Search

Zirconium-89 radiolabeled immuno-positron emission tomography (89Zr-iPET) has become a critical tool for patient stratification before and after immunotherapies for therapeutic evaluation. In this study, random and site-specific radiolabeling of 89Zr-iPET tracers were investigated. Traditional lysine-based conjugation and enzyme-based GlyCLICK® kit method were used to prepare DFO-anti-PD-L1-mAb conjugates with a chelator-to-antibody ratio (CAR) of 0–7 and 2.0, respectively. Then, conjugates with different CAR levels were radiolabeled with 89Zr to obtain randomly or site-specifically radiolabeled 89Zr-iPET tracer. [ABSTRACT FROM AUTHOR]

A gamma-ray spectrometry was used to measure radium isotopes in a radium-enriched hot spring area. The activity of 224Ra was highly correlated with 228Ra in water caused by their same chemical behavior and the origin of the decay series chain. Besides, the radioactivity between radium isotopes (226Ra, 228Ra) and the selected chemical analogues in sludge exhibited moderate (Ba and Sr) to strong (Pb) correlations according to linear regression analysis. In contrast, there is less correlation between radium isotopes and 40K. These results reveal that radium isotopes may be transported and distributed together in the environment. [ABSTRACT FROM AUTHOR]

Kinship care and child fostering are a common practice in certain parts of Africa. This narrative review seeks to explore and thematically code the contextual circumstances in which children leave their natal homes and are fostered across Africa and the corresponding outcomes for these children. It draws on case studies from Cameroon, the Democratic Republic of the Congo, Ethiopia, Kenya, and Namibia and other countries across the region to illustrate the diversity and cultural importance of kinship care and child fostering. These countries were selected based on their inclusion in the Thrive by Five International Program, a child rearing program promoting social, emotional, and cognitive development of children from birth to age five. The importance of kinship care and child fostering is also reinforced by outcomes from codesign workshops conducted for the Thrive by Five International Program in which parents, caregivers, and subject matter experts discussed their perspectives on child rearing practices and the challenges faced by caregivers in their home countries. The paper highlights the need to support kinship and foster caregivers in Africa with culturally adapted and place‐based child rearing programs to help ensure fostered children reach their full developmental potential. [ABSTRACT FROM AUTHOR]

Objective: Tracheal resection (TR) and cricotracheal resection (CTR) are performed for patients with airway stenosis, tracheal tumor, and tracheoesophageal fistula. Post‐operative complications include airway edema requiring reintubation, hematoma, anastomotic dehiscence, restenosis, and death. Although these complications and associated risk factors have been well described, the time where clinical suspicion should be highest post operatively has not been characterized. Methods: Patients who underwent TR or CTR at a single center between 2015 and 2022 were reviewed. Variables including demographics and comorbidities were recorded. Rate, nature, and time in days of post‐operative complications were evaluated. Results: Sixty‐nine cases were reviewed. Average patient age was 46.8 years old and 63.8% were male. The average follow‐up period was 625 ± 724 days. 19 (27.5%) patients experienced one or more major complications including four (5.8%) who died. Eight (11.6%) patients required reintubation and 4 (5.8%) patients underwent revision tracheostomy. Most complications occurred within 8 days of surgery. Restenosis was noted an average of 42.6 days after surgery, with no new restenosis occurring after 3 months. Conclusions: In this single‐center study, most post‐operative complications after TR or CTR, including hematoma and anastomotic dehiscence, occurred within 8 days post‐operatively. Restenosis was noted approximately 1–3 months after surgery. This may inform clinical decision‐making regarding patient monitoring and surveillance after open airway surgery. Level of Evidence: 4 Laryngoscope, 134:3527–3531, 2024 [ABSTRACT FROM AUTHOR]

Mobile health (mHealth) interventions in low-and middle-income countries (LMICs) have considerable potential to advance social and human development through the equitable delivery of health information and enabling self-care for disadvantaged populations. Involving stakeholders through co-design positively impacts the development of mHealth solutions and, in turn, their social, economic, and human development outcomes. The complex systems and multifaceted contexts confronted in co-design present barriers. This work focuses on barriers encountered in mHealth co-design in LMICs, related principally to culture, language, and technology. It presents a toolkit highlighting methods to best overcome such barriers, aiming to strengthen 'mobile phones for development' research and practice. Additionally, it provides an illustrative example of applying the toolkit. By presenting this toolkit to overcome barriers and create opportunities for realising health outcomes from information and communications technology (ICT) implementation, this article contributes to the fields of ICT for development, participatory design, and population and digital health. [ABSTRACT FROM AUTHOR]

Hypsizygus marmoreus mushroom is known for its pleasant flavour and delicious taste. However, its flavour quality deteriorates rapidly during postharvest storage. In the present work, we explored the dynamic changes in flavour-presenting substances and taste components in H. marmoreus packaged in polyethylene nanofilm (0.05 mm) during low temperature storage (12 days). We used headspace solid-phase microextraction combined with gas chromatography-mass spectrometry to analyse the volatile flavour components; high performance liquid chromatography and liquid chromatography-mass spectrometry to analyse the non-volatile flavour (taste-presenting) substances (e.g., soluble sugars, taste nucleotides, free amino acids, and organic acids); and the relative odour activity value (ROAV) and taste active value (TAV) methods to determine the flavour substances in fresh and stored H. marmoreus. Results revealed that n-octanal, 1-octene-3-one, and 1- octene-3-ol were the characteristic volatile flavour substances, and that trans-2-octenal was the key substance affecting the formation of volatile flavours in fresh H. marmoreus. Trans,trans-2,4-nonadienal, and 3-octanone were the key volatile substances that resulted in flavour deterioration. Among the non-volatile flavour substances, trehalose, 5'-GMP, glutamic acid, alanine, and arginine were the key taste-presenting substances. In addition, oxalic acid and lysine were the key taste substances after H. marmoreus deterioration. These results provided a theoretical basis for rapid quality detection, flavour identification, and shelf-life prediction of H. marmoreus. [ABSTRACT FROM AUTHOR]

