Apathy and impulsivity in frontotemporal lobar degeneration syndromes

Apathy and impulsivity are common and disabling consequences of frontotemporal lobar degeneration. They cause substantial carer distress, but their aetiology remains elusive. There are critical limitations to previous studies in this area including (i) the assessment of either apathy or impulsivity alone, despite their frequent co-existence; (ii) the assessment of behavioural changes within single diagnostic groups; and (iii) the use of limited sets of tasks or questions that relate to just one aspect of these multifactorial constructs. We proposed an alternative, dimensional approach that spans behavioural and language variants of frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome. This accommodates the commonalities of apathy and impulsivity across disorders and reveals their cognitive and anatomical bases. The ability to measure the components of apathy and impulsivity and their associated neural correlates across diagnostic groups would provide better novel targets for pharmacological manipulations, and facilitate new treatment strategies and strengthen translational models. We therefore sought to determine the neurocognitive components of apathy and impulsivity in frontotemporal lobar degeneration syndromes. The frequency and characteristics of apathy and impulsivity were determined by neuropsychological and behavioural assessments in 149 patients and 50 controls from the PIck’s disease and Progressive supranuclear palsy Prevalence and INcidence study (PiPPIN). We derived dimensions of apathy and impulsivity using principal component analysis and employed these in volumetric analyses of grey and white matter in a subset of 70 patients (progressive supranuclear palsy, n = 22; corticobasal syndrome, n = 13; behavioural variant, n = 14; primary progressive aphasias, n = 21) and 27 control subjects. Apathy and impulsivity were present across diagnostic groups, despite being criteria for behavioural variant frontotemporal dementia alone. Measures of apathy and impulsivity frequently loaded onto the same components reflecting their overlapping relationship. However, measures from objective tasks, patient-rated questionnaires and carer-rated questionnaires loaded onto separate components and revealed distinct neurobiology. Corticospinal tracts correlated with patients’ self-ratings. In contrast, carer ratings correlated with atrophy in established networks for goal-directed behaviour, social cognition, motor control and vegetative functions, including frontostriatal circuits, orbital and temporal polar cortex, and the brainstem. Components reflecting response inhibition deficits correlated with focal frontal cortical atrophy. The dimensional approach to complex behavioural changes arising from frontotemporal lobar degeneration provides new insights into apathy and impulsivity, and the need for a joint therapeutic strategy against them. The separation of objective tests from subjective questionnaires, and patient from carer ratings, has important implications for clinical trial design

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

Allometric Scaling of the Active Hematopoietic Stem Cell Pool across Mammals

BACKGROUND: Many biological processes are characterized by allometric relations of the type Y = Y (0) M(b) between an observable Y and body mass M, which pervade at multiple levels of organization. In what regards the hematopoietic stem cell pool, there is experimental evidence that the size of the hematopoietic stem cell pool is conserved in mammals. However, demands for blood cell formation vary across mammals and thus the size of the active stem cell compartment could vary across species. METHODOLOGY/PRINCIPLE FINDINGS: Here we investigate the allometric scaling of the hematopoietic system in a large group of mammalian species using reticulocyte counts as a marker of the active stem cell pool. Our model predicts that the total number of active stem cells, in an adult mammal, scales with body mass with the exponent ¾. CONCLUSION/SIGNIFICANCE: The scaling predicted here provides an intuitive justification of the Hayflick hypothesis and supports the current view of a small active stem cell pool supported by a large, quiescent reserve. The present scaling shows excellent agreement with the available (indirect) data for smaller mammals. The small size of the active stem cell pool enhances the role of stochastic effects in the overall dynamics of the hematopoietic system

Health Effects of Airborne Exposures from Concentrated Animal Feeding Operations

Toxic gases, vapors, and particles are emitted from concentrated animal feeding operations (CAFOs) into the general environment. These include ammonia, hydrogen sulfide, carbon dioxide, malodorous vapors, and particles contaminated with a wide range of microorganisms. Little is known about the health risks of exposure to these agents for people living in the surrounding areas. Malodor is one of the predominant concerns, and there is evidence that psychophysiologic changes may occur as a result of exposure to malodorous compounds. There is a paucity of data regarding community adverse health effects related to low-level gas and particulate emissions. Most information comes from studies among workers in CAFO installations. Research over the last decades has shown that microbial exposures, especially endotoxin exposure, are related to deleterious respiratory health effects, of which cross-shift lung function decline and accelerated decline over time are the most pronounced effects. Studies in naïve subjects and workers have shown respiratory inflammatory responses related to the microbial load. This working group, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, concluded that there is a great need to evaluate health effects from exposures to the toxic gases, vapors, and particles emitted into the general environment by CAFOs. Research should focus not only on nuisance and odors but also on potential health effects from microbial exposures, concentrating on susceptible subgroups, especially asthmatic children and the elderly, since these exposures have been shown to be related to respiratory health effects among workers in CAFOs

High cable forces deteriorate pinch force control in voluntary-closing body-powered prostheses

