Holy Grail Research Articles

Teacher Questioning for Engaging EMI: A Quest for the Holy Grail?

AbstractQuestions asked by teachers are vital to maintaining and sustaining learner engagement. In Hong Kong secondary classrooms where English is used as the medium of instruction (EMI), productive teacher questioning is key to promoting both language and content learning. Drawing on classroom observations and in-depth interviews, this study investigated the questioning practices of two teachers from EMI schools in Hong Kong. Quantitative and qualitative analyses of the data revealed that the teachers adopted different approaches to questioning. Their questioning practices can be captured by a dynamic model of two intersecting dimensions: cognitive demand (lower- and higher-order questions) and interactional orientation (authoritative and dialogic discourses). The findings of this study support the notion of teacher questioning as pedagogy and demonstrate how productive teacher questioning can mediate learner engagement. A guiding framework is proposed for productive teacher questioning that relies on the synergistic combination of cognitive demand and interactional orientation.

It all began in Issaquah 50 years ago

Abstract “Somehow scientists still pursue the same questions, if now on higher levels of theoretical abstraction rooted in deeper layers of empirical evidence… To paraphrase an old philosophy joke, science is more like it is today than it has ever been. In other words, science remains as challenging as ever to human inquiry. And the need to communicate its progress… remains as essential now as then.” — Tom Siegfried, Science News 2021 In fact, essential questions about pain have not changed since IASP's creation in Issaquah: what causes it and how can we treat it? Are we any closer to answering these questions, or have we just widened the gap between bench and bedside? The technology used to answer questions about pain mechanisms has certainly changed, whether the focus is on sensory neurons, spinal cord circuitry, descending controls or cortical pain processing. In this paper, we will describe how transgenics, transcriptomics, optogenetics, calcium imaging, fMRI, neuroimmunology and in silico drug development have transformed the way we examine the complexity of pain processing. But does it all, as our founders hoped, help people with pain? Are voltage-gated Na channels the new holy grail for analgesic development, is there a pain biomarker, can we completely replace opioids, will proteomic analyses identify novel targets, is there a “pain matrix,” and can it be targeted? Do the answers lie in our tangible discoveries, or in the seemingly intangible? Our founders could barely imagine what we know now, yet their questions remain.

Deliverable Capacity of Methane: Required Material Property Levels for the Ideal “Holy Grail” Adsorbent

Deliverable Capacity of Methane: Required Material Property Levels for the Ideal “Holy Grail” Adsorbent

Comparison of Sternotomy Access Versus Thoracotomy Access in the Surgical Treatment of Aortic Coarctation: A Propensity Score-matched Study.

The search for the "Holy Grail" of surgical repair for aortic coarctation involves finding an access and correction method that successfully and consistently avoids aortic recoarctation and arterial hypertension. The controversy persists as there is still no consensus on the best surgical approach and technique to achieve these objectives. The objective of this study is to compare sternotomy and left thoracotomy as surgical techniques for treating patients with aortic coarctation and hypoplasia of the distal aortic arch. From January 2008 to December 2020, 103 surgical procedures were performed using an extended oblique anastomosis. The patients were divided into 2 groups: oblique, extended anastomosis from thoracotomy access (n-68; 66%) and oblique extended anastomosis from sternotomy access (n-35; 34%). After performing a propensity score analysis (1:1) for the entire sample, 25 patients from sternotomy access were matched with 25 patients from thoracotomy access. The mortality rate in the thoracotomy group was 4%, with 1 patient, while it was 8% with 2 patients in the sternotomy group, p > 0.99. There were no significant differences in early postoperative complications between the two groups. Recurrence of aortic coarctation was observed more frequently in the thoracotomy group (20.8% vs 0%). Low weight was identified as the only risk factor for aortic re-coarctation. The mortality rates and early postoperative complications associated with the surgical repair of aortic coarctation were similar between the sternotomy and thoracotomy approaches. Nevertheless, sternotomy approach may be beneficial in reducing aortic recoarctation.

Assessment of surgical revascularization completeness with quantitative myocardial blood flow distribution derived from CCTA in severe coronary artery disease

Abstract Background Complete revascularization remained the "holy grail" in the treatment of patients with severe coronary artery disease (CAD). However, there is no universally accepted definition of complete revascularization after coronary bypass graft surgery (CABG). The current assessment methods are visual, categorical, and biased by the operator's intention. Moreover, no method to date provides an individualized quantification of residual ischemia burden. Purpose We aim to provide an individualized method to assess the completeness of surgical revascularization through quantitative myocardial blood flow distribution derived from coronary computed tomography angiography (CCTA) that could reflect the actual functional ischemia burden after CABG. Methods Patients with 3VD and/or left main CAD were enrolled in the first-in-human FAST TRACK CABG trial for surgical revascularization guided solely by CCTA and fractional flow reserve derived from CCTA (FFRCT). Following CABG, the study protocol mandated a 30-day follow-up CCTA, which provides graft patency and topographical adequacy of the bypass graft anastomoses. The pre- and post-CABG CCTA were analyzed. The FFRCT value and percent myocardial blood flow distribution (%MBF) were computed for all 16 SYNTAX score segments using the validated method of Keulards et al(1). On pre-CABG CCTA, the myocardium located distal to the site where the FFRCT value dropped below 0.80 on the vessel centerline was considered ischemic, and the %MBF of the subtended myocardium was summed into the total percent ischemic myocardium (Figure 1). Following CABG, the segment was considered adequately revascularized when a non-narrowed graft was anastomosed distally to the site of FFRCT≤0.8 on the pre-operative CCTA. The change in percent ischemic myocardium and the residual ischemic burden were calculated for each patient (Figure 2). Results CCTA, FFRCT, and %MBF were obtained pre- and post-CABG in 96 patients, and the percent ischemic myocardium was computed per patient. At baseline, the average percent ischemic myocardium was 72.0(19.1)%. Post-CABG, the residual percent ischemic myocardium was 13.6(15.1)%. Residual percent ischemic myocardium <10% was achieved in 44 patients (44.8%). The first diagonal branch(n=13), distal LCX(n=12), and the first obtuse marginal branch(n=10) were the most frequent segments not revascularized, which subtended an average MBF of 12.2(3.5)%, 16.7(8.4)%, and 11.3(7.3)%, respectively. The main reason for inadequate revascularization was surgical deferral, with graft occlusion accounting for only 13.6% of the residual ischemic segments. Conclusion Percent ischemic myocardium and the completeness of surgical revascularization can be assessed with CCTA-derived %MBF. This novel method allows clinicians to assess the individualized ischemia burden and the completeness of revascularization that could be incorporated into personalized CABG planning.Figure 1Figure 2

Opinion: How will advances in aerosol science inform our understanding of the health impacts of outdoor particulate pollution?

Abstract. Air pollution, characterized by high levels of particulate matter (PM), poses the greatest environmental threat to human health, causing an estimated 7 million deaths annually and accounting for 5 % of the global gross domestic product (GDP). While the health impacts of PM are influenced by the toxicity of its individual chemical constituents, the mortality burden of PM is solely based on its total mass concentration. This is because of a lack of large-scale, high-resolution data on PM chemical composition, needed for epidemiological assessments. Identifying which PM constituents are harmful to health has been the “holy grail” of atmospheric science since the landmark 1993 study on six US cities established a definitive link between PM and mortality. Ever since, atmospheric scientists have focused on understanding aerosol composition, emission sources, and formation pathways, while longitudinal epidemiological studies have required individual-level exposure data, employing land use regression models for the prediction of exposures at fine resolutions. In this opinion article, we argue that the time has come to shift the focus towards incorporating PM chemical composition into epidemiological health assessments, laying the foundation for the development of new regulatory metrics. This shift will enable the creation of targeted guidelines and subsequent regulations, prioritizing mitigation efforts against the most harmful anthropogenic emissions. Central to this shift is the availability of global, long-term, high-resolution data on PM chemical composition that are obtained through field observations and modelling outputs. In the article, we underscore key milestones within aerosol science that have been integral for advancing this foundational shift. Specifically, we examine emerging modelling tools for estimating exposure to individual PM components, present the type of ambient observations needed for model developments, identify key gaps in our fundamental understanding of emissions and their atmospheric transformation, and propose advancing cross-disciplinary collaboration between aerosol scientists and epidemiologists to understand the health impacts of individual PM components. We contend that aerosol science has now reached a pivotal moment in elucidating the differential health impacts of PM components, representing a first step towards their incorporation into air quality guidelines.

