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As natural habitats decline and wildlife adapts to increasing anthropogenic disturbance, it is crucial to understand humanwildlife relationships in residential areas. However, relevant studies are limited and mostly focused on single cities. To address this knowledge gap, we investigated people's preferences for seeing wild mammals in residential areas by conducting and analyzing an online survey distributed across Germany (n = 2997 participants). Our results revealed that preferred species (squirrels, hedgehogs, hares, roe deer) were frequently encountered, whereas unpreferred species were those encountered frequently (rats, martens), as well as those encountered rarely (wild boar, coypus, raccoons). We also found a moderately positive correlation between the number of encounters with mammals and them being preferred by humans. Finally, some socio-demographic variables, particularly gender, garden access, and urbanity, are significantly related to human preferences. Based on our results, we propose tailoring wildlife management in residential areas to promote the positive attributes of preferred wildlife as biodiversity ambassadors, while also addressing ways to mitigate encounters and negative perceptions associated with unpreferred species. [ABSTRACT FROM AUTHOR]

Purpose: Nutrition support in inoperable bowel obstruction (IBO) remains challenging. Parenteral nutrition (PN) is recommended if the prognosis is > 2 months. An elemental diet (ED) is licensed for strictures in Crohn’s disease but has not been used in malignant bowel obstruction. The aim of this study was to evaluate the use of ED in patients with IBO and provide a proof of concept of ED as an acceptable feeding option. Methods: This was a mixed-methods single-arm feasibility study. The primary endpoint was to provide a ‘proof of concept’ of ED as an acceptable feeding option for patients with IBO. Secondary endpoints included taste acceptability, incidences of vomiting and pain, the proportion of women who tolerated ED, the number of cartons drunk, quality of life (QOL) and the number of women treated with chemotherapy. Patients (> 18 years) with CT-confirmed IBO who could tolerate 500 ml of liquid in 24 h remained on the trial for 2 weeks. Results: A total of 29 patients were recruited; of those, 19 contributed to the analysis for the primary endpoint; 13 (68.4%) participants tolerated the ED; 26 patients contributed to MSAS and EORTC QLQ questionnaires at baseline to allow for the assessment of symptoms. At the start of the study, 18 (69%) of patients experienced vomiting, reducing to 4 (25%) by the end of day 15 of the study; 24 (92%) of patients reported pain at consent, reducing to 12 (75%) by the end of day 15. QOL scores improved from 36.2 (95% CI 27.7–44.7) at baseline to 53.1 (95% CI 40.3–66) at the end of day 15; 16 (84%) participants commenced chemotherapy within the first week of starting ED. The number of cartons across all participants showed a median of 1.3 cartons per day (range 0.8 to 2.5). Conclusion: ED is well tolerated by patients with IBO caused by gynaecological malignancies and may have a positive effect on symptom burden and QOL. [ABSTRACT FROM AUTHOR]

Peptide cyclization has dramatic effects on a variety of important properties, enhancing metabolic stability, limiting conformational flexibility, and altering cellular entry and intracellular localization. The hydrophilic, polyfunctional nature of peptides creates chemoselectivity challenges in macrocyclization, especially for natural sequences without biorthogonal handles. Herein, we describe a gaseous sulfonyl chloride derived reagent that achieves amine–amine, amine–phenol, and amine–aniline crosslinking through a minimalist linchpin strategy that affords macrocyclic urea or carbamate products. The cyclization reaction is metal‐mediated and involves a novel application of sulfine species that remains unexplored in aqueous or biological contexts. The aqueous method delivers unique cyclic or bicyclic topologies directly from a variety of natural bioactive peptides without the need for protecting‐group strategies. [ABSTRACT FROM AUTHOR]

Peptide cyclization has dramatic effects on a variety of important properties, enhancing metabolic stability, limiting conformational flexibility, and altering cellular entry and intracellular localization. The hydrophilic, polyfunctional nature of peptides creates chemoselectivity challenges in macrocyclization, especially for natural sequences without biorthogonal handles. Herein, we describe a gaseous sulfonyl chloride derived reagent that achieves amine–amine, amine–phenol, and amine–aniline crosslinking through a minimalist linchpin strategy that affords macrocyclic urea or carbamate products. The cyclization reaction is metal‐mediated and involves a novel application of sulfine species that remains unexplored in aqueous or biological contexts. The aqueous method delivers unique cyclic or bicyclic topologies directly from a variety of natural bioactive peptides without the need for protecting‐group strategies. [ABSTRACT FROM AUTHOR]

This paper posits that when an asset exhibits a bubble, its price process can be unbounded from above in finite time with positive probability if a quadratic variation (QV) risk premium is large enough. Based on the local martingale theory of bubbles, we provide sufficient conditions under which price explosion occurs via the QV channel provided that bubbles are present. This QV channel of price explosions is new to the literature and distinct from the explosive autoregressive (AR) dynamics, which is often identified with the presence of bubbles as defined in the time series literature. Using the S&P 500 index and a sample of individual stocks over 1996–2021, we document the existence of price explosions during periods when bubbles occur. Almost all price explosion episodes discovered are associated with the QV and not AR drift channel. [ABSTRACT FROM AUTHOR]

• HRV indices predict multidimensional driving-related fatigue. • Lower RMSSD associated with greater fatigue in young drivers. • Higher LF/HF ratio linked to higher fatigue levels. • Findings support HRV metrics as fatigue biomarkers. • Applied research needed to validate real-world use. Driver fatigue significantly impairs performance and is a major risk factor for road crashes. However, fatigue is difficult to objectively measure and quantify. This study aimed to elucidate associations between heart rate variability (HRV) metrics and multidimensional fatigue construct encompassing objective and subjective measures in young drivers with self-reported short sleep. Eighty-four young adults underwent assessments during simulated driving. HRV indices RMSSD and LF/HF ratio were derived from an electrocardiogram, while relative Theta power, oculography drowsiness, lane position variability, and Karolinska Sleepiness Score measured fatigue. RMSSD negatively correlated with Theta power, and LF/HF ratio positively correlated with position variability. Exploratory factor analysis extracted three factors, with RMSSD and LF/HF loading onto one. Structural equation modelling tested the prediction of a latent fatigue construct from HRV. Two models demonstrated an acceptable fit. RMSSD negatively predicted fatigue, explaining 6.4 % of the variance, while the LF/HF ratio positively predicted fatigue, accounting for 3.7 % of the variance. In summary, HRV, particularly RMSSD, showed significant relationships with multidimensional fatigue. Lower RMSSD and higher LF/HF ratio are associated with greater fatigue levels. This study demonstrates that HRV indices exhibit significant relationships within a multidimensional model of fatigue incorporating objective performance, ocular, and subjective measures. The findings provide initial evidence towards using HRV for monitoring complex manifestations of fatigue, rather than single dimensions. Further applied research should investigate translating these findings to naturalistic settings and validating HRV thresholds predictive of on-road impairment. [ABSTRACT FROM AUTHOR]