It is generally asserted that reliable and intuitive control of upper-limb prostheses requires adequate feedback of prosthetic finger positions and pinch forces applied to objects. Body-powered prostheses (BPPs) provide the user with direct proprioceptive feedback. Currently available BPPs often require high cable operation forces, which complicates control of the forces at the terminal device. The aim of this study is to quantify the influence of high cable forces on object manipulation with voluntary-closing prostheses. Able-bodied male subjects were fitted with a bypass-prosthesis with low and high cable force settings for the prehensor. Subjects were requested to grasp and transfer a collapsible object as fast as they could without dropping or breaking it. The object had a low and a high breaking force setting. Subjects conducted significantly more successful manipulations with the low cable force setting, both for the low (33 % more) and high (50 %) object’s breaking force. The time to complete the task was not different between settings during successful manipulation trials. In conclusion: high cable forces lead to reduced pinch force control during object manipulation. This implies that low cable operation forces should be a key design requirement for voluntary-closing BPPs

Systematic Evaluation of the Descriptive and Predictive Performance of Paediatric Morphine Population Models

Purpose: A framework for the evaluation of paediatric population models is proposed and applied to two different paediatric population pharmacokinetic models for morphine. One covariate model was based on a systematic covariate analysis, the other on fixed allometric scaling principles. Methods: The six evaluation criteria in the framework were 1) number of parameters and condition number, 2) numerical diagnostics, 3) prediction-based diagnostics, 4) η-shrinkage, 5) simulation-based diagnostics, 6) diagnostics of individual and population parameter estimates versus covariates, including measurements of bias and precision of the population values compared to the observed individual values. The framework entails both an internal and external model evaluation procedure. Results: The application of the framework to the two models resulted in the detection of overparameterization and misleading diagnostics based on individual predictions caused by high shrinkage. The diagnostic of individual and population parameter estimates versus covariates proved to be highly informative in assessing obtained covariate relationships. Based on the framework, the systematic covariate model proved to be superior over the fixed allometric model in terms of predictive performance. Conclusions: The proposed framework is suitable for the evaluation of paediatric (covariate) models and should be applied to corroborate the descriptive and predictive properties of these models

Assessing the ecological impacts of invasive species based on their functional responses and abundances

Invasive species management requires allocation of limited resources towards the proactive mitigation of those species that could elicit the highest ecological impacts. However, we lack predictive capacity with respect to the identities and degree of ecological impacts of invasive species. Here, we combine the relative per capita effects and relative field abundances of invader as compared to native species into a new metric, “Relative Impact Potential” (RIP), and test whether this metric can reliably predict high impact invaders. This metric tests the impact of invaders relative to the baseline impacts of natives on the broader ecological community. We first derived the functional responses (i.e. per capita effects) of two ecologically damaging invasive fish species in Europe, the Ponto-Caspian round goby (Neogobius melanostomus) and Asian topmouth gudgeon (Pseudorasbora parva), and their native trophic analogues, the bullhead (Cottus gobio; also C. bairdi) and bitterling (Rhodeus amarus), towards several prey species. This establishes the existence and relative strengths of the predator-prey relationships. Then, we derived ecologically comparable field abundance estimates of the invader and native fish from surveys and literature. This establishes the multipliers for the above per capita effects. Despite both predators having known severe detrimental field impacts, their functional responses alone were of modest predictive power in this regard; however, incorporation of their abundances relative to natives into the RIP metric gave high predictive power. We present invader/native RIP biplots that provide an intuitive visualisation of comparisons among the invasive and native species, reflecting the known broad ecological impacts of the invaders. Thus, we provide a mechanistic understanding of invasive species impacts and a predictive tool for use by practitioners, for example, in risk assessments

Instrumented fusion of thoracolumbar fracture with type I mineralized collagen matrix combined with autogenous bone marrow as a bone graft substitute: a four-case report

In order to avoid the morbidity from autogenous bone harvesting, bone graft substitutes are being used more frequently in spinal surgery. There is indirect radiological evidence that bone graft substitutes are efficacious in humans. The purpose of this four-case study was to visually, manually, and histologically assess the quality of a fusion mass produced by a collagen hydroxyapatite scaffold impregnated with autologous bone marrow aspirate for posterolateral fusion. Four patients sustained an acute thoracolumbar fracture and were treated by short posterior segment fusion using the AO fixateur interne. Autologous bone marrow (iliac crest) impregnated hydroxyapatite-collagen scaffold was laid on the decorticated posterior elements. Routine implant removal was performed after a mean of 15.3 months (12–20). During this second surgery, fusion mass was assessed visually and manually. A bone biopsy was sent for histological analysis of all four cases. Fusion was confirmed in all four patients intraoperatively and sagittal stress testing confirmed mechanical adequacy of the fusion mass. Three out of the four (cases 2–4) had their implants removed between 12 and 15 months after the index surgery. All their histological cuts showed evidence of newly formed bone and presence of active membranous and/or enchondral ossification foci. The last patient (case 1) underwent implant removal at 20 months and his histological cuts showed mature bone, but no active ossification foci. This four-case report suggests that the fusion mass produced by a mineralized collagen matrix graft soaked in aspirated bone marrow is histologically and mechanically adequate in a thoracolumbar fracture model. A larger patient series and/or randomized controlled studies are warranted to confirm these initial results

Respiratory symptoms and occupation: a cross-sectional study of the general population

BACKGROUND: This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. METHODS: The study subjects (aged 20–59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. RESULTS: Employment in the 'construction' (OR = 3.38; 95%CI 1.02 – 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 – 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 – 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 – 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 – 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. CONCLUSION: Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals