Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials

Objective To compare the long term efficacy and adverse events of dual blockade of the renin-angiotensin system with monotherapy. Design Systematic review and meta-analysis. Data sources PubMed, Embase, and the Cochrane central register of controlled trials, January 1990 to August 2012. Study selection Randomised controlled trials comparing dual blockers of the renin-angiotensin system with monotherapy, reporting data on either long term efficacy (≥1 year) or safety events (≥4 weeks), and with a sample size of at least 50. Analysis was stratified by trials with patients with heart failure versus patients without heart failure. Results 33 randomised controlled trials with 68 405 patients (mean age 61 years, 71% men) and mean duration of 52 weeks were included. Dual blockade of the renin-angiotensin system was not associated with any significant benefit for all cause mortality (relative risk 0.97, 95% confidence interval 0.89 to 1.06) and cardiovascular mortality (0.96, 0.88 to 1.05) compared with monotherapy. Compared with monotherapy, dual therapy was associated with an 18% reduction in admissions to hospital for heart failure (0.82, 0.74 to 0.92). However, compared with monotherapy, dual therapy was associated with a 55% increase in the risk of hyperkalaemia (P less than 0.001), a 66% increase in the risk of hypotension (P less than 0.001), a 41% increase in the risk of renal failure (P=0.01), and a 27% increase in the risk of withdrawal owing to adverse events (P less than 0.001). Efficacy and safety results were consistent in cohorts with and without heart failure when dual therapy was compared with monotherapy except for all cause mortality, which was higher in the cohort without heart failure (P=0.04 v P=0.15), and renal failure was significantly higher in the cohort with heart failure (P less than 0.001 v P=0.79). Conclusion Although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events such as hyperkalaemia, hypotension, and renal failure compared with monotherapy. The risk to benefit ratio argues against the use of dual therapy

GOAT: GO to Any Thing

In deployment scenarios such as homes and warehouses, mobile robots are expected to autonomously navigate for extended periods, seamlessly executing tasks articulated in terms that are intuitively understandable by human operators. We present GO To Any Thing (GOAT), a universal navigation system capable of tackling these requirements with three key features: a) Multimodal: it can tackle goals specified via category labels, target images, and language descriptions, b) Lifelong: it benefits from its past experience in the same environment, and c) Platform Agnostic: it can be quickly deployed on robots with different embodiments. GOAT is made possible through a modular system design and a continually augmented instance-aware semantic memory that keeps track of the appearance of objects from different viewpoints in addition to category-level semantics. This enables GOAT to distinguish between different instances of the same category to enable navigation to targets specified by images and language descriptions. In experimental comparisons spanning over 90 hours in 9 different homes consisting of 675 goals selected across 200+ different object instances, we find GOAT achieves an overall success rate of 83%, surpassing previous methods and ablations by 32% (absolute improvement). GOAT improves with experience in the environment, from a 60% success rate at the first goal to a 90% success after exploration. In addition, we demonstrate that GOAT can readily be applied to downstream tasks such as pick and place and social navigation

Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood

The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT- qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log- linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource- limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats

Secure data aggregation protocol for sensor networks

We propose a secure in-network data aggregation protocol with internal verification, to gain increase in the lifespan of the network by preserving bandwidth. For doing secure internal distributed operations, we show an algorithm for securely computing the sum of sensor readings in the network. Our algorithm can be generalized to any random tree topology and can be applied to any combination of mathematical functions. In addition, we represent an efficient way of doing statistical analysis for the protocol. Furthermore, we propose a novel, distributed and interactive algorithm to trace down the adversary and remove it from the network. Finally, we do bandwidth analysis of the protocol and give the proof for the efficiency of the protocol

PulmoScreen: A Novel Exhaled Breath Condensate Device

Exhaled breath condensate (EBC) carries abundant information on airway health and disease, as well as systemic disease. Current EBC samplers focus on volatile compounds and protein biomarkers. This approach does not allow for analysis of biomolecules (e.g. DNA, proteins, metabolites). We are developing an optimised EBC biomolecule sampler and analyser using EBC microbiomics (infectious disease) as a validation approach

