bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian Hierarchical Mixture Model for Platelet-Derived Growth Factor Receptor Phosphorylation to Improve Estimation of Progression-Free Survival in Prostate Cancer
Authors: Morita Satoshi , Thall Peter F. , Bekele B. Nebiyou , Mathew Paul
Published: September 2009

Advances in understanding the biological underpinnings of many cancers have led increasingly to the use of molecularly targeted anticancer therapies. Because the platelet-derived growth factor receptor (PDGFR) has been implicated in the progression of prostate cancer bone metastases, it is of great interest to examine possible relationships between PDGFR inhibition and therapeutic outcomes. We analyse the association between change in activated PDGFR (phosphorylated PDGFR) and progression-free survival time based on large within-patient samples of cell-specific phosphorylated PDGFR values taken before and after treatment from each of 88 prostate cancer patients. To utilize these paired samples as covariate data in a regression model for progression-free survival time, and be cause the phosphorylated PDGFR distributions are bimodal, we first employ a Bayesian hierarchical mixture model to obtain a deconvolution of the pretreatment and post-treatment within-patient phosphorylated PDGFR distributions. We evaluate fits of the mixture model and a non-mixture model that ignores the bimodality by using a supnorm metric to compare the empirical distribution of each phosphorylated PDGFR data set with the corresponding fitted distribution under each model. Our results show that first using the mixture model to account for the bimodality of the within-patient phosphorylated PDGFR distributions, and then using the posterior within-patient component mean changes in phosphorylated PDGFR so obtained as covariates in the regression model for progression-free survival time, provides an improved estimation.
Modified mixture of experts employing eigenvector methods and Lyapunov exponents for analysis of electroencephalogram signals
Authors: Übeyli Elif Derya
Published: September 2009

Abstract: The use of diverse features in detecting variability of electroencephalogram (EEG) signals is presented. The classification accuracies of the modified mixture of experts (MME), which was trained on diverse features, were obtained. Eigenvector methods (Pisarenko, multiple signal classification – MUSIC, and minimum‐norm) were selected to generate the power spectral density estimates. The features from the power spectral density estimates and Lyapunov exponents of the EEG signals were computed and statistical features were calculated to depict their distribution. The statistical features, which were used for obtaining the diverse features of the EEG signals, were then input into the implemented neural network models for training and testing purposes. The present study demonstrated that the MME trained on the diverse features achieved high accuracy rates (total classification accuracy of the MME is 98.33%).
Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: Initial experience
Authors: Reed KL , Black SB , Banta CJ , Will KR
Published: September 2009

A novel approach to the treatment of chronic migraine headaches based on neurostimulation of both occipital and supraorbital nerves was developed and reduced to clinical practice in a series of patients with headaches unresponsive to currently available therapies. Following positive trials, seven patients with chronic migraine and refractory chronic migraine headaches had permanent combined occipital nerve–supraorbital nerve neurostimulation systems implanted. The relative responses to two stimulation programs were evaluated: one that stimulated only the occipital leads and one that stimulated both the occipital and supraorbital leads together. With follow-up ranging from 1 to 35 months all patients reported a full therapeutic response but only to combined supraorbital–occipital neurostimulation. Occipital nerve stimulation alone provided a markedly inferior and inadequate response. Combined occipital nerve–supraorbital nerve neurostimulation systems may provide effective treatment for patients with chronic migraine and refractory chronic migraine headaches. For patients with chronic migraine headaches the response to combined systems appears to be substantially better than occipital nerve stimulation alone.
Topiramate modulates excitability of the occipital cortex when measured by transcranial magnetic stimulation
Authors: Aurora SK , Barrodale PM , Vermaas AR , Rudra CB
Published: September 2009

Summary

The aim of this study was to measure differences in occipital cortex excitability in migraineurs before and after administration of topiramate. We have previously demonstrated occipital cortex hyperexcitability in migraine using an objective technique of magnetic suppression of perceptual accuracy (MSPA). We hypothesized that a neuromodulator such as topiramate would demonstrate differences in MSPA in migraine compared with baseline. Ten migraine patients were recruited. To assess inhibitory function MSPA was measured using the following protocol. Timed transcranial magnetic stimulation were delivered at interstimulus intervals (ISI) varying from 40 to 190 ms (eight stimulations at each ISI) at 60% stimulus intensity. Subjects were asked to report letters projected at a fixed luminance on the screen. Visual suppression was calculated based on the number of errors the subjects made using automated analysis. This procedure was repeated at a minimum of two different dosages of topiramate when it was titrated for optimal migraine control. The interim dose was that at which an improvement in headache frequency was first observed, and the optimal dose was that at which the patient had a ≥ 50% reduction in headache frequency, or had reached a 100-mg dose. The mean [standard error (s.e.)] level of letters reported correct at baseline at 100-ms ISI was 91.6 (3.4) compared with 48.5 (6.0) ( P = 0.001) at an optimal dose of topiramate. Dose ranged from 50 to 100 mg; the average dose was 75 mg. The interim dose for most patients was 50 mg; the mean (s.e.) percentage of letters reported correct at interim was 75.9 (6.2) compared with baseline ( P = 0.01). Mean number of headaches at baseline was 27 per month, compared with eight headaches per month at interim dose and four headaches per month at optimal dose. There was no significant correlation between mean change in frequency of headache and mean change in inhibition from baseline to optimal dose (0.04, P = 0.89). Topiramate modulates occipital cortex excitability in chronic migraine possibly via mechanisms of cortical inhibition. Since there was not a strong correlation between the degree of inhibition and reduction of migraine frequency, it would appear that topiramate did have an independent effect on cortical excitability that was not dependent on reduction in migraine frequency.
Ophthalmoplegic migraine. Two patients with an absolute response to indomethacin
Authors: Pareja JA , Churruca J , de la Casa Fages B , de Silanes C López , Sánchez C , Barriga FJ
Published: September 2009

