Using position dependent damping forces around reaching targets for transporting heavy objects:A Fitts' law approach

Passive assistive devices that compensate gravity can reduce human effort during transportation of heavy objects. The additional reduction of inertial forces, which are still present during deceleration when using gravity compensation, could further increase movement performance in terms of accuracy and duration. This study investigated whether position dependent damping forces (PDD) around targets could assist during planar reaching movements. The PDD damping coefficient value increased linearly from 0 Ns/m to 200 Ns/m over 18 cm (long PDD) or 9 cm (short PDD). Movement performance of reaching with both PDDs was compared against damping free baseline conditions and against constant damping (40 Ns/m). Using a Fitts' like experiment design 18 subjects performed a series of reaching movements with index of difficulty: 3.5, 4.5 and 5.5 bits, and distances 18, 23 and 28 cm for all conditions. Results show that PDD reduced (compared to baseline and constant damping) movement times by more than 30% and reduced the number of target reentries, i.e. increasing reaching accuracy, by a factor of 4. Results were inconclusive about whether the long or short PDD conditions achieved better task performance, although mean human acceleration forces were higher for the short PDD, hinting at marginally faster movements. Overall, PDD is a useful haptic force to get humans to decrease their reaching movement times while increasing their targeting accuracy

Assisting walking balance using a bio-inspired exoskeleton controller

Background: Balance control is important for mobility, yet exoskeleton research has mainly focused on improving metabolic energy efficiency. Here we present a biomimetic exoskeleton controller that supports walking balance and reduces muscle activity. Methods: Humans restore balance after a perturbation by adjusting activity of the muscles actuating the ankle in proportion to deviations from steady-state center of mass kinematics. We designed a controller that mimics the neural control of steady-state walking and the balance recovery responses to perturbations. This controller uses both feedback from ankle kinematics in accordance with an existing model and feedback from the center of mass velocity. Control parameters were estimated by fitting the experimental relation between kinematics and ankle moments observed in humans that were walking while being perturbed by push and pull perturbations. This identified model was implemented on a bilateral ankle exoskeleton. Results: Across twelve subjects, exoskeleton support reduced calf muscle activity in steady-state walking by 19% with respect to a minimal impedance controller (p < 0.001). Proportional feedback of the center of mass velocity improved balance support after perturbation. Muscle activity is reduced in response to push and pull perturbations by 10% (p = 0.006) and 16% (p < 0.001) and center of mass deviations by 9% (p = 0.026) and 18% (p = 0.002) with respect to the same controller without center of mass feedback. Conclusion: Our control approach implemented on bilateral ankle exoskeletons can thus effectively support steady-state walking and balance control and therefore has the potential to improve mobility in balance-impaired individuals.Support Biomechanical Engineerin

Unconscious biases in neural populations coding multiple stimuli

Throughout the nervous system information is commonly coded in activity distributed over populations of neurons. In idealized situations where a single, continuous stimulus is encoded in a homogeneous population code, the value of the encoded stimulus can be read out without bias. However in many situations multiple stimuli are simultaneously present, for example, multiple motion patterns might overlap. Here we find that when multiple stimuli that overlap in their neural representation are simultaneously encoded in the population, biases in the read-out emerge. Although the bias disappears in the absence of noise, the bias is remarkably persistent at low noise levels. The bias can be reduced by competitive encoding schemes or by employing complex decoders. To study the origin of the bias, we develop a novel general framework based on Gaussian processes that allows for an accurate calculation of the estimate distributions of maximum likelihood decoders, and reveals that the distribution of estimates is bimodal for overlapping stimuli. The results have implications for neural coding and behavioural experiments on, for instance, overlapping motion patterns

Optimization of interneuron function by direct coupling of cell migration and axonal targeting

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb—a gene that is preferentially expressed by these cells—cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex

Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Upper limb rehabilitation using robotic exoskeleton systems: a systematic review

Exoskeleton assisted therapy has been reported as a significant reduction in impairment and gain in functional abilities of stroke patients. In this paper, we conduct a systematic review on the upper limb rehabilitation using robotic exoskeleton systems. This review is based on typical mechanical structures and control strategies for exoskeletons in clinical rehabilitation conditions. A variety of upper limb exoskeletons are classified and reviewed according to their rehabilitation joints. Special attentions are paid to the performance control strategies and mechanism designs in clinical trials and to promote the adaptability to different patients and conditions. Finally, we analyze and highlight the current research gaps and the future directions in this field. We intend to offer informative resources and reliable guidance for relevant researcher’s further studies, and exert a far-reaching influence on the development of advanced upper limb exoskeleton robotic systems

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar