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The International Olympic Committee’s (IOC) consensus statement on ‘methods for recording and reporting of epidemiological data on injury and illness in sport’ recommended standardising methods to advance data collection and reporting consistency. However, additional aspects need to be considered when these methods are applied to specific sports settings. Therefore, we have developed a snow sports-specific extension of the IOC statement to promote the harmonisation of injury and illness registration methods among athletes of all levels and categories in the different disciplines governed by the International Ski and Snowboard Federation (FIS), which is also applicable to other related snow sports such as biathlon, ski mountaineering, and to some extent, para snow sports. The panel was selected with the aim of representing as many different areas of expertise/backgrounds, perspectives and diversity as possible, and all members were assigned to thematic subgroups based on their profiles. After panel formation, all members were provided with an initial draft of this extension, which was used as a basis for discussion of aspects specific to the discipline, application context, level and sex within their snow sports subgroup topic. The outcomes were then aligned with the IOC’s existing consensus recommendations and incorporated into a preliminary manuscript draft. The final version of this snow sports-specific extension was developed and approved in two iterative rounds of manuscript revisions by all consensus panel members and a final meeting to clarify open discussion points. This snow sports-specific extension of the IOC statement is intended to guide researchers, international and national sports governing bodies, and other entities recording and reporting epidemiological data in snow sports to help standardise data from different sources for comparison and future research.

Ensuring predictability in modern real-time Systems-on-Chip (SoCs) is an increasingly critical concern for many application domains such as automotive, robotics, and industrial automation. An effective approach involves the modeling and development of hardware components, such as interconnects and shared memory resources, to evaluate or enforce their deterministic behavior. Unfortunately, these IPs are often closed-source, and these studies are limited to the single modules that must later be integrated with third-party IPs in more complex SoCs, hindering the precision and scope of modeling and compromising the overall predictability. With the coming-of-age of open-source instruction set architectures (RISC-V) and hardware, major opportunities for changing this status quo are emerging. This study introduces an innovative methodology for modeling and analyzing State-of-the-Art (SoA) open-source SoCs for low-power cyber-physical systems. Our approach models and analyzes the entire set of open-source IPs within these SoCs and then provides a comprehensive analysis of the entire architecture. We validate this methodology on a sample heterogenous low-power RISC-V architecture through RTL simulation and FPGA implementation, minimizing pessimism in bounding the service time of transactions crossing the architecture between 28% and 1%, which is considerably lower when compared to similar SoA works.

This article from Macworld - Digital Edition highlights some of the silliest iPhone apps of all time. The author discusses various apps that serve no practical purpose but are rather entertaining or bizarre. Some examples include an app that tells you if it's dark outside, an app that allows you to virtually pop pimples, and an app that simulates drinking beer without the consequences. The article also mentions the infamous "I Am Rich" app, which was priced at $999.99 and did nothing more than display a red ruby on the screen. [Extracted from the article]

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Dieser Artikel der Zeitschrift für Psychodrama und Soziometrie beschreibt und reflektiert ein in der Teamentwicklung erprobtes Tool zur Gruppenfindung. Ausgehend vom Hier und Jetzt der Gruppe, werden retrospektiv die individuellen Wege, die dazu geführt haben, sternförmig um eine Mitte aufgestellt und reflektierend mit der Gruppe geteilt. Das Erleben der einzelnen Wege, Geschichten und Persönlichkeiten, die in einem Team aufeinandertreffen, bildet den Startpunkt für die weitere gemeinsame Arbeit an aktuellen Themen, an der Vision und den Zielen.

