Cerebral Autoregulation Correlation With Outcomes and Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia remains one of the principal therapeutic targets after aneurysmal subarachnoid hemorrhage. While large vessel vasospasm may contribute to ischemia, increasing evidence suggests that physiological impairment through disrupted impaired cerebral autoregulation (CA) and spreading depolarizations (SDs) also contribute to delayed cerebral ischemia and poor neurological outcome. This study seeks to explore the intermeasure correlation of different measures of CA, as well as correlation with SD and neurological outcome. METHODS: Simultaneous measurement of 7 continuous indices of CA was calculated in 19 subjects entered in a prospective study of SD in aneurysmal subarachnoid hemorrhage undergoing surgical aneurysm clipping. Intermeasure agreement was assessed, and the association of each index with modified Rankin Scale score at 90 days and occurrence of SD was assessed. RESULTS: There were 4102 hours of total monitoring time across the 19 subjects. In time-resolved assessment, no CA measures demonstrated significant correlation; however, most demonstrate significant correlation averaged over 1 hour. Pressure reactivity (PRx), oxygen reactivity, and oxygen saturation reactivity were significantly correlated with modified Rankin Scale score at 90 days. PRx and oxygen reactivity also were correlated with the occurrence of SD events. Across multiple CA measure reactivity indices, a threshold between 0.3 and 0.5 was most associated with intervals containing SD. CONCLUSIONS: Different continuous CA indices do not correlate well with each other on a highly time-resolved basis, so should not be viewed as interchangeable. PRx and oxygen reactivity are the most reliable indices in identifying risk of worse outcome in patients with aneurysmal subarachnoid hemorrhage undergoing surgical treatment. SD occurrence is correlated with impaired CA across multiple CA measurement techniques and may represent the pathological mechanism of delayed cerebral ischemia in patients with impaired CA. Optimization of CA in patients with aneurysmal subarachnoid hemorrhage may lead to decreased incidence of SD and improved neurological outcomes. Future studies are needed to evaluate these hypotheses and approaches.

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder.

BACKGROUND: Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation. METHODS: A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks. RESULTS: Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7-113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety. CONCLUSIONS: The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit-risk ratio. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02999269.

Ictal Theta Power as an Electroconvulsive Therapy Safety Biomarker: A Pilot Study.

OBJECTIVE: Electroconvulsive therapy (ECT) remains the benchmark for treatment resistant depression, yet its cognitive adverse effects have a negative impact on treatment. A predictive safety biomarker early in ECT treatment is needed to identify patients at cognitive risk to maximize therapeutic outcomes and minimize adverse effects. We used ictal electroencephalography frequency analysis from suprathreshold treatments to assess the relationships between ECT dose, ictal power across different frequency domains, and cognitive outcomes. METHODS: Seventeen subjects with treatment resistant depression received right unilateral ECT. Structural magnetic resonance imaging was obtained pre-ECT for electric field modeling to assess ECT dose. Serial assessments with 24-lead electroencephalography captured ictal activity. Clinical and cognitive assessments were performed before and after ECT. The primary cognitive outcome was the change in Delis Kaplan Executive Function Verbal Fluency Letter Fluency. RESULTS: Ictal theta (4-8 Hz) power in the Fp1/Fp2 channels was associated with both whole-brain electric field strength (t(2,12) = 19.5, P = 0.007)/(t(2,10) = 21.85, P = 0.02) and Delis Kaplan Executive Function Verbal Fluency Letter Fluency scores (t(2,12) = -2.05, P = 0.05)/(t(2,10) = -2.20, P = 0.01). Other frequency bands (beta, alpha, delta, and gamma) did not demonstrate this relationship. CONCLUSIONS: This pilot data identify ictal theta power as a potential safety biomarker in ECT and is related to the strength of the ECT dose. Ictal theta power could prove to be a convenient and powerful tool for clinicians to identify those patients most susceptible to cognitive impairment early in the treatment series. Additional studies are needed to assess the role of longitudinal changes in ictal theta power throughout the ECT series.

The application of an age adjusted D-dimer threshold to rule out suspected venous thromboembolism (VTE) in an emergency department setting: a retrospective diagnostic cohort study.