Objectives: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea. Methods: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021. Results: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities. Conclusion: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs. [ABSTRACT FROM AUTHOR]

Bone grafting is a fundamental dental surgery procedure widely used for implant placement and periodontal disease management treatments. Despite its broad applications, vertical bone augmentation presents unique challenges, including the risk of graft displacement due to gravitational and masticatory forces. Traditional physical stabilization methods introduce additional complexities and risks, underscoring the need for innovative fixation technologies. This study aimed to develop an in situ photo-crosslinkable bioadhesive hydrogel (iPBAH) as a multifunctional bone graft binder to enhance the process of bone reconstruction. The bioadhesive is composed of mussel-derived adhesive protein (MAP) fused with the cell-adhesive peptide RGD. The numerous tyrosine residues in MAP facilitate rapid photo-crosslinking, enabling efficient hydrogel formation using visible blue light. Subsequently, iPBAH underwent comprehensive characterization to evaluate its suitability as a multifunctional bone graft binder. iPBAH efficiently underwent in situ crosslinking through harmless exposure to visible light within minutes and displayed several exceptional properties, including a microporous structure, underwater adhesion, extended durability, high compressive strength, and biocompatibility. In vivo assessments, using male Sprague-Dawley rats, demonstrated that iPBAH binder significantly enhanced bone regeneration in a rat calvarial bone defect model. The in situ crosslinking of the iPBAH binder during bone graft transplantation can effectively fill irregular and complex defect shapes while simultaneously preventing graft material leakage. The improved physical attributes of the bound graft material can enhance its resistance to external forces, thereby ensuring sustained retention over time. Moreover, the interaction between iPBAH and surrounding tissues promotes adhesion and integration of the graft material with host tissues in the defect area. In addition, the included RGD peptide in iPBAH can augment inherent cell recruitment, adhesion, and growth, consequently expediting osteogenesis. [ABSTRACT FROM AUTHOR]

Extreme climate events are becoming more frequent, with poorly understood implications for carbon sequestration by terrestrial ecosystems. A better understanding will critically depend on accurate and precise quantification of ecosystems responses to these events. Taking the 2019 US Midwest floods as a case study, we investigate current capabilities for tracking regional flux anomalies with "top‐down" inversion analyses that assimilate atmospheric CO2 observations. For this analysis, we develop a regionally nested version of the NASA Carbon Monitoring System‐Flux system for North America (CMS‐Flux‐NA) that allows high resolution atmospheric transport (0.5° × 0.625°). Relative to a 2018 baseline, we find the 2019 US Midwest growing season net carbon uptake is reduced by 11–57 TgC (3%–16%, range across assimilated CO2 data sets). These estimates are found to be consistent with independent "bottom‐up" estimates of carbon uptake based on vegetation remote sensing (15–78 TgC). We then investigate current limitations in tracking regional carbon budgets using "top‐down" methods. In a set of observing system simulation experiments, we show that the ability of atmospheric CO2 inversions to capture regional carbon flux anomalies is still limited by observational coverage gaps for both in situ and satellite observations. Future space‐based missions that allow for daily observational coverage across North America would largely mitigate these observational gaps, allowing for improved top‐down estimates of ecosystem responses to extreme climate events. Plain Language Summary: Extreme climate events, such as floods or heatwaves, can have major impacts on the carbon cycle. For example, widespread flooding in the US Midwest during 2019 delayed the planting of crops leading to reduced plant growth and carbon uptake relative to 2018. Here, we test how well this reduction in carbon uptake can be inferred from measurements of atmospheric CO2. We find that these data can identify reduced net carbon uptake to the US Midwest during the 2019 floods, but that sparse observational coverage limits our ability to quantify the anomaly in net carbon uptake. We show that expanded space‐based observations of CO2 would fill these gaps, allowing for improved estimates of interannual variations in the US CO2 budget. Key Points: Bottom‐up and top‐down methods capture reduced 2019 US Midwest carbon uptake relative to 2018Gaps in atmospheric CO2 observations drive uncertainties in top‐down estimatesNested inversion better localizes US Midwest ΔNEE relative to coarse global model [ABSTRACT FROM AUTHOR]

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC–MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4–2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of thyroidectomy‐related posts on TikTok, the fastest‐growing social media platform worldwide. Methods: Videos posted from April 2020 to September 2022 were queried on TikTok using the search terms "thyroidsurgery," "thyroidectomy," and "thyroidremoval." Two reviewers recorded thematic, demographic, and performance data of these posts. The DISCERN instrument was used to evaluate the quality and reliability of the information contained in the videos. Descriptive statistics were used to characterize post‐submitter demographics and video content. Simple and multiple linear regression analyses were used to evaluate the association between DISCERN scores and video characteristics. Univariate analysis of variance was performed to compare DISCERN scores between author types. Results: In this study, 228 TikTok videos were included which totaled over 23 million views. On average, each video accumulated more than 6000 "likes," 300 comments, and 70 shares. The average total DISCERN score was 27.46, which is deemed to be of poor overall quality. Upon multiple linear regression, video duration (β = 4.66, p <.001) and educational subject type (β = 3.97, p <.001) significantly positively predicted aggregate DISCERN scores, while journey subject type (β = −3.19, p =.006), and reassurance subject type (β = −2.52, p =.035) significantly negatively predicted aggregate DISCERN scores. Aggregate DISCERN scores varied significantly (p <.05) between author types. Conclusion: Social media posts on TikTok about thyroidectomy are mostly of poor quality and reliability but vary by authorship, subject type, and video characteristics. Given its widespread popularity, TikTok videos may have an increasing role in shaping patient perception of thyroidectomy and may represent an opportunity to provide education. Lay summary: TikTok posts about thyroidectomy are mostly of poor quality but vary by authorship, subject, and video characteristics. Given its popularity, TikTok videos may have a role in shaping the patient perception of thyroidectomy and may represent an opportunity to provide education. Level of evidence: Level 4. [ABSTRACT FROM AUTHOR]

Background Considering the prolongation of the COVID-19 pandemic, the lack of studies on burnout, particularly in healthcare workers, needs to be addressed. This report aimed to identify the risk factors of burnout by comparing the level of burnout between nurses in general wards and those in COVID-19-dedicated wards in a national university hospital. Methods A survey based on the Korean version of Burnout Assessment Tool (BAT-K) was conducted on nurses between 10 January and 31 January 2022. The BAT-K consists of exhaustion, mental distance, cognitive impairment, emotional impairment and secondary symptoms. Results A total of 165 nurses, including 81 nurses from the COVID-19-dedicated ward, completed the questionnaire. The percentage of general-ward nurses with an emotional impairment score above the clinical cutoff was higher than that of COVID-19 ward nurses. General ward compared to the COVID-19 ward increased the risk of presenting with total-core symptoms. Two factors increased the risk regarding mental distance: short career length and underlying disease. Conclusions In contrast to previous studies, the risk of burnout in the COVID-19-ward nurses was lower than that of the general ward nurses. The risk regarding mental distance was correlated with short career length and presence of an underlying disease. [ABSTRACT FROM AUTHOR]

In this research, 153 employees at a National Laboratory received one of four different phishing emails. All of the emails were similar in content, but systematically varied according to the number and combination of phishing tactics in the message. Participants were unaware they would be receiving the email, which was sent during regular business hours. After receiving the emails, participants completed online questionnaires designed to measure possible predictors of phishing attack susceptibility. The significant predictors included how suspicious participants were of the email and their reported level of distress related to their work prior to completing the study. [ABSTRACT FROM AUTHOR]

Background: Digital technologies are widely recognized for their equalizing effect, improving access to affordable health care regardless of gender, ethnicity, socioeconomic status, or geographic region. The Thrive by Five app is designed to promote positive interactions between children and their parents, extended family, and trusted members of the community to support socioemotional and cognitive development in the first 5 years of life and to strengthen connections to culture and community. Objective: This paper aims to describe the iterative co-design process that underpins the development and refinement of Thrive by Five's features, functions, and content. Minderoo Foundation commissioned this work as a quality improvement activity to support an engaging user experience and inform the development of culturally appropriate and relevant content for parents and caregivers in each country where the app is implemented. Methods: The app content, referred to as Collective Actions, comprises "The Why," that presents scientific principles that underpin socioemotional and cognitive development in early childhood. The scientific information is coupled with childrearing activities for parents, extended family, and members of the community to engage in with the children to support their healthy development and to promote positive connections between parents, families, and communities and these young children. Importantly, the initial content is designed and iteratively refined in collaboration with a subject matter expert group from each country (ie, alpha testing). This content is then configured into the app (either a beta version or localized version) for testing (ie, beta testing) by local parents and caregivers as well as experts who are invited to provide their feedback and suggestions for improvements in app content, features, and functions via a brief web-based survey and a series of co-design workshops. The quantitative survey data will be analyzed using descriptive statistics, whereas the analysis of qualitative data from the workshops will follow established thematic techniques. Results: To date, the co-design protocol has been completed with subject matter experts, parents, and caregivers from 9 countries, with the first results expected to be published by early 2023. The protocol will be implemented serially in the remaining 21 countries. Conclusions: Mobile technologies are the primary means of internet connection in many countries worldwide, which underscores the potential for mobile health programs to improve access to valuable, evidence-based, and previously unavailable parenting information. However, for maximum impact, it is critically important to ensure that mobile health programs are designed in collaboration with the target audience to support the alignment of content with parents' cultural values and traditions and its relevance to their needs and circumstances. [ABSTRACT FROM AUTHOR]

Objective  Skull base osteoradionecrosis (SB-ORN) is a serious, potentially lethal complication of radiation therapy. We aimed to review the clinical characteristics and outcomes of SB-ORN according to the extent of treatment. Design  Retrospective analysis design was used for this study. Setting  The study was conducted in two tertiary care hospitals. Participants  Patients included who had been clinically diagnosed with SB-ORN from January 2006 to 2017. Main Outcome Measures  Clinical characteristics, including demographics, predisposing factors, presenting symptoms, radiological findings, treatment modalities, and treatment outcomes, were reviewed. Treatment was classified into conservative and aggressive types. Aggressive treatment included radical surgical removal of soft tissue and bony sequestrum with the placement of vascularized tissue. Treatment outcome was analyzed in terms of clinical control, survival, and carotid artery blow out. Results  Fifteen patients (11 males and 4 females) were identified during the study period. Eight patients were managed conservatively, whereas seven patients were managed with aggressive treatment. The 2-year survival was 75% in the aggressive treatment group and 15% in the conservative group (log-rank, p  = 0.049). The estimated 2-year blow out free rate was 46.7% for the conservative group and 100% for the aggressive group (log-rank, p  = 0.100). Conclusion  In patients with SB-ORN, aggressive management, including surgical removal of sequestrum and coverage with a pedicled flap, is associated with increased survival. [ABSTRACT FROM AUTHOR]

We found the signatures of the multiple prompt penetration electric fields and the disturbance dynamo electric field having impacts on the East Asian sector ionosphere along the meridional chain thoroughly from the equator, low‐mid to high latitudes during the space weather event of 3–5 November 2021. The observation is made on global positioning system‐total electron content (GPS‐TEC), digisonde, and magnetometer stations. In the main phase of the storm, intense modulations of vertical total electron content (VTEC) and critical frequency (foF2) are observed as coherently fluctuating with interplanetary electric field (IEF) and IMF Bz reorientations. It is diagnosed that the oscillations in the disturbance polar current 2 (DP2) current system directly penetrate meridianally from high to equatorial latitudes, leading to the significant changes in ionospheric electrodynamics that governs the density fluctuations. The wavelet spectra of VTEC, foF2, h'F (virtual height), H‐components and IEF give a result of common and dominant periodicity occurring at ∼1 hr. This result suggests that the wavelike oscillations of VTEC and foF2 and H component are associated with prompt penetration electric fields. Plain Language Summary: Geomagnetic storm time electrodynamics of the ionosphere is severely affected by magnetospheric convection electric field induced by solar wind‐induced magnetospheric dynamo, and ionospheric disturbance dynamo (DD) generated by global thermospheric wind circulation and joule heating at high latitude. The Magnetospheric convection electric field can penetrate instantly into the equatorial ionosphere known as prompt penetration (PP) electric field, while, the thermospheric wind and its associated disturbances can reach the equator with a time delay. During the main phase of the storm, observations showed intense modulations in vertical total electron content (VTEC), critical frequency from equator to high latitudes associated with PP electric fields. In recovery phase, disturbances in VTEC, foF2, and virtual height (h'F) are caused by either DD electric field or traveling ionospheric disturbances. Further analysis in this study suggests the evidence of causal relationship among the interplanetary electric field, disturbance polar current 2 current system, and ionospheric density oscillations. Wavelets analysis shows a common and dominant periodicity of ∼1 hr in interplanetary and ionospheric parameters. Key Points: Prompt penetration electric fields signature observed along the ionosphere meridian in East‐AsiaInfiltration of disturbance polar current 2 current to the equator to cause the ionospheric density fluctuationsThe oscillations of the observed parameters (total electron content, frequency of F2, and H‐component) along the meridional chain coincide with that of interplanetary electric field at a ∼1 hr periodicity [ABSTRACT FROM AUTHOR]

Solar cells made from Cu2ZnSn(S,Se)4 (CZTS)-derived materials have been widely studied for their favourable material properties utilized in photovoltaic energy conversion. Drawbacks of the materials are associated with low open circuit voltage (Voc) resulting from non-radiative recombination at grain boundaries and interfaces. Considerable work has focused on the incorporation of sodium (Na), which is found to passivate trap states and reduce electronic losses. Here we present evidence that Na+ as well as several ionic species (Se2− and Zn2+), do not remain stationary after device fabrication, but in fact migrate under electrical biasing. Furthermore, this ionic migration can be manipulated at room temperature by exposing the device to an external electric forming field. We outline a novel procedure that can effectively control and adjust ionic movement and associated local distribution in fully fabricated devices. Our results show that this simple treatment leads to favourable improved device performance and provides insight into light-induced reduction in performance which may be partially reversible. [ABSTRACT FROM AUTHOR]

There is an increasing interest in using magnetic resonance imaging (MRI) as a tool for precision medicine in autism spectrum disorder (ASD). This study investigated the feasibility of MRI scanning in a large comprehensive, inclusive and test heavy clinical trial for children (aged 3–12 years) with ASD, without functioning constraints for participation. Of the 71 participants enrolled who consented to the MRI, 24 participants (38%) successfully completed an MRI scan at baseline along with other assessments. This scanning followed a familiarization procedure at two preceding visits. At post-treatment, 21 participants successfully completed the MRI scan. This study highlights the challenge of completing MRI assessments in ASD populations when conducted as one of a number of tests in a clinical trial. [ABSTRACT FROM AUTHOR]

In the pursuit of sustainable development, there is a rapid increase in the generation of biodiesel, which eventually results in the synthesis of glycerol as a major by-product. The surplus amount of glycerol from biodiesel industries is one of the rising environmental concerns. Alternatively, glycerol can serve as an attractive raw material for synthesizing value-added products that offer simultaneous management and valorization of this waste. 1,3-propanediol is a vital value-added material having extensive applications in the industrial domain. Microbial biosynthesis of 1,3-propanediol from glycerol has proven to be an economic and eco-friendly approach. However, biosynthesis of this bio-product is often affected by some environmental stresses, such as glycerol and 1,3-propanediol concentrations, accumulation of 3-hydroxypropionaldehyde, and by-product synthesis. To overcome the influences of these factors as well as to improve 1,3-propanediol yield, efforts have been devoted over the past years, which mostly included the application of metabolic engineering strategies to transform microbial strains into robust cell factories. This review focuses on the environmental stresses restricting 1,3-propanediol biosynthesis, and how these restrictions could be overcome using the metabolic engineering strategies. In this context, some technological and strategical aspects, including rechanneling metabolic flux in co-producing strains, rebalancing of co-factors and gene expression, co-culture and co-substrate fermentation, and application of untranslated region engineering. It also discusses the role of key enzymes involved in 1,3-propanediol biosynthesis and the influence of polyhydroxyalkanoate granule-associated protein on the tolerance to high concentration of this bio-product. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular "plaques". The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5–20 μM had no effect on contractility. Conversely, Aβ25-35 (1–50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD. [ABSTRACT FROM AUTHOR]

Recently, electrical switching of interface states in nonferromagnet/ferromagnet (FM)/antiferromagnet (AFM) heterostructure using spin–orbit torque (SOT) is promising due to its high efficiency, zero magnetic field, and multilevel memory state. However, the reversal mechanism of the AFM interface state is still unclear. In this work, we explained the bipolar current switching of the AFM interface state at zero magnetic field by spin–orbit torque (SOT) in a perpendicularly magnetized Pt/Co/IrMn multilayer. By considering symmetry, we reveal that the mechanism behind the AFM interface bipolar current switching is consistent with FM layers perpendicularly switching induced by SOT. The distinct AFM bipolar current switching by SOT is contributed to the symmetry broken by adjacent FM interface coupling. Under such broken symmetry, the antiparallel interface configuration (AP) between FM and AFM could be switched to parallel configuration (P) for both positive and negative currents; however, P is only allowed to be switched to the AFM multiple domain configuration (M), instead of AP. Our result will be helpful for the formulation of a comprehensive understanding of AFM switching induced by SOT and for the development of the interface AFM spintronic devices. [ABSTRACT FROM AUTHOR]

Background: Using uniaxial accelerometry approach in measuring physical activity levels of individuals with Down syndrome (DS) might underestimate their energy expenditure due to the unique mediolateral walking pattern. Therefore, the purpose of this study was to examine and compare the relationship between two types of accelerometer outputs, uniaxial and triaxial, and energy expenditure in individuals with and without DS. Methods: Eighteen participants with DS and 19 participants without DS wore a GT3X+ accelerometer and a portable metabolic system in three different walking conditions. Results: Correlations between V̇O2 and each of the two accelerometer outputs (uniaxial: r = 0.75, triaxial: r = 0.75) were not significantly different among individuals without DS (z = 0.14, P = 0.89); however, significant differences in the relationship between V̇O2 and accelerometer outputs (uniaxial: r = 0.53, triaxial: r = 0.64) were observed among individuals with DS (z = −1.72, P < 0.046). Conclusions: The findings suggest that when using accelerometers to measure physical activity levels for individuals with DS, triaxial outputs may better predict physical activity levels. [ABSTRACT FROM AUTHOR]

Differential diagnosis in adult cohorts with social difficulty is confounded by comorbid mental health conditions, common etiologies, and shared phenotypes. Identifying shared and discriminating profiles can facilitate intervention and remediation strategies. The objective of the study was to identify salient features of a composite test battery of cognitive and mood measures using a machine learning paradigm in clinical cohorts with social interaction difficulties. We recruited clinical participants who met standardized diagnostic criteria for autism spectrum disorder (ASD: n = 62), early psychosis (EP: n = 48), or social anxiety disorder (SAD: N = 83) and compared them with a neurotypical comparison group (TYP: N = 43). Using five machine-learning algorithms and repeated cross-validation, we trained and tested classification models using measures of cognitive and executive function, lower- and higher-order social cognition and mood severity. Performance metrics were the area under the curve (AUC) and Brier Scores. Sixteen features successfully differentiated between the groups. The control versus social impairment cohorts (ASD, EP, SAD) were differentiated by social cognition, visuospatial memory and mood measures. Importantly, a distinct profile cluster drawn from social cognition, visual learning, executive function and mood, distinguished the neurodevelopmental cohort (EP and ASD) from the SAD group. The mean AUC range was between 0.891 and 0.916 for social impairment versus control cohorts and, 0.729 to 0.781 for SAD vs neurodevelopmental cohorts. This is the first study that compares an extensive battery of neuropsychological and self-report measures using a machine learning protocol in clinical and neurodevelopmental cohorts characterized by social impairment. Findings are relevant for diagnostic, intervention and remediation strategies for these groups. [ABSTRACT FROM AUTHOR]

