unique reservoir properties of the Devonian Shales and the lack of stimulation technologies specifically designed for a shale reservoir. Since October 1978 Science Applications, Inc. has been conducting a review and evaluation of various shale well stimulation techniques with the objective of defining a rationale for selecting certain treatments given certain reservoir conditions. Although this review and evaluation is ongoing and much more data will be required before a definitive rationale can be presented, the studies to date do allow for many preliminary observations and recommendations. For the hydraulic type treatments the use of low-residual-fluid treatments is highly recommended. The excellent shale well production which is frequently observed with only moderate wellbore enlargement treatments indicates that attempts to extend fractures to greater distances with massive hydraulic treatments are not warranted. Immediate research efforts should be concentrated upon limiting production damage by fracturing fluids retained in the formation, and upon improving proppant transport and placement so as to maximize fracture conductivity. Recent laboratory, numerical modeling and field studies all indicate that the gas fracturing effects of explosive/propellant type treatments are the predominate production enhancement mechanism and that these effects can be controlled and optimized with properly designed charges. Future research efforts should be focused upon the understanding, prediction and control of wellbore fracturing with tailored-pulse-loading charges. 36 references, 7 figures, 2 tables.

  12. 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

  13. New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale.

    PubMed

    Grégoire, N; Mimoz, O; Mégarbane, B; Comets, E; Chatelier, D; Lasocki, S; Gauzit, R; Balayn, D; Gobin, P; Marchand, S; Couet, W

    2014-12-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.

  14. Permanent sample plots for natural tropical forests: a rationale with special emphasis on Central Africa.

    PubMed

    Picard, Nicolas; Magnussen, Steen; Banak, Ludovic Ngok; Namkosserena, Salomon; Yalibanda, Yves

    2010-05-01

    Permanent sample plots (PSP), where trees are individually and permanently marked, have received increased interest in Central Africa as a tool to monitor vegetation changes. Although techniques for mounting PSP in tropical forests are well known, their planning still deserves attention. This study aims at defining a rationale for determining the size and number of replicates for setting up PSP in mixed tropical forests. It considers PSP as a sampling plan to estimate a target quantity with its associated margin of error. The target quantity considered here is the stock recovery rate, which is a key parameter for forest management in Central Africa. It is computed separately for each commercial species. The number of trees to monitor for each species defines the margin of error on the stock recovery rate. The size and number of replicated plots is obtained as the solution of an optimization problem that consists in minimizing the margin of error for every species while ensuring that the mounting cost remains below a given threshold. This rationale was applied using the data from the M'Baïki experimental site in the Central African Republic. It showed that the stock recovery rate is a highly variable quantity, and that the typical cost that forest managers are prone to devote to PSP leads to high margins of error. It also showed that the size and number of replicated plots is related to the spatial pattern of trees: clustered or spatially heterogeneous patterns favor many small plots, whereas regular or spatially homogeneous patterns favor few large plots.

  15. Completing HST's Local Volume Legacy

    NASA Astrophysics Data System (ADS)

    Dalcanton, Julianne

    2007-07-01

    Nearby galaxies offer one of the few laboratories within which stellar populations can be tied to multi-wavelength observations. They are thus essential for calibrating and interpreting key astrophysical observables, such as broad-band luminosities, durations and energy input from starbursts, and timescales of UV, H-alpha, and FIR emission. The study of stellar populations in nearby galaxies requires high-resolution observations with HST, but HST's legacy for this limited set of galaxies remains incomplete.As a first attempt to establish this legacy, The ACS Nearby Galaxy Survey Treasury {ANGST} began observations in late 2006. ANGST was designed to carry out a uniform multi-color survey of a volume-limited sample of 70 nearby galaxies that could be used for systematic studies of resolved stellar populations. The resulting data provide nuanced constraints on the processes which govern star formation and galaxy evolution, for a well-defined population of galaxies. All photometry for the survey has been publicly released.However, the failure of ACS 4.5 months after ANGST began taking data led to a drastic reduction in the planned survey. The loss is two-fold. First, the goals of completeness and uniformity were greatly compromised, impacting global comparison studies. Second, the variety of observed star formation histories was reduced. Given that we have never found two galaxies with identical star formation histories, and fully sampling the population allows us to catch those few systems whose star formation rates and metallicities place the strongest constraints on key astrophysical processes.Here we propose WFPC2 observations of all remaining galaxies within the Local Volume {D<3.5Mpc} for which current HST observations are insufficient for meaningful stellar population studies. We will use these observations for research on the star formation histories of individual galaxies and the Local Volume, detailed calibrations of star formation rate indicators, and the

