Silicon Valley new focus on brain computer interface: hype or hope for new applications?

In the last year there has been increasing interest and investment into developing devices to interact with the central nervous system, in particular developing a robust brain-computer interface (BCI). In this article, we review the most recent research advances and the current host of engineering and neurological challenges that must be overcome for clinical application. In particular, space limitations, isolation of targeted structures, replacement of probes following failure, delivery of nanomaterials and processing and understanding recorded data. Neural engineering has developed greatly over the past half-century, which has allowed for the development of better neural recording techniques and clinical translation of neural interfaces. Implementation of general purpose BCIs face a number of constraints arising from engineering, computational, ethical and neuroscientific factors that still have to be addressed. Electronics have become orders of magnitude smaller and computationally faster than neurons, however there is much work to be done in decoding the neural circuits. New interest and funding from the non-medical community may be a welcome catalyst for focused research and development; playing an important role in future advancements in the neuroscience community

Blunt cerebrovascular trauma causing vertebral arteryd issection in combination with a laryngeal fracture: a case report

<p>Abstract</p> <p>Introduction</p> <p>The diagnosis and therapy of blunt cerebrovascular injuries has become a focus since improved imaging technology allows adequate description of the injury. Although it represents a rare injury the long-term complications can be fatal but mostly prevented by adequate treatment.</p> <p>Case presentation</p> <p>A 33-year-old Caucasian man fell down a 7-meter scarp after losing control of his quad bike in a remote area. Since endotracheal intubation was unsuccessfully attempted due to the severe cervical swelling as well as oral bleeding an emergency tracheotomy was performed on scene. He was hemodynamically unstable despite fluid resuscitation and intravenous therapy with vasopressors and was transported by a helicopter to our trauma center. He had a stable fracture of the arch of the seventh cervical vertebra and fractures of the transverse processes of C5-C7 with involvement of the lateral wall of the transverse foramen. An abort of the left vertebral artery signal at the first thoracic vertebrae with massive hemorrhage as well as a laryngeal fracture was also detected. Further imaging showed retrograde filling of the left vertebral artery at C5 distal of the described abort. After stabilization and reconfirmation of intracranial perfusion during the clinical course weaning was started. At the time of discharge, he was aware and was able to move all extremities.</p> <p>Conclusion</p> <p>We report a rare case of a patient with vertebral artery dissection in combination with a laryngeal fracture after blunt trauma. Thorough diagnostic and frequent reassessments are recommended. Most patients can be managed with conservative treatment.</p

Distinct Neural Signatures of Outcome Monitoring After Selection and Execution Errors

Losing a point in tennis could result from poor shot selection or faulty stroke execution. To explore how the brain responds to these different types of errors, we examined feedback-locked EEG activity while participants completed a modified version of a standard three-armed bandit probabilistic reward task. Our task framed unrewarded outcomes as the result of either errors of selection or errors of execution. We examined whether amplitude of a medial frontal negativity (the feedback-related negativity [FRN]) was sensitive to the different forms of error attribution. Consistent with previous reports, selection errors elicited a large FRN relative to rewards, and amplitude of this signal correlated with behavioral adjustment after these errors. A different pattern was observed in response to execution errors. These outcomes produced a larger FRN, a frontocentral attenuation in activity preceding this component, and a subsequent enhanced error positivity in parietal sites. Notably, the only correlations with behavioral adjustment were with the early frontocentral attenuation and amplitude of the parietal signal; FRN differences between execution errors and rewarded trials did not correlate with subsequent changes in behavior. Our findings highlight distinct neural correlates of selection and execution error processing, providing insight into how the brain responds to the different classes of error that determine future action

Incident Tuberculosis during Antiretroviral Therapy Contributes to Suboptimal Immune Reconstitution in a Large Urban HIV Clinic in Sub-Saharan Africa

Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm(3) (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100 pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm(3) (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm(3) [IQR; 107, 258, n = 118] vs 209 cells/mm(3) [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunological failure definitions.Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery

An unusual case of persistent groin pain after total hip arthroplasty: a case report

ABSTRACT: INTRODUCTION: Arthroplasty is a well-established routine elective surgical procedure in orthopaedics. To a great extent, diagnosis, treatment and post-operative rehabilitation in these patients is standardised. In a busy clinic, surgeons from time to time tend to focus their attention on common causes of joint pain, but it may lead them to overlook sinister but less common pathologies. Here we report a case of a patient with groin pain due to pre-operatively undetected pelvic metastases from a pyeloureteral carcinoma who underwent total hip arthroplasty. There are several case reports which deal with primary or secondary tumours which were either discovered at the time of replacement surgery or developed at the site of prosthesis years after total hip or knee replacement. To the best of our knowledge, this is the first case report in which a metastatic cancer was missed pre-operatively and intra-operatively both by the radiologist and by the orthopaedic surgeon and should be reported so that surgeons are reminded to be careful when dealing with seemingly routine cases. CASE PRESENTATION: A 79-year-old Caucasian woman presented to the arthroplasty clinic with groin pain. Initial radiographs showed subtle bilateral abnormalities in the pelvis. Neither the radiologist nor the orthopaedic surgeon recognized it. A diagnosis of osteoarthritis of the hip was established, and she underwent total hip arthroplasty. Despite initial improvement, the patient came back with worsening hip pain three months later. Further radiological examination revealed multiple metastatic lesions throughout the pelvis due to a pyeloureteral carcinoma. CONCLUSIONS: This case report emphasizes the importance of meticulous, unbiased pre-operative assessment of patients and their radiographs, even in so-called routine clinical cases. Often subtle radiological changes are classed as normal, especially if they are bilateral. Further radiological imaging should be recommended in all cases where unexplained clinical features or radiological findings are present