Background and aim: Tools that assist interventionists in selecting patients for post-dilation (PD) are needed. We aimed to assess whether pre-interventional aortic valve calcium (AVC) or the peri-interventional aortic regurgitation (ARI) ratio is a better predictor for a more than mild paravalvular leak (PVL) requiring PD after TAVI. Methods: Patients undergoing TAVI with available data on AVC derived from MSCTs and the ARI ratio derived from peri-interventional hemodynamic curves were studied. The main outcome was moderate-to-severe PVL requiring PD. Results: In 237 patients, more than mild PVL after valve deployment was present in 25.7%. PD was performed in 65 patients. The median (IQR) total AVC was 390.5 (211.5–665.4) mm3. All calcification values were significantly higher in patients who underwent PD. The median (IQR) individual threshold was 600 (550–685) Hus. The overall ARI ratio was 0.78 (0.61–0.96), with values being significantly lower in patients who underwent PD: 0.61 (0.49–0.80) vs. 0.82 (0.69–0.99) (p < 0.001). Both the ARI ratio (OR [95%CI] 0.053 [0.014–0.203]; p < 0.001) and AVC (1.01 [1.000–1.002]; p = 0.015) predicted PD need. ROC curves showed higher discrimination for the ARI ratio (AUC 0.73) than for any calcification parameter (all AUCs ≤ 0.62). Conclusions: The ARI ratio provides interventionists with a powerful predictive tool for PVL requiring PD after TAVI that is beyond the predictive value of pre-procedural valve calcification derived from MSCT. [ABSTRACT FROM AUTHOR]

Explosive cyclones (ECs), defined as extratropical cyclones that experience normalized pressure drops of at least 24 hPa in 24 h, are impactful weather events in the North Atlantic sector, but year-to-year changes in the frequency and impacts of these storms are sizeable. To analyze the sources of this interannual variability, we track cases of ECs and dissect them into two spatial groups: those that formed near the east coast of North America (coastal) and those in the north central Atlantic (high latitude). The frequency of high-latitude ECs is strongly correlated with the North Atlantic Oscillation, a well-known feature, whereas coastal EC frequency is statistically linked with an atmospheric wave train emanating from the North Pacific in the last 30 years. This wave train pattern of alternating high and low pressure is associated with heightened upper-level divergence and Eady growth rates along the east coast of North America, likely resulting in a stronger correspondence between the atmospheric wave train and coastal EC frequency. Using coupled model experiments, we show that the tropical and North Pacific oceans are an important factor for this atmospheric wave train and the subsequent enhancement of seasonal baroclinicity in the North Atlantic. [ABSTRACT FROM AUTHOR]

Objectives: The aims of Working Group 1 were to address the role (i) of the buccolingual bone dimensions after implant placement in healed alveolar ridge sites on the occurrence of biologic and aesthetic complications, and (ii) of soft tissue augmentation (STA) on the stability of clinical, radiographic, and patient‐related outcomes of implant treatments. Materials and Methods: Two systematic reviews were prepared in advance of the Consensus Conference and were discussed among the participants of Group 1. Consensus statements, clinical recommendations, recommendations for future research, and reflections on patient perspectives were based on structured group discussions until consensus was reached among the entire group of experts. The statements were then presented and accepted following further discussion and modifications as required by the plenary. Results: Dimensional changes of the alveolar ridge occurred after implant placement in healed sites, and a reduction in buccal bone wall thickness (BBW) of 0.3 to 1.8 mm was observed. In healed sites with a BBW of <1.5 mm after implant placement, increased vertical bone loss, and less favorable clinical and radiographic outcomes were demonstrated. Implants with buccal dehiscence defects undergoing simultaneous guided bone regeneration, showed less vertical bone loss, and more favorable clinical and radiographic outcomes, compared to non‐augmented dehiscence defects during initial healing. At healthy single implant sites, probing depths, bleeding and plaque scores, and interproximal bone levels evaluated at 1 year, remained stable for up to 5 years, with or without STA. When single implant sites were augmented with connective tissue grafts, either for soft tissue phenotype modification or buccal soft tissue dehiscence, stable levels of the soft tissue margin, and stable or even increased soft tissue thickness and/or width of keratinized mucosa could be observed from 1 to 5 years. In contrast, non‐augmented sites were more prone to show apical migration of the soft tissue margin in the long‐term. Favorable aesthetic and patient‐reported outcomes after STA were documented to be stable from 1 to 5 years. Conclusions: It is concluded that dimensional changes of the alveolar ridge occur after implant placement in healed sites and that sites with a thin BBW after implant placement are prone to exhibit less favorable clinical and radiographic outcomes. In addition, it is concluded that STA can provide stable clinical, radiographic, aesthetic, and patient‐reported outcomes in the medium and long‐term. [ABSTRACT FROM AUTHOR]

Background: D‐dimer testing is known to have a high sensitivity at simultaneously low specificity, resulting in nonspecific elevations in a variety of conditions. Methods: This retrospective study sought to assess diagnostic and prognostic features of D‐dimers in cancer patients referred to the emergency department for suspected pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 526 patients with a final adjudicated diagnosis of PE (n = 83) and DVT (n = 69) were enrolled, whereas 374 patients served as the comparative group, in which venous thromboembolism (VTE) has been excluded. Results: For the identification of VTE, D‐dimers yielded the highest positive predictive value of 96% (95% confidence interval (CI), 85–99) at concentrations of 9.9 mg/L and a negative predictive value of 100% at.6 mg/L (95% CI, 97–100). At the established rule‐out cut‐off level of.5 mg/L, D‐dimers were found to be very sensitive (100%) at a moderate specificity of nearly 65%. Using an optimised cut‐off value of 4.9 mg/L increased the specificity to 95% for the detection of life‐threatening VTE at the cost of moderate sensitivities (64%). During a median follow‐up of 30 months, D‐dimers positively correlated with the reoccurrence of VTE (p =.0299) and mortality in both cancer patients with VTE (p <.0001) and without VTE (p =.0008). Conclusions: Although D‐dimer testing in cancer patients is discouraged by current guidelines, very high concentrations above the 10‐fold upper reference limit contain diagnostic and prognostic information and might be helpful in risk assessment, while low concentrations remain useful for ruling out VTE. [ABSTRACT FROM AUTHOR]

Aims: Generalised epilepsy is thought to involve distributed brain networks. However, the molecular and cellular factors that render different brain regions more vulnerable to epileptogenesis remain largely unknown. We aimed to investigate epilepsy-related morphometric similarity network (MSN) abnormalities at the macroscale level and their relationships with microscale gene expressions at the microscale level. Methods: We compared the MSN of genetic generalised epilepsy with generalised tonic-clonic seizure patients (GGE-GTCS, n = 101) to demographically matched healthy controls (HC, n = 150). Cortical MSNs were estimated by combining seven morphometric features derived from structural magnetic resonance imaging for each individual. Regional gene expression profiles were derived from brain-wide microarray measurements provided by the Allen Human Brain Atlas. Results: GGE-GTCS patients exhibited decreased regional MSNs in primary motor, prefrontal and temporal regions and increases in occipital, insular and posterior cingulate cortices, when compared with the HC. These case-control neuroimaging differences were validated using split-half analyses and were not affected by medication or drug response effects. When assessing associations with gene expression, genes associated with GGE-GTCS-related MSN differences were enriched in several biological processes, including 'synapse organisation', 'neurotransmitter transport' pathways and excitatory/inhibitory neuronal cell types. Collectively, the GGE-GTCS-related cortical vulnerabilities were associated with chromosomes 4, 5, 11 and 16 and were dispersed bottom-up at the cellular, pathway and disease levels, which contributed to epileptogenesis, suggesting diverse neurobiologically relevant enrichments in GGE-GTCS. Conclusions: By bridging the gaps between transcriptional signatures and in vivo neuroimaging, we highlighted the importance of using MSN abnormalities of the human brain in GGE-GTCS patients to investigate disease-relevant genes and biological processes. [ABSTRACT FROM AUTHOR]