Two patients suffering from ophthalmoplegic migraine had a strictly unilateral headache absolutely responsive to indomethacin, but not to other non-steroidal anti-inflammatory drugs, analgesics or corticosteroids. Such observations raise a therapeutic alternative and suggest that ophthalmoplegic migraine may present with different headache phenotypes.
Landscape features and crustacean prey as predictors of the Southern river otter distribution in Chile.
Authors: Sepúlveda M. A. , Bartheld J. L. , Meynard C. , Benavides M. , Astorga C. , Parra D. , Medina‐Vogel G.
Published: September 2009

Understanding the processes that affect freshwater ecosystems at the watershed level is fundamental for the conservation and management of river otters. During 2 consecutive years, we surveyed the occurrence of the Southern river otter Lontra provocax and its main prey (crustaceans) in a watershed of 9900 km2 in the Chilean temperate forest. We modeled predator and prey distributions with a variety of statistical techniques by relating a set of environmental predictors to species occurrence records. Otter and crustaceans were associated with areas of intermediate to low human disturbance with a mosaic of riparian vegetation densities, mainly at low altitudes. The singularity of the Andean Range, with a very marked elevation gradient and oligotrophic watercourses in the higher areas, created more vulnerable conditions for otter presence because prey abundances were limited in those areas. Human impacts affected otter populations at a landscape scale through the presence of main roads, as these were mostly located in lower parts of the watershed where otters have their primary habitat. These results point to the importance of land management and protection of low‐elevation areas where otters still occur to ensure the long‐term viability of its freshwater populations.
Dating the divergence between Southern and European water voles using molecular coalescent‐based methods
Authors: Centeno‐Cuadros A. , Delibes M. , Godoy J. A.
Published: September 2009

Investigating the evolutionary history of the species is critical for understanding the evolution of biodiversity and for its conservation. Towards this goal, molecular approaches are becoming increasingly powerful with the incorporation of recent theoretical and analytical advances. Here, we apply an isolation‐with‐migration coalescent‐based model to control region and cytochrome b mitochondrial sequences to investigate the evolutionary history of European (Arvicola terrestris) and Southern (Arvicola sapidus) water voles throughout Eurasia. We date the time of the split of the common ancestor of European and Southern water voles around the fourth Mindel glacial (c. 252 000 bp), a date similar to that estimated by classical phylogenetic methods (c. 241 000 bp). Although postglacial expansions brought these species into secondary contact in Iberia and France, our results do not contain evidence of subsequent mitochondrial gene flow between descendant groups or current hybridization. We also estimate the effective population sizes of A. sapidus and Arvicola terrestris scherman on c. 199 000 and 52 000 individuals, respectively. This study illustrates the utility of modern coalescent‐based genetic tools to investigate recent species and population divergences and sheds some light on the evolution of the genus Arvicola in Eurasia.
Robot‐assisted task‐specific training in cerebral palsy
Authors: KREBS HERMANO I , LADENHEIM BARBARA , HIPPOLYTE CHRISTOPHER , MONTERROSO LINDA , MAST JOELLE
Published: September 2009

Our goal was to examine the feasibility of applying therapeutic robotics to children and adults with severe to moderate impairment due to cerebral palsy (CP). Pilot results demonstrated significant gains for both groups. These results suggest that robot‐mediated therapy may be an effective tool to ameliorate the debilitating effects of CP and provide new opportunities for reducing impairment and improving coordination.
Orthopaedic issues in the musculoskeletal care of adults with cerebral palsy
Authors: HORSTMANN HELEN M , HOSALKAR HARISH , KEENAN MARY ANN
Published: September 2009

Aims  Orthopaedic care of adults with cerebral palsy (CP) has not been well documented in orthopaedic literature. This paper focuses on some of the common problems which present themselves when adults with CP seek orthopaedic intervention. In particular, we review the most common orthopaedic issues which present to the Penn Neuro‐Orthopaedics Program.

