A multi-scale hierarchical framework for developing understanding of river behaviour to support river management

The work leading to this paper was funded through the European Union’s FP7 programme under Grant Agreement No. 282656 (REFORM). The framework methodology was developed within the context of Deliverable D2.1 of the REFORM programme, and all partners who contributed to the development of the four parts of this deliverable are included in the author list of this paper. More details on the REFORM framework can be obtained from part 1 of Deliverable D2.1 (Gurnell et al. 2014), which is downloadable from http://​www.​reformrivers.​eu/​results/​deliverables

Unfolding dermatologic spectrum of Behçet’s disease in Italy: real-life data from the International AIDA Network Behçet’s disease Registry

Behçet’s disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care

Fenfluramine and N-ethyl amphetamine: Comparison of the reinforcing and rate-decreasing actions in the rhesus monkey

N-ethyl amphetamine HCl (NEA) and fenfluramine HCl ( meta -trifluoromethyl N-ethyl amphetamine) were evaluated as reinforcers in rhesus monkeys that had been previously trained to press a lever using food presentations and cocaine HCl injections as reinforcers. Each daily session consisted of episodic opportunities to obtain reinforcers under a fixed-ratio schedule of 30. A drug period was interpolated between two periods in which lever-press responding was maintained by food presentations. Compared to saline, none of the drugs altered the rate of responding in the food periods which preceded the drug sessions, indicating the absence of residual response-disrupting drug actions from previous sessions. However, NEA and fenfluramine self-injection resulted in dose-related decreases in response rates during the food periods which immediately followed the drug sessions. Cocaine HCl (30 Μg/kg/injection) maintained high response rates at over one response/second during the drug periods, as did the same dose of NEA. Doses of 10 and 100 Μg/kg/injection of NEA as well as all doses of fenfluramine HCl (10 through 300 Μg/kg/injection) maintained rates that were not different from those associated with saline injections. These results substantiate and extend earlier findings with fenfluramine and indicate that its failure to act as a reinforcer is attributable to its meta -trifluoromethyl group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46392/1/213_2004_Article_BF00429257.pd

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Evaluation of Brain Iron Content Based on Magnetic Resonance Imaging (MRI): Comparison among Phase Value, R2* and Magnitude Signal Intensity

Background and Purpose: Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn’t commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. Methods: We measured both phase values and R2 * in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2 * and brain iron. Results: We found phase value correlated with R2 * in substantia nigra (r = 20.723, p,0.001) and putamen (r = 20.514, p = 0.010), while no correlations in red nucleus (r = 20.236, p = 0.268) and globus pallidus (r = 20.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = 20.593, p = 0.002), substantia nigra (r = 20.521, p = 0.009), globus pallidus (r = 20.750, p,0.001) and putamen (r = 20.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = 20.982, P,0.001). Conclusions: Our study indicates that phase value may not be used for assessing the iron content in some brain region

Deciphering the functional role of spatial and temporal muscle synergies in whole-body movements

International audienceVoluntary movement is hypothesized to rely on a limited number of muscle synergies, the recruitment of which translates task goals into effective muscle activity. In this study, we investigated how to analytically characterize the functional role of different types of muscle synergies in task performance. To this end, we recorded a comprehensive dataset of muscle activity during a variety of whole-body pointing movements. We decomposed the electromyographic (EMG) signals using a space-by-time modularity model which encompasses the main types of synergies. We then used a task decoding and information theoretic analysis to probe the role of each synergy by mapping it to specific task features. We found that the temporal and spatial aspects of the movements were encoded by different temporal and spatial muscle synergies, respectively, consistent with the intuition that there should a correspondence between major attributes of movement and major features of synergies. This approach led to the development of a novel computational method for comparing muscle synergies from different participants according to their functional role. This functional similarity analysis yielded a small set of temporal and spatial synergies that describes the main features of whole-body reaching movements

Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect

The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we noticed an age-related decline in IQ subscales in boys affected with the CRTR defect