The article discusses the historical practice of using large clinical target volume (CTV) margins in the treatment of glioblastoma (GBM) and explores the possibility of reducing these margins. The traditional approach in North America has been to employ large CTV margins to account for potential geographical misses, but recent studies have shown that reducing the margins does not increase the risk of failure. The article supports the use of a 1.5-cm CTV expansion beyond the gross tumor volume (GTV) and emphasizes the importance of MRI guidance in further reducing the CTV margin. The findings suggest that using smaller margins can spare healthy brain tissue and improve quality of life for patients. [Extracted from the article]

Background: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. Objectives: We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. Design: This is a multicentre cohort study conducted in five European FMT centres. Methods: Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. Results: In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402–1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). Conclusion: FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT. [ABSTRACT FROM AUTHOR]

The accurate assessment of cerebrospinal fluid opening pressure during spinal puncture provides important medical information in diagnosis, prognosis and therapy of several neurological conditions. However, purpose-specific spinal needle choice is debated. While atraumatic needles are associated with lower incidence of post-puncture headache and re-hospitalisation, some clinicians believe that they lack in accuracy of CSF opening pressure assessment. Our primary objective was to investigate different needle types on correctly assessing CSF opening pressure. We compared typical clinically utilised traumatic (0.9 mm outer diameter) and atraumatic (0.7 mm; 0.45 mm) spinal needles with regards to the assessment of the opening pressure in an experimental spinal puncture model testing experimental and cerebrospinal fluids in predefined pressures. Our goal was to measure the time until indicated pressure levels were correctly shown. Atraumatic needles of at least 0.7 mm diameter had a similar accuracy as traumatic needles without significant differences in time-to-equilibrium. These results were independent of protein and glucose concentration and the presence of haemoglobin. This study demonstrates that atraumatic needles can be used to accurately measure CSF opening pressure. This knowledge might guide clinicians in their choice of needle and help to reduce post-puncture headaches and re-hospitalisation. [ABSTRACT FROM AUTHOR]

Adult SMA REACH is a Real-World Data collection study for Adult Spinal Muscular Atrophy (SMA) patients across UK. The aim of Adult SMA REACH is to improve the knowledge about the impact of new treatments in the natural history of the diseases but also to support the approval of Nusinersen and Risdiplam in UK under the Managed Access Agreement Programme (MAA). The generation of Real-World data requires the standardization and systematic collection of data generated during routine clinical visits and the constant monitoring of data quality to ensure that the data reported meet the highest quality standards in terms of reliability and accuracy. Adult SMA REACH includes data from 19 different sites with 370 patients and 1200 follow-up visits. The manual monitoring of data for quality check is time consuming, and this highlights the need for innovative methods of data monitoring to improve quality. Our objective was to improve data quality by streamlining the data cleansing process by automating data monitoring activities. In doing so, we aim to achieve high quality data that facilitates complex data analysis using Artificial Intelligence (AI). Innovative data modelling techniques enable data representation as a structured collection of interconnected entities, enhanced with metadata. This format outperforms conventional tabular representations, facilitating more profound and intricate analysis. Using this methodology, we created an automated software for data validation, consistency checks, completeness analysis and treatment tracking. This enabled us to provide continuous, hands-free monitoring of evolving datasets, and reveal systematic issues on some sites impacting data quality. This methodology enables us to automatically connect data to an artificial intelligence pipeline, avoiding the data cleansing step and facilitating complex AI analysis. We consider the application of data modelling techniques as the initial step in data collection studies, with a direct impact on data quality as well as on data analysis. We plan to expand our work by standardizing a data-agnostic data modelling methodology, allowing for a quick and flexible adaptation to different project scenarios within the John Walton Muscular Dystrophy Research Centre, Newcastle. [ABSTRACT FROM AUTHOR]

Gradient-based optimization algorithms can be studied from the perspective of limiting ordinary differential equations (ODEs). Motivated by the fact that existing ODEs do not distinguish between two fundamentally different algorithms—Nesterov's accelerated gradient method for strongly convex functions (NAG-SC) and Polyak's heavy-ball method—we study an alternative limiting process that yields high-resolution ODEs. We show that these ODEs permit a general Lyapunov function framework for the analysis of convergence in both continuous and discrete time. We also show that these ODEs are more accurate surrogates for the underlying algorithms; in particular, they not only distinguish between NAG-SC and Polyak's heavy-ball method, but they allow the identification of a term that we refer to as "gradient correction" that is present in NAG-SC but not in the heavy-ball method and is responsible for the qualitative difference in convergence of the two methods. We also use the high-resolution ODE framework to study Nesterov's accelerated gradient method for (non-strongly) convex functions, uncovering a hitherto unknown result—that NAG-C minimizes the squared gradient norm at an inverse cubic rate. Finally, by modifying the high-resolution ODE of NAG-C, we obtain a family of new optimization methods that are shown to maintain the accelerated convergence rates of NAG-C for smooth convex functions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diagnostic performance of noise-optimized virtual monoenergetic images (VMI+) in dual-energy CT (DECT) of portal vein thrombosis (PVT) compared to standard reconstructions. Method: This retrospective, single-center study included 107 patients (68 men; mean age, 60.1 ± 10.7 years) with malignant or cirrhotic liver disease and suspected PVT who had undergone contrast-enhanced portal-phase DECT of the abdomen. Linearly blended (M_0.6) and virtual monoenergetic images were calculated using both standard VMI and noise-optimized VMI+ algorithms in 20 keV increments from 40 to 100 keV. Quantitative measurements were performed in the portal vein for objective contrast-to-noise ratio (CNR) calculation. The image series showing the greatest CNR were further assessed for subjective image quality and diagnostic accuracy of PVT detection by two blinded radiologists. Results: PVT was present in 38 subjects. VMI+ reconstructions at 40 keV revealed the best objective image quality (CNR, 9.6 ± 4.3) compared to all other image reconstructions (p < 0.01). In the standard VMI series, CNR peaked at 60 keV (CNR, 4.7 ± 2.1). Qualitative image parameters showed the highest image quality rating scores for the 60 keV VMI+ series (median, 4) (p ≤ 0.03). The greatest diagnostic accuracy for the diagnosis of PVT was found for the 40 keV VMI+ series (sensitivity, 96%; specificity, 96%) compared to M_0.6 images (sensitivity, 87%; specificity, 92%), 60 keV VMI (sensitivity, 87%; specificity, 97%), and 60 keV VMI+ reconstructions (sensitivity, 92%; specificity, 97%) (p ≤ 0.01). Conclusions: Low-keV VMI+ reconstructions resulted in significantly improved diagnostic performance for the detection of PVT compared to other DECT reconstruction algorithms. [ABSTRACT FROM AUTHOR]

To examine activity levels, types of activities and their distribution across the day in patients with severe acquired brain injury including disorders of consciousness admitted to subacute neurorehabilitation. In this observational cross-sectional study, a modified behavioural mapping tool was used to document activity of patients admitted to a specialized rehabilitation ward for three consecutive days from 8.00 am to 8.00 pm. Observers walked a fixed route and returned to each patient every 10 min. Complete data was obtained in 1722/1728 observations on eight patients. Patients were registered as being in any activity in 55.6% and resting or sleeping in 30.3% of all observations. Patients were alone for 50.4% and were lying or sitting for 98.5% of the time. The major part (45%) of rehabilitation activities occurred during the morning before noon. The odds of being engaged in a rehabilitation activity were significantly different from afternoon and evening p = 0.02. Patients with higher function were more active. Patients with severe ABI were involved in some kind of activity for more than half the day and resting approximately 1/3 of the day. Health personnel and visitors were present in most activities. Rehabilitation of patients with severe acquired brain injury (ABI) comprises a high level of a broad range of activities and interactions. In order to truly offer round the clock rehabilitation, rehabilitation hospitals need to focus on delivering rehabilitation activities evenly across the waking hours. The long periods of daytime sleep and rest in patients with severe ABI should be further examined as there might be a potential to intensify rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: A waiting‐list randomized controlled trial supported the effectiveness of the multimodal Untire app in reducing cancer‐related fatigue (CRF) in cancer patients and survivors. However, little is known about the causal mechanisms of different app components through which the intervention effect was achieved. We aim to examine whether specifically targeted factors (i.e., fatigue catastrophizing, depression, mindfulness, sleep, and physical activity) mediated the intervention effects of the Untire app on fatigue outcomes. Methods: Seven hundred ninety‐nine persons with CRF were randomized (2:1) into intervention (n = 519) and waiting‐list control (n = 280) groups. Self‐report data on the primary outcome fatigue severity and interference and the abovementioned potential mediators were collected at baseline and 12 weeks. Participants who completed the 12‐week assessment were included in the analyses (intervention = 159; control = 176). We performed longitudinal multi‐categorical multiple mediation analysis using PROCESS macro to examine whether the potential mediators explained the overall intervention effects. Results: Improvements in fatigue catastrophizing (bootstrap 95% CI (−0.110; −0.011)), depression (bootstrap 95% CI (−0.082; −0.004)), and mindfulness (bootstrap 95% CI (−0.082; −0.002)), significantly mediated the intervention effect on fatigue severity, whereas sleep quality (bootstrap 95% CI (−0.081; 0.009)), sleep disturbance (bootstrap 95% CI (−0.038; 0.029)), and physical activity (bootstrap 95% CI (−0.068; 0.000)) did not. Similar associations were found for fatigue interference. Conclusions: Untire app access reduces fatigue severity and interference mainly by decreasing fatigue catastrophizing, depression, and by increasing mindfulness. Supporting these psychological mechanisms is crucial for reducing fatigue among cancer patients and survivors. [ABSTRACT FROM AUTHOR]

Background: High-resolution computed tomography (HRCT) is essential in narrowing the possible differential diagnoses of diffuse and interstitial lung diseases. Purpose: To investigate the value of a novel computer-based decision support system (CDSS) for facilitating diagnosis of diffuse lung diseases at HRCT. Material and Methods: A CDSS was developed that includes about 100 different illustrations of the most common HRCT signs and patterns and describes the corresponding pathologies in detail. The logical set-up of the software facilitates a structured evaluation. By selecting one or more CT patterns, the program generates a ranked list of the most likely differential diagnoses. Three independent and blinded radiology residents initially evaluated 40 cases with different lung diseases alone; after at least 12 weeks, observers re-evaluated all cases using the CDSS. Results: In 40 patients, a total of 113 HRCT patterns were evaluated. The percentage of correctly classified patterns was higher with CDSS (96.8%) compared to assessment without CDSS (90.3%; P < 0.01). Moreover, the percentage of correct diagnosis (81.7% vs. 64.2%) and differential diagnoses (89.2% vs. 38.3%) were superior with CDSS compared to evaluation without CDSS (both P < 0.01). Conclusion: Addition of a CDSS using a structured approach providing explanations of typical HRCT patterns and graphical illustrations significantly improved the performance of trainees in characterizing and correctly identifying diffuse lung diseases. [ABSTRACT FROM AUTHOR]

Interoception refers to the sensation and perception of internal bodily sensations, and may be related to depressive symptoms. Schemata concerning the body vary across different cultures and may influence interoception and symptom presentations of depression. This study explored the relationship between interoception, depressive symptoms, and schema of somatic focus in Chinese people with subsyndromal depression. Thirty‐nine individuals with subsyndromal depression (SD) and 40 healthy controls (HCs) were assessed at baseline and after 3 months. Participants completed the self‐report questionnaires for assessing interoceptive sensibility, somatic and psychological symptoms of depression, and somatization tendency. They also completed the heartbeat perception behavioral task for estimating interoceptive accuracy. The results showed that both the SD and the HC groups showed similar interoceptive accuracy, although the SD group showed heightened interoceptive sensibility. The discrepancy between interoceptive sensibility and interoceptive accuracy is termed the interoceptive trait prediction error (ITPE). The ITPE was positive in SD participants but was negative in HCs. In the entire sample, interoceptive sensibility and the ITPE were correlated with somatic symptoms rather than with psychological symptoms of depression. Interoceptive sensibility partially mediated the relationship between somatization tendency and somatic symptoms, after controlling for psychological symptoms of depression. These results remained stable after 3 months. The shortcomings of the present study were a lack of clinical interview to ascertain diagnosis and a short follow‐up duration. In conclusion, our study suggests that altered interoception occurs in subsyndromal depression. Interoception is related to somatic symptoms of depression. The schema of body was related to depressive symptoms, partially through interoception, in Chinese people with subsyndromal depression. [ABSTRACT FROM AUTHOR]

Simple Summary: Indocyanine green (ICG) is a dye that helps surgeons see the blood supply to tissues. In this study, (MIRRORS ICG) researchers wanted to see if this dye could help find cancer in women with advanced ovarian cancer undergoing robotic surgery after chemotherapy. After injecting ICG, a special camera was used to look at the whole abdomen and pelvic area. In this study, 102 tissue samples were taken to see if ICG helped identify cancerous tissue. The results showed that ICG correctly identified cancer in 91.1% of cases but had a low specificity of 13.0%, meaning it often falsely indicated cancer. This technique did not significantly help in detecting cancer in patients with widespread disease, but it showed some potential in those who had responded well to chemotherapy and had few remaining cancer spots. Molecular imaging with targeted dyes could enhance precision surgery in the future. Indocyanine green (ICG) is a fluorescent dye used for sentinel lymph node assessment and the assessment of perfusion in skin flaps and bowel anastomoses. ICG binds serum proteins and behaves as a macromolecule in the circulation. Tumour tissue has increased vascular permeability and reduced drainage, causing macromolecules to accumulate within it. MIRRORS ICG is designed to determine whether indocyanine green (ICG) helped identify metastatic deposits in women undergoing robotic interval cytoreductive surgery for advanced-stage (3c+) ovarian cancer. Peritoneal surfaces of the abdominal and pelvic cavity were inspected under white light and near-infrared light (da Vinci Si and Xi Firefly Fluorescence imaging, Intuitive Surgical Inc.) following intravenous injection of 20 mg ICG in sterile water. Visibly abnormal areas were excised and sent to histopathology, noting IGC positivity. In total, 102 biopsies were assessed using ICG. Intravenous ICG assessment following neoadjuvant chemotherapy had a sensitivity of 91.1% (95% CI [82.6–96.4%]), a specificity of 13.0% (95% CI [2.8–33.6%]), a positive predictive value of 78.3% (95% CI [68.4–86.2%]), and a negative predictive value of 30.0% (95% CI [6.7–65.2%]) False-positive samples were seen in 9/20 patients. Psammoma bodies were noted in the histopathology reports of seven of nine of these patients with false-positive results, indicating that a tumour had been present (chemotherapy-treated disease). This study demonstrates the appearance of metastatic peritoneal deposits during robotic cytoreductive surgery following the intravenous administration of ICG in women who have undergone neoadjuvant chemotherapy for stage 3c+ advanced ovarian cancer. A perfusion assessment using indocyanine green (ICG) peritoneal angiography during robotic interval cytoreductive surgery for advanced ovarian cancer did not clinically improve metastatic disease identification in patients with high-volume disease. The use of ICG in patients with excellent response to chemotherapy where few tumour deposits remained shows some promise. The potential of molecular imaging to enhance precision surgery and improve disease identification using the robotic platform is a novel avenue for future research. [ABSTRACT FROM AUTHOR]