Background: Models including an interaction term and performing a joint test of SNP and/or interaction effect are often used to discover Gene-Environment (GxE) interactions. When the environmental exposure is a binary variable, analyses from exposure-stratified models which consist of estimating genetic effect in unexposed and exposed individuals separately can be of interest. In large-scale consortia focusing on GxE interactions in which only the joint test has been performed, it may be challenging to get summary statistics from both exposure-stratified and marginal (i.e not accounting for interaction) models. Results: In this work, we developed a simple framework to estimate summary statistics in each stratum of a binary exposure and in the marginal model using summary statistics from the "joint" model. We performed simulation studies to assess our estimators' accuracy and examined potential sources of bias, such as correlation between genotype and exposure and differing phenotypic variances within exposure strata. Results from these simulations highlight the high theoretical accuracy of our estimators and yield insights into the impact of potential sources of bias. We then applied our methods to real data and demonstrate our estimators' retained accuracy after filtering SNPs by sample size to mitigate potential bias. Conclusions: These analyses demonstrated the accuracy of our method in estimating both stratified and marginal summary statistics from a joint model of gene-environment interaction. In addition to facilitating the interpretation of GxE screenings, this work could be used to guide further functional analyses. We provide a user-friendly Python script to apply this strategy to real datasets. The Python script and documentation are available at https://gitlab.pasteur.fr/statistical-genetics/j2s. [ABSTRACT FROM AUTHOR]

The stability, structural geometry, and electronic structure of the La-doped Sr1.9375La0.0625TiO3.968 75 are investigated by first-principles calculations based on the density functional theory. The calculated results reveal that the oxygen vacancies have a tendency to distribute in the ab planes of the perovskite SrTiO3 layer. The structural stability of Sr1.9375La0.0625TiO3.968 75 is weakened by the simultaneous substitution of La for Sr and the introduction of oxygen vacancies. After electron doping, the lattice parameter a increases while the lattice parameter c decreases. The corner-shared TiO6 octahedra dominate the main electronic properties of Sr2TiO4 and the Sr1.9375La0.0625TiO3.968 75 system shows n-type degenerate semiconductor features. There is an incipient localization of some of the doped electrons being trapped in the oxygen vacancy. The introduction of oxygen vacancy in Sr2TiO4 makes little contribution to the electrical activity of Sr1.9375La0.0625TiO3.968 75. [ABSTRACT FROM AUTHOR]

We study the effects of plasma etching on the evolution of surface roughness of GaN and AlN. The etch-induced roughness is investigated using atomic force microscopy by systematically varying plasma power, chamber pressure, and Cl2/Ar mixture gas composition. GaN etches three to four times more rapidly than AlN for identical plasma conditions. For both GaN and AlN, we find that the surface roughness is correlated to etch rate. Induced roughness remains comparable to the as-grown value provided etching is carried out below rates 400 (GaN) and 90 nm/min (AlN). Above these cutoff etch rates, the roughness increases in proportion to etch rate. This result is independent of plasma parameters varied to produce the higher etching rates. By analyzing the surface properties through the power spectral density (PSD), we correlate roughness with the formation of fine-scale features present as a consequence of more aggressive etching. The cutoff etch rates and spatial-frequency dependence of the PSD are interpreted using the theory of kinetic roughening. A low-frequency range exhibits saturation corresponding to large-scale feature sizes, and a high-frequency regime exhibits scaling properties. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Luminescent silicon oxides containing radiative centers were obtained by using two different techniques. Silicon rich silicon oxides (SRSOs) were fabricated by rf magnetron sputter deposition and Ge-implanted SiO[sub 2] films were fabricated by ion implantation following the thermal oxidation of Si. Blue and violet photoluminescence were observed from the SRSO and the Ge-implanted SiO[sub 2], respectively. However, the electroluminescence (EL) spectra from both oxides exhibited red and near-infrared luminescence bands. Strong EL was observed only under reverse bias conditions on metal-luminescent oxide-semiconductor structures. The EL intensity and peak position were varied with applied voltages. According to the EL and current-voltage measurements, it is concluded that the possible EL mechanism is the impact ionization of ground state electrons in the radiative centers. [ABSTRACT FROM AUTHOR]

The way to calculate and share the total amount of ecological compensation for inter-basin water transfer project is directly related to the enthusiasm of the water-receiving area in participating in the ecological protection of the water source area. This paper takes the water source area of the South-to- North Water Diversion Project and the water-receiving areas of Beijing, Tianjin, Hebei and Henan as the research objects, and using the single-index method, the comprehensive index method and the deviation method to make appropriate calculation for the ecological compensation amount of 6.248 billion yuan paid to the water source area each year by the water receiving area. The results show that the method of deviation is more objective, comprehensive and reasonable, which can provide a new idea for the ecological compensation apportion calculation of the Central Line of South-to-North Water Diversion Project. [ABSTRACT FROM AUTHOR]

This study was conducted to characterize 17 sugarcane genotypes from Hawaii and Thailand using 12 target region amplification polymorphism (TRAP) markers and partial Sai nucleotide polymorphism. A total of 275 fragments were produced, of which 273 (99.27%) were polymorphic. The polymorphic information content (PIC) ranged from 0.912-0.959 with an average value of 0.938. Genetic similarity (GS) by Dice's similarity coefficient ranged from 0.19-0.81 with a mean of 0.44. The 14 sugarcane genotypes from the Thailand collection with different sugar content were also assessed. A total of 198 fragments were found, of which 174 (87.88%) were polymorphic. The PIC value ranged from 0.860-0.937 with an average value of 0.914. The GS ranged from 0.49-0.85 with a mean of 0.71. The dendrograms constructed by the UPGMA cluster indicate strong differentiation between the Thai sugarcane genotypes and the Hawaiian sugarcane genotypes. In addition, S. officinarum is the group most closely associated with modern sugarcane. The partial Sai nucleotide sequence of 16 sugarcane genotypes from Hawaii and Thailand comprised 608-692 bp, within exon 2. There were 49 single nucleotide polymorphisms (SNPs) and two sites of variation including insertion and deletion (In/Del). Sai nucleotide polymorphism data matrices produced a more refined phylogenetic tree that shows four distinct groups. The results derived from nucleotide sequencing were somewhat similar to those derived from the TRAP markers. Thus, the utilization of informative TRAP and Sai nucleotide sequencing for a genetic variation study can result in the selection of diverse sugarcane parents for trait of sucrose content. [ABSTRACT FROM AUTHOR]

Background: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited. Objectives: To assess the efficacy of DMF in Japanese patients with RRMS. Methods: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase. Results: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks. Conclusions: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients. [ABSTRACT FROM AUTHOR]

Microparticles (MP) are regarded both as biomarkers and mediators of many forms of pathology, including neurovascular inflammation. Here, we characterized vectorial release of apical and basolateral MPs (AMPs and BMPs) from control and TNF-α/IFN-γ treated human brain endothelial monolayers, studied molecular composition of AMPs and BMPs and characterized molecular pathways regulating AMP and BMP release. The effects of AMPs and BMPs on blood-brain barrier properties and human brain microvascular smooth muscle tonic contractility in vitro were also evaluated. We report that human brain microvascular endothelial cells release MPs both apically and basolaterally with both AMP and BMP release significantly increased following inflammatory cytokine challenge (3.5-fold and 3.9-fold vs. control, respectively). AMPs and BMPs both carry proteins derived from parent cells including those in BBB junctions (Claudin−1, −3, −5, occludin, VE-cadherin). AMPs and BMPs represent distinct populations whose release appears to be regulated by distinctly separate molecular pathways, which depend on signaling from Rho-associated, coiled-coil containing protein kinase (ROCK), calpain as well as cholesterol depletion. AMPs and BMPs modulate functions of neighboring cells including BBB endothelial solute permeability and brain vascular smooth muscle contractility. While control AMPs enhanced brain endothelial barrier, cytokine-induced AMPs impaired BBB. Cytokine-induced but not control BMPs significantly impaired human brain smooth muscle contractility as early as day 1. Taken together these results indicate that AMPs and BMPs may contribute to neurovascular inflammatory disease progression both within the circulation (AMP) and in the brain parenchyma (BMP). [ABSTRACT FROM AUTHOR]

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014–November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2–degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10−6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10−8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the factors that affect immediate (within 24 h after farrowing onset) postnatal piglet mortality in litters with hyperprolific sows, and investigate their associations with behaviour of postpartum sows in two different farrowing housing systems. A total of 30 sows were housed in: (1) CRATE (n =15): the farrowing crate closed (0.80×2.20 m) within a pen (2.50×1.70 m), and (2) OPEN (n =15): the farrowing crate open (0.80×2.20×1.80 m) within a pen (2.50×2.40 m) with a provision of 20 ls of hay in a rack. A total of 518 live born piglets, produced from the 30 sows, were used for data analyses during the first 24 h after the onset of parturition (T24). Behavioural observations of the sows were assessed via video analyses during T24. Total and crushed piglet mortality rates were higher in OPEN compared with CRATE (P <0.01, for both). During T24, the OPEN sows tended to show higher frequency of postural changes (P =0.07) and duration of standing (P =0.10), and showed higher frequencies of bar-biting (P <0.05) and piglet trapping (P <0.01), when compared with the CRATE sows. During T24, the mortality rates caused by crushing were correlated with the piglet trapping event (r =0.93, P <0.0001), postural changes (r =0.37, P <0.01), duration of standing (r =0.32, P <0.01) and frequency of bar-biting behaviour (r =0.51, P <0.01) of the sows (n =30). In conclusion, immediate postnatal piglet mortality, mainly due to crushing, may be associated with potential increases in frequency of postural changes, duration of standing and incidence of piglet trapping in postpartum sows in the open crate system with large litters. [ABSTRACT FROM AUTHOR]

Since the middle of the last decade, UCSD has incorporated magnetic field data in its Institute for Space‐Earth Environmental Research interplanetary scintillation tomographic analysis. These data are extrapolated upward from the solar surface using the Current Sheet Source Surface model (Zhao & Hoeksema, 1995, https://doi.org/10.1029/94JA02266) to provide predictions of the interplanetary field in RTN coordinates. Over the years this technique has become ever more sophisticated, and allows different types of magnetogram data (SOLIS, Global Oscillation Network Group, etc.,) to be incorporated in the field extrapolations. At Earth, these fields can be displayed in a variety of ways, including Geocentric Solar Magnetospheric (GSM) Bx, By, and Bz coordinates. Displayed daily, the Current Sheet Source Surface model‐derived GSM Bz shows a significant positive correlation with the low‐resolution (few day variation) in situ measurements of the Bz field. The nano‐Tesla variations of Bz maximize in spring and fall as Russell and McPherron (1973, https://doi.org/10.1029/JA078i001p00092) have shown. More significantly, we find that the daily variations are correlated with geomagnetic Kp and Dst index variations, and that a decrease from positive to negative Bz has a high correlation with minor‐to‐moderate geomagnetic storm activity, as defined by NOAA Space Weather Prediction Center planetary Kp values. Here we provide an 11‐year study of the predicted Bz field, from the extrapolation of the Global Oscillation Network Group‐magnetograms. We provide a skill‐score analysis of the technique's geomagnetic storm prediction capability, which allows forecasts of moderate enhanced geomagnetic storm activity. UCSD and the Korean Space Weather Center currently operate a website that predicts this low‐resolution GSM Bz field component variation several days in advance. Key Points: Solar magnetic fields are projected outward through the interplanetary medium to provide a daily prediction and forecast of GSM BzThe GSM Bz field decreases we predict are shown to provide a forecast of minor to moderate geomagnetic storm activityOur predicted GSM Bz amplitude variations are shown to maximize near the times of the vernal and autumnal equinoxes [ABSTRACT FROM AUTHOR]

