The neural engine: a reprogrammable low power platform for closed-loop optogenetics

Brain-machine Interfaces (BMI) hold great potential for treating neurological disorders such as epilepsy. Technological progress is allowing for a shift from open-loop, pacemaker-class, intervention towards fully closed-loop neural control systems. Low power programmable processing systems are therefore required which can operate within the thermal window of 2° C for medical implants and maintain long battery life. In this work, we developed a low power neural engine with an optimized set of algorithms which can operate under a power cycling domain. By integrating with custom designed brain implant chip, we have demonstrated the operational applicability to the closed-loop modulating neural activities in in-vitro brain tissues: the local field potentials can be modulated at required central frequency ranges. Also, both a freely-moving non-human primate (24-hour) and a rodent (1-hour) in-vivo experiments were performed to show system long-term recording performance. The overall system consumes only 2.93mA during operation with a biological recording frequency 50Hz sampling rate (the lifespan is approximately 56 hours). A library of algorithms has been implemented in terms of detection, suppression and optical intervention to allow for exploratory applications in different neurological disorders. Thermal experiments demonstrated that operation creates minimal heating as well as battery performance exceeding 24 hours on a freely moving rodent. Therefore, this technology shows great capabilities for both neuroscience in-vitro/in-vivo applications and medical implantable processing units

Theory of disk accretion onto supermassive black holes

Accretion onto supermassive black holes produces both the dramatic phenomena associated with active galactic nuclei and the underwhelming displays seen in the Galactic Center and most other nearby galaxies. I review selected aspects of the current theoretical understanding of black hole accretion, emphasizing the role of magnetohydrodynamic turbulence and gravitational instabilities in driving the actual accretion and the importance of the efficacy of cooling in determining the structure and observational appearance of the accretion flow. Ongoing investigations into the dynamics of the plunging region, the origin of variability in the accretion process, and the evolution of warped, twisted, or eccentric disks are summarized.Comment: Mostly introductory review, to appear in "Supermassive black holes in the distant Universe", ed. A.J. Barger, Kluwer Academic Publishers, in pres

An assessment of the levels of phthalate esters and metals in the Muledane open dump, Thohoyandou, Limpopo Province, South Africa

<p>Abstract</p> <p>Background</p> <p>This work reports the determination of the levels of phthalate esters (dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), diethyl hexyl phthalate (DEHP)) and metals (lead, cadmium, manganese, zinc, iron, calcium) in composite soil samples. The soil samples were collected randomly within the Muledane open dump, Thohoyandou, Limpopo province, South Africa. Control samples were collected about 200 m away from the open dump. The phthalate esters were separated and determined by capillary gas chromatography with a flame ionization detector, whilst the metals were determined by atomic absorption spectrophotometry.</p> <p>Results</p> <p>Open dump values for the phthalate esters and metals to be generally higher in comparison to control samples for DMP, DEP, DBP and DEHP – the mean values calculated were 0.31 ± 0.12, 0.21 ± 0.05, 0.30 ± 0.07, and 0.03 ± 0.01 mg/kg, respectively, for the open dump soil samples. Nonetheless, the mean open dump values for lead, cadmium, manganese, zinc, iron and calcium were 0.07 ± 0.04, 0.003 ± 0.001, 5.02 ± 1.92, 0.31 ± 0.02, 11.62 ± 9.48 and 0.12 ± 0.13 mg/kg, respectively. The results were compared statistically.</p> <p>Conclusion</p> <p>Our results revealed that the discarding of wastes into the open dump is a potential source of soil contamination in the immediate vicinity and beyond, <it>via </it>dispersal. Increased levels of phthalate esters and metals in the soil pose a risk to public health, plants and animals. Sustained monitoring of these contaminants is recommended, in addition to upgrading the facility to a landfill.</p

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Deep reinforcement learning for multi-class imbalanced training: applications in healthcare

With the rapid growth of memory and computing power, datasets are becoming increasingly complex and imbalanced. This is especially severe in the context of clinical data, where there may be one rare event for many cases in the majority class. We introduce an imbalanced classification framework, based on reinforcement learning, for training extremely imbalanced data sets, and extend it for use in multi-class settings. We combine dueling and double deep Q-learning architectures, and formulate a custom reward function and episode-training procedure, specifically with the capability of handling multi-class imbalanced training. Using real-world clinical case studies, we demonstrate that our proposed framework outperforms current state-of-the-art imbalanced learning methods, achieving more fair and balanced classification, while also significantly improving the prediction of minority classes