Holy Grail Research Articles

302 MONITORING FALLS RISK IN THE COMMUNITY USING AN IMPLANTABLE CARDIAC MONITOR WITH EMBEDDED ACCELEROMETER

Abstract Background Falls are the most common cause of injury amongst older adults. Falls can lead to hospitalisation, functional decline and are associated with increased morbidity and mortality. The holy grail for clinicians would be to predict increased likelihood of falls occurring and intervene before the event. Understanding underlying dynamic biophysiological changes may therefore inform novel predictor models and falls prevention. This study examines activity and cardiac data acquired from an implanted Medtronic Reveal LINQ™ Insertable Cardiac Monitor (ICM) with an embedded tri-axial accelerometer. Methods Thirty participants with at least one unexplained fall in the previous two years were prospectively recruited. All met criteria for ICM insertion following comprehensive assessment. Participants were followed for one year and attended every three-months for cardiac and gait assessment. Information pertaining to activity levels, posture changes and cardiac parameters were collected daily from the device. Summary metrics and trends were collected for inclusion in a continual assessment of falls risk. Results Mean age of participants was 68.0 years (±9.3). 19/30 (63.3%) were female. 22/30 (73.3%) had at least one cardiovascular condition documented in their medical history. There was seasonal variation in activity levels. Twelve participants had falls and cardiovascular, gait and activity variables were examined at the time of a fall to determine any trends in biophysiological changes. Conclusion Causes of falls are usually multifactorial. A holistic approach is necessary to manage and minimise risk factors. The use of an ICM with an embedded tri-axial accelerometer allows clinicians to formulate an algorithm to determine if a person is at an increased risk of falling based on biophysiological changes. This may create an opportunity for falls to be predicted and prevented.

When is a Knight a Knight?

The Middle Welsh Ystoryaeu Seint Greal, the ‘Stories of the Holy Grail’, are a late fourteenth-century translation of two thirteenth-century Old French Arthurian texts—La Queste del Saint Graal and Le Haut Livre du Graal (Perlesvaus). Statistical analysis shows evidence of a sophisticated and so far unique system for the use of the adjective urdaỼl (Mod. Welsh urddol) ‘ordained’ in qualifying the status of otherwise unknown knights.

Apport du coroscanner dans le syndrome coronaire chronique

Cardiac division imaging by coroscanner has progressed a lot in 20 years to gradually become an important and potentially indispensable tool of chronic coronary cardiology. The European and American recommendations are Grade I for the assessment of symptomatic patients at intermediate to high risk, at the same level as traditional functional tests. The development of sophisticated post-treatment algorithms that apply the equations of fluid mechanics makes it possible to calculate an FFR value at any point from the CT image of the coronary artery. This FFR-CT is correctly correlated with invasive FFR compared to a threshold value of 0.80 and helps guide therapeutic choices. Thus, the coroscanner is a complement or an alternative to traditional functional tests and is positioned as a filter of access to coronary angiography, especially since it combines, from the same examination, a precise anatomical description, and a functional evaluation of the various possible lesions. Which is the Holy Grail of coronary cardiology.

Multi-Year Sea Ice Conditions in the Northwest Passage: 1968–2020

ABSTRACT The Northwest Passage is often referred to as the “Holy Grail” of ship navigation as it provides a shorter route connecting the Atlantic and Pacific Oceans compared to the Northern Sea Route, Panama Canal, Suez Canal, and transiting around Cape Horn. Here, we summarize 52 years of observed multi-year ice (MYI) conditions from 1968 to 2020 in the western Canadian Arctic regions of the Northwest Passage updating a previous study that considered 1968–2006. Results indicate that on average, MYI area anomalies during the shipping season were +28% from 1968 to 2006 but −33% from 2007 to 2020 relative to the 1991–2020 climatology. The frequency of negative MYI area anomalies from 2007 to 2020 was unprecedented over the 52-year record. 13 of the past 14 years were negative in the Beaufort Sea, Franklin, and the Western Arctic Waterway; 10 of the past 14 years were negative in Western Parry Channel and Queen Elizabeth Islands; and 9 of the past 14 years were negative in the M’Clintock Channel. Despite strong and frequent negative MYI anomalies from 2007 to 2020, MYI recovery from first-year ice (FYI) aging and MYI dynamic import continued, but was reduced by 47% and 22%, respectively compared to 1968–2006. We demonstrate that from 2007 to 2020 (i) MYI dynamic recovery decreased because Arctic Ocean MYI has been primarily flowing into the Canadian Arctic via the smaller apertures in the Queen Elizabeth Islands and not from the Beaufort Sea via the M’Clure Strait and (ii) FYI aging decreased because recent changes in thermodynamic forcing have contributed to more melt. Overall, our results re-affirm that light MYI years in the Northwest Passage may occur more frequently as the Arctic continues to warm, but MYI recovery will continue to present a significant hazard to navigation for the foreseeable future.

A solid-state lithium-oxygen battery operating at ambient temperature and full charge-discharge

Solid-state Li-O2 batteries (SSLOBs) have been denoted as the holy grail in next-generation Li metal batteries for their high theoretical energy density, manipulation of ambient air to energy storage as well as high safety. However, the solid rigid interfaces both at the cathode and anode side introduce ultra-high resistances in the battery system and impede its operation under ambient temperature. Moreover, the high-reductive Li anode and semi-open cathode would cause severe side reactions during cycling which further degrade battery performance. To manage the above-mentioned issues, a rationally designed SSLOBs based on plastic crystal electrolyte is proposed in this study to enable SSLOBs operation at ambient temperature and in full charge-discharge mode. The brand-new Li-O2 battery has been improved mainly from two aspects. First, we propose a polyacrylonitrile (PAN) modified succinonitrile (SN) electrolyte (PAN-SN) to retard the polymerization of SN and meanwhile suppress the degradation of Li ionic conductivity. Second, we propose an alternative mixed electron/ion complex conductor (MEIC) cathode to coordinate with plastic crystal electrolyte with an expanded Li-O2 reactive zone and improved interfacial charge transfer during the charge-discharge process. The fabricated flexible SSLOBs based on PAN-SN electrolyte and MEIC cathode could be successfully fully charged-discharged (cutoff 2.0–4.5 V) for tens of cycles at ambient temperature under simulated air condition (20 vol% oxygen), with high-capacity retention of around 85 %.

Plasma-Assisted Cu/PCN for the Reforming of CH4 and O2 into C2+ Liquid Chemicals

Direct partial oxidation of methane to value-added chemicals and fuels under mild conditions is the “holy grail” in chemistry. Nonthermal plasma is a mild means to activate methane molecules with high efficiency, but the active species are complex, resulting in low liquid product selectivity. In this paper, Cu-decorated polymer carbon nitride (Cu/PCN-X) was prepared by a facile impregnation–calcination method. Benefiting from the strong CH4 adsorption ability, the conversion of methane was 27.6% and the selectivity of liquid products was 63.4% when catalyzed by Cu/PCN-5 in a nonthermal plasma system. Among the liquid products, CH3CH2OH and C3H6O are the main C2+ oxygenates via the acid sites for C–C coupling, and their selectivity in liquid products comes to 32.9%, higher than the previous report (13.4%).

Experimental Guidelines to Image Transient Single-Molecule Events Using Graphene Liquid Cell Electron Microscopy.

In quest of the holy grail to "see" how individual molecules interact in liquid environments, single-molecule imaging methods now include liquid-phase electron microscopy, whose resolution can be nanometers in space and several frames per second in time using an ordinary electron microscope that is routinely available to many researchers. However, with the current state of the art, protocols that sound similar to those described in the literature lead to outcomes that can differ. The key challenge is to achieve sample contrast under a safe electron dose within a frame rate adequate to capture the molecular process. Here, we present such examples from different systems─synthetic polymer, lipid assembly, DNA-enzyme─in which we have done this using graphene liquid cells. We describe detailed experimental procedures and share empirical experience for conducting successful experiments, starting from fabrication of a graphene liquid cell, to identification of high-quality liquid pockets from desirable shapes and sizes, to effective searching for target sample pockets under electron microscopy, and to discrimination of sample molecules and molecular processes of interest. These experimental tips can assist others who wish to make use of this method.

Conductive Iodine-Doped Red Phosphorus Enabled Dendrite-Free Lithium Deposition on MXene Matrix.

The highest theoretical capacity and lowest redox potential of lithium metal make lithium-based batteries the "holy grail" of the next-generation batteries. However, the uncontrollable dendrite growth and infinite volume change of lithium seriously hinder the real-world implementation of lithium-based batteries. Herein, a flexible MXene@iodine-doped red phosphorus (MXene@RP) paper with iodine-doped red phosphorous particles evenly distributed on the surface and interlayer of MXene matrix is designed by a simple vapor condensation reduction approach. The MXene@RP paper can be used as an efficient matrix to enable dendrite-free lithium deposition. On the one hand, the iodine doping alleviates the low conductivity shortcoming of red phosphorus, making it facilitate homogeneous lithium nucleation, thus promoting uniform lithium deposition and suppressing dendrite growth. On the other hand, the unique layered structure of conductive MXene paper provides ion transport channels and free spaces for lithium loading, alleviating the volume change induced structural damage. As a result, the MXene@RP paper with preloaded lithium exhibits long-term cycling stability. Particularly, a full cell based on Li-MXene@RP anode can maintain 81.4% of the initial capacity after 600 cycles at 4 C. The MXene@RP-based anode increases the potential applications of MXene and provides a guide for the design of dendrite-free lithium hosts.

The Future of Climate Modelling: Weather Details, Macroweather Stochastics—Or Both?

Since the first climate models in the 1970s, algorithms and computer speeds have increased by a factor of ≈1017 allowing the simulation of more and more processes at finer and finer resolutions. Yet, the spread of the members of the multi-model ensemble (MME) of the Climate Model Intercomparison Project (CMIP) used in last year’s 6th IPCC Assessment Report was larger than ever: model uncertainty, in the sense of MME uncertainty, has increased. Even if the holy grail is still kilometric scale models, bigger may not be better. Why model structures that live for ≈15 min only to average them over factors of several hundred thousand in order to produce decadal climate projections? In this commentary, I argue that alongside the development of “seamless” (unique) weather-climate models that chase ever smaller—and mostly irrelevant—details, the community should seriously invest in the development of stochastic macroweather models. Such models exploit the statistical laws that are obeyed at scales longer than the lifetimes of planetary scale structures, beyond the deterministic prediction limit (≈10 days). I argue that the conventional General Circulation Models and these new macroweather models are complementary in the same way that statistical mechanics and continuum mechanics are equally valid with the method of choice determined by the application. Candidates for stochastic macroweather models are now emerging, those based on the Fractional Energy Balance Equation (FEBE) are particularly promising. The FEBE is an update and generalization of the classical Budyko–Sellers energy balance models, it respects the symmetries of scaling and energy conservation and it already allows for both state-of-the-art monthly and seasonal, interannual temperature forecasts and multidecadal projections. I demonstrate this with 21st century FEBE climate projections for global mean temperatures. Overall, the projections agree with the CMIP5 and CMIP6 multi-model ensembles and the FEBE parametric uncertainty is about half of the MME structural uncertainty. Without the FEBE, uncertainties are so large that climate policies (mitigation) are largely decoupled from climate consequences (warming) allowing policy makers too much “wiggle room”. The lower FEBE uncertainties will help overcome the current “uncertainty crisis”. Both model types are complementary, a fact demonstrated by showing that CMIP global mean temperatures can be accurately projected using such stochastic macroweather models (validating both approaches). Unsurprisingly, they can therefore be combined to produce an optimum hybrid model in which the two model types are used as copredictors: when combined, the various uncertainties are reduced even further.

(Invited, Digital Presentation) Methane Conversion to High Value Chemicals By Photocatalysis

As underlined in the COP26, methane as a greenhouse gas is nearly 80 time more potent than CO2 while its reserve is much more than the sum of coal, oil and natural gas. Thus methane conversion not only involves the environmental issue but also is related to high-value chemical production /clean energy supply, which has been attracting substantial interest over the last decades. However CH4 activation is energy intensive and kinetically very challenging so that methane activation is regarded as the “holy grail” in the catalytically chemical process. [1] Photocatalysis provides a cost efficient potential to activation of such small molecule under very mild conditions, while to achieve the potential is a huge challenge.[2]Stimulated by our research outcomes on the charge dynamics in inorganic semiconductor photocatalysis, which reveal that the low reaction efficiency is due to both fast charge recombination and large bandgap of an inorganic semiconductor [3,4], together with the recent findings on atomic catalysis [5], we developed novel material strategies for photocatalytic methane conversion to methanol. Highly dispersed atomic level iron species immobilised on a TiO2 photocatalyst show an excellent activity for methane conversion, resulting into ~97% selectivity towards alcohols operated under ambient conditions by a one-step chemical process [6]. Such photocatalyst is also very stable, promising an attractive industrial process of methane upgrade. The dominating function of the iron species has also been investigated in detail. Furthermore, we designed a flow system for relatively efficient methane to C2, achieving the benchmark results in this area.[7] In addition, C1 oxygenates can be produced with nearly 100% by photocatalytic methane conversion due to the synergy between Au and Cu cocatalysts loaded on ZnO.[8] References ： Li, X. Wang, C., Tang, J. Nature Reviews Materials , 2022, Doi: 1038/s41578-022-00422-3.Wang Y., Suzuki H., Xie, J., Tomita, O., Martin, D. J., Higashi, M., Kong, D., Abe R. Tang, J., Chem. Rev., 2018, 118: 5201-5241.Tang, J. Durrant J. R., Klug, R ., J. Am. Chem. Soc ., 2008, 130(42) : 13885-13891.Miao, T., Wang, C., Xiong, L., Li, X., Xie, X., Tang, J., ACS Catalysis , 2021, 11, 8226-8238.Wang, A. Li J., Zhang. T., Nat . Rev. Chem ., 2018, 2; 65-81.Xie, J., Jin, R. ,Li, A., Bi, Y., Sankar, G. , Ma , Tang, J. Nature Catalysis , 2018, 1: 889-896.Li, X., Xie J.,Rao, H., Wang, , Tang, J., Angewandte Chemie International Edition , 2020, 132: 19870-19875.Luo, L., Gong, Z., Xu, Y., Ma, J., Liu, H., Xing, J., Tang, J., Journal of the American Chemical Society , 2022, 144, 2, 740–750.

Halide and Oxide Double Perovskites As Promising Semiconductor Photocatalysts Candidates for Artificial Photosynthesis of Solar Fuels

Artificial photosynthesis of solar fuels is deemed as one of the Holy grails of renewable energy technology for simultaneously solving energy and environmental issues. At the present, it is one of the most involved programs in the international Mission Innovation Challenge for Accelerating the Clean Energy Revolution. Solar-driven water splitting and CO2 conversion are the main research application of artificial photosynthesis. However, these reactions are extremely challenging due to energetically uphill (G>0) and non-spontaneous multi-electron transfer processes, which are difficult to be understood by traditional knowledge of catalysis. An efficient solar energy conversion system must simultaneously deal well with light absorption, charge separation and transfer, surface redox reactions. Particularly, efficient charge separation and transfer by retarding back electron transfer, are often regarded as the key determining steps for overall solar energy conversion. To solve the high recombination rates of photogenerated electron-hole pairs and their low reduction and oxidation abilities in a single photocatalyst, heterojunction manipulation is urgently required. Two mainstream heterojunctions—type-II and Z-scheme heterojunctions have been widely acknowledged [1].Recently, lead halide perovskites (LHPs) with the chemical formula of ABX3, where A is an organic or inorganic cation (A= Cs+, MA+, FA+), B is Pb2+, and X is a halogen anion (Br-, Cl-, I-), such as CH3NH3PbI3,FAPbI3, and CsPbBr3 have been widely investigated as auspicious semiconductor photocatalysts for photocatalytic H2 production and photocatalytic CO2 reduction owing to their impressive photoelectrochemical properties, facile to synthesize, high carrier mobility, low exciton binding energy, and long carrier lifetime [2]. However, the high toxicity and notorious instability upon exposure to light, moisture, and high temperature are the major obstacles to their practical use.Therefore, developing alternative lead-free semiconductor photocatalysts with similar optoelectronic properties to the LHPs is highly needed.Inorganic halide double-perovskites and analogous oxide double-perovskites with the chemical formula of A2B'B"X6 and A2B'B"O6, respectively, are layered 3D materials, which have been considered as a novel ecofriendly visible light responsive semiconductor photocatalysts to replace the toxic lead-halide perovskite. The main feature of the halide and oxide double-perovskites is that their structures can be accommodated with different transition metal combinations on B' and B" site cations to tune their intrinsic properties such as light absorption, carrier mobilities, chemical diversity, and so on. Theoretically, an auspicious photocatalytic activity can be realized from them owing to their impressive photophysical properties. However, poor charge separation and severe charge recombination have restricted their practical photocatalytic application. Recently, several halides and oxides double perovskites have been demonstrated as visible light-responsive photocatalysts for photocatalytic CO2 reduction and photocatalytic half-reaction (oxygen and hydrogen evolution reactions) such as Cs2AgBrBr6, Cs2AgSbBr6, Sr2CoTaO6, Sr2CoWO6, etc. [3-5]. However, for oxide double perovskites even though they have shown bifunctional photocatalytic oxygen and hydrogen two half-reactions with visible light but their potential as photocatalytic CO2 reduction and one-step overall water splitting have not been achieved so far. Therefore, further improvement of the material design and synthesis by assembling heterostructure based on two eco-friendly halide and oxide double perovskites may play a key role in achieving high efficient photocatalytic performance under visible-light-irradiation. Thought is a challenging task, but holds great potential in advancing science and technology in photocatalysis. References Liao, C. Li, S.-Y. Liu, B. Fang, H. Yang, Emerging frontiers of Z-scheme photocatalytic systems, Trends in Chemistry. 4 (2022) 111–127.-C. Wang, N. Li, A.M. Idris, J. Wang, X. Du, Z. Pan, Z. Li, Surface Defect Engineering of CsPbBr3 Nanocrystals for High Efficient Photocatalytic CO2 Reduction, Solar RRL. 5 (2021) 2100154.Idris, A. M.; Liu, T.; Shah, J. H.; Zhang, X.; Ma, C.; Malik, A. S.; Jin, A. Solar RRL 2020, 4 (3), 1900456.Idris, A. M.; Liu, T.; Hussain Shah, J.; Han, H.; Li, C. ACS Sustainable Chemistry&Engineering 2020, 8 (37), 14190-14197.Wang, H. Huang, Z. Zhang, C. Wang, Y. Yang, Q. Li, D. Xu, Lead-free perovskite Cs2AgBiBr6@g-C3N4 Z-scheme system for improving CH4 production in photocatalytic CO2 reduction, Applied Catalysis B: Environmental. 282 (2021).

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

Intra-beat biomarker for accurate continuous non-invasive blood pressure monitoring

Accurate continuous non-invasive blood pressure (CNIBP) monitoring is the holy grail of digital medicine but remains elusive largely due to significant drifts in signal and motion artifacts that necessitate frequent device recalibration. To address these challenges, we developed a unique approach by creating a novel intra-beat biomarker (Diastolic Transit Time, DTT) to achieve highly accurate blood pressure (BP) estimations. We demonstrated our approach’s superior performance, compared to other common signal processing techniques, in eliminating stochastic baseline wander, while maintaining signal integrity and measurement accuracy, even during significant hemodynamic changes. We applied this new algorithm to BP data collected using non-invasive sensors from a diverse cohort of high acuity patients and demonstrated that we could achieve close agreement with the gold standard invasive arterial line BP measurements, for up to 20 min without recalibration. We established our approach's generalizability by successfully applying it to pulse waveforms obtained from various sensors, including photoplethysmography and capacitive-based pressure sensors. Our algorithm also maintained signal integrity, enabling reliable assessments of BP variability. Moreover, our algorithm demonstrated tolerance to both low- and high-frequency motion artifacts during abrupt hand movements and prolonged periods of walking. Thus, our approach shows promise in constituting a necessary advance and can be applied to a wide range of wearable sensors for CNIBP monitoring in the ambulatory and inpatient settings.

Performative Memories

Performative Memories

Are Halide‐Perovskites Suitable Materials for Battery and Solar‐Battery Applications–Fundamental Reconsiderations on Solubility, Lithium Intercalation, and Photo‐Corrosion

AbstractIn recent years the development of autonomous photo‐rechargeable batteries has received growing attention. Especially highly integrated photobatteries based on multifunctional materials able to harvest sunlight and store charge carriers are the holy grail amongst such devices. Recently 2‐(1‐cyclohexenyl)ethyl ammonium lead iodide (CHPI) has been reported as multifunctional photoelectrode material for the design of highly integrated Li‐ion photobatteries. CHPI is thereby believed to be able to reversibly intercalate Li‐ions from polar carbonate‐based electrolytes, typically used in Li‐ion batteries (LIBs). Herein, CHPI is examined closer to investigate its stability against dissolution, the possibility of Li‐intercalation and photo‐assisted deintercalation, and its general behavior under illumination in standard carbonate‐based electrolytes as well as in a newly developed low polarity electrolyte based on ortho‐difluorobenzene (o‐DFB). This study demonstrates that CHPI dissolves in contact with carbonate‐based electrolytes while being stable in o‐DFB‐based electrolyte and that no Li‐intercalation takes place in the latter. Furthermore, CHPI irreversibly photo‐corrodes during illumination and photo‐assisted deintercalation of lithium ions is not detected. These results lead to the conclusion, that CHPI is neither a suitable nor a stable material for the design of Li‐ion‐based photo‐rechargeable batteries and similar behavior for other organic–inorganic lead halide perovskite materials is expected.

The Nanteos Cup: Folklore and Heritage from Country House to the Internet

The colourful urban legend that surrounds the Nanteos cup features escaping monks, secret tunnels, and a crusader, but perhaps more than any other factor, it is a tribute to the power of the Internet. This damaged medieval mazer bowl, unearthed during renovations at a monastic site, found its way into a stately home in Wales. It was exhibited at an archaeological meeting, gained a local reputation for ‘healing’, and was absorbed into early twentieth-century speculations about the holy grail. At the end of the twentieth century, references to the object could be found in a handful of paper scraps recording cures, occasional accounts in local newspapers and guides, and a series of family letters in the National Library of Wales, plus hints in popular works about the grail. In the twenty-first century, Internet notices have risen exponentially, and the object is now on display at the National Library in Aberystwyth.

Canada's Holy Grail, Lord Stanley's Political Motivation to Donate the Stanley Cup

Canada's Holy Grail, Lord Stanley's Political Motivation to Donate the Stanley Cup

In search of the Holy Grail? The EU Commission's new approach to Article 22 of the EU Merger Regulation

Recently in certain sectors of the economy, in particular in the digital, pharmaceutical and biotech sectors, an increase in the number of concentrations has been detected involving emerging and innovative undertakings with competitive potential but which generate little or no turnover at the time of the transaction. Many such transactions do not fall under the EU merger control system or the domestic merger control systems of the Member States but may, nevertheless, have a detrimental impact on competition in the internal market. The European Commission reacted to this situation by adopting, on 26 March 2021, Guidance on the application of Article 22 (Article 22 Guidance). In this Article 22 Guidance, the Commission announced that it will abandon its previous practice of not accepting Article 22 referral requests from National Competition Authorities (NCAs) which are not competent to review the concentration at stake under their domestic rules. Instead, the Commission will now encourage and accept Article 22 referral requests, particularly from NCAs which do not have jurisdiction over the transaction at stake under their national merger regimes. The Article 22 Guidance gives rise to a number of questions and problems which we discuss in this article.

The Holy Grail of Mathematics

The Holy Grail of Mathematics

The Holy Grail of Mathematics

The Holy Grail of Mathematics