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Toward automated preprocessing of untargeted LC-MS-based metabolomics feature lists from human biofluids
Maximizing the extraction of true, high-quality, nonredundant features from biofluids analyzed via LC-MS systems is challenging. Here, the R packages IPO and AutoTuner were used to optimize XCMS parameter settings for the retrieval of metabolite or lipid features in both ionization modes from either faecal or urine samples from two cohorts ( n = 621). The feature lists obtained were compared with those where the parameter values were selected manually. Three categories were used to compare feature lists: 1) feature quality through removing false positives, 2) tentative metabolite identification using the Human Metabolome Database (HMDB) and 3) feature utility such as analyzing the proportion of features within intensity threshold bins. Furthermore, a PCA-based approach to feature filtering using QC samples and variable loadings was also explored under this category. Overall, more features were observed after automated selection of parameter values for all data sets (1.3- to 3.7-fold), which propagated through comparative exercises. For example, a greater number of features (on average 51 vs 45%) had a coefficient of variation (CV) < 30%. Additionally, there was a significant increase (7.6-10.4%) in the number of faecal metabolites that could be tentatively annotated, and more features were present in higher intensity threshold bins. Considering the overlap across all three categories, a greater number of features were also retained. Automated approaches that guide selection of optimal parameter values for preprocessing are important to decrease the time invested for this step, while taking advantage of the wealth of data that LC-MS systems provide. </p
In the era of responsible artificial intelligence and digitalization: business group digitalization, operations and subsidiary performance
With the rapid development of digital technologies, responsible AI has become a critical focus for ensuring ethical and socially conscious advancements in business and operations management. The integration of responsible AI practices in business groups’ digital transformations is essential to mitigate potential risks and maximize the positive impact on operational efficiency, supply chain performance, and subsidiary performance. This study aims to examine the consequences and mechanisms through which responsible group digitalization influences business group’s operation management, as manifested in subsidiary performance within the context of the digital economy. Analyzing data from 202 affiliated subsidiaries, we examine the role of HRM collaboration and technological turbulence in facilitating group digitalization. This study enriches the operations management literature and expands the application of ethical and responsible AI practices in digitalization by investigating the relationship between business group digitalization and business operations. Furthermore, this study provides practical implications pertaining to how ethical and responsible practices can guide group digital transformations, business operations and enhance the performance of subsidiaries.<br/
A toolchain for the in-house education of cloud computing in a vendor agnostic and efficient manner
Adoption of cloud computing has led to increased demand by industry for cloud-ready graduates and pressure on universities to include cloud in their curriculum. While industry courses exist, these are almost all vendor specific and often require payment for access to resources and an exam fee, requiring expenditure every iteration. The focus of industry courses, especially certification, is narrow compared to a general cloud computing course, with little background or deep learning. Here we present how to implement a vendor agnostic in-house cloud environment which allows teaching of theory and practice for modest capital investment which can be used in future. The approach creates a scalable private cloud in which workloads can be deployed and concepts explored with no licencing costs. Used successfully for over five years and refined through feedback this can act as robust toolchain blueprint for others to use and tailor to their needs
Adversarial attention deficit: fooling deformable vision transformers with collaborative adversarial patches
Deformable vision transformers reduce the expensive quadratic time-complexity of attention modeling by using sparse attention structures, making it possible to use transformers in large-scale vision applications, such as multiview vision systems. We show that existing adversarial attacks against conventional vision transformers do not transfer to deformable transformers, primarily due to the data-dependent, dynamic nature of sparse attention. In this work, we present for the first time, adversarial attacks against deformable vision transformers by getting control of their attention-inferring module. We develop a novel collaborative attack where a source patch manipulates attention to point to a target patch containing the adversarial noise, which fools the model. We observe that our attack alters less than 1% of the patched area in the input field, completely disrupting object detection and resulting in 0% AP in single-view object detection using MS COCO, and 0% MODA in multi-view object detection using Wildtrack.<br/
Exploring the duality of perceptions: insights into uncertainties, aversion and appreciation towards algorithmic HRM
The human resource management (HRM) function has witnessed the rapid integration of algorithms into incumbent processes; however, significant employee resistance and aversion to algorithmic decision‐making have also been reported. Research on algorithmic HRM practices indicates an underlying duality of perceptual responses by HRM professionals towards this technology. We seek to understand how HRM professionals experience algorithmic HRM use and determine if there are bright sides to its organizational integration. We undertake a qualitative, open‐ended study based on written responses to open‐ended questions from 58 respondents in the United Kingdom and the United States of America. The data were thematically analyzed using grounded theory, which revealed four themes representing HRM professionals' overarching perspectives on why algorithmic HRM precipitates aversion or appreciation. The first two themes highlight HRM professionals' perceived subjective uncertainty regarding algorithmic HRM and its perceived negative effects on the organization. The third theme acknowledges the positive effect of algorithmic HRM, and the final theme discusses three critical coping strategies (embrace, avoid, and collaborate) that HRM professionals adopt to counteract their experienced fears. Our findings suggest that HRM professionals adopt a cautiously fearful rather than a wholly adverse outlook towards algorithmic HRM, wherein aversion and appreciation appear to emerge simultaneously. We contend this existence of a duality of perceptual responses to algorithmic HRM may be a precursor to setting a harmonious collaboration between humans and algorithms in the HRM domain, contingent on appropriate levels of oversight and governance. Implications for theory and managerial practice are also discussed
From automated Raman to cost-effective nanoparticle-on-film (NPoF) SERS spectroscopy: a combined approach for assessing micro- and nanoplastics released into the oral cavity from chewing gum
Microplastics (MPs) and Nanoplastics (NPs), a burgeoning health hazard, often go unnoticed due to suboptimal analytical tools, making their way inside our bodies through various means. Surface Enhanced Raman Spectroscopy (SERS), although is utilized in detecting NPs, challenges arise at low concentrations due to their low Raman cross section and inability to situate within hotspots owing to their ubiquitous size and shape. This study presents an innovative and cost-effective approach employing household metallic foils (aluminium and copper) as nanoparticle-on-film (NPoF) substrates for targeting such analytes. Leveraging from the near field enhancements due to plasmonic coupling amidst third-generation hotspots (TGHs) and second-generation hotspots (SGHs), the enhanced SERS activity is achieved. Furthermore, following an extensive comparison of the substrates' flexibility, sensitivity, reproducibility, and robustness, the copper foil-based NPoF platform was used to detect 100 nm polystyrene plastics down to 1 μg/ml concentration. Subsequently, a systematic detection of more than 250,000 MPs with automated Raman spectroscopy was performed, followed by the detection of NPs using SERS with a NPoF substrate in saliva samples released from the gum base in the oral cavity during a one-hour chewing activity. Overall, we report a cost-effective and versatile NPoF substrate, having the potential to screen a diverse array of environmental pollutants envisioned as a potential point-of-site tool by coupling it with a handheld Raman instrument.<br/
Developing a curriculum for deep thinking: the knowledge revival
This open access book discusses why the seemingly straightforward strategy of teaching children how to think deeply does not work and offers an alternative way forward for the curriculum to achieve these objectives. Over the years, the role of knowledge in the curriculum has, like a pendulum, shifted between two extremes, from highly visible to virtually invisible knowledge elements. Insights from cognitive and educational psychology, sociology, and curriculum studies are used to underpin the current knowledge revival that is widely being observed in education. A knowledge-rich curriculum is proposed by the authors as not only the soundest way forward to both effectively acquire knowledge and complex cognitive skills in school, but also as a crucial lever to achieve equitable opportunities for all students. In understanding how a knowledge-rich curriculum can enhance learning, three overarching principles are discussed: (1) content-richness, (2) coherence, and (3) clarity. These principles are illustrated through practical examples from schools and educators who have effectively integrated knowledge-rich curricula.<br/
Alterations in gut‐derived uremic toxins before the onset of azotemic chronic kidney disease in cats
Background: Although gut‐derived uremic toxins are increased in azotemic chronic kidney disease (CKD) in cats and implicated in disease progression, it remains unclear if augmented formation or retention of these toxins is associated with the development of renal azotemia. Objectives: Assess the association between gut‐derived toxins (ie, indoxyl‐sulfate, p‐cresyl‐sulfate, and trimethylamine‐N‐oxide [TMAO]) and the onset of azotemic CKD in cats. Animals: Forty‐eight client‐owned cats. Methods: Nested case‐control study, comparing serum and urine gut‐derived uremic toxin abundance at 6‐month intervals between initially healthy cats that developed azotemic CKD (n = 22) and a control group (n = 26) that remained healthy, using a targeted metabolomic approach. Results: Cats in the CKD group had significantly higher serum indoxyl‐sulfate (mean [SD], 1.44 [1.06] vs 0.83 [0.46]; P = .02) and TMAO (mean [SD], 1.82 [1.80] vs 1.60 [0.62]; P = .01) abundance 6 months before the detection of azotemic CKD. Furthermore, logistic regression analysis indicated that indoxyl‐sulfate (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.2‐9.0; P = .04) and TMAO (OR: 3.9; 95% CI: 1.4‐11; P = .03) were predictors for the onset of azotemia 6 months before diagnosis. However, renal function biomarkers creatinine, symmetric dimethylarginine, and urinary specific gravity were significantly correlated with indoxyl‐sulfate and TMAO abundance, causing a loss in predictive significance after correction for these factors. Conclusions: Impaired gut‐derived uremic toxin handling is apparent at least 6 months before the diagnosis of azotemia, likely reflecting an already ongoing decrease in GFR, tubular function, or both. A direct causal relationship between gut‐derived uremic toxicity and the initiation of CKD in cats is still lacking
Design and characterization of hollow microneedles for localized intrascleral drug delivery of ocular formulations
Effective drug delivery to the posterior segment of the eye remains a challenge owing to the limitations of conventional methods such as intravitreal injections, which are associated with significant side effects. This study explored the use of hollow microneedles (HMNs) for localized intrascleral drug delivery as a minimally invasive alternative. Stainless steel HMNs with bevel angles of 30°, 45°, 60°, and 75° were fabricated using wire electron discharge machining. The penetration force of these HMNs in ex vivo porcine sclera was assessed using a texture analyser, revealing that the 60° bevel angle required the lowest force (<2N), making it optimal for scleral penetration. To ensure precision in drug delivery, 3D-printed adapters were developed to control the injection angles and volumes. The distribution of a model dye, rhodamine B, was studied via digital imaging, multiphoton microscopy, and confocal microscopy. The results showed that HMNs with a 60° bevel angle could penetrate the sclera to a depth of approximately 450 µm at a 45° injection angle, providing enhanced distribution within the scleral layers. This study confirmed that the use of HMNs enables effective and controlled intrascleral drug delivery, resulting in the formation of localized depots with minimal tissue damage. This research demonstrates the potential of HMNs as a promising alternative to traditional ocular drug delivery methods, offering improved bioavailability and the potential to reduce patient discomfort.<br/
Changing patterns of general practice services during a period of public sector investment in Britain
IntroductionGiven the importance of GP care to the public’s health, it is important that we understand how patterns of service use change as levels of investment change. This study investigated GP use in Britain in conjunction with use of outpatient services during a period of investment and during a period of austerity.MethodThe study used data from the British Household Panel Survey (BHPS) that included service use, morbidity (as an indicator of need) and socio-demographic characteristics (e.g., employment, age, education, and sex). Data for 2000, 2004, and 2008, were specifically chosen for comparison with data from 2015, 2016 and 2017. Service use and respondent characteristics were described using measures of central tendency and dispersion. Multivariable analyses were undertaken using recursive bivariate probit (RBVP) and probit analyses separately for each study year. All analyses were adjusted for cross-sectional weighting.ResultsBHPS respondents who used outpatient services or GP services had higher morbidity compared to survey participants who did not. Older people, people with lower educational attainment and employed people had higher mean morbidity indices in each study year as did females. Morbidity among service users tended to decline slightly over time. RBVP analyses revealed a significant positive correlation in residuals between outpatient and GP functions in 2000 and 2004 but not 2008. GP consultations and outpatient use remained largely unrelated to socio-economic factors in each year. Survey participants who reported hearing or vision impairment conditions were consistently less likely to use GP or outpatient services in 2000 and 2004, in 2008.ConclusionThe results are broadly indicative of stable relationships in service use during a period of healthcare investment but change during austerity. Those who reported, vision, hearing, and skin conditions were consistently less likely to report use of GP or outpatient services, controlling for other aspects of health.<br/