  16. Complete Basis Set Model Chemistries

    NASA Astrophysics Data System (ADS)

    Ochterski, Joseph Wallace

    1994-01-01

    The major source of error in most ab initio calculations of molecular energies is the truncation of the one-electron basis set. Extrapolation to the complete basis set second -order (CBS2) limit using the N^{-1 } asymptotic convergence of N-configuration pair natural orbital (PNO) expansions can be combined with the use of relatively small basis sets for the higher-order correlation energy to develop cost effective computational models. Following this strategy, four new computational models denoted CBS-4, CBS-q, CBS-Q, and CBS-QCI/APNO are introduced. The mean absolute deviations (MAD) from experiment for the 125 energies of the G2 test set are 2.0, 1.7, 1.0 and 0.5 kcal/mol, respectively. The error distributions for all six models are indistinguishable from Gaussian distribution functions. Calculations on the cyclopropenyl radical and cyclopropenylidene provide new dissociation energies which are in accord with an interpretation of the thermochemistry emphasizing aromaticity. Several levels of theory are examined as candidates for the routine calculation of molecular geometries. The very simple UHF/3-21G* model gives bond lengths to an accuracy of +/-0.027 A compared with experiment for a test set of 69 small molecules. The commonly used MP2/6-31G* model (RMS error 0.025 A) offers virtually no improvement and use of the considerably more expensive QCISD calculations with the same basis set provides only a modest reduction to 0.020 A. However, spin projected MP3 calculations with a modified basis set including f -functions on Si, P, S, and Cl, reduce the RMS error to 0.010 A. This PMP3/6-31Gdf* model is recommended as a general scheme of geometry optimization for small molecules. The equilibrium structure and binding energy of the water dimer have been determined for several levels of ab initio theory. The basis set convergence of the SCF energy, the intramolecular and intermolecular MP2 energy, and higher-order effects, are examined separately and realistic error

  17. Link prediction via matrix completion

    NASA Astrophysics Data System (ADS)

    Pech, Ratha; Hao, Dong; Pan, Liming; Cheng, Hong; Zhou, Tao

    2017-02-01

    Inspired by the practical importance of social networks, economic networks, biological networks and so on, studies on large and complex networks have attracted a surge of attention in the recent years. Link prediction is a fundamental issue to understand the mechanisms by which new links are added to the networks. We introduce the method of robust principal component analysis (robust PCA) into link prediction, and estimate the missing entries of the adjacency matrix. On the one hand, our algorithm is based on the sparse and low-rank property of the matrix, while, on the other hand, it also performs very well when the network is dense. This is because a relatively dense real network is also sparse in comparison to the complete graph. According to extensive experiments on real networks from disparate fields, when the target network is connected and sufficiently dense, whether it is weighted or unweighted, our method is demonstrated to be very effective and with prediction accuracy being considerably improved compared to many state-of-the-art algorithms.

  18. Heavy duty complete extension slides

    NASA Astrophysics Data System (ADS)

    Bueno, José Ignacio; Vázquez, Javier

    2001-09-01

    The selection from available commercial market of a set of slides to be used in an habitable pressurised module in space, to draw a 660 mm box out of a rack, up to a completely extracted position in a safely supported configuration, seems in principle not to be a complicated task. That was the first approach taken in the design process of the telescopic guides of the Crew Work Bench (CWB) included in the Fluid Science Laboratory (FSL), part of "ESA Microgravity Facilities for Columbus" within the Columbus Orbital Facility (COF) of the International Space Station (ISS). Nevertheless, common space compatible requirements such as materials, specific environmental loads, available envelope, total weight, etc., can make the selection of telescopic slides from commercial market unfeasible. A specific development to design space compatible telescopic slides for the CWB was undertaken. A set of heavy duty space compatible telescopic slides were designed, manufactured and tested. They should be operative in both, 1-g environment and in orbit, and additionally should withstand an inadvertent astronaut kick or bump of 556 N in any direction.

  19. A complete model of turbulence

    NASA Technical Reports Server (NTRS)

    Wilcox, D. C.; Traci, R. M.

    1976-01-01

    A set of constitutive equations suitable for a priori computation of turbulent shear flows has been developed. Since no properties of a given turbulent flow need be known in advance in order to obtain a solution, the equations comprise a complete model of turbulence. Perturbation analysis shows that the model predicts a composite five-layer structure for an incompressible turbulent boundary layer, viz, a defect layer, a law-of-the-wall layer, a viscous sublayer, a near-surface roughness layer, and a viscous superlayer at the boundary-layer edge. Analysis of the defect layer demonstrates the key improvement of the model over its predecessor, the Saffman-Wilcox two-equation model of turbulence. Examination of model-predicted sublayer structure yields model-parameter boundary conditions appropriate for surfaces with roughness and mass injection. Results of numerical computations of compressible and incompressible equilibrium boundary layers show that, for such flows, the model is as accurate as mixing-length theory. Applications to transitional boundary layers and to nonequilibrium relaxation of a boundary layer passing from a rough to a smooth surface indicate that the model's applicability extends far beyond that of mixing-length theory's.

  20. A Model Incorporating the Rationale and Purpose for Conducting Mixed-Methods Research in Special Education and beyond

    ERIC Educational Resources Information Center

    Collins, Kathleen M. T.; Onwuegbuzie, Anthony J.; Sutton, Ida L.

    2006-01-01

    This article provides a typology of reasons for conducting mixed-methods research in special education. The mixed-methods research process is described along with the role of the rationale and purpose of study. The reasons given in the literature for utilizing mixed-methods research are explicated, and the limitations of these reason frameworks…

  1. 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…

  2. 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…

  3. Preliminary Reading Literacy Assessment Framework: Foundation and Rationale for Assessment and System Design. Research Report. ETS RR-13-30

    ERIC Educational Resources Information Center

    Sabatini, John; O'Reilly, Tenaha; Deane, Paul

    2013-01-01

    This report describes the foundation and rationale for a framework designed to measure reading literacy. The aim of the effort is to build an assessment system that reflects current theoretical conceptions of reading and is developmentally sensitive across a prekindergarten to 12th grade student range. The assessment framework is intended to…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 24 CFR 884.212 - Project completion.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 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...

  17. 24 CFR 884.212 - Project completion.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 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...

  18. 30 CFR 250.505 - Subsea completions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Subsea completions. 250.505 Section 250.505... OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Well-Completion Operations § 250.505 Subsea completions. No subsea well completion shall be commenced until the lessee obtains written approval from...

  19. 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

  20. Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial – Cell phone Intervention for You (CITY)

    PubMed Central

    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.

    2014-01-01

    Background 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. Purpose 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. Methods 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 12 months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. Conclusions If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. PMID:24462568

  1. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma.

    PubMed

    Milhollen, Michael A; Traore, Tary; Adams-Duffy, Jennifer; Thomas, Michael P; Berger, Allison J; Dang, Lenny; Dick, Lawrence R; Garnsey, James J; Koenig, Erik; Langston, Steven P; Manfredi, Mark; Narayanan, Usha; Rolfe, Mark; Staudt, Louis M; Soucy, Teresa A; Yu, Jie; Zhang, Julie; Bolen, Joseph B; Smith, Peter G

    2010-09-02

    MLN4924 is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor. In most cancer cells tested, inhibition of NAE leads to induction of DNA rereplication, resulting in DNA damage and cell death. However, in preclinical models of activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), we show that MLN4924 induces an alternative mechanism of action. Treatment of ABC DLBCL cells with MLN4924 resulted in rapid accumulation of pIkappaBalpha, decrease in nuclear p65 content, reduction of nuclear factor-kappaB (NF-kappaB) transcriptional activity, and G(1) arrest, ultimately resulting in apoptosis induction, events consistent with potent NF-kappaB pathway inhibition. Treatment of germinal-center B cell-like (GCB) DLBCL cells resulted in an increase in cellular Cdt-1 and accumulation of cells in S-phase, consistent with cells undergoing DNA rereplication. In vivo administration of MLN4924 to mice bearing human xenograft tumors of ABC- and GCB-DLBCL blocked NAE pathway biomarkers and resulted in complete tumor growth inhibition. In primary human tumor models of ABC-DLBCL, MLN4924 treatment resulted in NF-kappaB pathway inhibition accompanied by tumor regressions. This work describes a novel mechanism of targeted NF-kappaB pathway modulation in DLBCL and provides strong rationale for clinical development of MLN4924 against NF-kappaB-dependent lymphomas.

  2. 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.