Method  A formal review of consecutive surgeries performed by the senior author on adults with CP was previously conducted. This paper focuses on the health delivery care for the adult with orthopaedic problems related to cerebral palsy. Ninety‐two percent of these patients required lower extremity surgery. Forty percent had procedures performed on the upper extremities.

Results  The majority of problems seen in the Penn Neuro‐Orthopaedics Program are associated with the residuals of childhood issues, particularly deformities associated with contractures. Patients are also referred for treatment of acquired musculoskeletal problems such as degenerative arthritis of the hip or knee. A combination of problems contribute most frequently to foot deformities and pain with weight‐bearing, shoewear or both, most often due to equinovarus. The surgical correction of this is most often facilitated through a split anterior tibial tendon transfer. Posterior tibial transfers are rarely indicated. Residual equinus deformities contribute to a pes planus deformity. The split anterior tibial tendon transfer is usually combined with gastrocnemius‐soleus recession and plantar release. Transfer of the flexor digitorum longus to the os calcis is done to augment the plantar flexor power. Rigid pes planus deformity is treated with a triple arthrodesis. Resolution of deformity allows for a good base for standing, improved ability to tolerate shoewear, and/or braces. Other recurrent or unresolved issues involve hip and knee contractures. Issues of lever arm dysfunction create problems with mechanical inefficiency. Upper extremity intervention is principally to correct contractures. Internal rotation and adductor tightness at the shoulder makes for difficult underarm hygiene and predispose a patient to a spiral fracture of the humerus. A tight flexor, pronation pattern is frequently noted through the elbow and forearm with further flexion contractures through the wrist and fingers. Lengthenings are more frequently performed than tendon transfers in the upper extremity. Arthrodesis of the wrist or on rare occasions of the metacarpal‐phalangeal joints supplement the lengthenings when needed.

Conclusions  The Penn Neuro‐Orthopaedics Program has successfully treated adults with both residual and acquired musculoskeletal deformities. These deformities become more critical when combined with degenerative changes, a relative increase in body mass, fatigue, and weakness associated with the aging process.
Vibration therapy
Authors: RAUCH FRANK
Published: September 2009

Whole‐body vibration training is a method for muscle strengthening that is increasingly used in a variety of clinical situations. Key descriptors of vibration devices include the frequency, the amplitude, and the direction of the vibration movement. In a typical vibration session, the user stands on the device in a static position or performs dynamic movements. Most authors hypothesize that vibrations stimulate muscle spindles and alpha‐motoneurons, which initiate a muscle contraction. An immediate effect of a non‐exhausting vibration session is an increase in muscle power. Most studies of the longer term use of vibration treatment in various disorders have pursued three therapeutic aims: increasing muscle strength, improving balance, and increasing bone mass. In a small pilot trial in children we noted improvements in standing function, lumbar spine bone mineral density, tibial bone mass, and calf muscle cross‐sectional area.
Surgical treatment for hip pain in the adult cerebral palsy patient
Authors: ROOT LEON
Published: September 2009

Hip subluxation or dislocation in the cerebral palsy population is an acquired condition that can result in pain and limitation of function. The incidence is reported to be from 18 to 59%. Awareness of the factors that cause the problem are essential in order to prevent this condition. Early treatment consists of appropriate muscle lengthening or releases, varus rotation hip osteotomies and in some cases pelvic osteotomies to provide acetabular coverage for the femoral head. For painful hip subluxation or dislocation with arthrosis in the adolescent or adult salvage procedures such as hip arthrodesis, valgus osteotomy, proximal femoral resection, or total hip arthroplasty have all been done to relieve pain. The author recounts his experience of the surgical management of the hip in the individual with cerebral palsy.
Intrathecal baclofen use in adults with cerebral palsy
Authors: KRACH LINDA E
Published: September 2009

Intrathecal baclofen (ITB) is an effective treatment for both spasticity and dystonia in people with cerebral palsy (CP). Its use is becoming increasingly common. ITB is typically associated with fewer side effects than the oral form of the product, but there are risks related to the hardware needed for intrathecal delivery. Much of what has been reported in the literature about ITB is based on experience with children or groups of children and adults; few reports exclusively address its use in adults with CP. These reports indicate that muscle tone is consistently reduced, but there is some variability in functional outcomes. Few well‐controlled studies have been done. Controversies remain concerning ITB, including whether a trial is needed before pump implantation, proper catheter tip placement, and programming options, as well as whether it contributes to the development or progression of scoliosis. These and other unanswered questions should be addressed in a systematic way.
Pain in adults with cerebral palsy: impact and solutions
Authors: VOGTLE LAURA K
Published: September 2009