BACKGROUND: Venous Thromboembolic disease (VTE) poses a diagnostic challenge for clinicians in acute care. Over reliance on reference standard investigations can lead to over treatment and potential harm. We sought to evaluate the pragmatic performance and implications of using an age adjusted D-dimer (AADD) strategy to rule out VTE in patients with suspected disease attending an emergency department (ED) setting. We aimed to determine diagnostic test characteristics and assess whether this strategy would result in proportional imaging reduction and potential cost savings. METHODS: Design: Single centre retrospective diagnostic cohort study. All patients > 50 years old evaluated for possible VTE who presented to the emergency department over a consecutive 12-month period between January and December 2016 with a positive D-dimer result. Clinical assessment records and reference standard imaging results were followed up by multiple independent adjudicators and coded as VTE positive or negative. RESULTS: During the study period, there were 2132 positive D-dimer results. One thousand two hundred thirty-six patients received reference standard investigations. A total increase of 314/1236 (25.1%) results would have been coded as true negatives as opposed to false positive if the AADD cut off point had been applied, with 314 reference standard tests subsequently avoided. The AADD cut off had comparable sensitivity to the current cut off despite this increase in specificity; sensitivities for the diagnosis of DVT were 99.28% (95% CI 96.06-99.98%) and 97.72% for PE (95% CI 91.94% to 97.72). There were 3 false negative results using the AADD strategy. CONCLUSIONS: In patients with suspected VTE with a low or moderate pre-test probability, the application of AADD appears to increase the proportion of patients in which VTE can be excluded without the need for reference standard imaging. This management strategy is likely to be associated with substantial reduction in anticoagulation treatment, investigations and cost/time savings.

Electroconvulsive therapy treatment responsive multimodal brain networks.

Electroconvulsive therapy is regarded as the most effective antidepressant treatment for severe and treatment-resistant depressive episodes. Despite the efficacy of electroconvulsive therapy, the neurobiological underpinnings and mechanisms underlying electroconvulsive therapy induced antidepressant effects remain unclear. The objective of this investigation was to identify electroconvulsive therapy treatment responsive multimodal biomarkers with the 17-item Hamilton Depression Rating Scale guided brain structure-function fusion in 118 patients with depressive episodes and 60 healthy controls. Results show that reduced fractional amplitude of low frequency fluctuations in the prefrontal cortex, insula and hippocampus, linked with increased gray matter volume in anterior cingulate, medial temporal cortex, insula, thalamus, caudate and hippocampus represent electroconvulsive therapy responsive covarying functional and structural brain networks. In addition, relative to nonresponders, responder-specific electroconvulsive therapy related brain networks occur in frontal-limbic network and are associated with successful therapeutic outcomes. Finally, electroconvulsive therapy responsive brain networks were unrelated to verbal declarative memory. Using a data-driven, supervised-learning method, we demonstrated that electroconvulsive therapy produces a remodeling of brain functional and structural covariance that was unique to antidepressant symptom response, but not linked to memory impairment.

Applicability of the five case model to African eHealth investment decisions.

BACKGROUND: eHealth programmes in African countries face fierce competition for scarce resources. Such initiatives should not proceed without adequate appraisal of their probable impacts, thereby acknowledging their opportunity costs and the need for appraisals to promote optimal use of available resources. However, since there is no broadly accepted eHealth impact appraisal framework available to provide guidance, and local expertise is limited, African health ministries have difficulty completing such appraisals. The Five Case Model, used in several countries outside Africa, has the potential to function as a decision-making tool in African eHealth environments and serve as a key component of an eHealth impact model for Africa. METHODS: This study identifies internationally recognised metrics and readily accessible data sources to assess the applicability of the model's five cases to African countries. RESULTS: Ten metrics are identified that align with the Five Case Model's five cases, including nine component metrics and one summary metric that aggregates the nine. The metrics cover the eHealth environment, human capital and governance, technology development, and finance and economics. Fifty-four African countries are scored for each metric. Visualisation of the metric scores using spider charts reveals profiles of the countries' relative performance and provides an eHealth Investment Readiness Assessment Tool. CONCLUSION: The utility of these comparisons to strengthen eHealth investment planning suggests that the five cases are applicable to African countries' eHealth investment decisions. The potential for the Five Case Model to have a role in an eHealth impact appraisal framework for Africa should be validated through field testing.

BET 1: cervical spine immobilisation in the management of drowning victims.

A short cut review was carried out to establish whether patients presenting to the emergency department after a near drowning should have cervical spine immobilisation. A search of the literature found only three studies directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that cervical spine injuries are rare in drowning and near drowning unless there is a history of diving or a fall or signs of trauma. Cervical spine immobilisation should be reserved for cases where there is a reasonable suspicion of a spinal injury.

BET 2: CT head in investigation of near drowning.

A short cut review was carried out to establish whether patients presenting to the emergency department after a near drowning should have a CT head scan as part of their initial assessment. A search of the literature found only three studies directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that anyone with GCS≤4 should have a CT head as an abnormal scan at this stage heralds a very poor prognosis.

Nonlinear characterization of a silicon integrated Bragg waveguide filter.