Holy grail or convenient excuse? Stakeholder perspectives on the role of health system strengthening evaluation in global health resource allocation

BackgroundThe role of evaluation evidence in guiding health systems strengthening (HSS) investments at the global-level remains contested. A lack of rigorous impact evaluations is viewed by some as an obstacle to scaling resources. However, others suggest that power dynamics and knowledge hierarchies continue to shape perceptions of rigor and acceptability in HSS evaluations. This debate has had major implications on HSS resource allocation in global-level funding decisions. Yet, few studies have examined the relationship between HSS evaluation evidence and prioritization of HSS. In this paper, we explore the perspectives of key global health stakeholders, specifically around the nature of evidence sought regarding HSS and its potential impact on prioritization, the challenges in securing such evidence, and the drivers of intra- and inter-organizational divergences. We conducted a stakeholder analysis, drawing on 25 interviews with senior representatives of major global health organizations, and utilized inductive approaches to data analysis to develop themes.ResultsOur analysis suggests an intractable challenge at the heart of the relationship between HSS evaluations and prioritization. A lack of evidence was used as a reason for limited investments by some respondents, citing their belief that HSS was an unproven and potentially risky investment which is driven by the philosophy of HSS advocates rather than evidence. The same respondents also noted that the ‘holy grail’ of evaluation evidence that they sought would be rigorous studies that assess the impact of investments on health outcomes and financial accountability, and believed that methodological innovations to deliver this have not occurred. Conversely, others held HSS as a cross-cutting principle across global health investment decisions, and felt that the type of evidence sought by some funders is unachievable and not necessary – an ‘elusive quest’ – given methodological challenges in establishing causality and attribution. In their view, evidence would not change perspectives in favor of HSS investments, and evidence gaps were used as a ‘convenient excuse’. Respondents raised additional concerns regarding the design, dissemination and translation of HSS evaluation evidence.ConclusionsOngoing debates about the need for stronger evidence on HSS are often conducted at cross-purposes. Acknowledging and navigating these differing perspectives on HSS evaluation may help break the gridlock and find a more productive way forward.

Development of bacterial resistance in Germany from 2008 to 2022 - major culprit pathogens, antibacterial drugs, and prescribing practices.

Rising bacterial resistance is a global threat, causing rising financial burdens on healthcare systems and endangering effective treatment of bacterial infections. To ensure the efficacy of antibacterial drugs, it is essential to identify the most dangerous pathogens and vulnerable antibacterial drugs. Previous research by our group suggested irrational outpatient prescribing practices in Germany, supporting a growing bacterial resistance. This study analyses developments and characteristics for the ten most prescribed antibacterial drugs in Germany from 2008 to 2022. Conclusions are based on the development of bacterial resistance levels and an analysis of correlations between pathogens. We identified cefuroxime axetil, sulfamethoxazole-trimethoprim and nitrofurantoin as the most problematic drugs. Particularly problematic pathogens include E. faecalis, E. faecium, K. pneumoniae, and P. mirabilis. Besides increasing bacterial resistance, they are characterised by a high proportion of significant positive correlations, indicating a high potential for mutually reinforcing resistance development. Alarmingly, most of the antibacterial drugs analysed showed a growing resistance to at least one of the analysed pathogens. In most cases, the best treatment option is threatened by increasing bacterial resistance. We also identified several differences between current bacterial resistance data and therapeutic guidelines. In aggregate, our findings support irrational prescribing behaviour and underscore the urgent need for improved prescribing practices to counter rising bacterial resistance in Germany. Moreover, therapeutic guidelines for bacterial infections, the "holy grail" of pharmacotherapy, must be updated more frequently.

Non-consumable gamma-cyclodextrin additive constructing anti-solvation interphase realizing dendrites free and high-performance lithium metal batteries

Relying on surpassing high theoretical capacity (3,865 mAh/g) and the lowest relative electrode potential (0 V vs. metallic Li), lithium metal batteries (LMBs) have been regarded as the “holy grail” of next-generation energy storage technology. Whereases, the instability of pristine solid electrolyte interphase (SEI) layers and the disorderly growth of lithium dendrites are still significant challenges to the commercialisation of LMBs. In this study, a novel approach is introduced to homogenise Li deposition by incorporating an environmentally friendly electrolyte additive, gamma-cyclodextrin (γ-CD), in ether-based electrolytes. Through host-guest interactions, γ-CD additives not only form inclusion complexes to improve Li+ transference number to 0.86 but also encapsulate TFSI- anions and other solvent molecules within the “cavity effect” to relieve unfavourable solvent effect. Electrochemical characterisations demonstrate that introducing 1 wt% γ-CD elevates the oxidation decomposition voltage of ether electrolytes to 4.15 V, thereby inhibiting the decomposition of ether electrolytes and reducing the fracture of SEI layers. According to reduce the nucleate potential, the Li//Cu half battery exhibits improved stability for 100 cycles, with an improved average Coulombic efficiency (CE) maintained above 98.4 %. Even if applied at high current densities of 5.0 mA cm−2 for a capacity of 1.0 mAh cm−2, the Li//Li symmetric battery can cycle for over 800 h, and the Li//Li4Ti5O12 (LTO) full battery retains 98.8 % of the initial capacity after 1,400 cycles.

Evaluation of an engineered vascular graft exhibiting somatic growth in lambs to model repair of absent pulmonary artery branch

BackgroundGrowth is the holy grail of tissue implants in pediatrics. No vascular graft currently in use for surgical repairs of congenital heart defects has somatic growth capacity.MethodsBiologically-engineered grafts (6 mm) grown from donor ovine fibroblasts in a sacrificial fibrin gel were implanted into the left pulmonary branch of 3-month old lambs for 3, 6, and 18 months. A control group of Propaten® PTFE grafts was implanted for 6 months.ResultsThe engineered grafts exhibit extensive site-appropriate recellularization after only 3 months and near-normal increase of diameter from the preimplant value of 6 mm to 12.9 mm and also a doubling of length from 6.0 mm to 13.0 mm at 6 months (n = 3) associated with apparent somatic graft growth (collagen content increase of 265% over 18-month, n = 2), along with excellent hemodynamics and no calcification, in contrast to the Propaten® grafts. The left-right flow distribution is nearly 50–50 for the engineered grafts at 6 months (n = 3) compared to about 20–80 for the Propaten® grafts (n = 3), which have less than one-half the diameter, a 6-fold higher pressure gradient, and stunted vascular development downstream of the graft. The engineered grafts exhibit a stable diameter over months 12–18 when the lambs become adult sheep (n = 2).ConclusionsThis study supports the use of these regenerative grafts with somatic growth capacity for clinical trial in patients born with a unilateral absent pulmonary artery branch, and it shows their potential for improving development of the downstream pulmonary vasculature.

Monomeric metal species for low‐temperature methane oxidation

Direct oxidation of methane into value‐added chemicals is considered as one of the holy grails in chemistry and catalysis. Considerable efforts have been devoted to developing advanced catalyst systems operated under mild conditions, and mononuclear metal species, which are currently in the spotlight of methane oxidation, have shown great advantages and addressed significant attention. In this Concept, we highlight the recent breakthroughs and developments in monomeric metal species for low‐temperature (<100 °C) methane oxidation. Emphasis is put on the identification and validation of monomeric metal species as the intrinsic active sites. Promising characterization approaches for identifying catalytically relevant features of physicochemical properties of monomeric metal species are discussed, as well as the emerging insights on the development of in situ characterization technologies. Finally, the open challenges and outlooks for rational development of monomeric metal catalysts for methane valorization are examined for guiding further developments and inspiring the future work.

Emerging All-Solid-State Lithium–Sulfur Batteries: Holy Grails for Future Secondary Batteries

Emerging All-Solid-State Lithium–Sulfur Batteries: Holy Grails for Future Secondary Batteries

Molecular Architecture @ MOFs: Designing a Multifunctional Catalyst for the Cascade Reaction of Olefins via Epoxides to Cyclic Carbonates

Employing enzymatic reaction cascade principles to synthesize artificial materials with multiple autonomously operating active sites is one of the holy grails in modern catalysis research. In this regard, metal‐organic frameworks (MOFs) are promising host platforms. Yet, applying MOFs as enzyme‐mimicking catalysts is synthetically challenging. Herein, we present a design strategy for the synthesis of porphyrin‐based MOFs for the cascade catalysis of the conversion of olefins to epoxides and their cycloaddition with CO2 to cyclic carbonates. The MOFs feature tunable dual active sites with synthetically controllable metal variations. A clear dependence of the metal combination on the catalytic performance of the MOF catalysts is shown. This work advances the understanding essential for designing sophisticated, multifunctional porphyrin MOFs for efficient one‐pot cascade catalysis.

Metallization of Hydrogen Under High Pressure: Challenges and Experimental Progress

AbstractHydrogen, the first element in the periodic table, is predicted to become metallic at extremely high‐pressure conditions. Solid metallic hydrogen is believed to possess extraordinary physical properties, such as room‐temperature superconductivity and superfluidity, earning it the title of the “holy grail” in high‐pressure research. The pursuit of solid metallic hydrogen has spanned nine decades. Despite numerous fascinating discoveries related to dense hydrogen, metallic hydrogen has yet to be experimentally realized. This article aims to provide an overview of the major progress made in this field and offers an outlook on future developments.

