Reinforcement Motor Learning After Cerebellar Damage Is Related to State Estimation.

Recent work showed that individuals with cerebellar degeneration could leverage intact reinforcement learning (RL) to alter their movement. However, there was marked inter-individual variability in learning, and the factors underlying it were unclear. Cerebellum-dependent sensory prediction may contribute to RL in motor contexts by enhancing body state estimates, which are necessary to solve the credit-assignment problem. The objective of this study was to test the relationship between the predictive component of state estimation and RL in individuals with cerebellar degeneration. Individuals with cerebellar degeneration and neurotypical control participants completed two tasks: an RL task that required them to alter the angle of reaching movements and a state estimation task that tested the somatosensory perception of active and passive movement. The state estimation task permitted the calculation of the active benefit shown by each participant, which is thought to reflect the cerebellum-dependent predictive component of state estimation. We found that the cerebellar and control groups showed similar magnitudes of learning with reinforcement and active benefit on average, but there was substantial variability across individuals. Using multiple regression, we assessed potential predictors of RL. Our analysis included active benefit, somatosensory acuity, clinical ataxia severity, movement variability, movement speed, and age. We found a significant relationship in which greater active benefit predicted better learning with reinforcement in the cerebellar, but not the control group. No other variables showed significant relationships with learning. Overall, our results support the hypothesis that the integrity of sensory prediction is a strong predictor of RL after cerebellar damage.

Improving Rectal Cancer Outcomes with the National Accreditation Program for Rectal Cancer.

Background The treatment of rectal cancer has undergone dramatic changes over the past 50 years. It has evolved from a rather morbid disease usually requiring a permanent stoma, almost exclusively managed by surgeons, to one that involves experts across numerous disciplines to provide the best care for the patient. With significant improvements in surgical techniques, the use of chemotherapy and radiotherapy, advanced imaging, and standardization of pathological assessment, the perioperative morbidity and permanent colostomy rates have significantly decreased. We have seen improvements in the quality of the specimen and rates of recurrence as well as disease-free survival. Rectal cancer, as demonstrated in European trials, has now been recognized as a disease best managed by a multidisciplinary team. Objective The aim of this article is to evaluate the main body of literature leading to the advances made possible by the new American College of Surgeons Commission on Cancer National Accreditation Program for Rectal Cancer. Results Following the launch of the American College of Surgeons Commission on Cancer National Accreditation Program for Rectal Cancer, we expect dramatic increases in membership and accreditation, with associated improvement in center performance and, ultimately, in patient outcomes. Limitations The National Accreditation Program for Rectal Cancer began in 2017. To date, the only data that have been analyzed are from the preintervention phase. Conclusions Based on the results of studies within the United States and on the successes demonstrated in Europe, it remains our hope and expectation that the management of rectal cancer in the United States will rapidly improve.

Demyelinating symmetric motor polyneuropathy with high titers of anti-GM1 antibodies.

High titers of anti-GM1 ganglioside antibodies have been associated with multifocal motor neuropathy, a chronic asymmetric and exclusively motor disorder. We describe a patient with a progressive selective motor but symmetric polyneuropathy, followed over 5 years, with markedly elevated titers of anti-GM1 antibodies. The electrophysiological changes suggestive of motor demyelination were widespread, beyond conduction block alone, and involved contiguous nerve segments with complete sparing of sensory conduction. Progressive, predominantly motor, symmetric, demyelinating polyneuropathy may be an unusual relative of multifocal motor neuropathy, associated with anti-GM1 antibodies.

PillCam ESO versus esophagogastroduodenoscopy in esophageal variceal screening: A decision analysis.

OBJECTIVES: PillCam ESO has been evaluated as a possible strategy to screen patients with cirrhosis for esophageal varices, but current guidelines recommend patients undergo screening with esophagogastroduodenoscopy (EGD), as it is currently the gold standard. Although recent data have suggested that PillCam ESO may be an acceptable alternative for screening, there is limited data on its cost-effectiveness compared with other screening modalities. This study was performed to compare the cost-effectiveness of PillCam ESO versus EGD for esophageal variceal screening. METHODS: Markov models were constructed to compare 2 screening strategies: PillCam ESO versus EGD. In each arm, patients were followed for a time horizon of 15 years in 1-year transition intervals. All variables, transition probabilities, and costs were derived from the medical literature, and sensitivity analyses were performed on the different variables in the model. RESULTS: Base-case analysis shows that PillCam ESO is associated with an average expected cost of $22,589 and an average expected effectiveness measure of 12.81 life-years. EGD is associated with an average expected cost of $23,083 and an average expected effectiveness measure of 12.67 life-years. PillCam ESO was found to dominate EGD as a screening strategy for patients with cirrhosis. Sensitivity analyses found several variables within the model to have influential effects on the results. CONCLUSIONS: PillCam ESO is the dominant strategy for screening patients with cirrhosis for esophageal varices. However, based on a small difference in costs and effectiveness between each strategy, the results would suggest that PillCam ESO and EGD are essentially equivalent strategies.