Bragg waveguides are promising optical filters for pump suppression in spontaneous four-wave mixing (FWM) photon sources. In this work, we investigate the generation of unwanted photon pairs in the filter itself. We do this by taking advantage of the relation between spontaneous and classical FWM, which allows for the precise characterization of the nonlinear response of the device. The pair generation rate estimated from the classical measurement is compared with the theoretical value calculated by means of a full quantum model of the filter, which also allows investigation of the spectral properties of the generated pairs. We find a good agreement between theory and experiment, confirming that stimulated FWM is a valuable approach to characterize the nonlinear response of an integrated filter, and that the pairs generated in a Bragg waveguide are not a serious issue for the operation of a fully integrated nonclassical source.

A Cenozoic record of the equatorial Pacific carbonate compensation depth.

Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.

Programmable dispersion on a photonic integrated circuit for classical and quantum applications.

We demonstrate a large-scale tunable-coupling ring resonator array, suitable for high-dimensional classical and quantum transforms, in a CMOS-compatible silicon photonics platform. The device consists of a waveguide coupled to 15 ring-based dispersive elements with programmable linewidths and resonance frequencies. The ability to control both quality factor and frequency of each ring provides an unprecedented 30 degrees of freedom in dispersion control on a single spatial channel. This programmable dispersion control system has a range of applications, including mode-locked lasers, quantum key distribution, and photon-pair generation. We also propose a novel application enabled by this circuit - high-speed quantum communications using temporal-mode-based quantum data locking - and discuss the utility of the system for performing the high-dimensional unitary optical transformations necessary for a quantum data locking demonstration.

Defining a staged-based process for economic and financial evaluations of mHealth programs.

Mobile and wireless technology for health (mHealth) has the potential to improve health outcomes by addressing critical health systems constraints that impede coverage, utilization, and effectiveness of health services. To date, few mHealth programs have been implemented at scale and there remains a paucity of evidence on their effectiveness and value for money. This paper aims to improve understanding among mHealth program managers and key stakeholders of how to select methods for economic evaluation (comparative analysis for determining value for money) and financial evaluation (determination of the cost of implementing an intervention, estimation of costs for sustaining or expanding an intervention, and assessment of its affordability). We outline a 6 stage-based process for selecting and integrating economic and financial evaluation methods into the monitoring and evaluation of mHealth solutions including (1) defining the program strategy and linkages with key outcomes, (2) assessment of effectiveness, (3) full economic evaluation or partial evaluation, (4) sub-group analyses, (5) estimating resource requirements for expansion, (6) affordability assessment and identification of models for financial sustainability. While application of these stages optimally occurs linearly, finite resources, limited technical expertise, and the timing of evaluation initiation may impede this. We recommend that analysts prioritize economic and financial evaluation methods based on programmatic linkages with health outcomes; alignment with an mHealth solution's broader stage of maturity and stage of evaluation; overarching monitoring and evaluation activities; stakeholder evidence needs; time point of initiation; and available resources for evaluations.

BET 2: Striking the right balance: anticoagulation and isolated distal deep vein thrombosis.

A short-cut review was carried out to establish whether treatment of isolated distal deep vein thrombosis with therapeutic anticoagulation can reduce adverse clinical outcomes. A meta-analysis from 2011 and 11 subsequent directly relevant papers were found using the reported search strategy. Of these, 7 in total presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that patients diagnosed with isolated distal deep vein thrombosis should be individually risk assessed and treated according to their risk of thrombotic complication, bleeding with anticoagulation and personal preference.

Phase coherence length in silicon photonic platform.

We report for the first time two typical phase coherence lengths in highly confined silicon waveguides fabricated in a standard CMOS foundry's multi-project-wafer shuttle run in the 220nm silicon-on-insulator wafer with 248nm lithography. By measuring the random phase fluctuations of 800 on-chip silicon Mach-Zehnder interferometers across the wafer, we extracted, with statistical significance, the coherence lengths to be 4.17 ± 0.42 mm and 1.61 ± 0.12 mm for single mode strip waveguide and rib waveguide, respectively. We present a new experimental method to quantify the phase coherence length. The theory model is verified by both our and others' experiments. Coherence length is expected to become one key parameter of the fabrication non-uniformity to guide the design of silicon photonics.

Symmetrical polarization splitter/rotator design and application in a polarization insensitive WDM receiver.