  3. The rationale for simple approaches for sustainability assessment and management in contaminated land practice.

    PubMed

    Bardos, R Paul; Bone, Brian D; Boyle, Richard; Evans, Frank; Harries, Nicola D; Howard, Trevor; Smith, Jonathan W N

    2016-09-01

    The scale of land-contamination problems, and of the responses to them, makes achieving sustainability in contaminated land remediation an important objective. The Sustainable Remediation Forum in the UK (SuRF-UK) was established in 2007 to support more sustainable remediation practice in the UK. The current international interest in 'sustainable remediation' has achieved a fairly rapid consensus on concepts, descriptions and definitions for sustainable remediation, which are now being incorporated into an ISO standard. However the sustainability assessment methods being used remain diverse with a range of (mainly) semi-quantitative and quantitative approaches and tools developed, or in development. Sustainability assessment is site specific and subjective. It depends on the inclusion of a wide range of considerations across different stakeholder perspectives. Taking a tiered approach to sustainability assessment offers important advantages, starting from a qualitative assessment and moving through to semi-quantitative and quantitative assessments on an 'as required' basis only. It is also clear that there are a number of 'easy wins' that could improve performance against sustainability criteria right across the site management process. SuRF-UK has provided a checklist of 'sustainable management practices' that describes some of these. This paper provides the rationale for, and an outline of, and recently published SuRF-UK guidance on preparing for and framing sustainability assessments; carrying out qualitative sustainability assessment; and simple good management practices to improve sustainability across contaminated land management activities.

  4. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

    PubMed Central

    Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

    2016-01-01

    Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

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

    PubMed Central

    Deliyski, Dimitar D.; Hillman, Robert E.

    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 provided. Specific justification is described for each component of the term high-speed videoendoscopy, which is compared and contrasted with alternative terminologies in the literature. Results In addition to the ubiquitous high-speed descriptor, the term endoscopy is necessary to specify the appropriate imaging technology and distinguish among modalities such as ultrasound, magnetic resonance imaging, and nonendoscopic optical imaging. Furthermore, the term video critically indicates the electronic recording of a sequence of optical still images representing scenes in motion, in contrast to strobed images using high-speed photography and non-optical high-speed magnetic resonance imaging. High-speed videoendoscopy thus concisely describes the technology and can be appended by the desired anatomical nomenclature such as laryngeal. Conclusions Laryngeal high-speed videoendoscopy strikes a balance between conciseness and specificity when referring to the typical high-speed imaging method performed on human participants. Guidance for the creation of future terminology provides clarity and context for current and future experiments and the dissemination of results among researchers. PMID:26375398

  6. NESC Peer-Review of the Flight Rationale for Expected Debris Report. Version 1.0

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.; Raju, Ivatury S.; Stadler, John H.; Piascik, Robert S.; Kramer-White, Julie A.; Labbe, Steve G.; Ungar, Eugene K.; Rotter, Hank A.; Rogers, James H.; Null, Cynthia H.

    2005-01-01

    Since the loss of Columbia on February 1, 2003, the Space Shuttle Program (SSP) has significantly improved the understanding of launch and ascent debris, implemented hardware modifications to reduce debris, and conducted tests and analyses to understand the risks associated with expected debris. The STS-114 flight rationale for expected debris relies on a combination of all three of these factors. A number of design improvements have been implemented to reduce debris at the source. The External Tank (ET) thermal protection system (TPS) foam has been redesigned and/or process improvements have been implemented in the following locations: the bipod closeout, the first ten feet of the liquid hydrogen (LH2) tank protuberance air load (PAL) ramp, and the LH2 tank-to-intertank flange closeout. In addition, the forward bipod ramp has been eliminated and heaters have been installed on the bipod fittings and the liquid oxygen (LO2) feedline forward bellows to prevent ice formation. The Solid Rocket Booster (SRB) bolt catcher has been redesigned. The Orbiter reaction control system (RCS) thruster cover "butcher paper" has been replaced with a material that sheds at a low velocity. Finally, the pad area has been cleaned to reduce debris during lift-off.

  7. Rationale and Considerations for the Internet-Based Delivery of Parent-Child Interaction Therapy

    PubMed Central

    Comer, Jonathan S.; Furr, Jami M.; Cooper-Vince, Christine; Madigan, Ryan J.; Chow, Candice; Chan, Priscilla; Idrobo, Fabio; Chase, Rhea M.; McNeil, Cheryl B.; Eyberg, Sheila M.

    2014-01-01

    Given the enormous individual, familial, and societal costs associated with early disruptive behavior disorders, transformative efforts are needed to develop innovative options for overcoming traditional barriers to effective care and for broadening the availability of supported interventions. This paper presents the rationale and key considerations for a promising innovation in the treatment of early-onset disruptive behavior disorders—that is, the development of an Internet-based format for the delivery of Parent-Child Interaction Therapy (PCIT) directly to families in their own homes. Specifically, we consider traditional barriers to effective care, and discuss how technological innovations can overcome problems of treatment availability, accessibility, and acceptability. We then detail our current Internet-delivered PCIT treatment program (I-PCIT), which is currently being evaluated across multiple randomized clinical trials relative to waitlist comparison, and to traditional in-office PCIT. Embedded video clips of children treated with I-PCIT are used to illustrate novel aspects of the treatment. PMID:26120268

  8. Hepatocellular carcinoma detection by gallium scan and subsequent treatment by gallium maltolate: rationale and case study.