Cyclopentanone (CP), a cyclic hydrocarbon, is a potential biobased platform chemical for the synthesis of high-density jet fuel range cycloalkanes. The base-catalyzed self-condensation of CP yields 2-cyclopentylidene cyclopentanone (2-CP) and 2,5-dicyclopentylidene cyclopentanone (3-CP). 2-CP has applications in fuels, fragrances, and flavors, and 3-CP is used as a precursor for diesel-grade products. In this study, solid base activated carbon monolith (ACM)-supported hydrotalcite catalysts (HT/ACM) were synthesized using traditional thermal calcination, rehydration, and air plasma techniques and demonstrated for continuous cyclopentanone self-condensation. Among the ACM-supported hydrotalcites, the HT/ACM activated by air plasma at 100 W for 1 min (PHT/ACM-100W) displayed a higher 2-CP space time yield of 641 g L-cat–1h–1and selectivity of 27% (220 °C, 1 atm, 0.73 min vapor phase contact time). PHT/ACM-100W displayed a higher CP conversion (42%) compared to the unsupported calcined (34%, 500 °C for 4 h) and rehydrated (39.5%, 8 h at 105 °C) hydrotalcite catalysts yet significantly lower space time yields, suggesting low hydrotalcite distribution and loading on the carbon monolith. The plasma-activated carbon monolith-supported hydrotalcite catalysts synthesized in this work are promising alternatives to the thermally activated and rehydrated hydrotalcites for the catalytic upgrading of biobased cyclic and linear ketones.

Healthcare workers are at risk of adverse mental health outcomes due to occupational stress. Many organizations introduced initiatives to proactively support staff’s psychological well-being in the face of the COVID-19 pandemic. One example is the STEADY wellness program, which was implemented in a large trauma centre in Toronto, Canada. Program implementors engaged teams in peer support sessions, psychoeducation workshops, critical incident stress debriefing, and community-building initiatives. As part of a project designed to illuminate the experiences of STEADY program implementors, this article describes recommendations for future hospital wellness programs. Participants described the importance of having the hospital and its leaders engage in supporting staff’s psychological well-being. They recommended ways of doing so (e.g., incorporating conversations about wellness in staff onboarding and routine meetings), along with ways to increase program uptake and sustainability (e.g., using technology to increase accessibility). Results may be useful in future efforts to bolster hospital wellness programming.

Early spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron1. Alternatively, it can occur through an exon-defined pathway2–5, whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5′ splice site located directly downstream of it. The U4/U6.U5 tri-snRNP subsequently binds to produce a cross-intron (CI) or cross-exon (CE) pre-B complex, which is then converted to the spliceosomal B complex6,7. Exon definition promotes the splicing of upstream introns2,8,9and plays a key part in alternative splicing regulation10–16. However, the three-dimensional structure of exon-defined spliceosomal complexes and the molecular mechanism of the conversion from a CE-organized to a CI-organized spliceosome, a pre-requisite for splicing catalysis, remain poorly understood. Here cryo-electron microscopy analyses of human CE pre-B complex and B-like complexes reveal extensive structural similarities with their CI counterparts. The results indicate that the CE and CI spliceosome assembly pathways converge already at the pre-B stage. Add-back experiments using purified CE pre-B complexes, coupled with cryo-electron microscopy, elucidate the order of the extensive remodelling events that accompany the formation of B complexes and B-like complexes. The molecular triggers and roles of B-specific proteins in these rearrangements are also identified. We show that CE pre-B complexes can productively bind in transto a U1 snRNP-bound 5′ splice site. Together, our studies provide new mechanistic insights into the CE to CI switch during spliceosome assembly and its effect on pre-mRNA splice site pairing at this stage.

Global agri-food systems couple sustainability challenges in producing countries to consumption behavior and regulations in destination markets. We assume that trade relations can be prioritized according to (1) the relevance (share of imports) and (2) leverage (share of domestic production for destination market). This study analyzes the relevance and leverage of the EU’s crop imports in monetary values, footprints, and deforestation. Our results identify high relevance and leverage values in trade relations with specific partner countries, particularly palm oil and rubber specialists in East Asia and soy-producing MERCOSUR countries. High leverage values in imports from African-Caribbean-Pacific small sugar specialists and other small countries highlight the EU’s potential to establish sustainability criteria. We suggest that the EU revises incoherent foreign and domestic policies and proactively engages with trading partners to include sustainability safeguards in the whole value chain with particular focus on trade relations with high relevance and leverage values.

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.LPS and poly I:C impair tryptophan metabolism in the human placenta explants.Graphical Abstract

Unclear cystic masses in the pelvis in male patients are a rare situation and could be of benign or malignant origin. The underlying diseases demand for specific diagnostic and therapeutic approaches. We present a case series of 3 male patients with different clinical symptoms (perineal pain, urinary retention and a large scrotal cyst) related to cystic lesions in the pelvic region. On all patients initial histopathological workup was unclear. All patients underwent surgery with complete resection of the tumor which revealed a broad spectrum of histopathological findings: unusual form of cystic adenocarcinoma of the prostate, malignant transformation of a dysontogenetic cyst, and finally a very rare diagnosis of a malignant tumor of the Cowper gland. This case series and literature review provide clues for a possible diagnostic and therapeutic approach in the case of unclear pelvic cystic masses and could support urologists during the therapy selection in the future.

This article provides tips and tricks for optimizing the speed of a virtual private network (VPN). It explains that using a VPN can sometimes slow down internet speed and offers various methods to avoid this. The tips include testing the speed of the internet connection, changing the location of the VPN server, restarting the device and router, connecting the device to the router via a LAN cable, choosing a different protocol, changing the port, disabling firewall and antivirus software, using split tunneling, and considering switching to a different VPN provider. The article emphasizes that VPN speeds can vary depending on factors such as server selection and time of day. [Extracted from the article]

The agility to swiftly and efficiently reconfigure manufacturing systems is crucial in today’s rapidly evolving market demands. Traditional recon-figuration operations often fall short, presenting non-intuitive and error-prone tasks for human operators, without the aid of systematic approaches or supportive technologies. This gap not only complicates the reconfiguration process but also significantly increases the risk of errors. In response, we introduce a novel approach that integrates Mixed Reality and Digital Twins within Cyber-Physical Systems to address these challenges. This enhances the human element in manufacturing reconfigurations by facilitating intuitive trajectory planning for robot (re)programming and comprehensive documentation of physical processes, including human operations. The design and implementation of the approach aim to significantly enhance manufacturing reconfigurations by reducing downtime, complexity, and human error. Further, the paper outlines directions for future work, including comprehensive system validation within a Cyber-Physical-Human manufacturing system, emphasizing the critical role of human operators in the reconfiguration process and the potential for technology to address traditional shortcomings.

Background: Since its initial description the prostate biopsy technique for detection of prostate cancer (PCA) has constantly evolved. Multiparametric magnetic resonance imaging (mpMRI) has been proven to have a sensitivity exceeding 90% to detect the index lesion. This narrative review discusses the evidence around several biopsy strategies, especially in the context of patients that might be eligible for focal therapy. Method: A non-systematic literature research was performed on February 15th 2024 using the Medical Literature Analysis and Retrieval System Online (Medline), Web of Science and Google Scholar. Results: The transrectal (TR) route is associated with an increased postoperative sepsis rate, even with adequate antibiotic prophylaxis. The transperineal (TP) route is now recommended by international guidelines, firstly for its decreased rate of urosepsis. Recent evidence shows a non-inferiority of TP compared to TR route, and even a higher detection rate of clinically significant PCA (csPCA) in the anterior and apical region, that are usually difficult to target using the TR route. Several targeting techniques (cognitive, software-fusion or in-bore) enhance our ability to provide an accurate risk assessment of prostate cancer aggressiveness and burden, while reducing the number of cores and reducing the number of clinically insignificant prostate cancer (ciPCA). While MRI-TB have proven their role, the role of systematic biopsies (SB) is still important because it detects 5–16% of csPCA that would have been missed by MRI-TB alone. The strategies of SB depend mainly on the route used (TR vs. TP) and the number of cores to be collected (10–12 cores vs. saturation biopsies vs. trans-perineal template mapping-biopsies or Ginsburg Protocol vs. regional biopsies). Conclusion: Several biopsy strategies have been described and should be known when assessing patients for focal therapy. Because MRI systematically under evaluates the lesion size, systematic biopsies, and especially perilesional biopsies, can help to increase sensitivity at the cost of an increased number of cores.