Purpose: To present interobserver variability in thecal sac (TS) delineation based on contours generated by 8 radiation oncologists experienced in spine stereotactic body radiation therapy and to propose contouring recommendations to standardize practice.Methods and Materials: In the setting of a larger contouring study that reported target volume delineation guidelines specific to sacral metastases, 8 academically based radiation oncologists with dedicated spine stereotactic body radiation therapy programs independently contoured the TS as a surrogate for the cauda equina and intracanal spinal nerve roots. Uniform treatment planning simulation computed tomography datasets fused with T1, T2, and T1 post gadolinium magnetic resonance imaging for each case were distributed to each radiation oncologist. All contours were analyzed and agreement was calculated using both Dice similarity coefficient and simultaneous truth and performance level estimation with kappa statistics.Results: A fair level of simultaneous truth and performance level estimation agreement was observed between practitioners, with a mean kappa agreement of 0.38 (range, 0.210.55) and the mean Dice similarity coefficient (± standard deviation, with range) was 0.43 (0.36 ± 0.1 to -0.53 ±0.1). Recommendations for a reference TS contour, accounting for the variations in practice observed in this study, include contouring the TS to encompass all the intrathecal spinal nerve roots, and caudal to the termination of the TS, the bony canal can be contoured as a surrogate for the extra thecal nerves roots that run within it.Conclusions: This study shows that even among high-volume practitioners, there is a lack of uniformity when contouring the TS. Further modifications may be required once dosimetric data on nerve tolerance to ablative doses, and pattern of failure analyses of clinical data sets using these recommendations, become available. The contouring recommendations were designed as a guide to enable consistent and safe contouring across general practice. [ABSTRACT FROM AUTHOR]

Prospective memory (PM) refers to the ability to remember to carry out a delayed intention in the future. Evidence suggests that emotionally salient cues can enhance PM functions in healthy population, but whether the benefit exists in schizophrenia and bipolar patients remains unclear. This study aimed to examine and compare the potential enhancement effect of emotional PM cues in schizophrenia patients and bipolar patients. Twenty-eight clinically stable schizophrenia participants, 26 euthymic bipolar participants and 29 controls completed a computerized PM task involving PM cues with different types of valences (i.e., positive, neutral and negative). All the three groups showed better PM performance when negative PM cues were presented compared with positive and neutral PM cues. The sizes of the enhancement effects of negative PM cues were large (all Cohen's d ≥ 1.00) and comparable across three groups. Our findings suggested that patients with schizophrenia and bipolar disorders could benefit from negative PM cues to an extent similar to healthy individuals, thus extended the notion of psychosis continuum to the important area of emotion-cognition interaction. [ABSTRACT FROM AUTHOR]

This article studies the problem of joint selection of the state dimension and lag order for a class of Markov‐switching vector autoregressive models, in which all parameters are presumed to be regime‐dependent. To this end, three complexity‐penalized criteria are considered, and a new criterion is derived by minimizing the Kullback–Leibler divergence. The efficacy of the procedure is evaluated by means of Monte Carlo experiments. We illustrate the usefulness of the joint model selection procedure with empirical applications to the modeling of business cycles in the USA and Australia. [ABSTRACT FROM AUTHOR]

In addition to heme's role as the prosthetic group buried inside many different proteins that are ubiquitous in biology, there is new evidence that heme has substantive roles in cellular signaling and regulation. This means that heme must be available in locations distant from its place of synthesis (mitochondria) in response to transient cellular demands. A longstanding question has been to establish the mechanisms that control the supply and demand for cellular heme. By fusing a monomeric heme-binding peroxidase (ascorbate peroxidase, mAPX) to a monomeric form of green-fluorescent protein (mEGFP), we have developed a heme sensor (mAPXmEGFP) that can respond to heme availability. By means of fluorescence lifetime imaging, this heme sensor can be used to quantify heme concentrations; values of the mean fluorescence lifetime (tMean) for mAPX-mEGFP are shown to be responsive to changes in free (unbound) heme concentration in cells. The results demonstrate that concentrations are typically limited to one molecule or less within cellular compartments. These miniscule amounts of free heme are consistent with a system that sequesters the heme and is able to buffer changes in heme availability while retaining the capability to mobilize heme when and where it is needed. We propose that this exchangeable supply of heme can operate using mechanisms for heme transfer that are analogous to classical ligand-exchange mechanisms. This exquisite control, in which heme is made available for transfer one molecule at a time, protects the cell against the toxic effect of excess heme and offers a simple mechanism for heme-dependent regulation in single-molecule steps. [ABSTRACT FROM AUTHOR]

Several schools and state departments of education are leveraging prevention frameworks such as School-Wide Positive Behavior Support (SWPBS) to address problem behavior in schools, with the ultimate goal of improving academic achievement and producing lasting effects later in life. Much of the research demonstrating the promise of SWPBS has been conducted in the US and focused on near-term impacts, with less exploration of the various international adoptions of the model in other countries, and no studies exploring the longer term impact. This study leverages population-wide Danish administrative registry data (2006-2016) to examine the effect of the Danish/Norwegian adoption of SWPBS on the in-school outcome academic achievement and the out-of-school outcomes enrollment in upper secondary education, unemployment, and crime using a difference-in-differences (DD) design. The DD indicated an improvement in academic achievement in the 2nd and 3d year of implementation at schools likely to have implemented the program. [ABSTRACT FROM AUTHOR]

New alkali-free bioglasses of the ternary 60SiO 2 ·5P 2 O 5 ·35CaO parent glass wherein Ca is partially substituted by Sr (up to 10 mol%) were prepared by sol-gel method. The replacement of Ca with Sr induced the tendency to crystallisation of an apatite type phase. The bioactivity tested in vitro depends on Ca/Sr replacement degree, despite the fact that the theoretical network connectivity does not change with Ca/Sr substitution. After seven days of incubation in simulated body fluid, only on the samples with x ≥ 5 mol% SrO was developed a layer assumed of combined Ca/Sr composition of carbonated hydroxyapatite. Bactericidal activity was observed exclusively in case of strontium containing samples, for both Gram positive and negative bacteria. Structural effects of partial replacing of CaO by SrO were investigated by X-ray diffraction and FTIR analysis both before and after samples incubation in simulated body fluid. [ABSTRACT FROM AUTHOR]