Eagle\u27s syndrome: Viewing a rare disorder from a new perspective

Objective: To highlight a novel approach to evaluate a patient with an uncommon cerebrovascular condition via a versatile, safe, and cost-efficient option through a 3-Dimensional (3D) model. Background: In 1948, Dr. Eagle outlined a subset of cases where patients presented with a characteristic constellation of findings: carotidynia and headache. These symptoms were attributed to an elongated styloid process affecting the ipsilateral carotid artery, termed the styloid-carotid artery syndrome. Design/Methods: We report a 63-year-old gentleman who presented with transient episodes of left-hand weakness and right-eye vision loss following a lengthy airplane trip that was found to be secondary to the styloid-carotid artery syndrome. He reported that he had slept awkwardly for the duration of the flight with his head resting on his right shoulder. Results: The patient\u27s initial CT of the head and CTA of the head and neck revealed a right internal carotid artery (ICA) occlusion and suspected dissection. Subsequent MRI only revealed a punctate acute infarct in the right frontal white matter, but high suspicion remained for a significant abnormality of the R ICA. CTA was repeated after 6 weeks, demonstrating a recanalized vessel and revealing an elongated styloid process in the vicinity of the previous occlusion. Conventional angiography with reproduction of the head tilt that caused the initial event was considered; however, given the risk of instigating another event, a 3D model of the CTA data was created utilizing a 3D printer. The dynamic nature of the model with an artificial spine with flexible joints permitted free manipulation of the patient\u27s unique anatomy without posing any risk to his condition. Conclusions: This case not only exhibits an uncommon etiology for stroke, but also introduces an innovative method to visualize complex neuroanatomy. Given the relatively low cost and harmless creation of the model, this option may prove beneficial in other similar cases

Tacrolimus-associated posterior reversible encephalopathy syndrome

Objective: To highlight unique neuroradiologic findings in a patient who developed Posterior Reversible Encephalopathy Syndrome (PRES) shortly after starting Tacrolimus status-post liver transplant. Background: PRES is a condition that is characterized by clinical findings of headache, visual disturbances, altered mental status (AMS), and seizures while accompanied by distinctive white matter changes most commonly in the parieto-occipital regions. The brainstem and cerebellum can be affected, as well. Tacrolimus is an established agent known to cause PRES, postulated secondary to neurotoxic effects, as opposed to the more commonly studied hypertension etiology. Design/Methods: We report a case of a 65-year-old man who developed symptoms of PRES 1 day following the start of Tacrolimus therapy with neuroradiographic abnormalities located predominantly in the brainstem and subcortical white matter. Results: The patient acutely developed AMS on post-operative day 5 with progressive worsening of his symptoms. Initial investigation revealed a urinary tract infection, hyponatremia, and multiple doses of concomitant opioids and benzodiazepines. FK506 levels were found to be subtherapeutic. CT scan was obtained revealing hypodensities in the pons; however, these were interpreted to be artifactual. A routine electroencephalogram (EEG) revealed mild background slowing consistent with encephalopathy. Meanwhile, patient\u27s symptoms continued to progress despite correction of his toxometabolic abnormalities. MRI was eventually obtained, which revealed hyperintensities on T2 and FLAIR sequences located in the brainstem and subcortical white matter consistent with the brainstem variant of PRES. Tacrolimus was suspected as the etiology and discontinued. Patient\u27s mental status began to improve and he was ultimately able to be discharged home. Conclusions: This case demonstrates an atypical variant of PRES that was associated with a known etiological factor, Tacrolimus. The abrupt onset of symptoms despite a subtherapeutic FK506 level still managed to cause significant symptoms, emphasizing the need to keep Tacrolimus induced PRES as a part of the differential diagnosis

Double dorsiflexion sign (DDFS) and double finger tap sign (DFTS): More tricks in the neurologist\u27s bag for assessing non-physiological weakness?

Objective: Testing accuracy of DDFS and DFTS in identifying inorganic paresis. Background: While physical exam maneuvers, such as the Hoover\u27s and Abductor sign, can aid in differentiating patients with organic and non-organic weakness, many patients inevitably undergo intracranial imaging for evaluation. We propose two new physical exam techniques, DDFS and DFTS, which can assist in this differentiation. For DDFS, the patient dorsiflexes against resistance in both ankles individually, and then both simultaneously. Both groups of patients will have paresis in the affected limb when individually tested; however, during simultaneous testing, the inorganic patients will have transient improvement in the affected limb, followed by “give way” weakness in both limbs. For DFTS, the patient taps their index finger and thumb together in each hand individually, and then, simultaneously. Both groups of patients will have reduced speed in the affected hand when tested individually; however, during simultaneous testing, non-organic patients will have fluctuating speeds and amplitudes in both hands. Design/Methods: A prospective observational study of patients examined in a single center from 10/2016 - 10/2017. Patients were divided into controls (suspected organic weakness) and cases (suspected in organic weakness). DDF, DFT, Hoover and Abductor signs were performed. The exam findings were cross-verified using CT and MRI imaging, along with, attending assessments. Accuracy of the signs was analyzed using sensitivity and specificity along corresponding 95% confidence intervals. Results: 19 patients were enrolled, of which 16 were cases and 3 controls. DDFS identified inorganic paresis in 87.5% of patients (14/16) while DFTS identified inorganic paresis in 100% of the patients (11/11). All tests revealed high sensitivity with 100% specificity. Conclusions: In this selected group of patients, DDFS and DFTS appear a reliable method to screen between organic and non-organic paresis. Larger studies are warranted to further assess their validity in isolation, and in conjunction with the other established maneuvers