Intracoronary imaging in PCI for acute coronary syndrome: Insights from British Cardiovascular Intervention Society registry.

BACKGROUND: While previous studies have demonstrated the superiority of ICI-guided PCI over an angiography-based approach, there are limited data on all-comer ACS patients. This study aimed to identify the characteristics and in-hospital outcomes of patients undergoing intracoronary imaging (ICI) guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS: All patient undergoing PCI for ACS in England and Wales between 2006 and 2019 were retrospectively analyzed and stratified according to ICI utilization. The outcomes assessed were in-hospital all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) using multivariable logistic regression models. RESULTS: 598,921 patients underwent PCI for ACS, of which 41,716 (7.0 %) had ICI which was predominantly driven by IVUS use (5.6 %). ICI use steadily increased from 1.4 % in 2006 to 13.5 % in 2019. Adjusted odds of mortality (OR 0.69, 95%CI 0.58-0.83) and MACCE (OR 0.77, 95%CI 0.73-0.83) were significantly lower in the ICI group. The association between ICI and improved outcomes varied according to vessel treated with both left main stem (LMS) and LMS/left anterior descending (LAD) PCI associated with significantly lower odds of mortality (OR 0.34, 95%CI 0.27-0.44, OR 0.51 95%CI 0.45-0.56) and MACCE (OR 0.44 95%CI 0.35-0.54, OR 0.67 95%CI 0.62-0.72) respectively. CONCLUSIONS: Although ICI use has steadily increased, less than one in seven patients underwent ICI-guided PCI. The association between ICI use and improved in-hospital outcomes was mainly observed in PCI procedures involving LMS and LAD.

Switchable unidirectional waves on mono- and diatomic metamaterials.

We demonstrate switchable unidirectional propagation of slow waves of coupling within a metamaterial array of strongly coupled elements. We predict theoretically and verify experimentally that the direction of propagation of magnetoinductive waves for any chosen excitation pattern is dictated by the dispersion relations, with forward and backward waves propagating in opposite directions along a chain of meta-atoms. We further prove that the same fundamental phenomenon of direction selectivity due to the forward/backward wave nature is not limited to magnetoinductive waves: we predict analytically and verify numerically the same selective unidirectional signal propagation occurring in nanostructured metamaterial arrays with purely electric coupling. Generalising our method of unidirectional waveguiding to a diatomic magnetoinductive array featuring both forward-wave and backward-wave dispersion branches, switchable unidirectional signal propagation is achieved with distinct frequency bands with opposite directions of signal propagation. Finally, by expanding our technique of selective unidirectional waveguiding to a 2D metasurface, a selective directional control of waves in two dimensions is demonstrated opening up possibilities for directional wireless signal transfer via magnetoinductive surfaces. The observed phenomenon is analogous to polarisation-controlled near-field interference for unidirectional guiding of surface plasmon-polaritons.

Bayesian analyses of direct radiocarbon dates reveal geographic variations in the rate of rice farming dispersal in prehistoric Japan.

The adoption of rice farming during the first millennium BC was a turning point in Japanese prehistory, defining the subsequent cultural, linguistic, and genetic variation in the archipelago. Here, we use a suite of novel Bayesian techniques to estimate the regional rates of dispersal and arrival time of rice farming using radiocarbon dates on charred rice remains. Our results indicate substantial variations in the rate of dispersal of rice within the Japanese islands, hinting at the presence of a mixture of demic and cultural diffusion, geographic variations in the suitability of its cultivation, and the possible role of existing social networks in facilitating or hindering the adoption of the new subsistence economy.

Rates of Elective Percutaneous Coronary Intervention in England and Wales: Impact of COURAGE and ORBITA Trials.

Background There are limited data about how COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) and ORBITA (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trials have impacted percutaneous coronary intervention (PCI) practices at regional or national level. We evaluated temporal trends in elective PCI rates for stable angina and, specifically, examined the impact of the COURAGE and ORBITA trials on PCI practices in England and Wales. Methods and Results We used national PCI data comprising >1.2 million patients undergoing PCI between January 2006 and December 2019. Patient demographics, procedural details, and clinical outcomes were analyzed, and temporal trends in PCI rates for stable angina were compared before and after the publication of the COURAGE and ORBITA trials. Of 1 245 802 PCI procedures, 430 248 (34.5%) were performed for stable angina. Over the study period, the number of elective PCI procedures per year (30 823 in 2006 to 34 103 in 2019) and per 100 000 population estimates (50.7 in 2006 to 58.4 in 2019) remained stable. The proportion of patients undergoing elective PCI without angina symptoms almost doubled from 5.1% to 9.7%. The incidence rate of elective PCI volume after the COURAGE trial, published in 2007, was not different from before the trial was published (incidence rate ratio, 1.06 [95% CI, 0.69-1.62]). It also remained stable after the publication of the ORBITA trial in 2017 (incidence rate ratio, 0.96 [95% CI, 0.74-1.23]). Conclusions In this nationwide analysis, rates of elective PCI for stable angina remained stable over 14 years. Publication of the COURAGE and ORBITA trials had no impact on elective PCI activity.

A novel cost framework reveals evidence for competitive selection in the evolution of complex traits during plant domestication.

Most models of selection incorporate some notion of environmental degradation where the majority of the population becomes less fit concerning a character resulting in pressure to adapt. Such models have been variously associated with an adaptation cost, the substitution load. Conversely, adaptative mutations that represent an improvement in fitness in the absence of environmental change have generally been assumed to be associated with negligible cost. However, such adaptations could represent a competitive advantage that diminishes resource availability for others and so induces a cost. This type of adaptation in the form of seedling competition has been suggested as a mechanism for increases in seed sizes during domestication, a trait associated with the standard stabilizing selection model. We present a novel cost framework for competitive selection that demonstrates significant differences in behaviour to environmental-based selection in intensity, intensity over time and directly contrasts with the expectations of the standard model. Grain metrics of nine archaeological crops fit a mixed model in which episodes of competitive selection often emerge from shifting optimum episodes of stabilizing selection, highlighting the potential prevalence of the mechanism outlined here and providing fundamental insight into the factors driving domestication.

Emerging evidence of plant domestication as a landscape-level process.

The evidence from ancient crops over the past decade challenges some of our most basic assumptions about the process of domestication. The emergence of crops has been viewed as a technologically progressive process in which single or multiple localized populations adapt to human environments in response to cultivation. By contrast, new genetic and archaeological evidence reveals a slow process that involved large populations over wide areas with unexpectedly sustained cultural connections in deep time. We review evidence that calls for a new landscape framework of crop origins. Evolutionary processes operate across vast distances of landscape and time, and the origins of domesticates are complex. The domestication bottleneck is a redundant concept and the progressive nature of domestication is in doubt.

The Evolutionary History of Wild, Domesticated, and Feral Brassica oleracea (Brassicaceae).

Understanding the evolutionary history of crops, including identifying wild relatives, helps to provide insight for conservation and crop breeding efforts. Cultivated Brassica oleracea has intrigued researchers for centuries due to its wide diversity in forms, which include cabbage, broccoli, cauliflower, kale, kohlrabi, and Brussels sprouts. Yet, the evolutionary history of this species remains understudied. With such different vegetables produced from a single species, B. oleracea is a model organism for understanding the power of artificial selection. Persistent challenges in the study of B. oleracea include conflicting hypotheses regarding domestication and the identity of the closest living wild relative. Using newly generated RNA-seq data for a diversity panel of 224 accessions, which represents 14 different B. oleracea crop types and nine potential wild progenitor species, we integrate phylogenetic and population genetic techniques with ecological niche modeling, archaeological, and literary evidence to examine relationships among cultivars and wild relatives to clarify the origin of this horticulturally important species. Our analyses point to the Aegean endemic B. cretica as the closest living relative of cultivated B. oleracea, supporting an origin of cultivation in the Eastern Mediterranean region. Additionally, we identify several feral lineages, suggesting that cultivated plants of this species can revert to a wild-like state with relative ease. By expanding our understanding of the evolutionary history in B. oleracea, these results contribute to a growing body of knowledge on crop domestication that will facilitate continued breeding efforts including adaptation to changing environmental conditions.