Studies of health in adults with cerebral palsy (CP) have identified pain as a significant concern. Investigations regarding incidence, intensity, and location in adults with CP found that increasing age and inactivity appeared to be related to pain. Activity and participation in adults with CP seem to be only moderately affected by presence of pain. Various sources of pain have been identified in adults with CP but have not been well studied. These include orthopedic issues, poor bone mineral density and related fractures, dental and jaw problems, and nutrition‐related pain. Limited healthcare utilization studies suggest that adults with CP use healthcare services, especially preventative and rehabilitative services less, and do not consult physicians regarding pain. Medication solutions for chronic pain are not well studied. Botulinum toxin and intrathecal baclofen have been demonstrated to minimize pain; however, the impact of other medications needs further investigation. Other interventions for pain include small studies examining the use of biofeedback and exercise. Larger studies are needed to establish effectiveness. In order to prevent future generations of adults with CP from experiencing high levels of pain, environmental sources of pain need more specific study, as do interventions that are affordable and easily accessed.
Complementary and alternative methods in cerebral palsy
Authors: OPPENHEIM WILLIAM L
Published: September 2009

There are no published studies specifically addressing complementary and alternative treatments in adults with cerebral palsy (CP). However, national surveys of adults with chronic disabilities document that a majority of them use such treatments, that they are willing to pay out of pocket, if necessary, and that they believe that pursuing such treatment relieves pain, reduces stress and anxiety, and leads to improved feelings of fitness and well‐being. Individuals enjoy taking charge of their own health care decisions, and frequently feel more in control with these therapies than with more traditional methods. In contrast to adults, there is some information on complementary and alternative methods (CAM) in children with CP. This article discusses some of the CAM used in children that may be carried over into adulthood, as well as the pitfalls for patients and conventional physicians as they try to sort out what might be helpful and what might be harmful in this arena. Practitioners of both conventional and CAM therapies believe that exercise can be beneficial; accordingly, activities such as recreational sports, yoga, and hippotherapy may be continued from childhood into adulthood. General treatments for stress and anxiety, through such activities as yoga and meditation, though not directed at CP per se, may be more popular for adults than children. Research in this area should first identify what methods are being utilized and then subject these methods to well‐designed outcome studies that take into account any associated risks.
Neural plasticity and treatment across the lifespan for motor deficits in cerebral palsy
Authors: WITTENBERG GEORGE F
Published: September 2009

The past decade of research in neuroscience and stroke rehabilitation has demonstrated that the adult brain is capable of recovery through physiological processes (often called ‘plasticity’). Some of the recovery is spontaneous and some is a result of experience, including interventions such as physical therapy, which probably enhance or activate changes in brain structure and function. There is virtually no literature on physiological changes in the brains of children or adults with cerebral palsy (CP) after an intervention. It is unclear whether the principles of plasticity that have been deduced from animal models of stroke might also apply to children and adults with CP. But children with CP should have the potential to respond to experience in a similar way to adults, with the additional potential of regulation of neuronal development in response to injury. This article describes mechanisms of plasticity and a rehabilitation strategy to preserve the substrates for motor control in CP and then to apply later therapies for more refinement of motor control.
Motor mapping in cerebral palsy
Authors: WITTENBERG GEORGE F
Published: September 2009

The measurement of motor deficits in individuals with cerebral palsy (CP) has been largely based on clinical criteria. Yet functional imaging and non‐invasive stimulation methods provide a means to measure directly abnormalities of the motor system. The size and location of muscles and movement representations can be determined with transcranial magnetic stimulation (TMS) and functional magnetics resonance imaging. Thus the homunculus can be individually mapped in children with CP. Because size of representation within the homunculus relates to quality of motor control, measurement of the distance between body parts provides a metric that may be useful in classifying deficits. Bilateral motor control in one hemisphere, while normal in neonates, persists variably in CP, providing another physiological metric. In this study, we used TMS to measure hand and ankle representations in a convenience sample of children with spastic CP. Overlapping thumb and ankle maps were found in children with both hemiplegia and diplegia, and these maps may be from either side of the body. While more participants are required to make conclusions about disability and compression/bilaterality of the homunculus, it appears as if TMS‐derived metrics relate to motor abnormalities. These abnormal motor maps also are a therapeutic target, as stimulation methods are being developed as adjuncts to physical means of rehabilitation.
Aging with cerebral palsy and other disabilities: personal reflections and recommendations
Authors: JONES GWYN C
Published: September 2009

This article describes the lived experience of one 64‐year‐old woman who is aging with cerebral palsy (CP) and other multiple disabilities. Reflections are offered on coping with secondary conditions and functional decline; fighting the effects of pain and fatigue; and managing well‐meaning, but misdirected, medical advice. Recommendations based on the author’s personal and professional experience with disabilities, including CP, are presented on the aging process and on preventive care for adults living with CP.
Cerebral palsy and aging
Authors: HAAK PETERSON , LENSKI MADELEINE , HIDECKER MARY JO COOLEY , LI MIN , PANETH NIGEL
Published: September 2009

Cerebral palsy (CP), the most common major disabling motor disorder of childhood, is frequently thought of as a condition that affects only children. Deaths in children with CP, never common, have in recent years become very rare, unless the child is very severely and multiply disabled. Thus, virtually all children assigned the diagnosis of CP will survive into adulthood. Attention to the adult with CP has been sparse, and the evolution of the motor disorder as the individual moves through adolescence, young adulthood, middle age, and old age is not well understood. Nor do we know what happens to other functional domains, such as communication and eating behavior, in adults with CP. Although the brain injury that initially causes CP by definition does not progressively worsen through the lifetime, the effects of CP manifest differently throughout the lifespan. The aging process must inevitably interact with the motor disorder, but we lack systematic, large‐scale follow‐up studies of children with CP into adulthood and through adulthood with thorough assessments performed over time.

In this paper we summarize what is known of the epidemiology of CP throughout the lifespan, beginning with mortality and life expectancy, then survey what is known of functioning, ability, and quality of life of adults with CP. We conclude by describing a framework for future research on CP and aging that is built around the World Health Organization’s International Classification of Functioning, Disability, and Health (ICF) and suggest specific tools and approaches for conducting that research in a sound manner.
Cerebral palsy lifetime care – four musculoskeletal conditions
Authors: MURPHY KEVIN P
Published: September 2009

Cerebral palsy (CP) has always been considered a static condition in the neurological sense. Secondary and associated conditions that occur in the patient with CPcan progress over time and cause unwanted sequelae. This paper discusses four musculoskeletal conditions that present across the lifetime and can lead to progressive loss of function in the patient with CP. Patella alta can be particularly painful in the early adult years, limiting mobility particularly when associated with crouch gait. Adults with lower‐extremity weight‐bearing status having hip dysplasia, progressive over time, often develop pain and severe degenerative arthritis, with or without arthrodesis. Spondylolysis, particularly at the L5 S1 level, is fairly common in the ambulatory adult with diplegia and may, if not diagnosed early, progress to spondylolisthesis. Cervical stenosis appears to be more prevalent in adults with spastic quadriparesis and dystonia and is often associated with myelomalacia and/or radiculopathy. All four of these conditions may be lessened, or even prevented, with intervention and diagnosis in the younger years. Possible interventions and outcomes over time are discussed in the context of multidisciplinary team management of the individual with CP.
The role of fitness in health and disease: status of adults with cerebral palsy
Authors: THORPE DEBORAH
Published: September 2009

Physical activity has significant health benefits and is positively associated with health‐related quality of life and psychosocial functioning. Persons with disability are at particular risk of inactivity. For adults with cerebral palsy (CP), impaired health and function typically impede participation in physical activity, setting into motion a downward spiral of prolonged inactivity. Adults with CP may not be engaging in sufficient physical activity to produce the improvements in fitness required to experience associated health benefits. However, the literature related to physical activity and fitness in adults with CP is sparse. As more and more persons with CP lead productive lives into their golden years, it is imperative that the scientific community provide definitive information to help guide decisions related to the type and extent of fitness‐related activities most beneficial to these individuals. This information will facilitate development of physical training programs that promote maintenance of function and fitness while preventing the onset of secondary conditions. This presentation will address the state‐of‐the‐science regarding physical activity and fitness for adults with CP and how fitness training relates to physical activity and health in this population. Gaps in the evidence, as well as possible directions for future research, will be presented.
Muscle deficits in cerebral palsy and early loss of mobility: can we learn something from our elders?
Authors: SHORTLAND ADAM
Published: September 2009

Ambulant young people with cerebral palsy (CP) have reduced muscle volumes in their lower limbs (as low as 50% of their weight‐matched typically‐developing peers). Yet, they may complete a ‘timed up‐and‐go’ test at similar speeds to unaffected persons. Perhaps, these individuals are able to maintain high levels of function because their muscle deficits have not fallen below the threshold values required to perform certain motor tasks. This is consistent with data from studies of progressive strengthening in children with mild CP. These programmes improve muscular output but have limited immediate effect on functional capacity. Sarcopenia is responsible for much of the loss of muscle mass in the typically developing adult. The decline in muscle mass begins in the mid‐twenties and occurs rapidly after the 7th decade. It is possible that the muscle deficits characteristic of young people with CP, coupled with the decline of muscle properties in adulthood, contribute to an early loss of mobility in this group. In the typically developing elderly, progressive strengthening is thought to extend mobility. Perhaps, the real value of strengthening programmes in CP is to improve muscular reserve in the short‐term and to maintain muscle mass above critical thresholds in the long‐term.
The pathogenesis of osteoarthritis in cerebral palsy
Authors: CARTER DENNIS R , TSE BRIAN
Published: September 2009

The morphogenesis, remodeling, and degeneration of diarthroidial joints are directly under the control of the loading histories created by the musculoskeletal system during development and aging. The altered loading histories in individuals with cerebral palsy (CP) lead to aberrations in joint morphogenesis and an acceleration of joint degeneration. To understand this process in the hip, the normal ontogeny of the hip joint is reviewed with special attention to the mechano‐biological factors associated with joint morphogenesis, endochondral ossification, and cartilage degeneration. A contrast is then made with the mechano‐biological alterations observed with CP and the consequent influence on joint destruction. The features of the pathogenesis are: (1) altered muscular activity and restricted range of motion result in abnormal joint morphology, subluxation, and poor coverage of the femoral head; (2) joint incongruities created in early development cause local stress concentrations that can mechanically damage the articular cartilage; (3) the reduced magnitudes of muscular forces reduce the contact pressures at the joints, creating thinner cartilage and osteopenia; and (4) the thinner cartilage degenerates early, and subchondral bone collapse further contributes to the mechanical destruction of the remaining cartilage.
Investigation of goal change to optimize upper‐extremity motor performance in a robotic environment
Authors: BREWER BAMBI R , KLATZKY ROBERTA , MARKHAM HEATHER , MATSUOKA YOKY
Published: September 2009

Robotic devices for therapy have the potential to enable intensive, fully customized home rehabilitation over extended periods for individuals with stroke and traumatic brain injury, thus empowering them to maximize their functional recovery. For robotic rehabilitation to be most effective, systems must have the capacity to assign performance goals to the user and to increment those goals to encourage performance improvement. Otherwise, individuals may plateau at an artificially low level of function. Frequent goal change is needed to motivate improvements in performance by individuals with brain injury; but because of entrenched habits, these individuals may avoid striving for goals that they perceive as becoming ever more difficult. For this reason, implicit, undetectable goal change (distortion) may be more effective than explicit goal change at optimizing the motor performance of some individuals with brain injury. This paper reviews a body of work that provides a basis for incorporating implicit goal change into a robotic rehabilitation paradigm. This work was conducted with individuals without disability to provide foundational knowledge for using goal change in a robotic environment. In addition, we compare motor performance with goal change to performance with no goal or with a static goal for individuals without brain injury. Our results show that goal change can improve motor performance when participants attend to visual feedback. Building on these preliminary results can lead to more effective robotic paradigms for the rehabilitation of individuals with brain injury, including individuals with cerebral palsy.
Meeting the needs of young people and adults with childhood‐onset conditions: Gillette Lifetime Specialty Healthcare
Authors: LINROTH RONNA
Published: September 2009

This paper describes how Gillette Specialty Healthcare developed a program to meet the specialty‐care outpatient and in‐patient needs of children with cerebral palsy (CP) and other serious congenital disabilities as they made the transition to early adulthood. The program began in 2001, with the opening of a pilot clinic for adult outpatients. Several years later, the hospital opened a small in‐patient unit for selected patients. Careful planning, consultation with staff, and partnerships with caregivers were crucial to program development. Attention to the physical environment was also essential. Utilizing an integrative model of care, the patient, caregivers, and the program service providers create a comprehensive plan of care that reflects each patient’s needs, preferences, and priorities. The Gillette program, when evaluated over the long term, may serve as a model for meeting the emerging needs of the young adult with CP.
Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging
Authors: Martin George M.
Published: September 2009

Generations of biogerontologists have been puzzled by the marked intraspecific variations in lifespan of their experimental model organisms despite all efforts to control both genotype and environment. The most cogent example comes from life table studies of wild‐type Caenorhabditis elegans when grown in suspension cultures using axenic media. While nuclear and mitochondrial somatic mutations and ‘thermodynamic noise’ likely contribute to such lifespan variegations, I raise an additional hypothetical mechanism, one that may have evolved as a mechanism of phenotypic variation which could have preceded the evolution of meiotic recombination. I suggest that random changes in cellular gene expression (cellular epigenetic gambling or bet hedging) evolved as an adaptive mechanism to ensure survival of members of a group in the face of unpredictable environmental challenges. Once activated, it could lead to progressive epigenetic variegation (epigenetic drift) amongst all members of the group. Thus, while particular patterns of gene expression would be adaptive for a subset of reproductive individuals within a population early in life, once initiated, I predict that continued epigenetic drift will result in variable onsets and patterns of pathophysiology – perhaps yet another example of antagonistic pleiotropic gene action in the genesis of senescent phenotypes. The weakness of this hypothesis is that we do not currently have a plausible molecular mechanism for the putative genetic ‘randomizer’ of epigenetic expression, particularly one whose ‘setting’ may be responsive to the ecology in which a given species evolves. I offer experimental approaches, however, to search for the elusive epigenetic gambler(s).
Calorie restriction effects on silencing and recombination at the yeast rDNA
Authors: Smith Jr Daniel L. , Li Chonghua , Matecic Mirela , Maqani Nazif , Bryk Mary , Smith Jeffrey S.
Published: September 2009