UV radiation and organic matter composition shape bacterial functional diversity in sediments.

UV radiation and organic matter (OM) composition are known to influence the species composition of bacterioplankton communities. Potential effects of UV radiation on bacterial communities residing in sediments remain completely unexplored to date. However, it has been demonstrated that UV radiation can reach the bottom of shallow waters and wetlands and alter the OM composition of the sediment, suggesting that UV radiation may be more important for sediment bacteria than previously anticipated. It is hypothesized here that exposure of shallow OM-containing sediments to UV radiation induces OM source-dependant shifts in the functional composition of sediment bacterial communities. This study therefore investigated the combined influence of both UV radiation and OM composition on bacterial functional diversity in laboratory sediments. Two different OM sources, labile and recalcitrant OM, were used and metabolic diversity was measured with Biolog GN. Radiation exerted strong negative effects on the metabolic diversity in the treatments containing recalcitrant OM, more than in treatments containing labile OM. The functional composition of the bacterial community also differed significantly between the treatments. Our findings demonstrate that a combined effect of UV radiation and OM composition shapes the functional composition of microbial communities developing in sediments, hinting that UV radiation may act as an important sorting mechanism for bacterial communities and driver for bacterial functioning in shallow waters and wetlands.

Affective disorders in motor neuron disease: a population-based study.

Several studies have suggested that there may be an increased prevalence of affective disorders in people with motor neuron disease (MND). However, the literature is inconsistent, possibly because of small sample sizes in the existing studies. The Canadian province of Alberta has a universal health care system in which physician contacts are recorded along with ICD-9-CM diagnostic codes. In this analysis, diagnostic codes indicative of MND and affective disorders were used. Stratified analysis and logistic regression were used in the analysis. There were 336 cases of MND leading to a prevalence of 14.5 per 100,000 in provincial residents > or =20 years old. Affective disorders were identified in 8.6% of the total population during the same year. The crude odds ratio for affective disorders in MND was 2.3 (95% CI = 1.7-3.0). However, the prevalence of affective disorders declined with increasing illness duration.

Genotype/Phenotype Correlations in X-Linked Dominant Charcot-Marie-Tooth Disease.

We have studied the relationship between genotype, clinical phenotype, and pathology in 13 families with dominant X-linked Charcot-Marie-Tooth (CMT) neuropathy. Connexin32 (Cx32) gene mutations were spread throughout the coding region and included eight missense mutations, one 8-bp deletion/4-bp insertion frame shifting mutation, two nonsense mutations, and one deletion of the entire coding sequence. One hundred sixteen affected CMTX patients (53 males and 63 females) and 63 unaffected, at-risk individuals were compared by neurological and electrophysiological examinations and analyzed by gender; nerve biopsies were available from seven index cases. It was found that mutations within all regions of the Cx32 gene coding sequence caused an identical clinical phenotype. Male CMTX patients were affected more severely and showed an age-dependent progression of clinical signs and of the pathology; there was, however, variability in the severity of disease expression, irrespective of age, among males within families of defined genotype. All but 10% of female CMTX patients had only mild signs. Motor nerve conduction velocities were moderately slowed (median nerve MNCV: males 34.5 ± 6.2 m/sec; females 45.8 ± 7.3 m/sec), and motor and sensory nerve amplitudes were reduced (median nerve CMAP: males 3.7 ± 3.7 mV; females 7.8 ± 3.4 mV), with electromyographic evidence of chronic denervation. Differences were significant between gender and between affected and unaffected individuals. In agreement with the electrophysiological observations, pathological studies showed evidence of paranodal demyelination and of a length-related axonal degeneration in motor and sensory nerve fibers. Correlations between genotype and clinical phenotype suggested that missense mutations located within the second transmembrane domain and/or cytoplasmic loop might be associated with milder clinical phenotype, and therefore might be less disruptive of Connexin32 gap junction function. Missense, chain-terminating, or deletion mutations in all other locations of the Connexin32 protein caused severe forms of CMTX and disease onset in the first decade. Observed variability of disease severity among males within kinships suggests the influence of other modifying factors.