The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpinleads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members. Both SHARPIN-deficient and HOIP-deficient individuals showed a substantial reduction of secondary lymphoid germinal center B cell development. Treatment of one SHARPIN-deficient individual with anti-TNF therapies led to complete clinical and transcriptomic resolution of autoinflammation. These findings underscore the critical function of the LUBAC as a gatekeeper for cell death-mediated immune dysregulation in humans.

Für die Entwicklung einer geschlechtergerechten therapeutischen Grundhaltung ist die fortlaufende Reflexion von Frauen- und Männer-Szenenin einer von hegemonialer Männlichkeit geprägten Geschlechter- und Gesellschaftsordnung Voraussetzung. Diese Grundhaltung nimmt essentiellen Einfluss auf das psychotherapeutische Geschehen. Der Artikel versucht verschiedene Denkfiguren aufzugreifen, um eine Sensibilisierung für die komplexe Verflochtenheit der sozialen Konstruktion von geschlechtsspezifischen Verhaltensmustern nachzuzeichnen. Als weibliches Pendant zur hegemonialen Männlichkeit wird das Modell des anorektischen Subdominanzprinzips vorgestellt. Daran anknüpfend wird eine Kollektion des frauenspezifischen soziodramatischen Rolleninventars präsentiert und im Besonderen auf die affektpolitische Bedeutung der Scham für die Entwicklung der hegemonial geprägten weiblichen Rollenkonserven Bezug genommen. Schlussendlich werden Vorschläge zu einer Begegnung der Geschlechter auf Augenhöhe gemacht. A precondition for maintaining the continuous development of a gender equitable therapeutic approach is to reflect upon women’s and men’s scenesin a society that is characterized by a hegemonic male dominant gender order and social system. These influence psychotherapy practise in an essential manner. This article attempts to apprehend and elaborate on diverse figures of thought, in order to sensitize the reader for, as also outline, highly complex socially constructed gender behavioural patterns. The model of ’anorectic sub dominance’ is introduced as the female counterpart to hegemonic masculinity. Furthermore, a collection of specifically female roles from the sociodramatic role inventory is presented and the affect-political importance of ’shame’ for the development of hegemonically shaped female role conserves is highlighted. In conclusion proposals are made to enable equitable gender encounters.

Defects in atomically thin semiconductors and their moiré heterostructures have emerged as a unique testbed for quantum science. Strong light–matter coupling, large spin–orbit interaction and enhanced Coulomb correlations facilitate a spin–photon interface for future qubit operations and efficient single-photon quantum emitters. Yet, directly observing the relevant interplay of the electronic structure of a single defect with other microscopic elementary excitations on their intrinsic length, time and energy scales remained a long-held dream. Here we directly resolve in space, time and energy how a spin–orbit-split energy level of an isolated selenium vacancy in a moiré-distorted WSe2monolayer evolves under the controlled excitation of lattice vibrations, using lightwave scanning tunnelling microscopy and spectroscopy. By locally launching a phonon oscillation and taking ultrafast energy-resolved snapshots of the vacancy’s states faster than the vibration period, we directly measure the impact of electron–phonon coupling in an isolated single-atom defect. The combination of atomic spatial, sub-picosecond temporal and millielectronvolt energy resolution marks a disruptive development towards a comprehensive understanding of complex quantum materials, where the key microscopic elementary interactions can now be disentangled, one by one.

Isadora is a specification mining tool for creating information-flow properties for hardware. Isadora combines hardware information-flow tracking and specification mining to produce properties that are suitable for the hardware security validation and support a better understanding of the hardware’s security posture. Isadora is fully automated; the user provides only a hardware specification and a testbench—they do not need to supply a threat model or security requirements. Isadora is evaluated on a RISC-V processor, an SoC access control mechanism, and the OpenTitan hardware root of trust. Isadora generates security properties that align with Common Weakness Enumerations (CWEs) and with properties written manually by security experts.

Glaucoma is the leading cause of preventable sight loss in the United Kingdom and the provision of timely glaucoma care has been highlighted as a significant challenge in recent years. Following a recent high-profile investigation, The Healthcare Safety Investigation Branch recommended the validation of risk stratification models to safeguard the vision-related quality of life of glaucoma patients. There continues to be no nationally agreed evidence-based risk stratification model for glaucoma care across the United Kingdom. Some models have used simple measures of disease staging such as visual field mean deviation as surrogates for risk, but more refined, individualised risk stratification models should include factors related to both visual impairment and visual disability. Candidate tools should also incorporate both ocular and systemic co-morbidities, rate of disease progression, visual needs and driving status and undergo clinical refinement and validation to justify implementation. The disruption to routine glaucoma care caused by the COVID-19 pandemic has only highlighted the importance of such risk stratification models and has accelerated their development, application and evaluation. This review aims to critically appraise the available evidence underpinning current approaches for glaucoma risk stratification and to discuss how these may be applied to contemporary glaucoma care within the United Kingdom. Further research will be essential to justify and validate the utility of glaucoma risk stratification models in everyday clinical practice.

IMPORTANCE: Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. OBJECTIVE: To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)–derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. EXPOSURE: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. MAIN OUTCOMES AND MEASURES: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell–inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. RESULTS: This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (−0.34 μm [95% CI, −0.54 to −0.15 μm]; P = .001) and mRNFL (−0.16 μm [95% CI, −0.30 to −0.02 μm]; P = .03) thicknesses but not IOP (−0.01 mm Hg [95% CI, −0.09 to 0.07 mm Hg]; P = .84). CONCLUSIONS AND RELEVANCE: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

Establishing and maintaining protected areas (PAs) is a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting PAs based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences as well as real-time comparison of the outcome. Applying the tool across 1,346 terrestrial PAs, we demonstrate that decision makers frequently face trade-offs among conflicting objectives, e.g., between species protection and ecosystem integrity. Nevertheless, we show that transparent decision support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.

5-Methyl-2-pyridinesulfonamide is a regulatory starting material of endothelin receptor antagonist clazosentan. The original route to the key sulfonamide relied on the textbook conversion of the corresponding thiophenol to the intermediate sulfonyl chloride followed by its quenching with aqueous ammonia. However, this route suffered from a wide range of issues such as a low overall yield (29%), challenging aqueous workups and isolations, and the formation of a genotoxic benzyl chloride impurity. Therefore, we developed a conceptually novel production route for 5-methyl-2-pyridinesulfonamide. The new process relied on selectively oxidizing the thiophenol to the intermediate sulfinate salt followed by an electrophilic amination of the nucleophilic sulfinate sulfur-atom with hydroxylamine-O-sulfonic acid (HOSA). This oxidation/electrophilic amination sequence worked as a “one-pot” procedure by simply adding HOSA to the reaction mixture after complete oxidation of the thiophenol with 70% aq. t-BuOOH. The process was extensively optimized with regard to the oxidation step, increasing the stability of HOSA in the reaction mixture, and the final isolation of 5-methyl-2-pyridinesulfonamide. The new process was performed on a 22 kg scale, delivering the desired product as a white solid in 69% overall yield and excellent purity (>99.9% a/a).

If you are experiencing a full Google Drive storage even after deleting files, there is a simple explanation. Deleted files are actually moved to the Trash, where they continue to take up storage space. This is a security measure to prevent accidental deletion of important files. Normally, Google Drive keeps deleted files in the Trash for 30 days before permanently deleting them. However, if you need to free up storage space immediately, you can manually empty the Trash by clicking on the "Empty trash" button in Google Drive and confirming your choice. This will permanently remove all content in the Trash and immediately free up storage space in your Google Drive account. [Extracted from the article]

The article titled "The Amazon triangle scam: What it is, how it works, and what to do" discusses the concept of triangulation fraud, which is a type of scam that occurs on e-commerce marketplaces like Amazon. The scam involves three parties: the buyer, the scammer, and a legitimate seller. The scammer creates a fraudulent listing for a popular product at a significantly lower price, enticing the buyer to make a quick purchase. The scammer then uses stolen payment information to order a genuine copy of the product from a legitimate seller, while the buyer remains unaware. The legitimate seller may face chargebacks and financial losses, and the buyer may receive debt collection letters or fraud charges. To protect against triangulation fraud, buyers are advised to be vigilant, compare prices, check the sender's address, use secure payment methods, and report any fraud to the police, the legitimate seller, Amazon, and the payment service provider. [Extracted from the article]

Background.Despite local training opportunities for Cognitive Stimulation Therapy (CST) for occupational therapists, there has been limited evaluation of the feasibility of implementation in Canada. Purpose.This study explored the feasibility of CST delivery by an occupational therapist in an Ontario health care setting and the impact it may have on self-efficacy and hope measures of individuals with dementia. Methods.A mixed-methods experimental pre/post design was used. Survey measures included hope, self-efficacy, feasibility, satisfaction, and individual session evaluation. Semistructured focus groups were held for participants and facilitators. Findings.Quantitative findings are summarized descriptively for the 10 participants. Qualitative findings were grouped into themes: social connectedness, knowledge gained and shared, tailored implementation adjustments, and need for long-term programing. Implications.Occupational therapists are well-positioned to implement CST and should be a part of further research to test the intervention rigorously for applicability within a range of Canadian health care settings.

Transition-metal chromophores with earth-abundant transition metals are an important design target for their applications in lighting and nontoxic bioimaging, but their design is challenged by the scarcity of complexes that simultaneously have well-defined ground states and optimal target absorption energies in the visible region. Machine learning (ML) accelerated discovery could overcome such challenges by enabling the screening of a larger space but is limited by the fidelity of the data used in ML model training, which is typically from a single approximate density functional. To address this limitation, we search for consensus in predictions among 23 density functional approximations across multiple rungs of “Jacob’s ladder”. To accelerate the discovery of complexes with absorption energies in the visible region while minimizing the effect of low-lying excited states, we use two-dimensional (2D)efficient global optimization to sample candidate low-spin chromophores from multimillion complex spaces. Despite the scarcity (i.e., ∼0.01%) of potential chromophores in this large chemical space, we identify candidates with high likelihood (i.e., >10%) of computational validation as the ML models improve during active learning, representing a 1000-fold acceleration in discovery. Absorption spectra of promising chromophores from time-dependent density functional theory verify that 2/3 of candidates have the desired excited-state properties. The observation that constituent ligands from our leads have demonstrated interesting optical properties in the literature exemplifies the effectiveness of our construction of a realistic design space and active learning approach.

System-on-chip (SoC) architectures are a heterogeneous mix of microprocessors, custom accelerators, memories, interfaces, peripherals, and other resources. These resources communicate using complex on-chip interconnect networks that attempt to quickly and efficiently arbitrate memory transactions whose behaviors can vary drastically depending on the current mode of operation and system operating state. Security- and safety-critical applications require access control policies that define how these resources interact to ensure that malicious and unsafe behaviors do not occur. Aker is a design and verification framework for on-chip access control. The core of Aker is the access control wrapper (ACW)–a high-performance yet efficient hardware module that dynamically arbitrates on-chip communications. Aker distributes ACWs across the SoC and programs them to perform local access control. Aker provides a firmware generation tool and a property-driven security verification methodology to ensure that the ACWs are properly integrated and configured. Aker security verification confirms that the ACW behaves properly at IP level. It verifies the hardware root of trust firmware configures the ACW correctly. And it evaluates system-level security threats due to interactions between shared resources. Aker is experimentally validated on a Xilinx UltraScale+ programmable SoC. Additionally, an Aker access control system is integrated into the OpenPULP multicore archtiecture that uses OpenTitan hardware root-of-trust for firmware configuration.