Aging research has developed rapidly over the past decade, identifying individual genes and molecular mechanisms of the aging process through the use of model organisms and high throughput technologies. Calorie restriction (CR) is the most widely researched environmental manipulation that extends lifespan. Activation of the NAD+‐dependent protein deacetylase Sir2 (Silent Information Regulator 2) has been proposed to mediate the beneficial effects of CR in the budding yeast Saccharomyces cerevisiae, as well as other organisms. Here, we show that in contrast to previous reports, Sir2 is not stimulated by CR to strengthen silencing of multiple reporter genes in the rDNA of S. cerevisiae. CR does modestly reduce the frequency of rDNA recombination, although in a SIR2‐independent manner. CR‐mediated repression of rDNA recombination also does not correlate with the silencing of Pol II‐transcribed noncoding RNAs derived from the rDNA intergenic spacer, suggesting that additional silencing‐independent pathways function in lifespan regulation.
Relative roles of TGF‐β1 and Wnt in the systemic regulation and aging of satellite cell responses
Authors: Carlson Morgan E. , Conboy Michael J. , Hsu Michael , Barchas Laurel , Jeong Jaemin , Agrawal Anshu , Mikels Amanda J. , Agrawal Smita , Schaffer David V. , Conboy Irina M.
Published: September 2009

Muscle stem (satellite) cells are relatively resistant to cell‐autonomous aging. Instead, their endogenous signaling profile and regenerative capacity is strongly influenced by the aged P‐Smad3, differentiated niche, and by the aged circulation. With respect to muscle fibers, we previously established that a shift from active Notch to excessive transforming growth factor‐beta (TGF‐β) induces CDK inhibitors in satellite cells, thereby interfering with productive myogenic responses. In contrast, the systemic inhibitor of muscle repair, elevated in old sera, was suggested to be Wnt. Here, we examined the age‐dependent myogenic activity of sera TGF‐β1, and its potential cross‐talk with systemic Wnt. We found that sera TGF‐β1 becomes elevated within aged humans and mice, while systemic Wnt remained undetectable in these species. Wnt also failed to inhibit satellite cell myogenicity, while TGF‐β1 suppressed regenerative potential in a biphasic fashion. Intriguingly, young levels of TGF‐β1 were inhibitory and young sera suppressed myogenesis if TGF‐β1 was activated. Our data suggest that platelet‐derived sera TGF‐β1 levels, or endocrine TGF‐β1 levels, do not explain the age‐dependent inhibition of muscle regeneration by this cytokine. In vivo, TGF‐β neutralizing antibody, or a soluble decoy, failed to reduce systemic TGF‐β1 and rescue myogenesis in old mice. However, muscle regeneration was improved by the systemic delivery of a TGF‐β receptor kinase inhibitor, which attenuated TGF‐β signaling in skeletal muscle. Summarily, these findings argue against the endocrine path of a TGF‐β1‐dependent block on muscle regeneration, identify physiological modalities of age‐imposed changes in TGF‐β1, and introduce new therapeutic strategies for the broad restoration of aged organ repair.
The efficiency of mitochondrial electron transport chain is increased in the long‐lived mrg19 Saccharomyces cerevisiae
Authors: Mittal Nitish , Babu M. Madan , Roy Nilanjan
Published: September 2009

Integrity of mitochondrial functionality is a key determinant of longevity in several organisms. In particular, reduced mitochondrial ROS (mtROS) production leading to decreased mtDNA damage is believed to be a crucial aspect of longevity. The generation of low mtROS was thought to be due to low mitochondrial oxygen consumption. However, recent studies have shown that higher mitochondrial oxygen consumption could still result in low mtROS and contribute to longevity. This increased mitochondrial efficiency (i.e. low mtROS generated despite high oxygen consumption) was explained as a result of mitochondrial biogenesis, which provides more entry points for the electrons to the electron transport chain (ETC), thereby resulting in low mtROS production. In this study, we provide evidence for the existence of an alternative pathway to explain the observed higher mitochondrial efficiency in the long‐lived mrg19 mutant of Saccharomyces cerevisiae. Although we observe similar amounts of mitochondria in mrg19 and wild‐type (wt) yeast, we find that mrg19 mitochondria have higher expression of ETC components per mitochondria in comparison with the wt. These findings demonstrate that more efficient mitochondria because of increased ETC per mitochondria can also produce less mtROS. Taken together, our findings provide evidence for an alternative explanation for the involvement of higher mitochondrial activity in prolonging lifespan. We anticipate that similar mechanisms might also exist in eukaryotes including human.
Constitutional Anomie: Patterns of Democracy and ‘The Governance of Britain’
Authors: Flinders Matthew
Published: September 2009

