903 research outputs found
Increased Risk of Ischemic Stroke during Sleep in Apneic Patients.
BACKGROUND AND PURPOSE:The literature indicates that obstructive sleep apnea (OSA) increases the risk of ischemic stroke. However, the causal relationship between OSA and ischemic stroke is not well established. This study examined whether preexisting OSA symptoms affect the onset of acute ischemic stroke. METHODS:We investigated consecutive patients who were admitted with acute ischemic stroke, using a standardized protocol including the Berlin Questionnaire on symptoms of OSA prior to stroke. The collected stroke data included the time of the stroke onset, risk factors, and etiologic subtypes. The association between preceding OSA symptoms and wake-up stroke (WUS) was assessed using multivariate logistic regression analysis. RESULTS:We identified 260 subjects with acute ischemic strokes with a definite onset time, of which 25.8% were WUS. The presence of preexisting witnessed or self-recognized sleep apnea was the only risk factor for WUS (adjusted odds ratio=2.055, 95% confidence interval=1.035-4.083, p=0.040). CONCLUSIONS:Preexisting symptoms suggestive of OSA were associated with the occurrence of WUS. This suggests that OSA contributes to ischemic stroke not only as a predisposing risk factor but also as a triggering factor. Treating OSA might therefore be beneficial in preventing stroke, particularly that occurring during sleep
Creating Value with Acquisition Based Dynamic Capabilities (ABDC): A Study of Mergers and Acquisitions in the Regulated Energy Industry
M&A research has consistently shown that value is destroyed for a majority of acquirers. Despite initial small positive gains at deal announcement, within a year of closing the transaction a majority of acquirers experience overall negative returns. Nevertheless, the constant pressures to grow leave company leaders few other viable options than pursuing M&A. This ever present cycle of value destruction is of interest to both scholars and practitioners. Of interest is what can be done differently by the acquirer to prevent the inevitable value erosion from occurring. To investigate this question, the author develops an adapted version of the Acquisition Based Dynamic Capabilities (ABDC) framework, a theoretical extension of Dynamic Capability theory. The framework is helpful in identifying what corporate M&A capabilities contribute to value creation through a transaction lifecycle. The adapted ABDC framework provides a means to quantify the differing impacts to value creation among the M&A capabilities of “Selecting and Identifying”, “Transacting and Executing” and “Reconfiguring and Integrating”.
The empirical study utilizes 337 regulated energy, public company transactions, closed between 1995 and 2014. This industry is appropriate to study the application of this theory as it benefits from long dated deal timelines and specific milestone events (deal announcement, regulatory approval, financial closing, etc.) providing clear points of delineation for measurement purposes. Performance is measured using weak and semi-strong specifications of shareholder returns with a “golden set” of measures identified. Additionally, the impacts on the ABDC measures from shock waves, bandwagon effects, management traits, financial factors, deal complexity and other relevant factors are all evaluated to test for their impacts on the analyzed transactions. The results suggest that despite many acquirers receiving some positive value accretion from announcement and short-term post-closing returns, larger one year post-close reductions in value eclipse previous gains for most acquirers. The results validate the importance of the Reconfiguring and Integrating (R&I) phase of an acquisition. Comparisons to Top and Poor Performers provide a clear set of recommendations for future energy industry acquirers
HierSpeech++: Bridging the Gap between Semantic and Acoustic Representation of Speech by Hierarchical Variational Inference for Zero-shot Speech Synthesis
Large language models (LLM)-based speech synthesis has been widely adopted in
zero-shot speech synthesis. However, they require a large-scale data and
possess the same limitations as previous autoregressive speech models,
including slow inference speed and lack of robustness. This paper proposes
HierSpeech++, a fast and strong zero-shot speech synthesizer for text-to-speech
(TTS) and voice conversion (VC). We verified that hierarchical speech synthesis
frameworks could significantly improve the robustness and expressiveness of the
synthetic speech. Furthermore, we significantly improve the naturalness and
speaker similarity of synthetic speech even in zero-shot speech synthesis
scenarios. For text-to-speech, we adopt the text-to-vec framework, which
generates a self-supervised speech representation and an F0 representation
based on text representations and prosody prompts. Then, HierSpeech++ generates
speech from the generated vector, F0, and voice prompt. We further introduce a
high-efficient speech super-resolution framework from 16 kHz to 48 kHz. The
experimental results demonstrated that the hierarchical variational autoencoder
could be a strong zero-shot speech synthesizer given that it outperforms
LLM-based and diffusion-based models. Moreover, we achieved the first
human-level quality zero-shot speech synthesis. Audio samples and source code
are available at https://github.com/sh-lee-prml/HierSpeechpp.Comment: 16 pages, 9 figures, 12 table
A Novel Defined TLR3 Agonist as an Effective Vaccine Adjuvant
Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to be stable since its appearance, concentration, and molecular size were unaffected under 6 months of accelerated storage conditions. Moreover, preclinical evaluation of toxicity under good laboratory practices showed that NVT is a safe substance without any signs of serious toxicity. NVT stimulated TLR3 and increased the expression of viral nucleic acid sensors TLR3, MDA-5, and RIG-1. When intramuscularly injected into C57BL/6 mice, ovalbumin (OVA) plus NVT highly increased the migration of dendritic cells (DCs), macrophages, and neutrophils into inguinal lymph node (iLN) compared with OVA alone. In addition, NVT substantially induced the phenotypic markers of DC maturation and activation including MHC-II, CD40, CD80, and CD86 together with IFN-β production. Furthermore, NVT exhibited an appropriate adjuvanticity because it elevated OVA-specific IgG, in particular, higher levels of IgG2c (Th1-type) but lower IgG1 (Th2-type). Concomitantly, NVT increased the levels of Th1-type T cells such as IFN-γ+CD4+ and IFN-γ+CD8+ cells in response to OVA stimulation. Collectively, we suggest that NVT with appropriate safety and effectiveness is a novel and promising adjuvant for vaccines, especially those requiring T cell mediated immunity such as viral and cancer vaccines
Materials and extracellular matrix rigidity highlighted in tissue damages and diseases: Implication for biomaterials design and therapeutic targets
Rigidity (or stiffness) of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors, such as contractility, motility, and spreading, and the resultant pathophysiological phenomena. Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events, including migration, lineage specification, and mechanical memory. Moreover, the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control, tissue repair, and disease progression. Thus, here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors, with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems, further discussion of the events and considerations in tissue-mimicking 3D conditions, and then examination of the in vivo findings that concern material/matrix rigidity. The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues
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