Direct Oxidation of Methane to C1 Oxygenates on Cu/ZSM‐5: Reaction Property and Configuration of Cu Species

AbstractDirect oxidation of methane (DOM) under mild conditions is arguably one of the holy grails in chemistry. Cu‐based zeolite catalysts have attracted much attention for their high yield and selectivity of C1 oxygenates. However, the structure‐activity relationships of DOM remain controversial due to the complex configurations of Cu on zeolites. Herein, we prepared Cu/ZSM‐5 catalysts with various Cu loading and investigated the effects of Cu configurations on the DOM reaction. By combining the characterization techniques and evaluating the catalytic performance, we found that the configurations of Cu species could significantly affect the yield and distribution of C1 oxygenates, which was strongly dependent on Cu loading. The highly dispersed mononuclear CuII in the channels of ZSM‐5 is proved to be highly active. While the multinuclear Cu species inhibit the formation of HCOOH, simultaneously suppressing the overall reaction yield. The agglomerated CuO species on the surface of ZSM‐5 show a relatively low correlation with DOM reaction. Thus, the relationship between the yield of C1 oxygenates and Cu loading exhibits a typical volcanic curve and 2.2 wt.% Cu/ZSM‐5 possess the best performance using H2O2 as oxidant (productivity of 17,000 μmol gcat−1 h−1 with 98.6 % selectivity at 50 °C).

Shear-Induced Cycloreversion Leading to Shear-Thinning and Autonomous Self-Healing in an Injectable, Shape-Holding Collagen Hydrogel.

In vivo injectable extracellular matrix (ECM) derived hydrogels that are suitable for cell encapsulation have always been the holy grail in tissue engineering. Nevertheless, these hydrogels still fall short today of meeting three crucial criteria: (a) flexibility on the injectability time window, (b) autonomous self-healing of the injected hydrogel, and (c) shape-retention under aqueous conditions. Here we report the development of a collagen-based injectable hydrogel, cross-linked by cycloaddition reaction between furan and maleimide groups, that (a) is injectable up to 48 h after preparation, (b) can undergo complete autonomous self-healing after injection, (c) can retain its shape and size over several years when stored in the buffer, (d) can be degraded within hours when treated with collagenase, (e) is biocompatible as demonstrated by in vitro cell-culture, and (f) is completely resorbable in vivo when implanted subcutaneously in rats without causing any inflammation.

The Holy Grail revisited: What works for whom?

The Holy Grail revisited: What works for whom?

GREEN HUMAN RESOURCE MANAGEMENT AND MOTIVATION - INNOVATIONS, TRADITIONS AND BEST PRACTICES

Motivation and its relatedness to the high performance of organisations is of undeniable interest to management at all levels. This is perhaps the “perpetuum mobile” or the “holy grail” for every manager. In the changing environmental conditions of recent years and in line with the changing climate and its impact on every human being, decisions related to environmental protection, to green policies in all areas are increasingly relevant. This paper aims to present basic ideas related to the concept of Green Human resource management (GHRM) and to highlight some key features in rethinking the applicability of this concept in the practice of modern organisations. It focuses on the current state of GHRM practices in Bulgaria, which is expanding in importance and is a leading theme in which good practices and ideas can be brought forward.

Is It the Holy Grail or Snake Oil?

Is It the Holy Grail or Snake Oil?

Recent advances in functionalized separator for dendrites‐free and stable lithium metal batteries

AbstractLithium (Li) metal anode is considered the “Holy grail” for the most promising next‐generation rechargeable lithium metal batteries (LMBs) because of ultra‐high theoretical specific capacity, ultra‐low reduction potential and small density. However, uncontrolled lithium dendrite growth and inevitable side reaction seriously hindered the application of practical LMBs because of the deteriorating electrochemical performances and exacerbating the safety issues of LMBs. Thus, improving the electrochemical performances of LMBs by constructed of functionalized separator is promising for overcoming the above‐mentioned challenges due to its' significantly advantages, such as enhancing mechanical and thermal stability, regulating the diffusion and migration of Li ions, homogenizing Li ion flux, forming protective layer on Li anode surfaces, etc. The relational investigations have significantly increased since 2020, while the comprehensive reviews on this research direction are relatively rare, especially in the detailed mechanism aspects. In this review, an overview in functionalized separator for stable LMBs is discussed in detail. Firstly, the current issues of LMBs are in‐depth discussion and the general strategies are summarized. Subsequently, the requirements and limitations of separator, as well as the advantages of functionalized separator are summarized and reviewed. Most importantly, the protection mechanisms and research advances of advanced functionalized separator are comprehensively discussed and summarized. Furthermore, the applications of functionalized separator in rechargeable lithium metal‐based full cells are reviewed. Finally, the challenges and potential opportunities for the future development and rational design of functionalized separator are highlighted in rechargeable LMBs to obtain future research directions related to the significant strategy of constructing dendrite‐free and stable LMBs.