•Patients with negative MRI can be safely followed-up without a prostate biopsy.•PSA Density levels should guide prostate cancer screening in the community.•Age, PSA Density and Likert score are associated with the risk of significant cancer.•The RosCaP score may support decision to biopsy in low to equivocal risk cases.

The continued loss of unfragmented intact forest landscapes (IFLs) despite numerous global conservation initiatives indicates the need for improved knowledge of proximate and underlying drivers. Yet the role of non-agricultural activities in forest degradation and fragmentation has not received adequate attention. We focus on IFL loss caused by various economic activities and investigate the influence of global consumption and trade via the multi-regional input-output model. For IFL loss associated with the 2014 world economy, over 60% was related to final consumption of non-agricultural products. More than one-third of IFL loss was linked to export, primarily from Russia, Canada, and tropical regions to mainland China, the EU, and the United States. Of IFL loss associated with export, 51% and 26% was directly caused by logging and mining or energy extraction, respectively. The dispersed nature of IFL loss drivers and their indirect links to individual final consumers call for stronger government engagement and supply chain interventions.

We describe the security verification of OpenTitan. We illustrate how information flow tracking turns human knowledge of assets and security requirements into formal security properties verified using Cycuity’s Radix. The verification uncovered weaknesses and helped produce hardware fixes to eliminate vulnerabilities.

Introduction Music is commonly played in operating rooms. Because microsurgery demands utmost concentration and precise motor control, we conducted the present study to investigate a potentially beneficial impact of music on performing a microsurgical anastomosis.

Tuning a material to the cusp between two distinct ground states can produce physical properties that are unlike those in either of the neighbouring phases. Advances in the fabrication and control of quantum systems have raised the tantalizing prospect of artificial quantum simulators that can capture such behaviour. A tunable array of coupled qubits should have an appropriately rich phase diagram, but realizing such a system with either tunnel-coupled semiconductor quantum dots or metal nanostructures has proven difficult. The challenge for scaling up to clusters or lattices is to ensure that each element behaves essentially identically and that the coupling between elements is uniform, while also maintaining tunability of the interactions. Here we study a nanoelectronic circuit comprising two coupled hybrid metal–semiconductor islands, combining the strengths of both materials to form a potentially scalable platform. The semiconductor component allows for controllable inter-site couplings at quantum point contacts, while the metal component’s effective continuum of states means that different sites can be made equivalent by tuning local potentials. The couplings afforded by this architecture can realize an unusual quantum critical point resulting from frustrated Kondo interactions. The observed critical behaviour matches theoretical predictions, verifying the success of our experimental quantum simulation.

Incoming policies will cause the European Union to harvest more wood, shift one-fifth of cropland to bioenergy and outsource deforestation, analysis shows.

Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.

The COVID-19 pandemic has amplified systemic gaps in patient safety, including social frailty for vulnerable populations such as older adults (Briguglio et al., 2020). Public health measures, such as prolonged and frequent lockdowns, restricted access to visitors and support networks and in extreme cases led to confinement within a single room, The negative impact of these restrictions has focused new attention on social frailty, which has hitherto been a somewhat neglected patient safety issue. Since social frailty is a multifaceted construct, it needs to be considered in a variety of settings and from a range of disciplinary perspectives. This practitioner-led panel consisting of an internist, a human factors engineer, an occupational therapist, and an implementation scientist, examines the impact of the pandemic on social interaction, and social frailty amongst older people in three different settings (hospital, long term care home, community). Through a set of case studies, the panelists provided applied experiences and perspectives on the impact of the pandemic on patient safety and on social frailty in particular. The panel covered theory, and real-world application of human factors principles. The question of how to design safety into the healthcare system were also explored. In this paper we review the problem of social frailty, list some brief case studies and discuss possible intervention strategies.