    PubMed

    Bernstein, Lawrence R; van der Hoeven, Jacobus J M; Boer, Robbert O

    2011-07-01

    Gallium is antiproliferative to many types of cancer, due primarily to its ability to act as a non-functional mimic of ferric iron (Fe(3+)). Because Fe(3+) is needed for ribonucleotide reductase activity--and thus DNA synthesis--gallium can inhibit DNA production and cell division. Diagnostic gallium scans have shown that hepatocellular carcinoma (HCC) is commonly avid for gallium. Furthermore, in vitro studies have found that gallium nitrate, and particularly gallium maltolate (GaM), have dose-dependent antiproliferative activity against HCC cell lines. Rationale thus exists to use GaM, an orally active compound that has been well tolerated in Phase I clinical trials, to treat patients whose HCC is gallium-avid in a gallium scan. Because gallium absorbed from orally administered GaM is bound predominately to serum transferrin, which travels to all tissues in the body, GaM has the potential to treat even distant metastases. A patient with advanced HCC (20 × 10 cm primary tumor, ascites around liver and spleen, resistant to Nexavar(®) (sorafenib)), whose cancer was highly gallium-avid in a (67)Ga-scan, was treated with oral gallium maltolate at 1500 mg/day q.d. After four weeks of treatment, the patient had a large reduction in pain, with greatly increased mobility and quality of life, and significantly lowered serum bilirubin and inflammation-related liver enzymes. At eight weeks, CT scans showed apparent necrosis of the tumor.

  9. Development of a buccal mucoadhesive film for fast dissolution: mathematical rationale, production and physicochemical characterization.

    PubMed

    Vila, Marta M D C; Tardelli, Edgard R; Chaud, Marco V; Tubino, Matthieu; Balcão, Victor M

    2014-11-01

    The validity of a mathematical rationale for preparation of a fast-dissolving buccal mucoadhesive was tested. A buccal mucoadhesive biopolymeric formulation has been developed having pullulan as the main component. The formulation was duly evaluated physicochemically, via assays for intrinsic viscosity (resulting in 71.61 cm3 g(-1)), differential scanning calorimetry analysis (resulting in a Tg = 63 °C), thermogravimetric analysis (244-341 °C), moisture content determinations (14%, w/w), dissolution timeframe (41.6 s), mucoadhesion force (40 kg/cm2), scanning electron microscopy analyses (critical ray under 1.0 μm), mechanic strength (tensile strength = 58 N/mm2, deformation = 4.4%). The mucoadhesive formulation exhibited important characteristics for a drug carrier, that is, a 6 cm2 area, a fast dissolution timeframe, an adequate mucoadhesivity, resistance to both oxygen and water vapor penetration, increased viscosity in solution (ranging from 33.2 cm3/g to 71.61 cm3/g), easy molding, suitable water solubility and transparency.

  10. Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation.

    PubMed

    MacVane, Shawn H; Kuti, Joseph L; Nicolau, David P

    2014-02-01

    Given the sparse antibiotic pipeline and the increasing prevalence of resistant organisms, efforts should be made to optimise the pharmacodynamic exposure of currently available agents. Prolonging the infusion duration is a strategy used to increase the percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (fT>MIC), the pharmacodynamic efficacy driver for time-dependent antibiotics such as β-lactams. β-Lactams, the most commonly prescribed class of antibiotics owing to their efficacy and safety profile, have been the mainstay of therapy since the discovery of penicillin over 60 years ago. Mounting evidence, including the use of population pharmacokinetic modelling and Monte Carlo simulation, suggests that prolonging the infusion time of β-lactam antibiotics may have advantages over standard infusion techniques, including an enhanced probability of achieving requisite fT>MIC exposures, lower mortality and potentially reductions in infection/antibiotic-related costs. As a result of these favourable attributes, clinical practice guidelines support the use of prolonged-infusion β-lactams in the treatment of many severe infections. This article discusses the rationale and evidence for prolonging the infusion of β-lactam antibiotics and provides guidance for the implementation of a prolonged-infusion programme.

  11. Rationale and Design of the Pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial

    PubMed Central

    Carcillo, Joseph; Holubkov, Richard; Dean, J. Michael; Berger, John; Meert, Kathleen L.; Anand, K. J. S.; Zimmerman, Jerry; Newth, Christopher J. L.; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

    2010-01-01

    Despite implementation of CDC recommendations and bundled interventions for preventing catheter-associated blood stream infection, ventilator-associated pneumonia, or urinary catheter–associated infections, nosocomial infections and sepsis remain a significant cause of morbidity and mortality in critically ill children. Recent studies suggest that acquired critical illness stress-induced immune suppression (CRISIS) plays a role in the development of nosocomial infection and sepsis. This condition can be related to inadequate zinc, selenium, and glutamine levels, as well as hypoprolactinemia, leading to stress-induced lymphopenia, a predominant TH2 monocyte/macrophage state, and subsequent immune suppression. Prolonged immune dysfunction increases the likelihood of nosocomial infections associated with invasive devices. Although strategies to prevent common complications of critical illness are routinely employed (eg, prophylaxis for gastrointestinal bleeding, thrombophlebitis), no prophylactic strategy is used to prevent stress-induced immune suppression. This is the authors’ rationale for the pediatric CRISIS prevention trial (NCT00395161), designed as a randomized, double-blind, controlled clinical investigation to determine if daily enteral supplementation with zinc, selenium, and glutamine as well as parenteral metoclopramide (a dopamine 2 receptor antagonist that reverses hypoprolactinemia) prolongs the time until onset of nosocomial infection or sepsis in critically ill children compared to enteral supplementation with whey protein. If effective, this combined nutritional and pharmacologic approach may lessen the excess morbidity and mortality as well as resource utilization associated with nosocomial infections and sepsis in this population. The authors present the design and analytic plan for the CRISIS prevention trial. PMID:19380753

  12. Rationale and design for the Asymptomatic Carotid Artery Plaque Study (ACAPS). The ACAPS Group.

    PubMed

    1992-08-01

    An NHLBI-sponsored randomized, double-masked, placebo-controlled, multicenter clinical trial is underway to test the efficacy of the lipid-lowering agent lovastatin and/or the antithrombotic agent warfarin in slowing the progression of early carotid atherosclerosis--as defined by ultrasonographic intimal-medial arterial wall thickening--in a high-risk, asymptomatic population consisting of 919 men and women aged 40-79 years with moderately elevated serum LDL-cholesterol. The Asymptomatic Carotid Artery Plaque Study's (ACAPS) factorial design permits evaluation of each of the two treatments alone as well as assessment of the treatments in combination with each other over a 2.5- to 3.0-year treatment period. Randomized participants receive either 20-40 mg/day lovastatin or lovastatin placebo and either 1 mg/day (minidose) warfarin or warfarin placebo. All participants were encouraged to take low-dose (81 mg/day) aspirin. The primary outcome is the ultrasonographic measurement of the mean of maximum intimal-medial thickness (IMT) across up to 12 preselected segments in the carotid arteries. The secondary outcome of the trial measures the single maximum IMT measurement among the same preselected carotid artery segments. This report describes the rationale for ACAPS, its design, and some baseline characteristics of the study population.

  13. A new scenario of hypothalamic organization: rationale of new hypotheses introduced in the updated prosomeric model

    PubMed Central

    Puelles, Luis; Rubenstein, John L. R.

    2015-01-01

    In this essay, we aim to explore in depth the new concept of the hypothalamus that was presented in the updated prosomeric model (Puelles et al., 2012b; Allen Developing Mouse Brain Atlas). Initial sections deal with the antecedents of prosomeric ideas represented by the extensive literature centered on the alternative columnar model of Herrick (1910), Kuhlenbeck (1973) and Swanson (1992, 2003); a detailed critique explores why the columnar model is not helpful in the search for causal developmental explanations. In contrast, the emerging prosomeric scenario visibly includes many possibilities to propose causal explanations of hypothalamic structure relative to both anteroposterior and dorsoventral patterning mechanisms, and insures the possibility to compare hypothalamic histogenesis with that of more caudal parts of the brain. Next the four major changes introduced in the organization of the hypothalamus on occasion of the updated model are presented, and our rationale for these changes is explored in detail. It is hoped that this example of morphological theoretical analysis may be useful for readers interested in brain models, or in understanding why models may need to change in the quest for higher consistency. PMID:25852489

  14. Pharmabiotic manipulation of the microbiota in gastrointestinal disorders, from rationale to reality.

    PubMed

    Shanahan, Fergus; Collins, Stephen M

    2010-09-01

    The viewpoints of enthusiasts and skeptics in relation to the role of probiotics should not be allowed to distract clinicians from the bigger issue, which is the pivotal role of the microbiota in the protection against many disorders and in the pathogenesis of others. However, all probiotics, like all bacteria, are not created equal, and therapeutic deployment in a generic sense is as absurd as the administration of pills or tablets without regard for the nature of the active ingredient and the intended effect. The rationale for therapeutic manipulation or supplementation of the microbiota is sound in conditions where the intestinal ecosystem is poorly developed, such as in low birth weight neonates, or where it is profoundly disturbed, such as after broad-spectrum antibiotics. In other conditions, such as irritable bowel disorder (IBD), the efficacy of some, but not all, probiotics has been a welcome surprise. However, the impact of probiotics is likely to be modest and is probably more complicated in IBD. In choosing a probiotic strategy, clinicians should adhere to the principles of evidence-based therapeutics. These include: selection from a reputable supplier, with appropriate documentation of contents and shelf life; anticipation of strain-specific effects; avoidance of cocktails without documentation of the activities of each ingredient with absence of interstrain antagonism; and published evidence of efficacy from clinical trials.

  15. Spinal shock and brain death': somatic pathophysiological equivalence and implications for the integrative-unity rationale.

    PubMed

    Shewmon, D A

    1999-05-01

    The somatic pathophysiology of high spinal cord injury (SCI) not only is of interest in itself but also sheds light on one of the several rationales proposed for equating 'brain death' (BD) with death, namely that the brain confers integrative unity upon the body, which would otherwise constitute a mere conglomeration of cells and tissues. Insofar as the neuropathology of BD includes infarction down to the foramen magnum, the somatic pathophysiology of BD should resemble that of cervico-medullary junction transection plus vagotomy. The endocrinologic aspects can be made comparable either by focusing on BD patients without diabetes insipidus or by supposing the victim of high SCI to have pre-existing therapeutically compensated diabetes insipidus. The respective literatures on intensive care for BD organ donors and high SCI corroborate that the two conditions are somatically virtually identical. If SCI victims are alive at the level of the 'organism as a whole', then so must be BD patients (the only significant difference being consciousness). Comparison with SCI leads to the conclusion that if BD is to be equated with death, a more coherent reason must be adduced than that the body as a biological organism is dead.

  16. Transition of Care for Young Adult Survivors of Childhood and Adolescent Cancer: Rationale and Approaches

    PubMed Central

    Freyer, David R.

    2010-01-01

    Purpose Young adult survivors of childhood and adolescent cancer are an ever-growing population of patients, many of whom remain at lifelong risk for potentially serious complications of their cancer therapy. Yet research shows that many of these older survivors have deficient health-related knowledge and are not engaging in recommended health promotion and screening practices that could improve their long-term outcomes. The purpose of this review is to address these disparities by discussing how formal transition of care from pediatric to adult-focused survivorship services may help meet the unique medical, developmental, and psychosocial challenges of these young adults. Design Literature review and discussion. Results This article summarizes current research documenting the medical needs of young adult survivors, their suboptimal compliance with recommended follow-up, and the rationale, essential functions, current models, and innovative approaches for transition of follow-up care. Conclusion Systematic health care transition constitutes the standard of care for young adult survivors of childhood cancer. In developing a transitional care program, it is necessary to consider the scope of services to be provided, available resources, and other local exigencies that help determine the optimal model for use. Additional research is needed to improve health services delivery to this population. Effective advocacy is needed, particularly in the United States, to ensure the availability of uninterrupted health insurance coverage for survivorship services in young adulthood. PMID:20351333

  17. Alloplastic temporomandibular joint replacement: rationale for the use of custom devices.

    PubMed

    Mercuri, L G

    2012-09-01

    The essential life functions of mastication, speech, airway support and deglutition are supported by temporomandibular joint (TMJ) function and form. Over a lifetime, this puts the TMJ complex under more cyclical loading and unloading than any other joint. Therefore, to provide long-term effective outcomes, the TMJ total joint replacement (TJR) device selected must be capable of managing the anatomical, functional and aesthetic discrepancies that dictated its use. The primary goal of TMJ TJR is the restoration of mandibular function and form. Outcomes data confirm that any pain relief attained must be considered of only secondary benefit. Despite persistent but reduced chronic pain, increased mandibular function and form improvement have been reported, resulting in quality of life improvement for 85% of custom TMJ TJR patients studied long-term. Based on the literature and the accepted orthopaedic criteria for the development and utilisation of successful TJR devices, this paper presents a rationale for the use of custom TMJ TJR devices as a 'fitting' management option for end-stage TMJ disorders.

