•The type and volume of frames changes as a sustainability transition undergoes deepening or expansion.•Political and industry opportunity structures affect changes in how actors frame their policy ...positions.•As a transition advances, incumbent resistance may increase and opportunity structures may close.•When industry opportunity structures close, the volume of framing activity increases and challenger-incumbent frames diverge.•When political opportunity structures close, economic-consumer frames may increase over environmental frames.
Sustainability transitions often involve policy conflicts, especially when incumbents perceive threats to their business models, and conflicts involve framing of competing positions in the public sphere. Using the case of the growth of distributed solar energy in the U.S. electricity sector, this study shows how the concepts of industry and political opportunity structures can help to explain variation in discursive strategy. First, when incumbents perceive the growth of the challenger as a threat, the industry opportunity structure closes, the volume of framing activity in the public sphere increases as contention grows, and the differentiation in framing (the ratio of pro- to anti-transition frames) between incumbents and challengers increases. Second, with respect to the political opportunity structure, the selection of frame types (environmental versus economic-consumer) varies in relationship to control of the government by conservative or progressive parties. Theoretical implications for transitions studies are discussed.
We have demonstrated that intensive cognitive training can produce sustained improvements in cognitive performance in adolescents. Few studies, however, have investigated the neural basis of these ...training effects, leaving the underlying mechanism of cognitive plasticity during this period unexplained.
In this study, we trained 51 typically developing adolescents on cognitive control tasks and examined how their intrinsic brain networks changed by applying graph theoretical analysis. We hypothesized that the training would accelerate the process of network integration, which is a key feature of network development throughout adolescence.
We found that the cognitive control training enhanced the integration of functional networks, particularly the cross-network integration of the cingulo-opercular network. Moreover, the analysis of additional data from older adolescents revealed that the cingulo-opercular network was more integrated with other networks in older adolescents than in young adolescents.
These findings are consistent with the hypothesis that cognitive control training may speed up network development, such that brain networks exhibit more mature patterns after training.
Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of ...suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
One dimension of the emerging politics of connected and automated vehicles (CAVs) is the development of public concerns over their societal implications and associated policy issues. This ...study uses original survey data from the United States to contribute to the anticipation of future policy and political issues for CAVs. Several studies have surveyed the public regarding CAVs; however, there are few studies that highlight the multidimensional public concerns that CAVs will most likely bring. The study breaks down the concept of “public” by showing that the demographic variables of gender, age, race, ethnicity, income, location (rural, suburban, urban), and political ideology (conservative, moderate, liberal) are significantly associated with three of the most salient public concerns to date (safety, privacy, and data security). Furthermore, the effects of demographic variables also vary across the type of policy issue. For example, women tend to be more concerned about safety than their male counterparts, and Hispanics (Latinx) tend to be more concerned about privacy than non-Hispanics. The research shows how the social scientific analysis of the “politics” of CAVs will require attention to the variegated connections between different types of public concern and different demographic variables.
Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the ...most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.
Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological ...mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls.
Neuroinflammation was measured as the distribution volume ratio (DVR) of 11C-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls.
Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of 11C-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls.
To the authors' knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using 11C-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adolescence is a unique period in which higher cognition develops to adult-level, while plasticity of neuron and behavior is at one of its peak. Notably, cognitive training studies for adolescents ...has been sparse and neural correlates of the training effects yet to be established. This study investigated the effects of multi-component training of cognitive control (MTCC) in order to examine whether the training enhanced adolescents' cognitive control ability and if the effects were generalizable to other cognitive domains. Cognitive control refers to the ability to adjust a series of thoughts and behaviors in correspondence to an internal goal, and involves inhibition, working memory, shifting, and dual tasking as subcomponents. The participants were middle school students (aged 11-14) and randomly assigned to either a training group or an active control group. The training group performed 30 min of MTCC per day for 6 weeks. To identify the training effects, we examined the cognitive performance, regional gray matter, and their relationship. The training group showed modest improvement in a visuospatial fluid intelligence test (Block Design) after MTCC, which was not significant after correcting for multiple comparisons. In addition, the training effect on the gray matter volume (time × group interaction) was observed in the right inferior cortex (rIFC). While the control group showed a typical reduction in the rIFC volume, the training group showed a relative increase in the homologous region. The relative change in rIFC volume was associated with the change in Stroop performance. These results imply that MTCC may affect brain structure relevant to inhibitory control process.
In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased ...quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population and considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root-
consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer.
Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function ...remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses.
In this study, 750 older adults with mild cognitive impairment and Alzheimer's disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion.
The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions.
Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous group of mature T-cell neoplasms that comprise 10–15% of non-Hodgkin lymphoma cases in the United States. All subtypes of PTCL, except for ...ALK
+
anaplastic T-cell lymphoma, are associated with poor prognosis, with median overall survival (OS) rates of 1–3 years. The diagnosis of PTCL is mainly based on clinical presentation, morphologic features, and immunophenotypes. Recent advances in genome sequencing and gene expression profiling have given new insights into the pathogenesis and molecular biology of PTCL. An enhanced understanding of its genomic landscape holds the promise of refining the diagnosis, prognosis, and management of PTCL. In this review, we examine recently discovered genetic abnormalities identified by molecular profiling in 3 of the most common types of PTCL:
RHOA
G
17
V
and epigenetic regulator mutations in angioimmunoblastic T-cell lymphoma, ALK expression and JAK/STAT3 pathway mutations in anaplastic T-cell lymphoma, and T-follicular helper phenotype and GATA3/TBX21 expression in PTCL-not otherwise specified. We also discuss the implications of these abnormalities for clinical practice, new/potential targeted therapies, and the role of personalized medicine in the management of PTCL.
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