Conflict, violence, and warfare amongst early farmers in north western Europe

Bioarchaeological evidence of interpersonal violence and early warfare presents important insights into conflict in past societies. This evidence is critical for understanding the motivations for violence and its effects on opposing and competing individuals and groups across time and space. Selecting the Neolithic of northwestern Europe as an area for study, the present paper examines the variation and societal context for the violence recorded in the human skeletal remains from this region as one of the most important elements of human welfare. Compiling data from various sources, it becomes apparent that violence was endemic in Neolithic Europe, sometimes reaching levels of intergroup hostilities that ended in the utter destruction of entire communities. While the precise comparative quantification of healed and unhealed trauma remains a fundamental problem, patterns emerge that see conflict likely fostered by increasing competition between settled and growing communities, e.g., for access to arable land for food production. The further development of contextual information is paramount in order to address hypotheses on the motivations, origins, and evolution of violence as based on the study of human remains, the most direct indicator for actual small- and large-scale violence

"Spontaneous" late recovery from stuttering: Dimensions of reported techniques and causal attributions

Purpose: (1) To survey the employed techniques and the reasons/occasions which adults who had recovered from stuttering after age 11 without previous treatment reported as causal to overcome stuttering, (2) to investigate whether the techniques and causal attributions can be reduced to coherent (inherently consistent) dimensions, and (3) whether these dimensions reflect common therapy components.Methods: 124 recovered persons from 8 countries responded by SurveyMonkey or paper-and-pencil to rating scale questions about 49 possible techniques and 15 causal attributions.Results: A Principal Component Analysis of 110 questionnaires identified 6 components (dimensions) for self-assisted techniques (Speech Restructuring; Relaxed/Monitored Speech; Elocution; Stage Performance; Sought Speech Demands; Reassurance; 63.7% variance explained), and 3 components of perceived causal attributions of recovery (Life Change, Attitude Change, Social Support; 58.0% variance explained).Discussion: Two components for self-assisted techniques (Speech Restructuring; Elocution) reflect treatment methods. Another component (Relaxed/Monitored Speech) consists mainly of items that reflect a common, non-professional understanding of effective management of stuttering. The components of the various perceived reasons for recovery reflect differing implicit theories of causes for recovery from stuttering. These theories are considered susceptible to various biases. This identification of components of reported techniques and of causal attributions is novel compared to previous studies who just list techniques and attributions.Conclusion: The identified dimensions of self-assisted techniques and causal attributions to reduce stuttering as extracted from self-reports of a large, international sample of recovered formerly stuttering adults may guide the application of behavioral stuttering therapies.</p

Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease

We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson’s disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35–75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2–3 and Unified Parkinson’s Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations. Drug delivery devices were implanted and putamenal volume coverage was required to exceed a predefined threshold at a test infusion prior to randomization. Six pilot stage patients (randomization 2:1) and 35 primary stage patients (randomization 1:1) received bilateral intraputamenal infusions of GDNF (120 mg per putamen) or placebo every 4 weeks for 40 weeks. Efficacy analyses were based on the intention-to-treat principle and included all patients randomized. The primary outcome was the percentage change from baseline to Week 40 in the OFF state (UPDRS-III). The primary analysis was limited to primary stage patients, while further analyses included all patients from both study stages. The mean OFF state UPDRS motor score decreased by 17.3 17.6% in the active group and 11.8 15.8% in the placebo group (least squares mean difference: 4.9%, 95% CI: 16.9, 7.1, P = 0.41). Secondary endpoints did not show significant differences between the groups either. A post hoc analysis found nine (43%) patients in the active group but no placebo patients with a large clinically important motor improvement (510 points) in the OFF state (P = 0.0008). 18F-DOPA PET imaging demonstrated a significantly increased uptake throughout the putamen only in the active group, ranging from 25% (left anterior putamen; P = 0.0009) to 100% (both posterior putamina; P50.0001). GDNF appeared to be well tolerated and safe, and no drug-related serious adverse events were reported. The study did not meet its primary endpoint. 18F-DOPA imaging, however, suggested that intermittent convection-enhanced delivery of GDNF produced a putamen-wide tissue engagement effect, overcoming prior delivery limitations. Potential reasons for not proving clinical benefit at 40 weeks are discussed

Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease

Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson’s disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen. Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. Results: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: –13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (–9.6±6.7 vs. –3.8±4.2 points, p = 0.0108) and activities of daily living score (–6.9±5.5 vs. –1.0±3.7 points, p = 0.0003). No treatment-emergent safety concerns were identified. Conclusions: The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose

“Spontaneous” late recovery from stuttering: Dimensions of reported techniques and causal attributions

Purpose: (1) To survey the employed techniques and the reasons/occasions which adults who had recovered from stuttering after age 11 without previous treatment reported as causal to overcome stuttering, (2) to investigate whether the techniques and causal attributions can be reduced to coherent (inherently consistent) dimensions, and (3) whether these dimensions reflect common therapy components. Methods: 124 recovered persons from 8 countries responded by SurveyMonkey or paper-and-pencil to rating scale questions about 49 possible techniques and 15 causal attributions. Results: A Principal Component Analysis of 110 questionnaires identified 6 components (dimensions) for self-assisted techniques (Speech Restructuring; Relaxed/Monitored Speech; Elocution; Stage Performance; Sought Speech Demands; Reassurance; 63.7% variance explained), and 3 components of perceived causal attributions of recovery (Life Change, Attitude Change, Social Support; 58.0% variance explained). Discussion: Two components for self-assisted techniques (Speech Restructuring; Elocution) reflect treatment methods. Another component (Relaxed/Monitored Speech) consists mainly of items that reflect a common, non-professional understanding of effective management of stuttering. The components of the various perceived reasons for recovery reflect differing implicit theories of causes for recovery from stuttering. These theories are considered susceptible to various biases. This identification of components of reported techniques and of causal attributions is novel compared to previous studies who just list techniques and attributions. Conclusion: The identified dimensions of self-assisted techniques and causal attributions to reduce stuttering as extracted from self-reports of a large, international sample of recovered formerly stuttering adults may guide the application of behavioral stuttering therapies