The aims of this randomised controlled study were to determine whether the application of silicone adhesive dressings with standard preventive care would reduce the impairment of skin integrity and to evaluate the subepidermal moisture (SEM) value in anatomical locations to predict impairment of skin integrity. Of the 71 intensive care unit patients enrolled, 35 and 31 were randomly assigned to the intervention and control groups, respectively. The SEM value was measured at each site (the coccyx, sacrum, and both buttocks) repeatedly three times at every dressing change. Collected data were analysed by multivariate linear regression, and least square means analysis was used to compare the SEM value at the sites of pressure injury (PI) and blanching erythema. There were fewer PIs (1 vs 9) and incidences of blanching erythema (5 vs 6) in the intervention group than in the control group (P = 0.006). The SEM value and difference of the SEM value from the initial value was higher in the group with PIs than in the group without PIs (P < 0.0001 and P = 0.001, respectively). There was a statistically significant difference in the incidence of impaired skin integrity between the groups. The SEM value may be an indicator for detecting impairment of skin integrity. [ABSTRACT FROM AUTHOR]

Pressure ulcers result in financial losses, including the cost of unnecessary medical expenses because of extended hospital stays, treatment, and examination. This was a retrospective, observational, methodological study to develop quality indicators related to pressure ulcer development and validate risk adjustment factors for pressure ulcer development. We performed a literature review to develop risk adjustment factors, and an expert group performed a content validity test. To validate risk adjustment factors for pressure ulcer development using electronic medical records, 127 patients admitted to a long‐term care hospital in South Korea from June to September 2015 were enrolled in the study. Pressure ulcer risk factors were peripheral vascular disease, end‐stage disease, past pressure ulcer history, high risk group for pressure ulcer development, fever, haemoglobin, and albumin (all P < 0.05); only albumin (odds ratio: 0.210, P < 0.001) was significantly associated with pressure ulcer development as an independent risk factor. Further research with a large sample size is needed for the validation of risk adjustment factors. Risk‐adjusted quality indicators for pressure ulcer development can be used to evaluate the quality of nursing care and compare outcomes after preventive pressure ulcer care activities or between long‐term care hospitals. [ABSTRACT FROM AUTHOR]

This study aimed to investigate Korean nurses' level of knowledge, attitude, and performance of pressure ulcer prevention in long‐term care facilities. A descriptive study was performed. Convenience sampling was used, and registered nurses were recruited from the attendees of a continuing education programme for nurses in long‐term care facilities. A total of 282 participants (RN) completed the questionnaire. Data were collected from September to December 2015. Nurses participating in this study demonstrated a moderate level of knowledge of pressure ulcer prevention (60.1%) and exhibited positive attitudes towards pressure ulcer prevention (33.80 ± 2.48). Nurses regularly assessed the risk factors of pressure ulcers during the hospitalisation period for all patients in the hospital when performing pressure ulcer prevention care. However, the plan for preventive nursing care was not properly reviewed. It was also found that nurses did not consider changes in the patient's condition as important to why they had to change their nursing plans to prevent pressure ulcer. Therefore, this study suggested that appropriate guidelines, education programmes, and an environment that makes it possible to provide continuing education should be created for nurses to prevent pressure ulcers in Korea's long‐term care facilities. [ABSTRACT FROM AUTHOR]

Aims Salivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance. Methods We verified the relationship between AMY1 CNVs and homeostatic model assessment.insulin resistance (HOMA-IR) in a cohort of 1257 Korean men aged 20.65 years who visited two medical centres for regular health check-ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≤ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded. Results AMY1 CNVs correlated negatively with HOMA-IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMAIR were more evident among non-smokers and regular drinkers and were non-significant among smokers and nonregular drinkers. Conclusions Low AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

This paper examines the effect of different tax rates (domestic and foreign) on cash holdings between multinational firms and non-multinational firms. Our major findings are: 1) multinational firms' cash holdings level (cash-to-asset ratio) is affected by both the domestic tax rates and the foreign tax rates. The higher the domestic tax rates and/or foreign tax rates, the lower the cash held by the multinational firms. 2) Domestic tax rates negatively affect non-multinational firms' cash holdings level. The higher the domestic tax rates, the lower the holding of cash (cash-to-asset ratio); 3) Compared to non-multinational firms, multinational firms' cash holding is less affected by domestic tax rates; 4) Multinational firms tend to shift income from US to foreign countries when domestic tax rates are higher than foreign tax rates. 5) Among multinational firms, those with higher proportion of income in foreign countries tend to have higher levels of cash holdings when domestic tax rates are higher than the foreign tax rates. Our findings are also consistent with the precautionary motive of cash holding for the non-multinational firms. i.e. those smaller, and hence more likely to be financially constrained firms, are more likely to hold more cash. [ABSTRACT FROM AUTHOR]

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension. [ABSTRACT FROM AUTHOR]