Magnetospheric compression due to impact of enhanced solar wind dynamic pressure Pdyn has long been considered as one of the generation mechanisms of electromagnetic ion cyclotron (EMIC) waves. With ...the Van Allen Probe‐A observations, we identify three EMIC wave events that are triggered by Pdyn enhancements under prolonged northward interplanetary magnetic field (IMF) quiet time preconditions. They are in contrast to one another in a few aspects. Event 1 occurs in the middle of continuously increasing Pdyn while Van Allen Probe‐A is located outside the plasmapause at postmidnight and near the equator (magnetic latitude (MLAT) ~ −3°). Event 2 occurs by a sharp Pdyn pulse impact while Van Allen Probe‐A is located inside the plasmapause in the dawn sector and rather away from the equator (MLAT ~ 12°). Event 3 is characterized by amplification of a preexisting EMIC wave by a sharp Pdyn pulse impact while Van Allen Probe‐A is located outside the plasmapause at noon and rather away from the equator (MLAT ~ −15°). These three events represent various situations where EMIC waves can be triggered by Pdyn increases. Several common features are also found among the three events. (i) The strongest wave is found just above the He+ gyrofrequency. (ii) The waves are nearly linearly polarized with a rather oblique propagation direction (~28° to ~39° on average). (iii) The proton fluxes increase in immediate response to the Pdyn impact, most significantly in tens of keV energy, corresponding to the proton resonant energy. (iv) The temperature anisotropy with T⊥ > T|| is seen in the resonant energy for all the events, although its increase by the Pdyn impact is not necessarily always significant. The last two points (iii) and (iv) may imply that in addition to the temperature anisotropy, the increase of the resonant protons must have played a critical role in triggering the EMIC waves by the enhanced Pdyn impact.
Key Points
Three EMIC wave events triggered by various dynamic pressure conditions
Exhibit proton flux increases in expected resonant energy
Exhibit temperature anisotropy with T⊥ > T|| in the resonant energy
There has been a resurgence of complex oxides of late owing to their ferroelectric and ferromagnetic properties. Although these properties had been recognized decades ago, the renewed interest stems ...from modern deposition techniques that can produce high quality materials and attractive proposed device concepts. In addition to their use on their own, the interest is building on the use of these materials in a stack also. Ferroelectrics are dielectric materials that have spontaneous polarization in certain temperature range and show nonlinear polarization-electric field dependence called a hysteresis loop. The outstanding properties of the ferroelectrics are due to non-centro-symmetric crystal structure resulting from slight distortion of the cubic perovskite structure. The ferroelectric materials are ferroelastic also in that a change in shape results in a change in the electric polarization (thus electric field) developed in the crystal and vice versa. Therefore they can be used to transform acoustic waves to electrical signal in sonar detectors and convert electric field into motion in actuators and mechanical scanners requiring fine control. In a broader sense the ferroelectric materials can be used for pyroelectric and piezoelectric sensors, voltage tunable capacitors, infrared detectors, surface acoustic wave (SAW) devices, microactuators, and nonvolatile random-access memories (NVRAMs), including the potential production of one transistor memory cells, and applications requiring nonlinear optic components. Another set of potential applications seeks to exploit the ferroelastic properties in stacked templates where they are juxtaposed to ferromagnetic materials. Doing so would allow the control of magnetic properties with electric field, which is novel. Such templates taking advantage two or more properties acquired a new name and now goes by multiferroics. After a brief historical development, this article discusses technological issues such as growth and processing, electrical and optical properties, piezo, pyro, and ferroelectric properties, degradation, measurements methods, and application of mainly lead-zirconate-titanate (PZT = PbZr
1−x
Ti
x
O
3
). The focus on PZT stems from its large electromechanical constant, large saturation polarization and large dielectric constant.
Summary
Background
Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR‐α). Recent studies demonstrated the disruptive role of ...oltipraz on LXR‐α‐dependent lipogenesis in hepatocytes and a high‐fat diet mouse model.
Aim
To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non‐alcoholic fatty liver disease (NAFLD).
Methods
We performed a multicentre, double‐blind, placebo‐controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome.
Results
Compared with the placebo group (−3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose‐dependent manner: −7.7 ± 7.0% and −13.9 ± 10.7% for the low‐dose and high‐dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high‐dose group than in the placebo group (−34.6 ± 29.4% vs. −0.6 ± 62.9%, P = 0.046). Body mass indices (−1.0 ± 0.9% vs. −0.5 ± 1.4%, P = 0.04) significantly decreased in the high‐dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups.
Conclusions
Twenty‐four‐week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).
Linked ContentThis article is linked to Ajmera and Loomba, Wang and Lin, and Kim and Kim papers. To view this article visit https://doi.org/10.1111/apt.14081, https://doi.org/10.1111/apt.14122 and https://doi.org/10.1111/apt.14146.
We investigated the effects of road transportation and administration of the vitamin E and selenium (ESe) on circulating cortisol, haptoglobin, blood metabolites, oxidative biomarkers, white blood ...cell profiles, and behaviors in pregnant dairy heifers. Forty pregnant Holstein heifers were randomly assigned to one of 4 treatments: no transportation and no ESe administration; no transportation and ESe administration; transportation and no administration; transportation and ESe administration. The ESe (70 IU/kg dry matter feed of DL-α-tocopheryl acetate and 0.3 mg/kg dry matter feed of sodium selenite) was orally delivered once a day from 7 d before transportation to 3 d after transportation. The heifers were transported in trucks designed for cattle transportation. Blood was collected 1 h before transportation, immediately after transportation (IAT), and at 6, 24, and 48 h after transportation. Behaviors were recorded using a video camera for 2 consecutive days after transportation. Transported/non-ESe-administered heifers had greater cortisol at IAT, haptoglobin at 6 h and 24 h after transportation, total oxidative status at 6 h after transportation, and nonesterified fatty acid levels, white blood cell numbers, and neutrophil percentages at IAT and 6 h after transportation in the blood than non-transported heifers. Transported/non-ESe administered heifers had lower total antioxidative status levels at 48 h after transportation and lymphocyte percentages at IAT and 6 h after transportation than non-transported heifers. Lying time was shorter in transported heifers than non-transported/non-ESe-administered heifers. Transported/ESe-administered heifers had lower cortisol, total oxidative status, nonesterified fatty acid levels at IAT, and haptoglobin concentrations at 6 h and 24 h after transportation than transported/non-ESe-administered heifers. Transported/ESe-administered heifers had greater total antioxidative status levels at 48 h after transportation than transported/non-ESe-administered heifers. No ESe administration effects were observed for white blood cell number and neutrophil and lymphocyte percentages and lying time. In conclusion, road transportation caused temporal oxidative stress. Administrating ESe partially alleviated the stress, suggesting that ESe administration could be a viable strategy to reduce stress in transported pregnant heifers, providing a novel role of vitamin E and selenium for improving animal welfare.
Background and Objective: Acupuncture is widely used in complementary and alternative medicine to reduce body weight. However, a systematic review and meta-analysis to assess an effect of acupuncture ...has not yet been performed. Aim of this study is to critically assess evidence for reduction of body weight and to evaluate adverse events of acupuncture therapy based on the results of randomized controlled trials (RCTs) that evaluate the effect of various types of acupuncture therapies. Data sources: A total of 19 electronic databases, including English, Korean, Japanese and Chinese databases, were systematically searched for RCTs of acupuncture for reduction of body weight or improvement in obesity up to March 2008 with no language restrictions. Methods: RCTs for acupuncture compared either with placebo controlled or with comparator intervention were considered. Studies' methodological qualities were assessed using the Jadad scale. If no evidence of heterogeneity existed across study results, statistical pooling of data was performed using a fixed effects model; otherwise, a random effects model was used. Publication bias was assessed using funnel plots. Subgroup analyses were performed according to types of acupuncture. Results: A total of 31 studies, which comprised a total of 3013 individual cases, were systematically reviewed. Owing to insufficient data in 2 RCTs, 29 RCTs were used for meta-analysis. About two-thirds of the trials (20 out of 31) showed the lowest score of the Jadad. Compared to control of lifestyle, acupuncture was associated with a significant reduction of average body weight (95% confidence interval, CI) of 1.72 kg (0.50-2.93 kg) and associated with an improvement in obesity (relative risk=2.57; 95% CI, 1.98-3.34). Acupuncture significantly reduced a body weight of 1.56 kg (0.74-2.38 kg), on average, compared to placebo or sham treatments. Acupuncture also showed more improved outcomes for body weight (mean difference=1.90 kg; 1.66-2.13 kg), as well as for obesity (relative risk=1.13; 1.04-1.22), than conventional medication. Only four RCTs reported acupuncture-related adverse events, which were mostly minimal. Conclusions: Our review suggests that acupuncture is an effective treatment for obesity. However, the amount of evidence is not fully convincing because of the poor methodological quality of trials reviewed. In conclusion, there is an urgent need for well-planned, long-term studies to address the effectiveness of acupuncture for treating obesity.
Protein glycation is a slow natural process involving the chemical modification of the reactive amino and guanidine functions in amino acids by sugars and carbohydrates-derived reactive carbonyls. ...Its deleterious consequences are obvious in the case of long-lived proteins in aged people and are exacerbated by the high blood concentration of sugars in diabetic patients. The non-enzymatic glycation of proteins occurs through a wide range of concurrent processes comprising condensation, rearrangement, fragmentation, and oxidation reactions. Using a few well established intermediates such as Schiff base, Amadori product and reactive a-dicarbonyls as milestones and the results of in vitro glycation investigations, an overall detailed mechanistic analysis of protein glycation is presented for the first time. The pathways leading to several advanced glycation end products (AGEs) such as (carboxymethyl)lysine, pentosidine, and glucosepane are outlined, whereas other AGEs useful as potential biomarkers of glycation are only briefly mentioned. The current stage of the development of glycation inhibitors has been reviewed with an emphasis on their mechanism of action.
Background
Inadequate nurse staffing has been reported to lead nurses to omit required nursing care. In South Korea, to reduce informal caregiving by patient families and sitters and to improve the ...quality of nursing care, a public hospital operated by the Seoul Metropolitan Government has implemented a policy of increasing nurse staffing from 17 patients per registered nurse to 7 patients per registered nurse in 4 out of 13 general nursing units since January 2013.
Aim
The study aims to compare missed nursing care (omission of required care) in high‐staffing (7 patients per nurse) units vs. low‐staffing (17 patients per nurse) units to examine the effects of nurse staffing on missed care.
Methods
A nurse survey conducted in July 2013 targeted all staff nurses in all four high‐staffing and all nine low‐staffing units; 115 nurses in the high‐staffing units (response rate = 94.3%) and 117 nurses in the low‐staffing units (response rate = 88.6%) participated. Missed nursing care was measured using the MISSCARE survey that included 24 nursing care elements. Nurses were asked how frequently they had missed each element on a 4‐point scale from ‘rarely’ to ‘always’.
Results
Overall, nurses working in high‐staffing units had a significantly lower mean score of missed care than those in low‐staffing units. Seven out of 24 nursing care elements were missed significantly less often in high‐staffing (vs. low‐staffing) units: turning, mouth care, bathing/skin care, patient assessments in each shift, assistance with toileting, feeding and setting up meals.
Conclusion
The findings suggest that increasing nurse staffing is associated with a decrease in missed care. Less omission of required nursing care is expected to improve nursing surveillance and patient outcomes, such as patient falls, pressure ulcers and pneumonia.
Implications for nursing and health policy
Adequate nurse staffing should be ensured to reduce unmet nursing needs and improve patient outcomes.
In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer ...(NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression.
Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan–Meier-estimated medians).
In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%–24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups HR, 95% confidence interval (CI); medians: TC ≥25% (0.41, 0.26–0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43–0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33–0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48–1.11; 10.7 versus 5.6 months), 1%–24% 0.49, 0.30–0.80; not reached (NR) versus 9.0 months, and unknown (0.59, 0.42–0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30–0.83; NR versus 21.1 months), <25% (0.89, 0.63–1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41–0.83; NR versus 29.6 months), 1%–24% (0.67, 0.41–1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43–0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71–1.84; 33.1 versus 45.6 months). Safety was similar across subgroups.
PFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.
•Tumour tissue acquisition (pre-chemoradiotherapy) and tumour cell (TC) PD-L1 expression testing were not mandated.•However, outcomes were assessed based on PD-L1 expression in subgroups defined by pre-specified and post hoc TC cut-offs.•Treatment benefit with durvalumab, versus placebo, was observed irrespective of PD-L1 expression in terms of PFS.•OS improvement was demonstrated overall and across all subgroups, apart from the post hoc TC <1% subgroup.•Limitations (few events and baseline imbalances) and a wide CI for OS HR (includes 1) prevent robust conclusions for TC <1%.
This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by ...South Korea's snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation.
Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed.
One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5-83.5)% in the complete VICC group; factor X:94 (83-102) in the non-VICC group vs. 70 (66.5-79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups.
VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC.
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