In integrated photonics, the design goal of a polarization splitter/rotator (PSR) has been separating the TE0 and TM0 modes in a waveguide. This is a natural choice. But in theory, a PSR only needs to project the incoming State Of Polarization (SOP) orthogonally to its output ports, using any orthogonal mode basis set in the fiber. In this article, we introduce a novel PSR design that alternatively takes the linear combination of TE0 and TM0 (TE0 +/- TM0) as orthogonal bases. By contrast, existing approaches exclusively use TE0 and TM0 as their basis set. The design is based on two symmetric and robust structures: a bi-layer taper and a Y-junction, and involves no bends. To prove the concept, we incorporated it into a four-channel polarization insensitive wavelength division multiplexing (PI-WDM) receiver fabricated in a standard CMOS Si photonics process. 40 Gb/s data rate and 0.7 +/- 0.2 dB polarization dependent loss (PDL) is demonstrated on each channel. Lastly, we propose an improved PSR design with 12 µm device length, < 0.1 dB PDL, < 0.4 dB insertion loss and < 0.05 dB wavelength dependence across C-band for both polarizations. Overall, our PSR design concept is simple, easy to realize and presents a new perspective for future PSR designs.

Quantifying Residues from Postharvest Propylene Oxide Fumigation of Almonds and Walnuts.

A novel analytical approach involving solvent extraction with methyl tert-butyl ether (MTBE) followed by GC was developed to quantify residues that result from the postharvest fumigation of almonds and walnuts with propylene oxide (PPO). Verification and quantification of PPO, propylene chlorohydrin (PCH) [1-chloropropan-2-ol (PCH-1) and 2-chloropropan-1-ol (PCH-2)], and propylene bromohydrin (PBH) [1-bromopropan-2-ol (PBH-1) and 2-bromopropan-1-ol (PBH-2)] was accomplished with a combination of electron impact ionization MS (EIMS), negative ion chemical ionization MS (NCIMS), and electron capture detection (ECD). Respective GC/EIMS LOQs for PPO, PCH-1, PCH-2, PBH-1, and PBH-2 in MTBE extracts were [ppm (µg/g nut)] 0.9, 2.1, 2.5, 30.3, and 50.0 for almonds and 0.8, 2.2, 2.02, 41.6, and 45.7 for walnuts. Relative to GC/EIMS, GC-ECD analyses resulted in no detection of PPO, similar detector responses for PCH isomers, and >100-fold more sensitive detection of PBH isomers. NCIMS did not enhance detection of PBH isomers relative to EIMS and was, respectively, approximately 20-, 5-, and 10-fold less sensitive to PPO, PCH-1, and PCH-2. MTBE extraction efficiencies were >90% for all analytes. The 10-fold concentration of MTBE extracts yielded recoveries of 85-105% for the PBH isomers and a concomitant decrease in LODs and LOQs across detector types. The recoveries of PCH isomers and PPO in the MTBE concentrate were relatively low (approximately 50 to 75%), which confound improvements in LODs and LOQs regardless of detector type.

Translating between social worlds of policy and everyday life: The development of a group-based method to support policymaking by exploring behavioural aspects of sustainable consumption.

A large international literature on how lay citizens make sense of various aspects of science and technology has been generated by investigations which utilise small group methods. Within that literature, focus group and other group-based methods have come to co-exist, and to some extent, hybridise, with the use of small groups in citizen engagement initiatives. In this article, we report on how we drew upon these methodological developments in the design and operationalisation of a policymaking support tool (STAVE). This tool has been developed to gain insight, in a relatively speedy and cost-effective way, into practical details of the everyday lived experience of people's lives, as relating to the sustainability of corresponding practices. An important challenge we faced was how, in Kuhn's terms, to 'translate' between the forms of life corresponding to the world of policymaking and the world of everyday domestic life. We examine conceptual and methodological aspects of how the tool was designed and assembled, and then trialled in the context of active real-world collaborations with policymaking organisations. These trials were implemented in six European countries, where they were used to support work on live policy issues concerned with sustainable consumption.

Design and optimization of a novel silicon-on-insulator wavelength diplexer.

We propose a novel silicon-on-insulator (SOI) wavelength diplexer design based on an adiabatic bent taper and an unconventional multimode waveguide. The geometry of the device is optimized using particle swarm optimization (PSO). The device has an ultra-short length of 15 µm. Simulated insertion loss at peak wavelength is less than 0.25 dB with 1-dB bandwidth around 100 nm for both O band and C band. The device is fabrication tolerant as demonstrated by simulated yield estimates. The reported design targets 1310 and 1550 nm as peak wavelengths; the design methodology is easily applicable to other wavelengths of interest.

High efficiency germanium-assisted grating coupler.

We propose a fiber to submicron silicon waveguide vertical coupler utilizing germanium-on-silicon gratings. The germanium is epitaxially grown on silicon in the same step for building photodetectors. Coupling efficiency based on FDTD simulation is 76% at 1.55 µm and the optical 1dB bandwidth is 40 nm.