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon‐13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C‐labeled NiII‐acyl complexes, formed from a 13CO insertion step with NiII‐alkyl intermediates, rapidly react in less than one minute with 2,2'‐dipyridyl disulfide to quantitatively form the corresponding 2‐pyridyl thioesters. Either the use of 13C‐SilaCOgen or 13C‐COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one‐pot acylation of a series of structurally diverse amines provides the desired 13C‐labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII‐acyl complexes and the disulfide providing a reactive NiIII‐acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon‐11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C‐labeled liraglutide and insulin degludec, representing two antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Purpose: Recent advancements in medical imaging have transformed diagnostic assessments, offering exciting possibilities for extracting biomarker-based information. This study aims to investigate the capabilities of a machine learning classifier that incorporates dual-energy computed tomography (DECT) radiomics. The primary focus is on discerning and predicting outcomes related to pulmonary embolism (PE). Methods: The study included 131 participants who underwent pulmonary artery DECT angiography between January 2015 and March 2022. Among them, 104 patients received the final diagnosis of PE and 27 patients served as a control group. A total of 107 radiomic features were extracted for every case based on DECT imaging. The dataset was divided into training and test sets for model development and validation. Stepwise feature reduction identified the most relevant features, which were used to train a gradient-boosted tree model. Receiver operating characteristics analysis and Cox regression tests assessed the association of texture features with overall survival. Results: The trained machine learning classifier achieved a classification accuracy of 0.94 for identifying patients with acute PE with an area under the receiver operating characteristic curve of 0.91. Radiomics features could be valuable for predicting outcomes in patients with PE, demonstrating strong prognostic capabilities in survival prediction (c-index, 0.991 [0.979–1.00], p = 0.0001) with a median follow-up of 130 days (IQR, 38–720). Notably, the inclusion of clinical or DECT parameters did not enhance predictive performance. Conclusion: In conclusion, our study underscores the promising potential of leveraging radiomics on DECT imaging for the identification of patients with acute PE and predicting their outcomes. This approach has the potential to improve clinical decision-making and patient management, offering efficiencies in time and resources by utilizing existing DECT imaging without the need for an additional scoring system. [ABSTRACT FROM AUTHOR]

Overexpression of γ-glutamyl transpeptidase (GGT1) has been implicated in an array of human diseases including asthma, reperfusion injury, and cancer. Inhibitors are needed for therapy, but development of potent, specific inhibitors of GGT1 has been hampered by a lack of structural information regarding substrate binding and cleavage. To enhance our understanding of the molecular mechanism of substrate cleavage, we have solved the crystal structures of human GGT1 (hGGT1) with glutathione (a substrate) and a phosphateglutathione analog (an irreversible inhibitor) bound in the active site. These are the first structures of any eukaryotic GGT with the cysteinylglycine region of the substrate-binding site occupied. These structures and the structure of apo-hGGT reveal movement of amino acid residues within the active site as the substrate binds. Asn-401 and Thr-381 each form hydrogen bonds with two atoms of GSH spanning the γ-glutamyl bond. Three different atoms of hGGT1 interact with the carboxyl oxygen of the cysteine of GSH. Interactions between the enzyme and substrate change as the substrate moves deeper into the active site cleft. The substrate reorients and a new hydrogen bond is formed between the substrate and the oxyanion hole. Thr-381 is locked into a single conformation as an acyl bond forms between the substrate and the enzyme. These data provide insight on a molecular level into the substrate specificity of hGGT1 and provide an explanation for seemingly disparate observations regarding the enzymatic activity of hGGT1 mutants. This knowledge will aid in the design of clinically useful hGGT1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Rates of aggression in inpatient secure care are higher than in other psychiatric inpatient settings. People with intellectual disabilities in secure care require adapted psychological treatments. Interpersonal art psychotherapy incorporates the use of creative art making approaches by participants, thus reducing sole reliance upon verbal interactions during psychotherapy for people who may have communication difficulties. During interpersonal art psychotherapy, participants are individually supported by their therapist to consider how they conduct relationships. This includes the influence and impact of interpersonal issues resulting in repeated patterns of conflict. The key feasibility objectives were to assess recruitment and retention rates, follow-up rates and trial procedures such as randomisation, allocation and identifying any practical or ethical problems. In addition, a preliminary 'signal' for the intervention was considered and an indicative sample size calculation completed. The acceptability of a potential third trial arm attentional control condition, mindful colouring-in, was assessed using four single-case design studies and a UK trial capacity survey was conducted. Methods: Adult patients with intellectual disabilities in secure care were recruited and randomised to either interpersonal art psychotherapy or delayed treatment in this multi-site study. Outcomes were assessed using weekly observations via the Modified Overt Aggression Scale and a range of self-report measures. Within study reporting processes, qualitative interviews and a survey were completed to inform trial feasibility. Results: Recruitment procedures were successful. The target of recruiting 20 participants to the trial from multiple sites was achieved within 8 months of the study opening. All participants recruited to the treatment arm completed interpersonal art psychotherapy. Between-group differences of interpersonal art psychotherapy versus the delayed treatment control showed a 'signal' effect-size of.65 for total scores and.93 in the verbal aggression sub-scale. There were no amendments to the published protocol. The assessment of key feasibility objectives were met and the trial procedures were acceptable to all involved in the research. Conclusion: This study suggested that a randomised controlled trial of interpersonal art psychotherapy is acceptable and feasible. Trial registration: ISRCTN14326119 (Retrospectively Registered). [ABSTRACT FROM AUTHOR]

Background: Rates of aggression in inpatient secure care are higher than in other psychiatric inpatient settings. People with intellectual disabilities in secure care require adapted psychological treatments. Interpersonal art psychotherapy incorporates the use of creative art making approaches by participants, thus reducing sole reliance upon verbal interactions during psychotherapy for people who may have communication difficulties. During interpersonal art psychotherapy, participants are individually supported by their therapist to consider how they conduct relationships. This includes the influence and impact of interpersonal issues resulting in repeated patterns of conflict. The key feasibility objectives were to assess recruitment and retention rates, follow-up rates and trial procedures such as randomisation, allocation and identifying any practical or ethical problems. In addition, a preliminary 'signal' for the intervention was considered and an indicative sample size calculation completed. The acceptability of a potential third trial arm attentional control condition, mindful colouring-in, was assessed using four single-case design studies and a UK trial capacity survey was conducted. Methods: Adult patients with intellectual disabilities in secure care were recruited and randomised to either interpersonal art psychotherapy or delayed treatment in this multi-site study. Outcomes were assessed using weekly observations via the Modified Overt Aggression Scale and a range of self-report measures. Within study reporting processes, qualitative interviews and a survey were completed to inform trial feasibility. Results: Recruitment procedures were successful. The target of recruiting 20 participants to the trial from multiple sites was achieved within 8 months of the study opening. All participants recruited to the treatment arm completed interpersonal art psychotherapy. Between-group differences of interpersonal art psychotherapy versus the delayed treatment control showed a 'signal' effect-size of.65 for total scores and.93 in the verbal aggression sub-scale. There were no amendments to the published protocol. The assessment of key feasibility objectives were met and the trial procedures were acceptable to all involved in the research. Conclusion: This study suggested that a randomised controlled trial of interpersonal art psychotherapy is acceptable and feasible. Trial registration: ISRCTN14326119 (Retrospectively Registered). [ABSTRACT FROM AUTHOR]

Objective: Medial temporal lobe epilepsy (TLE) is the most common form of medication‐resistant focal epilepsy in adults. Despite removal of medial temporal structures, more than one‐third of patients continue to have disabling seizures postoperatively. Seizure refractoriness implies that extramedial regions are capable of influencing the brain network and generating seizures. We tested whether abnormalities of structural network integration could be associated with surgical outcomes. Methods: Presurgical magnetic resonance images from 121 patients with drug‐resistant TLE across 3 independent epilepsy centers were used to train feed‐forward neural network models based on tissue volume or graph‐theory measures from whole‐brain diffusion tensor imaging structural connectomes. An independent dataset of 47 patients with TLE from 3 other epilepsy centers was used to assess the predictive values of each model and regional anatomical contributions toward surgical treatment results. Results: The receiver operating characteristic area under the curve based on regional betweenness centrality was 0.88, significantly higher than a random model or models based on gray matter volumes, degree, strength, and clustering coefficient. Nodes most strongly contributing to the predictive models involved the bilateral parahippocampal gyri, as well as the superior temporal gyri. Interpretation: Network integration in the medial and lateral temporal regions was related to surgical outcomes. Patients with abnormally integrated structural network nodes were less likely to achieve seizure freedom. These findings are in line with previous observations related to network abnormalities in TLE and expand on the notion of underlying aberrant plasticity. Our findings provide additional information on the mechanisms of surgical refractoriness. ANN NEUROL 2020;88:970–983 [ABSTRACT FROM AUTHOR]

