Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements. Main Outcome Measures: Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES. Results: With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects. Conclusions: Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics

Nostril-Specific Olfactory Modulation of Visual Perception in Binocular Rivalry

It is known that olfaction and vision can work in tandem to represent object identities. What is yet unclear is the stage of the sensory processing hierarchy at which the two types of inputs converge. Here we study this issue through a well established visual phenomenon termed binocular rivalry. We show that smelling an odor from one nostril significantly enhances the dominance time of the congruent visual image in the contralateral visual field, relative to that in the ipsilateral visual field. Moreover, such lateralization-based enhancement extends to category selective regions so that when two images of words and human body, respectively, are engaged in rivalry in the central visual field, smelling natural human body odor from the right nostril increases the dominance time of the body image compared with smelling it from the left nostril. Semantic congruency alone failed to produce this effect in a similar setting. These results, taking advantage of the anatomical and functional lateralizations in the olfactory and visual systems, highlight the functional dissociation of the two nostrils and provide strong evidence for an object-based early convergence of olfactory and visual inputs in sensory representations

Personal preferences for Personalised Trials among patients with chronic diseases: an empirical Bayesian analysis of a conjoint survey.

OBJECTIVE: To describe individual patient preferences for Personalised Trials and to identify factors and conditions associated with patient preferences. DESIGN: Each participant was presented with 18 conjoint questions via an online survey. Each question provided two choices of Personalised Trials that were defined by up to eight attributes, including treatment types, clinician involvement, study logistics and trial burden on a patient. SETTING: Online survey of adults with at least two common chronic conditions in the USA. PARTICIPANTS: A nationally representative sample of 501 individuals were recruited from the Chronic Illness Panel by Harris Poll Online. Participants were recruited from several sources, including emails, social media and telephone recruitment of the target population. MAIN OUTCOME MEASURES: The choice of Personalised Trial design that the participant preferred with each conjoint question. RESULTS: There was large variability in participants\u27 preferences for the design of Personalised Trials. On average, they preferred certain attributes, such as a short time commitment and no cost. Notably, a population-level analysis correctly predicted 62% of the conjoint responses. An empirical Bayesian analysis of the conjoint data, which supported the estimation of individual-level preferences, improved the accuracy to 86%. Based on estimates of individual-level preferences, patients with chronic pain preferred a long study duration (p≤0.001). Asthma patients were less averse to participation burden in terms of data-collection frequency than patients with other conditions (p=0.002). Patients with hypertension were more cost-sensitive (p\u3c0.001). CONCLUSION: These analyses provide a framework for elucidating individual-level preferences when implementing novel patient-centred interventions. The data showed that patient preference in Personalised Trials is highly variable, suggesting that individual differences must be accounted for when marketing Personalised Trials. These results have implications for advancing precise interventions in Personalised Trials by indicating when rigorous scientific principles, such as frequent monitoring, is feasible in a substantial subset of patients

DNA nanostructure-based magnetic beads for potentiometric aptasensing

In this work, a simple, general, and sensitive potentiometric platform is presented, which allows potentiometric sensing to be applied to any class of molecule irrespective of the analyte charge. DNA nanostructures are self-assembled on magnetic beads via the incorporation of an aptamer into a hybridization chain reaction. The aptamer target binding event leads to the disassembly of the DNA nanostructures, which results in a dramatic change in the surface charge of the magnetic beads. Such a surface charge change can be sensitively detected by a polycation-sensitive membrane electrode using protamine as an indicator. With an endocrine disruptor bisphenol A as a model, the proposed potentiometric method shows a wide linear range from 0.1 to 100 nM with a low detection limit of 80 pM (3 sigma). The proposed sensing strategy will lay a foundation for the development of potentiometric sensors for highly sensitive and selective detection of various targets

