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City Region Food System (CRFS) initiatives exist in various forms, featuring a diversified set of social, economic and environmental performances and impacts. The CRFS approach includes all actors, processes, and relationships involved in the food chain (from production and processing to the distribution and consumption of food) in a given geographical area. Therefore, it encompasses the most crucial elements for facilitating interactions between rural, peri-urban and urban areas. Existing policies may have the potential to support or hinder the progress and development of CRFS initiatives. This research addresses international and national policies as well as the related constraints and challenges that affect CRFS development in six European countries. The overall goal of this research relates to the research questions of how this all-encompassing policy system impacts urban food production and how stakeholders, researchers, and practitioners perceive the current policies at the multi-national level. Various strategic plans with positive and negative impacts, as well as current policy gaps, were compiled from both theoretical and practical perspectives. Data collection was conducted through desktop research, stakeholder interviews and a workshop. Thus, expanding upon the analysis of the results, the study discusses the current challenges in the field of CRFS policies by providing examples, proposing potential improvements, and offering recommendations.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 ., Correction published: Biopsychosoc Med. 2023 Aug 4;17(1):28. doi: 10.1186/s13030-023-00284-3.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 ., Correction published: Biopsychosoc Med. 2023 Aug 4;17(1):28. doi: 10.1186/s13030-023-00284-3.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 ., Correction published: Biopsychosoc Med. 2023 Aug 4;17(1):28. doi: 10.1186/s13030-023-00284-3.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 ., Correction published: Biopsychosoc Med. 2023 Aug 4;17(1):28. doi: 10.1186/s13030-023-00284-3.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. METHODS: Four participants aged 62-70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. RESULTS: Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. CONCLUSIONS: The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441 ., Correction published: Biopsychosoc Med. 2023 Aug 4;17(1):28. doi: 10.1186/s13030-023-00284-3.

Purpose: In high-grade soft-tissue sarcomas (STS) the standard of care encompasses multimodal therapy regimens. While there is a growing body of evidence for prognostic pretreatment radiomic models, we hypothesized that temporal changes in radiomic features following neoadjuvant treatment ("delta-radio mics") may be able to predict the pathological complete response (pCR). Methods: MRI scans (T1-weighted with fat-saturation and contrast-enhancement (T1FSGd) and T2 weighted with fat-saturation (T2FS)) of patients with STS of the extremities and trunk treated with neoadjuvant therapy were gathered from two independent institutions (training: 103, external testing: 53 patients). pCR was defined as <5% viable cells. After segmentation and preprocessing, 105 radiomic features were extracted. Delta-radiomic features were calculated by subtraction of features derived from MRI scans obtained before and after neoadjuvant therapy. After feature reduction, machine learning modeling was performed in 100 iterations of 3-fold nested cross-validation. Delta-radiomic models were compared with single timepoint models in the testing cohort. Results: The combined delta-radiomic models achieved the best area under the receiver operating characteristic curve (AUC) of 0.75. Pre-therapeutic tumor volume was the best conventional predictor (AUC 0.70). The T2FS-based delta-radiomic model had the most balanced classification performance with a balanced accuracy of 0.69. Delta-radiomic models achieved better reproducibility than single timepoint radiomic models, RECIST or the peri-therapeutic volume change. Delta-radiomic models were significantly associated with survival in multivariate Cox regression. Conclusion: This exploratory analysis demonstrated that MRI-based delta-radiomics improves prediction of pCR over tumor volume and RECIST. Delta-radiomics may one day function as a biomarker for personalized treatment adaptations. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Purpose: In high-grade soft-tissue sarcomas (STS) the standard of care encompasses multimodal therapy regimens. While there is a growing body of evidence for prognostic pretreatment radiomic models, we hypothesized that temporal changes in radiomic features following neoadjuvant treatment ("delta-radio mics") may be able to predict the pathological complete response (pCR). Methods: MRI scans (T1-weighted with fat-saturation and contrast-enhancement (T1FSGd) and T2 weighted with fat-saturation (T2FS)) of patients with STS of the extremities and trunk treated with neoadjuvant therapy were gathered from two independent institutions (training: 103, external testing: 53 patients). pCR was defined as <5% viable cells. After segmentation and preprocessing, 105 radiomic features were extracted. Delta-radiomic features were calculated by subtraction of features derived from MRI scans obtained before and after neoadjuvant therapy. After feature reduction, machine learning modeling was performed in 100 iterations of 3-fold nested cross-validation. Delta-radiomic models were compared with single timepoint models in the testing cohort. Results: The combined delta-radiomic models achieved the best area under the receiver operating characteristic curve (AUC) of 0.75. Pre-therapeutic tumor volume was the best conventional predictor (AUC 0.70). The T2FS-based delta-radiomic model had the most balanced classification performance with a balanced accuracy of 0.69. Delta-radiomic models achieved better reproducibility than single timepoint radiomic models, RECIST or the peri-therapeutic volume change. Delta-radiomic models were significantly associated with survival in multivariate Cox regression. Conclusion: This exploratory analysis demonstrated that MRI-based delta-radiomics improves prediction of pCR over tumor volume and RECIST. Delta-radiomics may one day function as a biomarker for personalized treatment adaptations. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and

Attention to urban agriculture (UA) has recently grown among practitioners, scientists, and the public, resulting in several initiatives worldwide. Despite the positive perception of modern UA and locally grown, fresh produce, the potential food safety risks connected to these practices may be underestimated, leading to regulatory gaps. Thus, there is a need for assessment tools to evaluate the food safety risks connected to specific UA initiatives, to assist practitioners in self-evaluation and control, and to provide policy makers and scholars a means to pursue and assess food safety in city regions, avoiding either a lack or an excess of regulation that could ultimately hinder the sector. To address this aim, this paper reviews the most recent and relevant literature on UA food safety assessments. Food safety indicators were identified first. Then, a food safety assessment framework for UA initiatives was developed. The framework uses business surveys and food analyses (if available) as a data source for calculating a food safety index for single UA businesses and the whole UA landscape of a given city region. The proposed framework was designed to allow its integration into the CRFS (City Region Food System) toolkit developed by FAO (Food and Agriculture Organization of the United Nations), RUAF foundation (Resource Centres on Urban Agriculture and Food Security) and Wilfrid Laurier University.

Background. Generalised anxiety disorder (GAD) is prevalent among older adults. These patients exhibit impaired response to cognitive behaviour therapy (CBT), and physical exercise has been recommended as a potential add-on intervention to improve efficacy. The current study is a randomised clinical trial that will compare CBT augmented with physical exercise, or CBT combined with attention placebo, and the current study assessing the feasibility of testing procedures and the experimental combined treatment measures. Methods. 4 participants were included in the feasibility study, and feasibility was assessed trough completion and attendance rates of testing and treatment sessions. Primary outcome measures were remission as assessed by an independent clinical rater using the Anxiety Disorders Interview Schedule for DSM-IV, and by symptom reduction on Penn State Worry Questionnaire. Manipulation check was assessed by physical tests of change in aerobic capacity and strength. Participants were measured on clinical, biological, physiological and neuropsychological tests at pre-, interim and post-treatment. Results. Completed treatment protocol for the RCT will be presented. 3 of 4 participants completed the full protocol including testing and the experimental augmented treatment. Participants completed 100% and 80% of CBT and physical exercise content, respectively. The three completers had large improvements on primary outcome and on manipulation checks. Conclusion. The testing procedures and experimental augmented treatment appear to be feasible. The preliminary findings indicate that this combined intervention can be efficacious.

Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exerc

Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exerc

Gene expression profiles provide important information about the biology of breast tumors and can be used to develop prognostic tests. However, the implementation of quantitative RNA-based testing in routine molecular pathology has not been accomplished, so far. The EndoPredict assay has recently been described as a quantitative RT-PCR-based multigene expression test to identify a subgroup of hormone-receptor-positive tumors that have an excellent prognosis with endocrine therapy only. To transfer this test from bench to bedside, it is essential to evaluate the test-performance in a multicenter setting in different molecular pathology laboratories. In this study, we have evaluated the EndoPredict (EP) assay in seven different molecular pathology laboratories in Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded tumors was tested in the different labs, and the variance and accuracy of the EndoPredict assays were determined using predefined reference values. Extraction of a sufficient amount of RNA and generation of a valid EP score was possible for all 70 study samples (100%). The EP scores measured by the individual participants showed an excellent correlation with the reference values, respectively, as reflected by Pearson correlation coefficients ranging from 0.987 to 0.999. The Pearson correlation coefficient of all values compared to the reference value was 0.994. All laboratories determined EP scores for all samples differing not more than 1.0 score units from the pre-defined references. All samples were assigned to the correct EP risk group, resulting in a sensitivity and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken together, the EndoPredict test could be successfully implemented in all seven participating laboratories and is feasible for reliable decentralized assessment of gene expression in luminal breast cancer.

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BACKGROUND AND PURPOSE: Postoperative analgesia after primary total hip arthroplasty (THA) using opioids is associated with troublesome side effects such as nausea and dizziness, and epidural analgesic means delayed mobilization. Thus, local infiltration analgesia (LIA) during surgery prolonged with local infusion analgesia (LINFA) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track settings within a short period of time. LIA at the time of surgery is a validated treatment. We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery. PATIENTS AND METHODS: 60 consecutive patients undergoing non-cemented THA were randomized into two groups in a double-blind and controlled study. During surgery, all patients received standardized pain treatment with LIA. Postoperatively, they were treated either with a solution of Ropivacain, Ketorolac, and Adrenaline (LINFA group) or placebo (placebo group) administered through a catheter to the hip 10 and 22 h after surgery. Pain score, opioid consumption, and length of stay (LOS) were evaluated. RESULTS: After adjustment for multiple testing, there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness. We found some evidence of a short-term effect on nausea and vomiting. Opioid consumption and length of stay were similar in the two groups. INTERPRETATION: We found some evidence of a short-term effect of LINFA on nausea and vomiting, but no evidence of an effect on postoperative pain and tiredness. Thus, LINFA cannot be recommended as a standard pain treatment in patients with THA

BACKGROUND AND PURPOSE: Postoperative analgesia after primary total hip arthroplasty (THA) using opioids is associated with troublesome side effects such as nausea and dizziness, and epidural analgesic means delayed mobilization. Thus, local infiltration analgesia (LIA) during surgery prolonged with local infusion analgesia (LINFA) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track settings within a short period of time. LIA at the time of surgery is a validated treatment. We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery. PATIENTS AND METHODS: 60 consecutive patients undergoing non-cemented THA were randomized into two groups in a double-blind and controlled study. During surgery, all patients received standardized pain treatment with LIA. Postoperatively, they were treated either with a solution of Ropivacain, Ketorolac, and Adrenaline (LINFA group) or placebo (placebo group) administered through a catheter to the hip 10 and 22 h after surgery. Pain score, opioid consumption, and length of stay (LOS) were evaluated. RESULTS: After adjustment for multiple testing, there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness. We found some evidence of a short-term effect on nausea and vomiting. Opioid consumption and length of stay were similar in the two groups. INTERPRETATION: We found some evidence of a short-term effect of LINFA on nausea and vomiting, but no evidence of an effect on postoperative pain and tiredness. Thus, LINFA cannot be recommended as a standard pain treatment in patients with THA

BACKGROUND AND PURPOSE: Postoperative analgesia after primary total hip arthroplasty (THA) using opioids is associated with troublesome side effects such as nausea and dizziness, and epidural analgesic means delayed mobilization. Thus, local infiltration analgesia (LIA) during surgery prolonged with local infusion analgesia (LINFA) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track settings within a short period of time. LIA at the time of surgery is a validated treatment. We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery. PATIENTS AND METHODS: 60 consecutive patients undergoing non-cemented THA were randomized into two groups in a double-blind and controlled study. During surgery, all patients received standardized pain treatment with LIA. Postoperatively, they were treated either with a solution of Ropivacain, Ketorolac, and Adrenaline (LINFA group) or placebo (placebo group) administered through a catheter to the hip 10 and 22 h after surgery. Pain score, opioid consumption, and length of stay (LOS) were evaluated. RESULTS: After adjustment for multiple testing, there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness. We found some evidence of a short-term effect on nausea and vomiting. Opioid consumption and length of stay were similar in the two groups. INTERPRETATION: We found some evidence of a short-term effect of LINFA on nausea and vomiting, but no evidence of an effect on postoperative pain and tiredness. Thus, LINFA cannot be recommended as a standard pain treatment in patients with THA

Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition.

Copyright: Elsevier The publication is available at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYV-3WXP0T8-5&_user=106421&_coverDate=07%2F16%2F1999&_rdoc=5&_fmt=high&_orig=browse&_srch=doc-info%28%23toc%234844%231999%23999919997%23108971%23FLA%23display%23Volume%29&_cdi=4844&_sort=d&_docanchor=&_ct=10&_acct=C000007358&_version=1&_urlVersion=0&_userid=106421&md5=0f0c2fc05666436c49600525bfd82379, The relationship between activity within the human auditory cortices and the duration of heard tones was investigated by measuring the hemodynamic response with functional magnetic resonance imaging. We demonstrate that there is no significant influence of stimulus duration as used here on the intensity and spatial extent of the hemodynamic response in the auditory cortices. We found however, that the time course of the hemodynamic response to the repeated stimulus presentation exhibited a characteristic decline after the first stimulus exposure during the activation period. The possible reasons for this time course are currently unknown, however, several factors may be involved, including top-down mechanisms and/or the interplay of tissue perfusion and oxygen consumption.

Contains fulltext : 148954.pdf (publisher's version ) (Open Access), Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional Mill and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximate to 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Contains fulltext : 148954.pdf (publisher's version ) (Open Access), Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional Mill and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximate to 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Contains fulltext : 148954.pdf (publisher's version ) (Open Access), Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional Mill and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximate to 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Ziel der Arbeit war es, das Expressionsverhalten von sechs in der Literatur mit Metastasierung in Verbindung gebrachte Gene ( ADAM 17, AXL, LMNB1, Her-2/neu, COL1A1, Col 1A2) bei 32 primären Mammakarzinomen und den dazugehörenden axillären Lymphknotenmetastasen zu vergleichen. Nach Durchführung von Mikrodissektion von Tumorgewebe und anschließender quantitativer RT-PCR konnten bei 23 der Fälle ( 73%) unterschiedliche mRNA Mengen der untersuchten Gene in Primärtumor und Lymphknotenmetastasen nachgewiesen werden. Unter dem Aspekt der molekulargenetischen Heterogenität von Tumorzellen spricht ein Teil der Ergebnisse dafür, dass die Fähigkeit zur Metastasierung nur einer Minderheit von Tumorzellen innerhalb eines Primärtumors vorbehalten bleibt. Weiterhin könnte die für Her-2/neu bei 41% der Studienfälle nachgewiesene Diskordanz der mRNA Mengen in Primärtumor und Lymphknotenmetastase in der Zukunft praktische Bedeutung für den therapeutischen Einsatz von Trastuzumab ( Herceptin ™) erlangen., Purpose of the thesis was to compare the expression behaviour of six genes, which relevant literature mentions in connection with metastasis formation (ADAM 17, AXL, LMNB1, Her-2/new, COL1A1, Col 1A2) in 32 primary mammary carcinomas and the appertaining axillary lymph node metastases. After micro-dissection of tumour tissue and subsequent quantitative RT-PCR, is was possible to identify differing mRNA quantities of the examined genes in primary tumours and lymph node metastases in 23 cases (73%). Considering the molecular-genetic heterogeneity of tumour cells, part of the results appears to indicate that the ability to form metastases is reserved only to a minority of tumour cells within a primary tumour. Furthermore, the discordance between mRNA quantities in primary tumour and lymph node metastasis proven for Her-2/new in 41% of the study cases may in future acquire practical relevance for the therapeutic application of Trastuzumab (Herceptin™).

Ziel der Arbeit war es, das Expressionsverhalten von sechs in der Literatur mit Metastasierung in Verbindung gebrachte Gene ( ADAM 17, AXL, LMNB1, Her-2/neu, COL1A1, Col 1A2) bei 32 primären Mammakarzinomen und den dazugehörenden axillären Lymphknotenmetastasen zu vergleichen. Nach Durchführung von Mikrodissektion von Tumorgewebe und anschließender quantitativer RT-PCR konnten bei 23 der Fälle ( 73%) unterschiedliche mRNA Mengen der untersuchten Gene in Primärtumor und Lymphknotenmetastasen nachgewiesen werden. Unter dem Aspekt der molekulargenetischen Heterogenität von Tumorzellen spricht ein Teil der Ergebnisse dafür, dass die Fähigkeit zur Metastasierung nur einer Minderheit von Tumorzellen innerhalb eines Primärtumors vorbehalten bleibt. Weiterhin könnte die für Her-2/neu bei 41% der Studienfälle nachgewiesene Diskordanz der mRNA Mengen in Primärtumor und Lymphknotenmetastase in der Zukunft praktische Bedeutung für den therapeutischen Einsatz von Trastuzumab ( Herceptin ™) erlangen., Purpose of the thesis was to compare the expression behaviour of six genes, which relevant literature mentions in connection with metastasis formation (ADAM 17, AXL, LMNB1, Her-2/new, COL1A1, Col 1A2) in 32 primary mammary carcinomas and the appertaining axillary lymph node metastases. After micro-dissection of tumour tissue and subsequent quantitative RT-PCR, is was possible to identify differing mRNA quantities of the examined genes in primary tumours and lymph node metastases in 23 cases (73%). Considering the molecular-genetic heterogeneity of tumour cells, part of the results appears to indicate that the ability to form metastases is reserved only to a minority of tumour cells within a primary tumour. Furthermore, the discordance between mRNA quantities in primary tumour and lymph node metastasis proven for Her-2/new in 41% of the study cases may in future acquire practical relevance for the therapeutic application of Trastuzumab (Herceptin™).

Contains fulltext : 56891.pdf (publisher's version ) (Closed access)

Contains fulltext : 49988.pdf (publisher's version ) (Closed access), PURPOSE: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. PATIENTS AND METHODS: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. RESULTS: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. CONCLUSION: Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

Contains fulltext : 56394.pdf (publisher's version ) (Closed access)

Contains fulltext : 41459.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 56891.pdf (publisher's version ) (Closed access)

Contains fulltext : 49988.pdf (publisher's version ) (Closed access), PURPOSE: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. PATIENTS AND METHODS: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. RESULTS: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. CONCLUSION: Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

Contains fulltext : 56394.pdf (publisher's version ) (Closed access)

Contains fulltext : 41459.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 56891.pdf (publisher's version ) (Closed access)

Contains fulltext : 49988.pdf (publisher's version ) (Closed access), PURPOSE: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. PATIENTS AND METHODS: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. RESULTS: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. CONCLUSION: Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

Contains fulltext : 56394.pdf (publisher's version ) (Closed access)

Contains fulltext : 56989.pdf (publisher's version ) (Closed access), The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.

Contains fulltext : 56989.pdf (publisher's version ) (Closed access), The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.