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC

Lorentz violation and Crab synchrotron emission: a new constraint far beyond the Planck scale

Special relativity asserts that physical phenomena appear the same for all inertially moving observers. This symmetry, called Lorentz symmetry, relates long wavelengths to short ones: if the symmetry is exact it implies that spacetime must look the same at all length scales. Several approaches to quantum gravity, however, suggest that there may be a Lorentz violating microscopic structure of spacetime, for example discreteness, non-commutativity, or extra dimensions. Here we determine a very strong constraint on a type of Lorentz violation that produces a maximum electron speed less than the speed of light. We use the observation of 100 MeV synchrotron radiation from the Crab nebula to improve the previous limits by a factor of 40 million, ruling out this type of Lorentz violation, and thereby providing an important constraint on theories of quantum gravity.Comment: 12 pages. Presentation shortened and revised for letter to Nature. New title "A strong astrophysical constraint on the violation of special relativity by quantum gravity". Maximum observed synchrotron frequency lowered, resulting in weakening the constraint from E_QG>4.5*10^27 GeV to E_QG>10^26 GeV. The role of the effective field theory assumptions underlying the analysis is highlighte

The Relationship between Amygdala Activation and Passive Exposure Time to an Aversive Cue during a Continuous Performance Task

The allocation of attention modulates negative emotional processing in the amygdala. However, the role of passive exposure time to emotional signals in the modulation of amygdala activity during active task performance has not been examined. In two functional Magnetic Resonance Imaging (fMRI) experiments conducted in two different groups of healthy human subjects, we examined activation in the amygdala due to cued anticipation of painful stimuli while subjects performed a simple continuous performance task (CPT) with either a fixed or a parametrically varied trial duration. In the first experiment (N = 16), engagement in the CPT during a task with fixed trial duration produced the expected attenuation of amygdala activation, but close analysis suggested that the attenuation occurred during the period of active engagement in CPT, and that amygdala activity increased proportionately during the remainder of each trial, when subjects were passively exposed to the pain cue. In the second experiment (N = 12), the duration of each trial was parametrically varied, and we found that amygdala activation was linearly related to the time of passive exposure to the anticipatory cue. We suggest that amygdala activation during negative anticipatory processing depends directly on the passive exposure time to the negative cue

Expansion and subfunctionalisation of flavonoid 3',5'-hydroxylases in the grapevine lineage

<p>Abstract</p> <p>Background</p> <p>Flavonoid 3',5'-hydroxylases (F3'5'Hs) and flavonoid 3'-hydroxylases (F3'Hs) competitively control the synthesis of delphinidin and cyanidin, the precursors of blue and red anthocyanins. In most plants, <it>F3'5'H </it>genes are present in low-copy number, but in grapevine they are highly redundant.</p> <p>Results</p> <p>The first increase in <it>F3'5'H </it>copy number occurred in the progenitor of the eudicot clade at the time of the γ triplication. Further proliferation of <it>F3'5'H</it>s has occurred in one of the paleologous loci after the separation of Vitaceae from other eurosids, giving rise to 15 paralogues within 650 kb. Twelve reside in 9 tandem blocks of ~35-55 kb that share 91-99% identity. The second paleologous <it>F3'5'H </it>has been maintained as an orphan gene in grapevines, and lacks orthologues in other plants. Duplicate <it>F3'5'H</it>s have spatially and temporally partitioned expression profiles in grapevine. The orphan <it>F3'5'H </it>copy is highly expressed in vegetative organs. More recent duplicate <it>F3'5'H</it>s are predominately expressed in berry skins. They differ only slightly in the coding region, but are distinguished in the structure of the promoter. Differences in <it>cis</it>-regulatory sequences of promoter regions are paralleled by temporal specialisation of gene transcription during fruit ripening. Variation in anthocyanin profiles consistently reflects changes in the <it>F3'5'H </it>mRNA pool across different cultivars. More <it>F3'5'H </it>copies are expressed at high levels in grapevine varieties with 93-94% of 3'5'-OH anthocyanins. In grapevines depleted in 3'5'-OH anthocyanins (15-45%), fewer <it>F3'5'H </it>copies are transcribed, and at lower levels. Conversely, only two copies of the gene encoding the competing F3'H enzyme are present in the grape genome; one copy is expressed in both vegetative and reproductive organs at comparable levels among cultivars, while the other is transcriptionally silent.</p> <p>Conclusions</p> <p>These results suggest that expansion and subfunctionalisation of <it>F3'5'H</it>s have increased the complexity and diversification of the fruit colour phenotype among red grape varieties.</p