Thiol-Functionalized Mesoporous Silica for Effective Trap of Mercury in Rats

The chance of exposure to heavy metal for human being rises severely today due to the increasing water contamination and air pollution. Here, we prepared a series of thiol-functionalized mesoporous silica as oral formulation for the prevention and treatment of heavy metal poisoning. The successful incorporation of thiol was verified by the FTIR spectra. SBA15-SH-10 was used for the study as it is of uniform mesopores and fine water dispersibility. In simulated gastrointestinal fluid, the thiol-functionalized mesoporous silica can selectively capture heavy metal, showing a very high affinity for inorganic mercury (II). The blood and urine mercury levels of rats fed with a diet containing Hg (II) and material were significantly lower than those of rats fed with the metal-rich diet only. On the contrary, the mercury content in fecal excretion of the treatment group increased more than twice as much as that of the control group. This result indicated that SBA15-SH-10 could effectively remove mercury (II) in vivo and the mercury loaded on SBA15-SH-10 would be excreted out. Hence, SBA15-SH-10 has potential application in preventing and treating heavy metal poisoning via digestive system

A Potentiometric Flow Biosensor Based on Ammonia-Oxidizing Bacteria for the Detection of Toxicity in Water

A flow biosensor for the detection of toxicity in water using the ammonia-oxidizing bacterium (AOB) Nitrosomonas europaea as a bioreceptor and a polymeric membrane ammonium-selective electrode as a transducer is described. The system is based on the inhibition effects of toxicants on the activity of AOB, which can be evaluated by measuring the ammonium consumption rates with the ammonium-selective membrane electrode. The AOB cells are immobilized on polyethersulfone membranes packed in a holder, while the membrane electrode is placed downstream in the flow cell. Two specific inhibitors of the ammonia oxidation. allylthiourea and thioacetamide. have been tested. The IC50 values defined as the concentration of an inhibitor causing a 50% reduction in the ammonia oxidation activity have been measured as 0.17 mu M and 0.46 mu M for allylthiourea and thioacetamide, respectively. The proposed sensor offers advantages of simplicity, speed and high sensitivity for measuring toxicity in water.A flow biosensor for the detection of toxicity in water using the ammonia-oxidizing bacterium (AOB) Nitrosomonas europaea as a bioreceptor and a polymeric membrane ammonium-selective electrode as a transducer is described. The system is based on the inhibition effects of toxicants on the activity of AOB, which can be evaluated by measuring the ammonium consumption rates with the ammonium-selective membrane electrode. The AOB cells are immobilized on polyethersulfone membranes packed in a holder, while the membrane electrode is placed downstream in the flow cell. Two specific inhibitors of the ammonia oxidation. allylthiourea and thioacetamide. have been tested. The IC50 values defined as the concentration of an inhibitor causing a 50% reduction in the ammonia oxidation activity have been measured as 0.17 mu M and 0.46 mu M for allylthiourea and thioacetamide, respectively. The proposed sensor offers advantages of simplicity, speed and high sensitivity for measuring toxicity in water

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Lanthanide-Loaded Nanoscaffolds for Multimodal Imaging and Therapy

Multimodal imaging techniques are emerging in medical diagnosis. The synergistic combination of imaging techniques, such as MRI and PET/SPECT, is highly useful to strengthen each of the individual imaging modalities while reducing any of their disadvantages. In recent years, the progress of technical integration of imaging scanners has led to a clear motivation to design multimodal agents by chemists that can be used simultaneously and hence profit optimally of the new hybrid imaging scanners. Nanoscaffolds combining discrete functions (e.g. magnetic, radioactive, optical or therapeutic) are particularly interesting in this regard. There has been an increasing endeavour to design and synthesize multifunctional nanocomposites for practical applications in dual imaging modalities such as MRI-optical, MRI-PET, PET-optical, PET-CT, MRI-SPECT. Chapter 1 of this thesis summarizes the state-of-the-art in the development of multimodal probes for medical imaging and therapy, in which the roles of metal ions are highlighted. Chapters 2-5 focus on the exploration of porous nanomaterials, e.g. zeolite LTL in particular, which is suitable for the above-mentioned purposes due to their ability to accommodate large amounts of lanthanide ions through ion-exchange of alkali cations that counterbalance the AlO4- of the crystalline framework. The surface chemistry and biocompatibility study are also included. Chapter 6 describes a facile methodology to synthesize the lanthanide-nanoparticles with controllable size and application of the synthesized materials as MRI contrast agents. Chapter 7 shows that these versatile materials are also applicable in a very different field: they are very efficient in the storage and release of oxygen.In conclusion, the findings of the thesis mainly provide insights into the merits and understanding of zeolite-based MR imaging probes.BT/Biocatalysi