Effect of Location on Treatment and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction in England & Wales.

We investigated the incidence, management, and outcomes of acute myocardial infarction (AMI) patients according to cardiac arrest location. Patients admitted with a diagnosis of AMI between January 1, 2010 to March 31, 2017 from the Myocardial Ischaemia National Audit Project (MINAP) were studied. We used logistic regression models to evaluate predictors of the clinical outcomes and treatment strategy. The study population consisted of 580,796 patients admitted with AMI stratified into three groups: out of hospital cardiac arrest (OOHCA) (16,278[2.8%]), in-hospital cardiac arrest (IHCA) (21,073[3.7%]), plus a reference group consisting of those without cardiac arrest (non-cardiac arrest (543,418[93.5%]). IHCA declined steadily (from 666 per 1000 in 2010 to 477 per 1000 AMI with cardiac arrest admissions in 2017) with a commensurate rise in OOHCA (from 344 per 1000 to 533 per 1000 AMI with cardiac arrest admissions). Coronary angiography utilization (OOHCA 81.1% vs IHCA 60.3% vs non-cardiac arrest 70.4%, p < 0.001) and PCI (OOHCA 40% vs IHCA 32.8% vs non-cardiac arrest 45.2%, p < 0.001) were higher in OOHCA. In-hospital mortality odds were greatest for IHCA (OR 35.3, 95% CI 33.4-37.2) compared to OOHCA (OR 12.7, 95% CI 11.9-13.6), with the worse outcomes seen in patients on medical wards (OR 97.37, 95% CI 87.02-108.95) and the best outcomes seen in the emergency department (OR 8.35, 95% CI 7.32-9.53). In conclusion, outcomes of AMI complicated by cardiac arrest depended on cardiac arrest location, especially the outcomes of the IHCA.

Experimental evaluation of spectral efficiency from a circular array antenna producing a Laguerre-Gauss mode.

We present the four-dimensional volumetric electromagnetic field measurements (x, y, z and frequency) of the complex radiated field produced by an 8-element circular antenna array. The array is designed to produce a Laguerre-Gauss (LG) mode l = +1 over the frequency range of 9-10 GHz. We evaluate our findings in terms of far-field LG mode purity and spectral efficiency in terms of the quadrature amplitude modulation (QAM) modulation scheme that can be supported. The application of LG modes in radio systems is as a means of multiplexing several data streams onto the same frequency, polarization and time slot, thus making a highly spectrally efficient transmission system or enhancing radar systems by means of exploiting mode behaviour as an additional degree of freedom. Our results show that for the circular antenna array, we find that mode purity is sufficient to support binary phase shift keying or quadrature phase shift keying modulation over a 0.3 GHz bandwidth, which corresponds to a spectral efficiency of 1.5 b s-1 Hz-1 per mode. Closer to the antennas' design frequency, 256QAM modulation may be supported over a 0.05 GHz band, and which corresponds to a spectral efficiency of 11 b s-1 Hz-1 per mode. We anticipate the practical insights provided in this paper contribute to the successful design of such systems.

New findings on the significance of Jebel Moya in the eastern Sahel.

This paper presents new excavation data and new radiometric dates for Jebel Moya, south-central Sudan. These data suggest revisions to previous chronological understandings of the site. New excavations, initiated in 2017, show a longer, more continuous occupation of the site than has been previously recognised. Archaeozoological and archaeobotanical analyses provide evidence for domesticated taxa. Archaeobotanical evidence is dominated by domesticated sorghum (Sorghum bicolor), radiocarbon dated to c. 2550-2210 BC. Faunal remains include cattle and goat/sheep. A late third-millennium BC date on the human skeleton excavated in the 2017 season also shows that mortuary activity began early in the site's history, contemporary with domesticated faunal and botanical remains. These initial results indicate the long-term association of the site with pastoralism and agriculture and with environmental change. Jebel Moya's continued potential to serve as a chronological and cultural reference point for future studies in south-central Sudan and the eastern Sahel is reinforced.

A 3,000-year-old Egyptian emmer wheat genome reveals dispersal and domestication history.

Tetraploid emmer wheat (Triticum turgidum ssp. dicoccon) is a progenitor of the world's most widely grown crop, hexaploid bread wheat (Triticum aestivum), as well as the direct ancestor of tetraploid durum wheat (T. turgidum subsp. turgidum). Emmer was one of the first cereals to be domesticated in the old world; it was cultivated from around 9700 BC in the Levant1,2 and subsequently in south-western Asia, northern Africa and Europe with the spread of Neolithic agriculture3,4. Here, we report a whole-genome sequence from a museum specimen of Egyptian emmer wheat chaff, 14C dated to the New Kingdom, 1130-1000 BC. Its genome shares haplotypes with modern domesticated emmer at loci that are associated with shattering, seed size and germination, as well as within other putative domestication loci, suggesting that these traits share a common origin before the introduction of emmer to Egypt. Its genome is otherwise unusual, carrying haplotypes that are absent from modern emmer. Genetic similarity with modern Arabian and Indian emmer landraces connects ancient Egyptian emmer with early south-eastern dispersals, whereas inferred gene flow with wild emmer from the Southern Levant signals a later connection. Our results show the importance of museum collections as sources of genetic data to uncover the history and diversity of ancient cereals.

The utility of endotracheal aspirate bacteriology in identifying mechanically ventilated patients at risk for ventilator associated pneumonia: a single-center prospective observational study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a well-known, life-threatening disease that persists despite preventative measures and approved antibiotic therapies. This prospective observational study investigated bacterial airway colonization, and whether its detection and quantification in the endotracheal aspirate (ETA) is useful for identifying mechanically ventilated ICU patients who are at risk of developing VAP. METHODS: 240 patients admitted to 3 ICUs at the Lahey Hospital and Medical Center (Burlington, MA) between June 2014 and June 2015 and mechanically ventilated for > 2 days were included. ETA samples and clinical data were collected. Airway colonization was assessed, and subsequently categorized into "heavy" and "light" by semi-quantitative microbiological analysis of ETAs. VAP was diagnosed retrospectively by the study sponsor according to a pre-specified pneumonia definition. RESULTS: Pathogenic bacteria were isolated from ETAs of 125 patients. The most common species isolated was S. aureus (56.8%), followed by K. pneumoniae, P. aeruginosa, and E. coli (35.2% combined). VAP was diagnosed in 85 patients, 44 (51.7%) with no bacterial pathogen, 18 associated with S. aureus and 18 Gram-negative-only cases, and 5 associated with other Gram-positive or mixed species. A higher proportion of patients who were heavily colonized with S. aureus developed VAP (32.4%) associated with S. aureus compared to those lightly colonized (17.6%). The same tendency was seen for patients heavily and lightly colonized with Gram-negative pathogens (30.0 and 0.0%, respectively). Detection of S. aureus in the ETA preceded S. aureus VAP by approximately 4 days, while Gram-negative organisms were first detected 2.5 days prior to Gram-negative VAP. VAP was associated with significantly longer duration of mechanical ventilation and hospitalization regardless of microbiologic cause when compared to patients who did not develop VAP. CONCLUSIONS: The overall VAP rate was 35%. Heavy tracheal colonization supported identification of patients at higher risk of developing a corresponding S. aureus or Gram-negative VAP. Detection of bacterial ETA-positivity tended to precede VAP.