  18. A Thematic Review of Interactive Whiteboard Use in Science Education: Rationales, Purposes, Methods and General Knowledge

    NASA Astrophysics Data System (ADS)

    Ormanci, Ummuhan; Cepni, Salih; Deveci, Isa; Aydin, Ozhan

    2015-10-01

    In Turkey and many other countries, the importance of the interactive whiteboard (IWB) is increasing, and as a result, projects and studies are being conducted regarding the use of the IWB in classrooms. Accordingly, in these countries, many issues are being researched, such as the IWB's contribution to the education process, its use in classroom settings and problems that occur when using the IWB. In this context, the research and analysis of studies regarding the use of the IWB have important implications for educators, researchers and teachers. This study aims to review and analyze studies conducted regarding the use of the IWB in the field of science. Accordingly, as a thematic review of the research was deemed appropriate, extant articles available in the literature were analyzed using a matrix that consisted of general features (type of journal, year and demographic properties) and content features (rationales, aims, research methods, samples, data collections, results and suggestions). According to the findings, it was concluded that the studies regarding the use of IWBs were conducted due to deficiencies in the current literature. However, there are rare studies in which the reasons for the research were associated with the nature of science education. There were also studies that focused on the effects of the IWB on student academic success and learning outcomes. Within this context, it is evident that there is a need for further research concerning the use of IWBs in science education and for studies regarding the effect of IWBs on students' skills.

  19. Rationale and Design of the Echocardiographic Study of Hispanics / Latinos (ECHO-SOL)

    PubMed Central

    Rodriguez, Carlos J.; Dharod, Ajay; Allison, Matthew A.; Shah, Sanjiv J.; Hurwitz, Barry; Bangdiwala, Shrikant I.; Gonzalez, Franklyn; Kitzman, Dalane; Gillam, Linda; Spevack, Daniel; Dadhania, Rupal; Langdon, Sarah; Kaplan, Robert

    2015-01-01

    Background Information regarding the prevalence and determinants of cardiac structure and function (systolic and diastolic) among the various Hispanic background groups in the United States is limited. Methods and Results The Echocardiographic Study of Latinos (ECHO-SOL) ancillary study recruited 1,824 participants through a stratified-sampling process representative of the population-based Hispanic Communities Health Study – Study of Latinos (HCHS-SOL) across four sites (Bronx, NY; Chicago, Ill; San Diego, Calif; Miami, Fla). The HCHS-SOL baseline cohort did not include an echo exam. ECHO-SOL added the echocardiographic assessment of cardiac structure and function to an array of existing HCHS-SOL baseline clinical, psychosocial, and socioeconomic data and provides sufficient statistical power for comparisons among the Hispanic subgroups. Standard two-dimensional (2D) echocardiography protocol, including M-mode, spectral, color and tissue Doppler study was performed. The main objectives were to: 1) characterize cardiac structure and function and its determinants among Hispanics and Hispanic subgroups; and 2) determine the contributions of specific psychosocial factors (acculturation and familismo) to cardiac structure and function among Hispanics. Conclusion We describe the design, methods and rationale of currently the largest and most comprehensive study of cardiac structure and function exclusively among US Hispanics. ECHO-SOL aims to enhance our understanding of Hispanic cardiovascular health as well as help untangle the relative importance of Hispanic subgroup heterogeneity and sociocultural factors on cardiac structure and function. (Ethn Dis. 2015;25[2]:180–186) PMID:26118146

  20. The sleep apnea cardiovascular endpoints (SAVE) trial: Rationale and start-up phase.

    PubMed

    McEvoy, R Doug; Anderson, Craig S; Antic, Nick A; Chen, Baoyuan; He, Quanying; Heeley, Emma; Huang, Shaoguang; Huang, Yining; Wang, Jiguang; Zhong, Nanshan

    2010-09-01

    THE SLEEP APNEA CARDIOVASCULAR ENDPOINTS (SAVE) STUDY (CLINICAL TRIALS REGISTRATION NUMBER: NCT00738170) is an academic initiated and conducted, multinational, open, blinded endpoint, randomised controlled trial designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the incidence of serious cardiovascular events in patients with established cardiovascular disease. The answer to this question is of major importance to populations undergoing ageing and lifestyle changes all over the world. The SAVE study brings together respiratory, sleep and cardiovascular clinician-scientists in a unique interdisciplinary collaborative effort with industry sponsors to conduct the largest and most ambitious clinical trial yet conducted in the field of sleep apnea, with a global recruitment target of 5000 patients. Following its launch in Australia and China in late 2008, SAVE has now entered a phase of international expansion with new recruitment networks being established in New Zealand, India and Latin America. This article describes the rationale for the SAVE study, the considerations behind its design, and progress thus far in establishing the recruitment network. The report emphasises the important role that Chinese sleep and cardiovascular investigators have played in the start-up phase of this landmark international project.