Ubiquitylation is an essential post-translational modification that regulates intracellular signalling networks by triggering proteasomal substrate degradation, changing the activity of substrates or mediating changes in proteins that interact with substrates. Hundreds of enzymes participate in reversible ubiquitylation of proteins, some acting globally and others targeting specific proteins. Ubiquitylation is essential for innate immune responses, as it facilitates rapid regulation of inflammatory pathways, thereby ensuring sufficient but not excessive responses. A growing number of inborn errors of immunity are attributed to dysregulated ubiquitylation. These genetic disorders exhibit broad clinical manifestations, ranging from susceptibility to infection to autoinflammatory and/or autoimmune features, lymphoproliferation and propensity to malignancy. Many autoinflammatory disorders result from disruption of components of the ubiquitylation machinery and lead to overactivation of innate immune cells. An understanding of the disorders of ubiquitylation in autoinflammatory diseases could enable the development of novel management strategies.

The Mo/W-containing metalloenzyme formate dehydrogenase (FDH) is an efficient and selective natural catalyst that reversibly converts CO2to formate under ambient conditions. In this study, we investigate the impact of the greater protein environment on the electrostatic potential (ESP) of the active site. To model the enzyme environment, we used a combination of classical molecular dynamics and multiscale quantum-mechanical (QM)/molecular-mechanical (MM) simulations. We leverage charge shift analysis to systematically construct QM regions and analyze the electronic environment of the active site by evaluating the degree of charge transfer between the core active site and the protein environment. The contribution of the terminal chalcogen ligand to the ESP of the metal center is substantial and dependent on the chalcogen identity, with similar, less negative ESPs for Se and S terminal chalcogens in comparison to O regardless of whether the metal is Mo or W. The orientation of the side chains and conformations of the cofactor also affect the ESP, highlighting the importance of sampling dynamic fluctuations in the protein. Overall, our observations suggest that the terminal chalcogen ligand identity plays an important role in the enzymatic activity of FDH, suggesting opportunities for a rational bioinspired catalyst design.

Die wichtigste Aufgabe des Funktionskreis Milz-Pankreas ist die Bildung von Qi und Blut. Die Hauptrezepturen dafür sind Si Jun Zi Tang und Gut Pi Tang.

The deregulation of the power generation industry has resulted in increased competitive pressure and is forcing operators to improve plant operating economy while maintaining high levels of plant safety. A key factor to meeting this challenge is to apply a comprehensive plant life management (PLIM) approach which addresses all relevant ageing and degradation mechanisms regarding the safety concept, plant component structures and documentation, plant personnel, consumables, operations management system and administrative controls. For this reason, Framatome ANP GmbH has developed an integrated PLIM concept applicable for both new and operating plants and focusing on the safety concept, plant component structures and documentation.

AimsTo recommend a list of complications of glaucoma surgery to be used in future glaucoma surgery research and reporting by exploring the spectrum of complications’ names, the variety of definitions and time frames used for reporting them in glaucoma surgical trials.MethodsComplications’ names, definitions and time frames identified from a previously conducted systematic review of glaucoma surgery trials (registration number: CRD42019121226) were reviewed. Only postoperative complications were considered. Surgical techniques described in the papers from the previous systematic review were retrieved and grouped according their mechanism of action.Reviewers independently recommended each complication’s inclusion or exclusion in a list to be proposed as a potential standard for reporting in glaucoma interventions. A literature-based definition of a ‘surgical complication’ was used to inform these decisions. Recorded complication’s details were used to inform the development of clinically relevant definitions, a consensus-driven exercise between reviewers resolved disagreements.ResultsWe identified 48/111 (43.2%) of the reported complications as suitable for inclusion, of which 17 were merged into other included complications having a broader meaning making up a final table of 32 postoperative complications. For 25 of them, the authors kept ‘names’ that were previously used in the systematic review, but provided a definition that was not mentioned in these papers. Five included complications were given both ‘names’ and definitions not previously mentioned. The authors maintained the name and definition for one complication. There were 16 complications that were in common to all the procedures retrieved from the previous review.ConclusionsWe propose a table of revised names and comprehensive definitions of postoperative complications, to simplify the process of reporting complications after glaucoma surgery and to improve consistency among surgical trials.

BackgroundDiagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited.ObjectiveThe aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis.MethodsWe applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool.FindingsAreas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1–V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training.InterpretationUsing a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.