Sedentism and plant cultivation in northeast China emerged during affluent conditions.

The reasons and processes that led hunter-gatherers to transition into a sedentary and agricultural way of life are a fundamental unresolved question of human history. Here we present results of excavations of two single-occupation early Neolithic sites (dated to 7.9 and 7.4 ka) and two high-resolution archaeological surveys in northeast China, which capture the earliest stages of sedentism and millet cultivation in the second oldest center of domestication in the Old World. The transition to sedentism coincided with a significant transition to wetter conditions in north China, at 8.1-7.9 ka. We suggest that these wetter conditions were an empirical precondition that facilitated the complex transitional process to sedentism and eventually millet domestication in north China. Interestingly, sedentism and plant domestication followed different trajectories. The sedentary way of life and cultural norms evolved rapidly, within a few hundred years, we find complex sedentary villages inhabiting the landscape. However, the process of plant domestication, progressed slowly over several millennia. Our earliest evidence for the beginning of the domestication process appear in the context of an already complex sedentary village (late Xinglongwa culture), a half millennia after the onset of cultivation, and even in this phase domesticated plants and animals were rare, suggesting that the transition to domesticated (sensu stricto) plants in affluent areas might have not played a substantial role in the transition to sedentary societies.

Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study of the Penetration of a Monoclonal Antibody Combination (ASN100) Targeting Staphylococcus aureus Cytotoxins in the Lung Epithelial Lining Fluid of Healthy Volunteers.

ASN100 is a novel antibody combination of two fully human IgG1(κ) monoclonal antibodies (MAbs), ASN-1 and ASN-2, which neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five bicomponent leukocidins. We assessed the safety, tolerability, and serum and lung pharmacokinetics of ASN100 in a randomized, double-blind, placebo-controlled single-dose-escalation first-in-human study. Fifty-two healthy volunteers were enrolled and randomized to receive either ASN-1, ASN-2, a combination of both MAbs (ASN100), or a corresponding placebo. Thirty-two subjects in the double-blind dose escalation portion of the study received ASN-1 or ASN-2 at a 200-, 600-, 1,800-, or 4,000-mg dose, or placebo. Eight subjects received both MAbs simultaneously in a 1:1 ratio (ASN100) at 3,600 or 8,000 mg, or they received placebos. Twelve additional subjects received open-label ASN100 at 3,600 or 8,000 mg to assess the pharmacokinetics of ASN-1 and ASN-2 in epithelial lining fluid (ELF) by bronchoalveolar lavage fluid sampling. Subjects were monitored for 98 days (double-blind cohorts) or 30 days (open-label cohorts) for safety assessment. No dose-limiting toxicities were observed, and all adverse events were mild and transient, with only two adverse events considered possibly related to the investigational product. ASN100 exhibited linear serum pharmacokinetics with a half-life of approximately 3 weeks and showed detectable penetration into the ELF. No treatment-emergent anti-drug antibody responses were detected. The toxin neutralizing potency of ASN100 in human serum was confirmed up to 58 days postdosing. The favorable safety profile, ELF penetration, and maintained functional activity in serum supported the further clinical development of ASN100.

Between domestication and civilization: the role of agriculture and arboriculture in the emergence of the first urban societies.

The transition to urbanism has long focused on annual staple crops (cereals and legumes), perhaps at the expense of understanding other changes within agricultural practices that occurred between the end of the initial domestication period and urbanisation. This paper examines the domestication and role of fruit tree crops within urbanisation in both Western Asia and China, using a combination of evidence for morphological change and a database that documents both the earliest occurrence of tree fruit crops and their spread beyond their wild range. In Western Asia the domestication of perennial fruit crops likely occurs between 6500 bc and 3500 bc, although it accompanies a shift in location from that of the earliest domestications within the Fertile Crescent to Mesopotamia, where the earliest urban societies arose. For China, fruit-tree domestication dates between ca 4000 and 2500 bc, commencing after millet domestication and rice domestication in Northern and Southern China, respectively, but within the period that led up to the urban societies that characterised the Longshan period in the Yellow River basin and the Liangzhu Culture in the Lower Yangtze. These results place the domestication of major fruit trees between the end of the domestication of staple annual crops and the rise of urbanism. On this basis it is argued that arboriculture played a fundamental role within the re-organisation of existing land use, shifting the emphasis from short-term returns of cereal crops into longer term investment in the developing agricultural landscape in both Western and East Asia. In this respect perennial tree crops can be placed alongside craft specialisation, such as metallurgy and textiles, in the formation of urban centres and the shaping the organisational administration that accompanied the rise of urbanism.

A domestication history of dynamic adaptation and genomic deterioration in Sorghum.

The evolution of domesticated cereals was a complex interaction of shifting selection pressures and repeated episodes of introgression. Genomes of archaeological crops have the potential to reveal these dynamics without being obscured by recent breeding or introgression. We report a temporal series of archaeogenomes of the crop sorghum (Sorghum bicolor) from a single locality in Egyptian Nubia. These data indicate no evidence for the effects of a domestication bottleneck, but instead reveal a steady decline in genetic diversity over time coupled with an accumulating mutation load. Dynamic selection pressures acted sequentially to shape architectural and nutritional domestication traits and to facilitate adaptation to the local environment. Later introgression between sorghum races allowed the exchange of adaptive traits and achieved mutual genomic rescue through an ameliorated mutation load. These results reveal a model of domestication in which genomic adaptation and deterioration were not focused on the initial stages of domestication but occurred throughout the history of cultivation.

Development of a Multispectral Albedometer and Deployment on an Unmanned Aircraft for Evaluating Satellite Retrieved Surface Reflectance over Nevada's Black Rock Desert.

Bright surfaces across the western U.S. lead to uncertainties in satellite derived aerosol optical depth (AOD) where AOD is typically overestimated. With this in mind, a compact and portable instrument was developed to measure surface albedo on an unmanned aircraft system (UAS). This spectral albedometer uses two Hamamatsu micro-spectrometers (range: 340⁻780 nm) for measuring incident and reflected solar radiation at the surface. The instrument was deployed on 5 October 2017 in Nevada's Black Rock Desert (BRD) to investigate a region of known high surface reflectance for comparison with albedo products from satellites. It was found that satellite retrievals underestimate surface reflectance compared to the UAS mounted albedometer. To highlight the importance of surface reflectance on the AOD from satellite retrieval algorithms, a 1-D radiative transfer model was used. The simple model was used to determine the sensitivity of AOD with respect to the change in albedo and indicates a large sensitivity of AOD retrievals to surface reflectance for certain combinations of surface albedo and aerosol optical properties. This demonstrates the need to increase the number of surface albedo measurements and an intensive evaluation of albedo satellite retrievals to improve satellite-derived AOD. The portable instrument is suitable for other applications as well.

Evolving the Anthropocene: linking multi-level selection with long-term social-ecological change.

To what degree is cultural multi-level selection responsible for the rise of environmentally transformative human behaviors? And vice versa? From the clearing of vegetation using fire to the emergence of agriculture and beyond, human societies have increasingly sustained themselves through practices that enhance environmental productivity through ecosystem engineering. At the same time, human societies have increased in scale and complexity from mobile bands of hunter-gatherers to telecoupled world systems. We propose that these long-term changes are coupled through positive feedbacks among social and environmental changes, coevolved primarily through selection acting at the group level and above, and that this can be tested by combining archeological evidence with mechanistic experiments using an agent-based virtual laboratory (ABVL) approach. A more robust understanding of whether and how cultural multi-level selection couples human social change with environmental transformation may help in addressing the long-term sustainability challenges of the Anthropocene.