Delocalized photonic deep learning on the internet's edge.

Advanced machine learning models are currently impossible to run on edge devices such as smart sensors and unmanned aerial vehicles owing to constraints on power, processing, and memory. We introduce an approach to machine learning inference based on delocalized analog processing across networks. In this approach, named Netcast, cloud-based "smart transceivers" stream weight data to edge devices, enabling ultraefficient photonic inference. We demonstrate image recognition at ultralow optical energy of 40 attojoules per multiply (<1 photon per multiply) at 98.8% (93%) classification accuracy. We reproduce this performance in a Boston-area field trial over 86 kilometers of deployed optical fiber, wavelength multiplexed over 3 terahertz of optical bandwidth. Netcast allows milliwatt-class edge devices with minimal memory and processing to compute at teraFLOPS rates reserved for high-power (>100 watts) cloud computers.

Large-alphabet encoding for higher-rate quantum key distribution.

The manipulation of high-dimensional degrees of freedom provides new opportunities for more efficient quantum information processing. It has recently been shown that high-dimensional encoded states can provide significant advantages over binary quantum states in applications of quantum computation and quantum communication. In particular, high-dimensional quantum key distribution enables higher secret-key generation rates under practical limitations of detectors or light sources, as well as greater error tolerance. Here, we demonstrate high-dimensional quantum key distribution capabilities both in the laboratory and over a deployed fiber, using photons encoded in a high-dimensional alphabet to increase the secure information yield per detected photon. By adjusting the alphabet size, it is possible to mitigate the effects of receiver bottlenecks and optimize the secret-key rates for different channel losses. This work presents a strategy for achieving higher secret-key rates in receiver-limited scenarios and marks an important step toward high-dimensional quantum communication in deployed fiber networks.

Analysis of Limiting Factors Across the Life Cycle of Delta Smelt (Hypomesus transpacificus).

We developed a mechanistic life-cycle model derived from the elicitation of multiple factors influencing the success of individual life-stages of the imperiled delta smelt (Hypomesus transpacificus). We discuss the relevance of limiting factors in population ecology and problems with additive models in detecting them. We identify limiting factors and assess their significance using a non-linear optimization routine, combined with traditional metrics to assess the value of covariates and model performance. After reviewing previous conceptual models and multivariate analyses, we identified a set of factors that were consistent with conceptual models and useful in explaining the erratic fluctuations in a common abundance index: food at certain times in certain locations, predation by introduced species primarily in the spring, and entrainment. The analytical approach provides a transparent and intuitive framework in which to consider the contribution of covariates and consequences for population trends, and has the potential to assist with the evaluation of proposed recovery measures.

Multi-aperture digital coherent combining for free-space optical communication receivers.

Space-to-ground optical communication systems can benefit from reducing the size, weight, and power profiles of space terminals. One way of reducing the required power-aperture product on a space platform is to implement effective, but costly, single-aperture ground terminals with large collection areas. In contrast, we present a ground terminal receiver architecture in which many small less-expensive apertures are efficiently combined to create a large effective aperture while maintaining excellent receiver sensitivity. This is accomplished via coherent detection behind each aperture followed by digitization. The digitized signals are then combined in a digital signal processing chain. Experimental results demonstrate lossless coherent combining of four lasercom signals, at power levels below 0.1 photons/bit/aperture.

Effect of endovascular reperfusion in relation to site of arterial occlusion.

OBJECTIVE: To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). METHODS: We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. RESULTS: Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). CONCLUSIONS: The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery.

Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies.

BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSION: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

Scalable modulator for frequency shift keying in free space optical communications.

Frequency shift keyed (FSK) modulation formats are well-suited to deep space links and other high loss links. FSK's advantage comes from its use of bandwidth expansion. I.e., FSK counteracts power losses in the link by using an optical bandwidth that is greater than the data rate, just as pulse position modulation (PPM) does. Unlike PPM, increasing FSK's bandwidth expansion does not require increased bandwidth in electronic components. We present an FSK modulator whose component count rises logarithmically with the bandwidth expansion. We tested it with four-fold bandwidth expansion at 5 and 20 Gbit/s. When paired with a pre-amplified receiver, the required received power was about 4 and 5 dB from the theoretical best for such receivers. We also tested the FSK transmitter with a photon counting receiver.

MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study.

BACKGROUND: Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. METHODS: In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data. FINDINGS: 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7). INTERPRETATION: Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted. FUNDING: National Institute for Neurological Disorders and Stroke.

A comparison of cooling techniques to treat cardiac arrest patients with hypothermia.

Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair.

Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after subacute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human vascular endothelial growth factor (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier integrity and suppression of inflammation was followed by a delayed spatiotemporal regulated increase in neovascularization. These events coincided with a bimodal pattern of functional recovery, with, an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multimodal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component.

Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.

BACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. METHODS: We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. FINDINGS: Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. INTERPRETATION: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. FUNDING: None.

High-order temporal coherences of chaotic and laser light.

We demonstrate a new approach to measuring high-order temporal coherences that uses a four-element superconducting nanowire single-photon detector. The four independent, interleaved single-photon-sensitive elements parse a single spatial mode of an optical beam over dimensions smaller than the minimum diffraction-limited spot size. Integrating this device with four-channel time-tagging electronics to generate multi-start, multi-stop histograms enables measurement of temporal coherences up to fourth order for a continuous range of all associated time delays. We observe high-order photon bunching from a chaotic, pseudo-thermal light source, measuring maximum third- and fourth-order coherence values of 5.87 +/- 0.17 and 23.1 +/- 1.8, respectively, in agreement with the theoretically predicted values of 3! = 6 and 4! = 24. Laser light, by contrast, is confirmed to have coherence values of approximately 1 for second, third and fourth orders at all time delays.

Mouse model of focal cerebral ischemia using endothelin-1.

Intracerebral injection of the vasoconstrictor peptide, endothelin-1 (ET-1), has been used as a method to induce focal ischemia in rats. The relative technical simplicity of this model makes it attractive for use in mice. However, the effect of ET-1 on mouse brains has not been firmly established. In this study, we determined the ability of ET-1 to induce focal cerebral ischemia in four different mouse strains (CD1, C57/BL6, NOD/SCID, and FVB). In contrast to rats, intracerebral injection of ET-1 did not produce a lesion in any mouse strain tested. A combination of ET-1 injection with either CCA occlusion or N(G)-nitro-l-arginine methyl ester (l-NAME) injection produced only a small infarct and its size was strain-dependent. A triple combination of CCA occlusion with co-injection of ET-1 and l-NAME produced a lesion in all mouse strains tested, and this resulted in a significant motor deficit. However, lesion size was still relatively small and strain-dependent. This study shows that ET-1 has a much less potent effect for producing an infarct in mice than rats.

Efficient performance optimization of SOA-MZI devices.

We present a novel characterization method for semiconductor optical amplifier Mach-Zehnder interferometer (SOA-MZI) switches which combines a pump-probe measurement with an interferometer bias scan. In addition to a wealth of information on the switching dynamics for all operating points of the switch, we can create an extinction map to pinpoint regions of highest extinction for optimizing all-optical ultrafast switching. We experimentally verify the accuracy of this characterization method by performing a wavelength characterization at the optimal bias point and a nearby, non-optimal point. A 1-dB penalty was observed.

781 Mbit/s photon-counting optical communications using a superconducting nanowire detector.

We demonstrate 1550 nm photon-counting optical communications with a NbN-nanowire superconducting single-photon detector. Source data are encoded with a rate-1/2 forward-error correcting code and transmitted by use of 32-ary pulse-position modulation at 5 and 10 GHz slot rates. Error-free performance is obtained with -0.5 detected photon per source bit at a source data rate of 781 Mbits/s. To the best of our knowledge, this is the highest reported data rate for a photon-counting receiver.

Testing for loss of protective sensation in patients with foot ulceration: a cross-sectional study.

Current recommendations for the prevention of foot ulceration and amputation include screening at-risk individuals by testing for loss of protective sensation at eight sites using 10-g (5.07) nylon monofilaments. Yet measurement of the cutaneous pressure threshold to differentiate one-point from two-point static touch stimuli may allow identification of these at-risk individuals earlier in the clinical course of diabetic neuropathy. The present study tested this hypothesis using a prospective, cross-sectional, multicenter design that included sensibility testing of 496 patients with diabetic neuropathy, 17 of whom had a history of ulceration or amputation. Considering the cutaneous pressure threshold of the 5.07 Semmes-Weinstein nylon monofilament to be equivalent to the 95 g/mm(2) one-point static touch measured using the Pressure-Specified Sensory Device (Sensory Management Services LLC, Baltimore, Maryland), only 3 of these 17 patients with a history of foot ulceration or amputation would have been identified using the Semmes-Weinstein nylon monofilament screening technique. In contrast, using the Pressure-Specified Sensory Device, all 17 patients were identified as having abnormal sensibility, defined as greater than the 99% confidence limit for age, for two-point static touch on the hallux pulp. We conclude that patients at risk for foot ulceration can best be identified by actual measurement of the cutaneous sensibility of the hallux pulp.

All-optical pulse regeneration in an ultrafast nonlinear interferometer with Faraday mirror polarization stabilization.

We demonstrate the folded ultrafast nonlinear interferometer (FUNI) as a 3R all-optical regenerator. Faraday rotation provides inherent polarization stabilization, and the optical fiber nonlinear medium provides ultrafast operation and switching window tunability. We demonstrate 3R regeneration of 10-Gbit/s data with 5-pJ pulse switching energy and 4-ps timing-jitter tolerance.

ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke.

BACKGROUND AND PURPOSE: Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator (tPA) in stroke patients. METHODS: We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study who were randomized to receive intravenous tPA or placebo within 3 hours of symptom onset. RESULTS: Despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of < or = 1) on the National Institutes of Health Stroke Scale at 90 days (P=0.01). CONCLUSIONS: These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset.