Feedback and feedforward adaptation to visuomotor delay during reaching and slicing movements

It has been suggested that the brain and in particular the cerebellum and motor cortex adapt to represent the environment during reaching movements under various visuomotor perturbations. It is well known that significant delay is present in neural conductance and processing; however, the possible representation of delay and adaptation to delayed visual feedback has been largely overlooked. Here we investigated the control of reaching movements in human subjects during an imposed visuomotor delay in a virtual reality environment. In the first experiment, when visual feedback was unexpectedly delayed, the hand movement overshot the end‐point target, indicating a vision‐based feedback control. Over the ensuing trials, movements gradually adapted and became accurate. When the delay was removed unexpectedly, movements systematically undershot the target, demonstrating that adaptation occurred within the vision‐based feedback control mechanism. In a second experiment designed to broaden our understanding of the underlying mechanisms, we revealed similar after‐effects for rhythmic reversal (out‐and‐back) movements. We present a computational model accounting for these results based on two adapted forward models, each tuned for a specific modality delay (proprioception or vision), and a third feedforward controller. The computational model, along with the experimental results, refutes delay representation in a pure forward vision‐based predictor and suggests that adaptation occurred in the forward vision‐based predictor, and concurrently in the state‐based feedforward controller. Understanding how the brain compensates for conductance and processing delays is essential for understanding certain impairments concerning these neural delays as well as for the development of brain–machine interfaces.     

The role of salivary duct morphology in the aetiology of sialadenitis: statistical analysis of sialographic features

Morphologic characteristics of salivary ducts may contribute to stagnation of saliva. The authors hypothesized that some features might contribute to development of submandibular and parotid sialadenitis. 106 digital subtraction sialograms (DSS) were retrospectively reviewed for: degree of sialadenitis, length of Wharton's and Stensen's ducts (SD), and angle of Wharton's duct (WD) genu. Student's t test was used for independent samples to statistically compare normal and sialadenitis groups. The effect of independent variables (age, gender, side, degree of sialadenitis) on the dependent variable (length or angle) were tested using regression analysis. Submandibular duct sialadenitis was mild (67%), moderate (8%), or severe (25%); parotid duct sialadenitis was mild (57%), moderate (18%), or severe (25%). Mean length of normal WD was 58.2 mm, and 56.3 mm with sialadenitis. Mean length of normal SD was 52 mm, and 53 mm with sialadenitis. The mean angle of WD genu was 115° in normal ducts, and 119° with sialadenitis. None of the independent variables affected variation in length or angle. There were no statistical differences in duct length or measured angle between normal and sialadenitis groups. There is a wide variation in salivary duct morphology but this does not appear to be associated with the cause of sialadenitis.     

Intrahepatic cholangiocarcinoma: current management and emerging therapies

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify ‘target-able’ molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients.

Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies.

Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.     

Particulate vs. block bone grafts: Three-dimensional changes in graft volume after reconstruction of the atrophic maxilla,a 2-year radiographic follow-up

BackgroundExtensive alveolar bone resorption in the maxilla limits the possibility of successful placement and osseointegration of endosseous implants for future prosthetic rehabilitation. Autogenous bone from the iliac crest may be used as lateral onlays in the atrophic maxilla, both as block and particulate bone. To our knowledge, there is no three-dimensional 2-year follow-up study measuring the volumetric reduction of the augmented areas comparing particulate and block bone grafts.PurposeThe aim of this study was to conduct a radiographic 2-year follow-up study, using computed tomographic (CT) images in order to evaluate and compare the extent of bone graft resorption in the frontal maxillae augmented by particulate (test) and block bone (control).Material and methodsEleven patients treated with iliac bone grafts and oral implants in the maxilla were followed with CT examinations directly post grafting and after 2 years.ResultThe volumetric changes after 6 months were extensive. Additionally, the changes in particulate bone tended to be larger after 2 years compared to block bone, using this protocol. However, the difference was not statistically significant.ConclusionThe present follow-up study showed that there is radiographically complete integration and embedding of implants installed in grafted bone despite extensive initial graft resorption. There was no significant difference in the amount of volumetric reduction between particulate bone and block bone grafts.     

Psychological and Sociocultural Adaptation: Acculturation,Depressive Symptoms,and Life Satisfaction Among Older Iranian Immigrants in Canada

Informed by Ward’s (1996) theory of psychological and sociocultural adaptation, this study identified links between acculturation and the mental health of older Iranian immigrants living in Canada (N = 103). According to Ward and colleagues, both psychological and sociocultural adaptation change at different rates and extend into later life. For this study, participants 50+ years of age and born in Iran completed questionnaires measuring life satisfaction, depressive symptoms, acculturation, and demographic and sociocultural variables (e.g., pre- and post-immigration occupational status). We collected study data anonymously in Persian to obtain responses from long-term residents of Canada as well as more recent immigrants who may not read or write English. We examined both life satisfaction and (the absence of) depressive symptoms as distinct forms of psychological adaptation; these emerged as independent predictors of acculturation. Contrary to theory, acculturation appears to predict life satisfaction, not vice versa; moreover, there seems to be no direct link between depressive symptoms and acculturation. Our findings suggest that integration within Canadian society is associated with higher life satisfaction. In contrast, sociocultural factors are indirectly associated with life satisfaction (except age) and acculturation (except ethnic diversity of social interactions). Involuntary migrants reported higher levels of depression, whereas loss of occupational status is associated with reduced life satisfaction. Implications for future research and health policy are discussed.     

UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects and methods: Allele frequencies of SNPs UGT1A4^24Thr, UGT1A4^48Val, UGT2B15^85Tyr, UGT2B15^523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A4^48Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations.

Conclusion: North African populations show a high frequency of carriers of UGT2B15^523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17^del, a variant associated with high concentrations of testosterone and oestradiol.