A double-layer ceramic electronic packaging technology that survives the Venusian surface temperature of 465°C was developed using a ceramic interlayer dielectric with gold conductors. A 60-mm ceramic interlayer dielectric served as the insulator between the top and bottom gold conductors on highpurity ceramic substrates. Test devices with AuPtPd metallization were attached to the top gold pads using a thick-film gold paste. Thermal aging for 115 h at 500°C and thermal cycling from room temperature to 450°C were performed. Dielectric leakage tests of the interlayer ceramic layer between the top and bottom gold conductors revealed a leakage current density of less than 5031027 A/cm2 at 600 V after thermal cycling. Gold conductor resistance increased slightly after thermal cycling. The die shear test showed a 33% decrease in die shear strength after thermal tests and its 6.16 kg-F die shear strength satisfies the Military Standard Product Testing Services (MIL-STD) method. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate magnetic resonance elastography (MRE) as a response parameter in patients who received transarterial chemoembolization (TACE) for the treatment of colorectal liver metastases.Materials and Methods: Forty-two patients (29 male patients; mean age, 61.5 years; range, 41-84 years) with repeated TACE therapy of colorectal liver metastases underwent on average 2 repetitive magnetic resonance imaging (MRI) and MRE exams in 4- to 6-week intervals using a 1.5-T scanner. MRE-based liver stiffness measurements were performed in normal liver parenchyma and in metastatic lesions. Moreover, the size of the liver metastases was assessed during treatment and compared with the results of the MRE analysis.Results: Liver metastases showed a significantly higher degree of stiffness compared with the normal liver parenchyma (p < 0.001). However, only a weak correlation was found between the lesion size and stiffness (r = - 0.32, p = 0.1). MRE analysis revealed an increase in stiffness of the colorectal liver metastases from 4.4 to 7.1 kPa after three cycles of TACE (p < 0.001). Also, the mean size of the metastases decreased from 17.0 to 11.3 cm2 (p < 0.001). Finally, the entire liver stiffness increased from 2.9 to 3.1 kPa over the three cycles of TACE therapy.Conclusion: In conclusion, MRE showed a significant change in stiffness and size of liver metastases. Therefore, MRE may provide an added value for an evaluation of treatment response in patients with colorectal liver metastases undergoing TACE.Key Points: • MRE showed an increase in stiffness of the colorectal liver metastases during TACE therapy. • Liver metastases showed a significantly higher degree of stiffness compared with the normal liver parenchyma. • However, only a weak correlation was found between the lesion size and stiffness. [ABSTRACT FROM AUTHOR]

A high-input voltage 2-phase series-capacitor (2-pscB) DC-DC buck converter is theoretically analyzed, designed, and implemented. A new design approach for an automatic current sharing scheme was presented for a 2-phase series-capacitor synchronous buck converter. The series-capacitor voltage is used to achieve current sharing between phases without a current sensing circuit or external control loop as each phase inductor charges and discharges the series capacitor to maintain its average capacitor voltage constant. A novel isolated gate driver circuit to accommodate an energy storage capacitor is proposed to deliver isolated gate voltages to the switching transistors. An I2 control scheme that uses only one feedback path control for the four gate drivers is proposed to enable higher voltage conversion. An experimental 110-12 V 6 A load prototype converter was designed, and its current sharing characteristics were experimentally verified. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of two optimization-driven biomechanical modeling approaches has been compared with an electromyography-assisted optimization (EMGAO) approach to predict lumbar spine loading while walking with backpack loads.Background: The EMGAO approach adopts more variables in the optimization process and is complex in data collection and processing, whereas optimization-driven approaches are simple and include the fewest possible variables. However, few studies have been conducted on the efficacy of using the optimization-driven approach to predict lumbar spine loading while walking with backpack loads.Method: Anthropometric information of 10 healthy male adults as well as their kinematic, kinetic, and electromyographic data acquired while they walked with various backpack loads (no-load, 5%, 10%, 15%, and 20% of body weight) served as inputs into the model for predicting lumbosacral joint compression forces. The efficacy of two optimization-driven models, namely double linear optimization with constraints on muscle intensity and single linear optimization without any constraints, was investigated by comparing the resulting force profile with that provided by a current EMGAO approach.Results: The double and single linear optimization approaches predicted mean deviations in peak force of -5.1%, and -19.2% as well as root-mean-square differences in force profile of 16.2%, and 25.4%, respectively.Conclusion: The double linear optimization approach was a relatively comparable estimator to the EMGAO approach in terms of its consistency, slight bias, and efficiency for predicting peak lumbosacral joint compression forces.Application: The double linear optimization approach is a useful biomechanical model for estimating peak lumbar compression forces while walking with backpack loads. [ABSTRACT FROM AUTHOR]

An extensive range of functionalized aliphatic ketones with good functional‐group tolerance has been prepared by a NiI‐promoted coupling of either primary or secondary alkyl iodides with NN2 pincer NiII‐acyl complexes. The latter were easily accessed from the corresponding NiII‐alkyl complexes with stoichiometric CO. This Ni‐mediated carbonylative coupling is adaptable to late‐stage carbon isotope labeling, as illustrated by the preparation of isotopically labelled pharmaceuticals. Preliminary investigations suggest the intermediacy of carbon‐centered radicals. [ABSTRACT FROM AUTHOR]

An extensive range of functionalized aliphatic ketones with good functional‐group tolerance has been prepared by a NiI‐promoted coupling of either primary or secondary alkyl iodides with NN2 pincer NiII‐acyl complexes. The latter were easily accessed from the corresponding NiII‐alkyl complexes with stoichiometric CO. This Ni‐mediated carbonylative coupling is adaptable to late‐stage carbon isotope labeling, as illustrated by the preparation of isotopically labelled pharmaceuticals. Preliminary investigations suggest the intermediacy of carbon‐centered radicals. [ABSTRACT FROM AUTHOR]

An electronic packaging technology that survives the simulated Venusian surface temperature of 465°C and 96 bar pressure in carbon dioxide (CO2) and nitrogen environments, without the corrosive trace gases, was developed. Alumina ceramic substrates and gold conductors on alumina were evaluated for electrical and mechanical performance. The most promising dieattach materials are thick-film gold and alumina-based ceramic pastes. Alumina, sapphire, silicon, and silicon carbide dies were attached to the alumina substrates using these die-attach materials and exposed to 96 bar pressure in a CO2 environment at 465°C for 244 h. The ceramic die-attach material showed consistent shear strengths before and after the test. An alumina ceramic encapsulation material was also evaluated for thermomechanical stability. The devices on the packaging substrates were encapsulated by a ceramic encapsulation with no significant increase in cracks and voids after the Venusian simulator test. Wire pull strength tests were conducted on the gold bond wire to evaluate mechanical durability before and after the Venusian simulator exposure. The average gold bond wire pull strengths before and after exposure were 5.78 g-F and 4 g-F for 1-mil gold bond wires, respectively, meeting the minimum MIL-STD-885 2011.9 standard. The overall wire bond daisy chain resistance change was .47% after the Venus simulator test, indicating a promising wire bond integrity. A titanium package was fabricated to house the ceramic packaging substrate and a two-level metalized feedthrough was fabricated to provide electrical interfaces to the package. [ABSTRACT FROM AUTHOR]

Shielding disks play an important role in intraoperative electron radiation therapy, and different designs are currently used in clinical practice. This paper investigates the dosimetric impact of the shielding disk used during intraoperative electron radiation therapy (IOERT). This paper focuses on the study of four shielding disks types that have been used in our clinic: Aluminum (Al)/Lead (Pb), PMMA/Copper(Cu)/PMMA, Aluminum (Al)/Copper (Cu) and Aluminum (Al)/Steel with their specific thicknesses. The theoretical study was conducted with the EGSnrc Monte Carlo (MC) code. On the other hand, the measurements were carried out with gafchromic films for the four shielding disks for the same setup inside the water phantom. Finally, a comparison of the simulated and measured PDD curves was performed for the four material combinations. MC simulation and gafchromic measurements illustrated that dose values under the four shielding disks types were close to 0, whereas the backscattering enhancement of the disks were 103% with Al/Pb shielding disk, 102% with Al/Steel shielding disk, 102% with Al/Cu shielding disk, 95% with PMMA/Cu/PMMA shielding disk. The PDDs values of the gafchromic films in front of the disks were: 107%, 105%, 104%, and 94% for the Al/Pb, Al/Steel, Al/Cu, and PMMA/Cu/PMMA disks respectively. The dose values above and under the shielding disks were acceptable for the four studied shielding types. Demonstrated it is possible to use any of them clinically, while the best shielding disk was the Al/Pb since it has minimum thickness and a small backscatter enhancement. [ABSTRACT FROM AUTHOR]

Stochastic gradient Langevin dynamics (SGLD) is a fundamental algorithm in stochastic optimization. Recent work by Zhang et al. (2017) presents an analysis for the hitting time of SGLD for the first and second order stationary points. The proof in Zhang et al. (2017) is a two-stage procedure through bounding the Cheeger's constant, which is rather complicated and leads to loose bounds. In this paper, using intuitions from stochastic differential equations, we provide a direct analysis for the hitting times of SGLD to the first and second order stationary points. Our analysis is straightforward. It only relies on basic linear algebra and probability theory tools. Our direct analysis also leads to tighter bounds comparing to Zhang et al. (2017) and shows the explicit dependence of the hitting time on different factors, including dimensionality, smoothness, noise strength, and step size effects. Under suitable conditions, we show that the hitting time of SGLD to first-order stationary points can be dimension-independent. Moreover, we apply our analysis to study several important online estimation problems in machine learning, including linear regression, matrix factorization, and online PCA. [ABSTRACT FROM AUTHOR]

Introduction: Evidence suggests that schizophrenia patients have olfactory dysfunctions, but the relationship between olfactory identification, hedonic judgement, and negative symptomatology remains unclear. Few studies have investigated whether co-activation of pleasant and unpleasant emotions are more prevalent in schizophrenia patients. Methods: Thirty schizophrenia outpatients with prominent negative symptoms (PNS), 30 outpatients without PNS, and 30 controls completed the University of Pennsylvania Smell Identification Test, and were asked to identify the odourants and to rate their emotions. The effects of gender and medications on olfactory function were examined. Results: Schizophrenia patients exhibited olfactory identification impairments, even after accounting for gender and medication effects. Patients with PNS demonstrated larger magnitude of deficit than those without. Patients with PNS reported less pleasure to positive-valenced odourants, and less unpleasantness to negative-valenced odourants than controls. Olfactory anhedonia in patients with PNS disappeared after controlling for medication effect. Schizophrenia patients do not exhibit affective ambivalence in olfaction. Conclusions: Schizophrenia patients with PNS exhibit deficits in olfactory identification and hedonic judgement, even after controlling for gender and medication effects. Our findings support the close relationship between olfactory dysfunctions and negative symptoms. Further studies should investigate the effect of dopamine-blocking agents on the olfactory hedonic judgment in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Background: The total ankle replacement versus ankle arthrodesis (TARVA) trial aims to determine which surgical procedure confers the greatest improvement in pain-free function for patients with end-stage ankle osteoarthritis. Both procedures are effective but there has not yet been a direct comparison to establish which is superior. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown.Design and Methods: TARVA is a randomised, un-blinded, parallel group trial of total ankle replacement versus ankle arthrodesis. The primary outcome is the Manchester-Oxford Foot Questionnaire walking/standing domain score at 52 weeks post-surgery. Secondary outcomes include measures of pain, social interaction, physical function, quality of life, and range of motion. We describe in detail the statistical aspects of TARVA: the outcome measures, the sample size calculation, general analysis principles including treatment of missing data, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses.Discussion: The TARVA statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in January 2020 when follow-up for the trial is completed.Trial Registration: ISRCTN registry number 60672307, ClinicalTrials.gov registration number NCT02128555. Registered 1 May 2014. Recruitment started in January 2015 and ended in January 2019. [ABSTRACT FROM AUTHOR]

Aims: Acinic cell carcinoma (ACC) of the breast is a rare histological form of triple‐negative breast cancer (TNBC). Despite its unique histology, targeted sequencing analysis has failed to identify recurrent genetic alterations other than those found in common forms of TNBC. Here we subjected three breast ACCs to whole‐exome and RNA sequencing to determine whether they would harbour a pathognomonic genetic alteration. Methods and results: DNA and RNA samples from three breast ACCs were subjected to whole‐exome sequencing and RNA‐sequencing, respectively. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined with state‐of‐the‐art bioinformatics methods. Our analyses revealed TP53 hotspot mutations associated with loss of heterozygosity of the wild‐type allele in two cases. Mutations affecting homologous recombination DNA repair‐related genes were found in two cases, and an MLH1 pathogenic germline variant was found in one case. In addition, copy number analysis revealed the presence of a somatic BRCA1 homozygous deletion and focal amplification of 12q14.3–12q21.1, encompassing MDM2, HMGA2, FRS2, and PTPRB. No oncogenic in‐frame fusion transcript was identified in the three breast ACCs analysed. Conclusions: No pathognomonic genetic alterations were detected in the breast ACCs analysed. These tumours have somatic genetic alterations similar to those of common forms of TNBC, and may show homologous recombination deficiency or microsatellite instability. These findings provide further insights into why breast ACCs, which are usually clinically indolent, may evolve into or in parallel with high‐grade TNBC. [ABSTRACT FROM AUTHOR]

Hypertension (HT) is associated with cardiovascular events and increased mortality, and identification of persons at risk in due time is therefore important. Finding a biomarker to identify those at risk will enable early preventive treatment, and high-sensitivity cardiac troponin (hs-cTn) seems to be a highly relevant candidate. To gather the existing knowledge on the association between hs-cTn and future HT, a systematic literature review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines and using the PICOS system. Medline was searched until August 2018. Of 45 extracted papers, eleven papers were eligible for the study. None were randomized controlled trials. Three studies assessed hs-cTnI, eight studies assessed hs-cTnT. All studies found statistically significant associations between hs-cTn concentrations and future HT, but the studies included different types of blood pressure (diastolic, systolic, diurnal). Due to differences in troponin assay construction and test capability, a direct comparison of test performance in terms of specificity, sensitivity and predictive values was not possible, and a specific hs-cTn cutoff value for HT prediction could therefore not be defined. Furthermore, a number of conditions known to affect troponin concentrations (e.g. gender, renal function, and co-morbidities) were not sufficiently studied. All retrieved studies found significant associations between hs-cTn concentrations and future HT; although the findings are promising, the studies were too heterogeneous, and many conditions affecting troponin concentrations needs investigation at these low concentrations before hs-cTn can be considered a useful HT predictor. [ABSTRACT FROM AUTHOR]