‘The Governance of Britain’ agenda represents Gordon Brown's attempt to respond to long-standing criticisms regarding the way in which Labour governments have since 1997 approached the topic of constitutional reform and democratic renewal. The central argument of this article is that the Labour Party remains afflicted by constitutional anomie and these recent documents, combined with the behaviour of politicians, have done little in response. This article is of methodological importance because it assesses the cumulative impact of recent reforms through the application of Lijphart's framework and reflects on the utility of this tool. It is of conceptual importance because the results of the systematic analysis add further weight to the accusation of constitutional anomie while also allowing the development of a new conceptual tool – bi-constitutionality – which offers a way of understanding long-standing debates. The article is of normative importance because it avoids the descriptive-prescriptive approach to constitutional literature that has dominated British political studies, and it is relevant for comparative politics because it replicates and takes forward a methodology that has been applied around the world. In doing so it provides a critical case of executive politics and statecraft vis-à-vis constitutional reform.
New Modes of Political Participation and Singapore's Nominated Members of Parliament
Authors: Rodan Garry
Published: September 2009

Despite growing recognition that authoritarianism can be far more durable than transition theorists previously expected, transition theory assumptions continue to constrain attempts to understand authoritarian regimes. In particular, alternative avenues of political participation to opposition political parties and electoral contests are under examined. Singapore's authoritarian regime involves a range of such innovative institutional and ideological initiatives, one of the most significant being the Nominated Members of Parliament scheme. This promotes notions of representation different from democratic parliamentary representation that are not without appeal to targeted, emerging social forces. Singapore's political economy dynamics contribute to this responsiveness by obstructing independent power bases.
The haplotype of the MxA gene promoter is associated with hepatitis B virus infection in a Chinese population
Authors: Cao Bangwei , Liu Xing , Hou Fang , Li Wende , Han Zhonggang , Zhang Qipeng , Dai Yue , Xu Changqing , Qi Huimin
Published: September 2009

Background/Aim: The Myxovirus resistance protein A gene (MxA) is a key component of the innate antiviral response and has previously been shown to inhibit several viruses. This study was designed to assess whether the haplotype in the MxA promoter region was associated with hepatitis B virus (HBV) infection in a Chinese population.

Methods: Three hundred and twelve HBV‐infected patients and 317 healthy volunteers were enrolled in this study. Two polymorphisms of −88 and −123 located in the MxA gene promoter were identified by the polymerase chain reaction‐restriction fragment length polymorphism method.

Results: The individual possessing haplotype GA, which was constructed by the two polymorphisms of −88G and −123A in the MxA gene promoter, was significantly associated with HBV infection [possessing one copy odds ratio (OR)=1.69, 95% confidence interval (CI) 1.21–2.35; two copy OR=2.84, 95% CI 1.12–7.21 respectively].

Conclusions: This case–control study suggested that the haplotype GA in the MxA gene promoter region would increase the susceptibility to HBV infection in a Chinese population.
Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection
Authors: Mederacke Ingmar , Wursthorn Karsten , Kirschner Janina , Rifai Kinan , Manns Michael P. , Wedemeyer Heiner , Bahr Matthias J.
Published: September 2009

Background and aims:  Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease‐specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow.

Methods:  In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast.

Results:  Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness ≤10 kPa. An increase of at least 1 kPa after food intake was found in 24 out of 43 (56%) patients with initial stiffness ≤10 kPa. Notably, nine out of 23 (39%) patients with normal initial liver stiffness (<6 kPa) had a value of >6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures.

Conclusion:  Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition.
Flufenamic acid suppresses epileptiform activity in hippocampus by reducing excitatory synaptic transmission and neuronal excitability
Authors: Fernández Miriam , Lao‐Peregrín Cristina , Martín Eduardo D.
Published: September 2009

Purpose: In this study, we explore the antiepileptic effects of flufenamic acid (FFA) in order to identify the cellular mechanisms that underlie the potential anticonvulsant properties of this nonsteroidal antiinflammatory compound.

Methods: The mechanisms of FFA action were analyzed using an in vitro model in which epileptiform activity was induced in hippocampal slices by perfusion with 100 μm4‐aminopyridine (4‐AP) added to a modified Mg2+‐free solution. The activity of CA1 pyramidal neurons as well as the synaptic connection between CA3 and CA1 was monitored using extracellular and patch‐clamp recordings.

Results: Epileptiform activity was suppressed in hippocampal neurons by FFA at concentrations between 50 and 200 μm. Glutamatergic excitatory synaptic transmission was diminished by FFA without modifying recurrent γ‐aminobutyric acid (GABA)ergic synaptic inhibition. Several lines of evidence indicated that FFA did not decrease neurotransmitter release probability, implicating a postsynaptic mechanism of action. FFA also potently reduced neuronal excitability, but did not alter the amplitude, duration, or undershoot of action potentials.

Conclusions: Our results suggest that FFA exerts an anticonvulsive effect on hippocampal pyramidal neurons by simultaneously decreasing glutamatergic excitatory synaptic activity and reducing neuronal excitability. Therefore, our study provides experimental evidence that FFA may represent an effective pharmacologic agent in the treatment of epilepsy in the mammalian central nervous system.