Introduction: Ventricular arrhythmia (VA) from the left ventricular summit (LVS) is a common origin of VA, which resulting LV dysfunction in some patients. However, the predictors of LV cardiomyopathy were not well-elucidated. The present study sought to investigate the risk factor of LV cardiomyopathy and the outcome in patients with LVS VA Methods: Between 2013 and 2018, a total of 139 patients (60.7% men; mean age 53.2 ± 13.9 years-old) underwent catheter ablation for LVS VA from two centers. Detailed patient demographics, electrocardiograms, electrophysiological characteristics, and clinical outcomes were extracted for analysis. LV cardiomyopathy was defined as LV ejection fraction (LVEF) <50%. Results: Acute procedural success was achieved in 92.8 % of patients. There were 40 patients (28.8%) with LV cardiomyopathy, and the mean LVEF improved from 37.5 ± 9.3% to 48.5 ± 10.2% after ablation ( p < 0.001). After multivariate analysis, the independent predictors of LV dysfunction were wider QRS duration of the VA (odds ratio [OR]1.02; 95% confidence interval [CI]: 1.00-1.04; p = 0.046) and the absolute earliest activation time discrepancy (AEAD) between epicardium and endocardium (OR 1.05; 95% confidence interval CI: 1.00-1.09; p = 0.048). After ablation, the LV function was completely recovered in 20 patients (50%). The predictors for irreclaimable LV function included wider PVC QRS duration (OR 1.09; 95% CI: 1.02-1.17; p = 0.012) and poorer LVEF (OR 0.85; 95% CI: 0.74-0.97; p = 0.020). Conclusion: In patients with VA from LVS, PVC QRS duration and AEAD predicted the deteriorating LV systolic function. Catheter ablation could reverse the LV remodeling. Narrower QRS duration and better LVEF predicted a better recovery of LV function after ablation.

Accurate assessment of wind energy potential can provide important implication regarding the optimalization of micro-siting of wind turbines and increase of wind power generation. It is, however, noteworthy that most previous studies on wind energy resource assessment focused solely on wind speed, whereas the dependence of wind energy on wind direction was much less considered and documented. In the current study, a copula-based method is proposed to better characterize the direction-related wind energy potential at six typical sites in Hong Kong. In the first step, several widely used statistical models are adopted to fit the marginal distributions of wind speed and direction. The joint probability density function (JPDF) of wind speed and wind direction is therewith constructed by various copula models. The goodness-of-fit evaluation indicates that Frank copula has the best performance to fit the JPDF at hilltop and offshore sites, while Gumbel copula outperforms other models at downtown sites. More importantly, the derived JPDFs are applied to estimate the direction-related wind power density at each of the considered sites, finding a maximum value of wind energy potential of 506.4 W/m2 at a hilltop site. In addition, site-to-site variability is also identified regarding the prevailing wind resource directions. The outcome of this study is expected to be useful for the site selection of wind turbines, as well as the strategic development of wind energy in Hong Kong. Notably, the proposed copula-based method can also be applied to characterize the direction-related wind energy potential somewhere other than Hong Kong.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease. Case: A 56-year-old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX-2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune-related adverse events successfully treated with steroids.Conclusion: Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

Background: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist, and to examine the association between cluster membership and in-hospital outcomes. Methods: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n=242) and 2018/2019 (n=115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 hours of the hospital stay. K-medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth’s logistic regression were used to examine the association between cluster membership and clinical outcomes. Results: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95%CI: 1.49,21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95%CI: 0.2,2.7) and C173 (mean 1.4 days longer, 95%CI: 0.3,2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation.

For better serving people's complex needs the subsequent movement to person-centered integrated care, requires inter-organizational cooperation and service provision by domain-overarching networks and alliances. In the development to these networks, it is relevant to explore which accountability approaches are appropriate for local inter-organizational healthcare governance. Therefore, in a scoping review we studied the current state of knowledge and practice of accountability in healthcare in the Netherlands. We found that two of the included 41 studies show characteristics of accountability towards healthcare with characteristics of integration care components, such as integration of services with accompanying accountability arrangements and development of networked accountability. The first studies are found in the literature which report on accountability in integrated care. With this we add to the international discussion about accountability as an aspect of integrated care governance, by providing insight into the current state of art of accountability in Dutch healthcare.

Although the dispersal is important for riparian plants, few studies have evaluated the patterns in species richness and composition of propagules deposited by different dispersal types. In the present study we evaluate the temporal and spatial patterns in the diversity of propagules deposited by hydrochory and by other types of dispersal along mountain rivers. To do this, we sampled the propagules deposited in the riparian zone in a distance gradient with respect to the site of origin of the rivers in two seasons. Regarding the temporal analyses, we found no differences in the number of propagules between seasons. In the rainy season we observed a greater number of species deposited by hydrochory, while for other types of dispersal there was a greater number of species in the dry season. Differences in composition were observed for hydrochory but not for other types of dispersal. Regarding the spatial analyses, there were no changes in the number of propagules deposited along the river by hydrochory, while for other types of dispersal an increase was observed in the dry season. A lower number of species deposited by hydrochory along the river in the rainy season was observed. Finally, we observed that turnover increases by other types of dispersal in the dry season but not for hydrochory. The results underline the importance of types of dispersal other than hydrochory in the contribution of propagules dispersed and the temporal and spatial particularities of the hydrochory in mountain rivers.

Atomoxetine is mainly metabolized by CYP2D6 while CYP2C19 plays a secondary role. It is known that patients carrying genotypes encoding decreased/absent CYP2D6 metabolism obtain higher atomoxetine concentrations and are at increased risk of adverse effects. Here, we aimed to investigate the added effects of reduced-function CYP2C19 genotype on atomoxetine concentrations in real-world settings. Serum atomoxetine concentrations and CYP2D6/2C19 genotypes were included from a therapeutic drug monitoring service. Patients were first subgrouped according to CYP2D6 encoding normal, reduced or absent CYP2D6 metabolism, referred to as normal (NM), intermediate (IM) or poor metabolizers (PM). Then, the effect of reduced-function CYP2C19 genotypes was investigated. Genotyping of the CYP2D6 nonfuctional or reduced variant alleles comprised CYP2D6*3-*5, *9-*10 and *41. For CYP2C19, the CYP2C19*2 was analysed to define metabolizer phenotype. Dose-adjusted serum atomoxetine concentration was the exposure measure. Using a patient cohort (n=315), it was found that CYP2D6 IM and PM patients had 1.9-fold (95%CI: 1.4-2.7) and 9.6-fold (5.9-16) higher exposure of atomoxetine compared with CYP2D6 NMs. CYP2C19*2 carriers had 1.5-fold (1.1-2.2) higher atomoxetine exposure than non-carriers regardless of CYP2D6 genotype. CYP2D6 genotype has a great impact on atomoxetine exposure, where our real-world data suggest atomoxetine dose requirements to be around half and one-tenth in CYP2D6 IM and PM vs. NM patients, respectively. When adding CYP2C19 genotype as a factor of relevance for personalized atomoxetine dosing, CYP2C19*2 carriers should further reduce the dose by a third. These findings suggest that pre-emptive CYP2D6/CYP2C19 genotyping should be performed to individualize atomoxetine dosing and prevent adverse effects.

When performing bimanual tasks, hands are typically not controlled individually but rather as a coupled system to achieve high spatiotemporal coordination. On a brain level, intra- and interhemispheric connections networks that control the left and right hand are necessary to exchange information between hemispheres and to couple movements. Behaviorally, coupling is, however, highly task-specific requiring, for example, to maintain a specific relative phase in cyclic tasks (e.g., in- or antiphase) or to perform a role differentiated task where one hand is modulating and the other hands is stabilizing and needs to be kept as still as possible (e.g., holding a notepad and writing on it). In this study, we used electroencephalography to investigate functional brain network characteristics (task-related activation and connectivity) in bimanual force-control tasks with different coordination modes: inphase, antiphase and role-differentiated with the left- or right-hand stabilizing and the other hand manipulating. We aimed to examine i) how network characteristics differ with respect to the coordination mode and ii) how they are related to the performance. Results showed, task-related differences in the overall activation and connectivity, but no task-specific patterns (i.e., different regions being more active or integrated during some tasks than others). We did show, however, that the strength of bimanual coupling is modulated in a task-specific way through networks including C3, FC3 and F3 electrodes. Results suggest that interhemispheric crosstalk for bimanual coordination is modulated in a task-specific way through left frontocentral networks.

Streptococcus equi subspecies equi (S. equi) is the causative organism of the upper respiratory disease of equids, strangles, characterised by pyrexia, lymphadenopathy, and mucopurulent nasal discharge. Strangles was first reported over 750 years ago and continues to be of significance in equine populations across the globe. This review discusses how S. equi has adapted, the clinical manifestation of strangles, and how clinicians and caregivers can tackle the disease in the future. S. equi evolved from the commensal, and occasionally opportunistic pathogen, Streptococcus equi subspecies zooepidemicus refining its capabilities as it became host restricted. The success of S. equi can be attributed to its ability to cause both acute and persistent infection, the latter occurring in about 10% of those infected. In this carrier state, S. equi persists in the guttural pouch without causing clinical signs, intermittently shedding into the environment, and encountering naïve animals. Insight into the S. equi genome and lifestyle has led to advances in diagnostic assays and the development of a safe and efficacious recombinant-fusion vaccine, giving clinicians and caregivers the tools to better combat this infection. Alongside rigorous biosecurity protocols and pragmatic control measures such as screening new arrivals for exposure and carrier status, these new technologies demonstrate that strangles can be an increasingly preventable infection.

Snowpack dynamics have a major influence on wildlife movement ecology and predator-prey interactions. Specific snow properties such as density, hardness, and depth determine how much an animal sinks into the snowpack, which in turn drives both the energetic cost of locomotion and predation risk. Here, we quantified the relationships between 15 field-measured snow variables and snow track sink depths for widely distributed predators (bobcats [Lynx rufus], coyotes [Canis latrans], wolves [C. lupus]) and sympatric ungulate prey (caribou [Rangifer tarandus], white-tailed deer [Odocoileus virginianus], mule deer [O. hemionus], and moose [Alces alces]) in interior Alaska and northern Washington, USA. We first used generalized additive models to identify which snow metrics best predicted sink depths for each species and across all species. For species occurring in both sites, we then tested whether the snow metric-sink depth relationship differed across regions. Finally, we used breakpoint regression to identify thresholds for the best-performing predictor of sink depth for each species (i.e., values wherein tracks do not appreciably sink into the snow). Near-surface (0-10cm) snow density was the strongest predictor of sink depth across species. This relationship varied slightly by region for wolves and moose but did not differ for coyotes. Thresholds of support occurred at snow densities of 230 kg/m3 for coyotes, 280 kg/m3 for bobcats, 290 kg/m3 for wolves, 340 kg/m3 for deer, 440 kg/m3 for caribou, and 550 kg/m3 for moose. Together, these critical thresholds define the bounds of “danger zones,” the range of snow density in which carnivores have a comparative movement advantage over ungulates. These results can be used to link predator-prey relationships with spatially explicit snow modeling outputs and projected future changes in snow density. As climate change rapidly reshapes snowpack dynamics, these danger zones provide a useful framework to anticipate likely winners and losers of future winter conditions.

Root traits and functioning: from individual plants to ecosystemsFine roots, the most distal portions of the root system, are responsible for the uptake of water and nutrients by plants, represent the main type of plant tissue contributing to soil organic matter accrual, and are key drivers of mineral weathering and soil microbial dynamics (Bardgett et al. 2014). Despite the overwhelming importance of fine root traits for plant and plant community functioning and biogeochemical cycles, basic information about their ecology is lacking, particularly compared to the wealth of information developed for leaves and stems. Testing hypotheses on how root traits underlie these ecosystem processes has been particularly hampered due to (1) a paucity of systematically collected data and (2) the complexity of the relationships between root traits and root, plant and ecosystem functioning. Nonetheless, the development of the field of root ecology in the last two decades has been outstanding, in particular in the compilation of belowground trait datasets (Iversen et al. 2017), methodological root ecological handbooks (Freschet et al. 2021b), novel conceptual frameworks to describe root trait diversity (Bergmann et al. 2020), its connection with belowground plant and community function (Bardgett et al. 2014, Freschet et al. 2021a), species’ distributions (Laughlin et al. 2021), and scaling up traits from the individual root to the ecosystem level (McCormack et al. 2017). The papers that feature in this Special Issue on Root traits and functioning: from individual plants to ecosystems cover different climate regions, taxonomic and spatial scales, and a diversity of traits (Table 1) and form perfect examples of this upward moment of the belowground component in plant ecology.

Indirect genetic effects describe phenotypic variation that results from differences in the genotypic composition of social partners. Such effects represent heritable sources of environmental variation in eusocial organisms because individuals are typically reared by their siblings. In the fire ant Solenopsis invicta, a social supergene exhibits striking indirect genetic effects on worker regulation of colony queen number, such that the genotypic composition of workers at the supergene determines whether colonies contain a single or multiple queens. We assessed the direct and indirect genetic effects of this supergene on gene expression in brains and abdominal tissues from lab-reared workers and compared these with previously published data from field-collected pre-reproductive queens. We found that direct genetic effects caused larger gene expression changes and were more consistent across tissue types and castes than indirect genetic effects. Indirect genetic effects influenced the expression of many loci but were generally restricted to the abdominal tissues. Further, indirect genetic effects were only detected when the genotypic composition of social partners differed throughout the development and adult life of focal workers, and were often only significant with relatively lenient statistical cutoffs. Our study provides insight into direct and indirect genetic effects of a social supergene on gene regulatory dynamics across tissues and castes in a complex society.

Increasing rice yield has always been one of the primary objectives of rice breeding. However, panicle degeneration, a complex phenomenon regulated by many genetic and environmental factors, often occurs in rice-growing regions and severely curbs rice yield. In this study, we obtained a new apical panicle degeneration mutant named ym48, which induces a marked degeneration rate and diminishes the final grain yield. Cellular and physiological analyses revealed that the apical panicle in ym48 undergoes programmed cell death, accompanied by excessive accumulations of peroxides. Following, the panicle degeneration gene OsCAX1a was identified, which was involved in Ca2+ transport in the ym48 mutant. In OsCAX1a, a relative conserved T to A substitution was noted at the 64th amino acid, which disrupted Ca2+ transport. Hydroponics assays and Ca2+ quantification confirmed that Ca2+ transport and distribution to apical tissues were restricted and over-accumulated in mutant sheath. Ca2+ transport between cytoplasm and vacuole was affected, and the reduced content of Ca2+ in vacuole and cell wall and the decreased of Ca2+ absorption were appeared in ym48 mutant. RNA-Seq data indicated that the abnormal CBL (calcineurin b-like proteins) pathway mediated by deficient Ca2+ might occur in mutant, resulting in the burst of ROS and programmed cell death in panicles. Our results explained the key role of OsCAX1a in Ca2+ transport and distribution and laid a foundation to further explore the genetic and molecular mechanisms of panicle degeneration and the efficiency of Ca2+ fertilization in rice.

Linear IgA bullous dermatosis (LABD) is an autoimmune/inflammatory skin condition. Here, we report on a patient who developed treatment resistant LABD. At diagnosis, elevations of IL-6 and C-reactive protein in the blood and extreme elevations in LABD bullous fluid were seen. The patient responded well to tocilizumab (anti-IL-6 receptor) treatment.

Conventional solid-state power amplifier (SSPA) design approach isolates RF design from communication theory. In this paper, a unified SSPA design approach is proposed which optimizes SSPA parameters (bias voltage and input RF signal power) to minimize total DC power consumption while satisfying received SNR constraint specified by the link budget. The effect of SSPA nonlinearity is quantified by the error vector magnitude measured at its output and the corresponding received SNR degradation is analyzed. Using the quantitative metrics for received SNR, it is possible to evaluate highly nonlinear SSPA classes such as Class-B or deep-Class AB which are normally not considered in conventional SSPA design approach to be used in satellite communication applications.

We recount the life, work, and legacy of the theoretical physicist Roy Glauber (1925-2018). Admitted to Harvard at age sixteen, called upon to participate in the Manhattan Project at age eighteen, and appointed to the Harvard Physics faculty at age twenty-nine, Glauber is credited with seminal contributions to three separate fields of physics: nuclear scattering, statistical physics, and foundational work in quantum optics, which earned him the 2005 Nobel Prize in Physics. Over decades, Glauber was also a dedicated teacher of high-school, college, and graduate students. His pedagogical gifts are reflected in his lucid papers that read as if they were written yesterday.

We describe the case of a patient with a diagnosis of rheumatoid arthritis experiencing a mucocutaneous delayed reaction to golimumab. Anyway, there is no consensus regarding the best management of delayed reactions to biologics. Excluding allergic cross-reactivity or sensitization, we finally tested adalimumab by a graded challenge.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of peripheral T-cell lymphomas (PTCL) and is extremely uncommon in the pediatric population. We present a case of a 15-year-old girl with SPTCL and an unusual involvement of the breast. The FDG-PET/CT showed avid uptake of 18F-FDG in the breast predominantly involving the subcutaneous tissue that improves post treatment. To our knowledge, this is the first case of breast SPTCL reported in pediatric patient. A study published by Goto-et-al in 2019 [(1)](#ref-0001), found only 27 cases of SPTCL under 15 years, including four infants and none of them shown breast involvement.