This paper presents theoretical characterizations and analysis for the physical layer of multihop wireless communications channels. Four channel models are considered and developed: the decoded ...relaying multihop channel; the amplified relaying multihop channel; the decoded relaying multihop diversity channel; and the amplified relaying multihop diversity channel. Two classifications are discussed: decoded relaying versus amplified relaying, and multihop channels versus multihop diversity channels. The channel models are compared, through analysis and simulations, with the "singlehop" (direct transmission) reference channel on the basis of signal-to-noise ratio, probability of outage, probability of error, and optimal power allocation. Each of the four channel models is shown to outperform the singlehop reference channel under the condition that the set of intermediate relaying terminals is selected intelligently. Multihop diversity channels are shown to outperform multihop channels. Amplified relaying is shown to outperform decoded relaying despite noise propagation. This is attributed to the fact that amplified relaying does not suffer from the error propagation which limits the performance of decoded relaying channels to that of their weakest link.
Automated Arrhythmia Discrimination Using a Smartphone
Background
Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health ...applications by older patients at risk for AF and may be useful for AF screening.
Objectives
To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs).
Methods
We analyzed two hundred and nineteen 2‐minute pulse recordings from 121 participants with AF (n = 98), PACs (n = 15), or PVCs (n = 15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from preexisting AF. The PULSE‐SMART app conducted pulse analysis using 3 methods (Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot). We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12‐lead EKG or 3‐lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n = 65) of app users.
Results
The smartphone‐based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real‐time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was “useful” and “not complex” to use.
Conclusion
A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs.
A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
Two similarly designed, double-masked, randomized, ...phase 3 trials, VISTA(DME) and VIVID(DME).
We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
To evaluate Ozurdex (dexamethasone intravitreal implant DEX implant; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic ...macular edema (DME).
Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial.
Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled.
Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed.
The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP).
The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required.
There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone.
Proprietary or commercial disclosure may be found after the references.
The desert regions of the Arabian Peninsula and Levant are criss-crossed by innumerable pathways. Across large areas of north-west Arabia, many of these pathways are flanked by stone monuments, the ...vast majority of which are ancient tombs. Recent radiometric dating indicates that the most abundant of these monuments, elaborate and morphologically diverse ‘pendant’ structures, were constructed during the mid-to-late third millennium BCE. Thousands of kilometres of these composite path and monument features, ‘funerary avenues’, can be traced across the landscape, especially around and between major perennial water sources. By evidencing routes of human movement during this period, these features provide an emerging source for reconstructing important aspects of ancient mobility and social and economic connectivity. They also provide significant new evidence for human/environment interactions and subsistence strategies during the later Middle Holocene of north-west Arabia, and suggest the parallel existence of mobile pastoralist lifeways and more permanent, oasis-centred settlement. This paper draws upon the results of recent excavations and intensive remote sensing, aerial and ground surveys in Saudi Arabia to present the first detailed examination of these features and the vast cultural landscape that they constitute.
We have developed a convenient development-scale reactor (0.44 mol/h) to prepare diazomethane from N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in ∼80% yield. Diazomethane (CH2N2) made with this ...reactor is extracted into nitrogen gas from the liquid reaction mixture, effectively removing it from reagents and byproducts that may interfere in subsequent reactions. Vertically oriented tubular reactors were used to produce and consume diazomethane in situ. Key features of this reactor include high productivity and correspondingly low reactor volume (reactor volume/liquid flow rate = 6.5 min) and a commercially available gas/liquid separator equipped with a selectively permeating hydrophilic membrane. The design of the reactor keeps the inventory below 53 mg of CH2N2 during normal operation. The reactor was demonstrated by generating CH2N2 that was used in a connected continuous reactor. We evaluated esterification reactions and a continuous Pd-catalyzed cyclopropanation reaction with the reactor and achieved high conversion with 1.5 and 4.1 equiv of MNTS precursor, respectively.
Bacillus anthracis was identified in a 61-year-old man hospitalized in Minnesota, USA. Cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen. ...Treatment comprising antimicrobial drugs, anthrax immune globulin, and pleural drainage led to full recovery; however, the role of passive immunization in anthrax treatment requires further evaluation.
The monumental stone structures of the Arabian Peninsula have been notoriously difficult to date. Due to their visibility in the landscape, they have suffered from extensive robbing and later reuse, ...which has compromised dating methodologies. In particular, our understanding of when the elaborate “pendants” (also known as “tailed cairns” or “tailed tower tombs”) of north‐west Arabia were first constructed has remained incomplete. Recent work undertaken by the Aerial Archaeology in the Kingdom of Saudi Arabia – Khaybar project provides some of the first radiometric dates for the pendants of Saudi Arabia. These structures can now be dated as far back as the third millennium BCE, revealing for the first time a hitherto undocumented, large‐scale, monumental funerary landscape dating to the Early Bronze Age. These radiocarbon dates bring the advent of the pendant building tradition in line with funerary developments across the wider Arabian Peninsula, and may mark a profound reconfiguring of the wider Harrat Khaybar landscape during the third millennium BCE.
The Decapolis town of Gerasa became a sizeable urban centre in the province of Arabia in the 2nd century CE. The study of its monumental fountain, the so-called Nymphaeum, has been neglected despite ...its excellent state of preservation. This small but imposing late 2nd-century monument functioned as an aesthetic display and public water supply, although public access was restricted to the frontal spouts. This article comprehensively reappraises the evidence, identifying new material and providing a diachronic analysis of the monument's function and hydraulic operation. It is proposed that the original monument was also designed to supply secondary fountain installations. The later extension of this role to supply the expanded Cardo fountain network, marked a change to a wholly utilitarian function. Later changes included the removal of a previously added wall to the parapet and spout modifications. Subsequent earthquakes severely damaged the monument, and it remained in a ruinous state until cleared in the mid-1920s.
Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. Danicopan is an investigational, first-in-class ...inhibitor of factor D, an essential AP activation enzyme. We assessed danicopan distribution to the posterior segment of the eye after oral dosing.
Tissue distribution of drug-derived radioactivity was evaluated using whole-body autoradiography following oral administration of 14C-danicopan to pigmented and albino rats. Pharmacokinetics and ocular tissue distribution were studied in pigmented and albino rabbits following single and multiple oral dosing of danicopan. The melanin binding property was characterized in vitro.
Radioactivity was distributed widely in rats and became nonquantifiable in most tissues 24 hours postdose except in the pigmented rat uvea (quantifiable 672 hours postdose). Danicopan binding to melanin was established in vitro. After single dosing, the maximum concentration (Cmax) and area under the curve (AUC) in neural retina and plasma were similar in both rabbit types. After multiple dosing, AUC in neural retina was 3.4-fold higher versus plasma in pigmented rabbits. Drug levels in choroid/Bruch's membrane (BrM)/retinal pigment epithelium (RPE) were similar to plasma in albino rabbits but higher in pigmented rabbits: Cmax and AUC were 2.9- and 23.8-fold higher versus plasma after single dosing and 5.8- and 62.7-fold higher after multiple dosing. In pigmented rabbits, ocular tissue exposures slowly declined over time but remained quantifiable 240 hours postdose.
The results demonstrate that danicopan crosses the blood-retina barrier and binds melanin reversibly, leading to a higher and more sustained exposure in melanin-containing ocular tissues (choroid/BrM/RPE) and in the neural retina as compared to in plasma after repeated oral dosing in pigmented animals.
These findings suggest that oral danicopan possesses potential for treating geographic atrophy because AP dysregulation in the posterior segment of the eye is reported to be involved in the disease pathogenesis.
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