•A fully-coupled three dimensional analytical model of the monopile offshore wind turbine with a semi-active tuned mass damper (STMD) has been established.•Dynamic response under the combined wind, ...wave and seismic loading is evaluated considering soil effects and damage.•The proposed control algorithm can track the response variation in real-time.•The natural frequency and damping property of the STMD are retuned by the control algorithm.•The STMD outperforms the passive TMD in mitigating the structural and foundation dynamic responses.
The present paper studies the control of monopile offshore wind turbines subjected to multi-hazards consisting of wind, wave and earthquake. A Semi-active tuned mass damper (STMD) with tunable natural frequency and damping ratio is introduced to control the dynamic response. A new fully coupled analytical model of the monopile offshore wind turbine with an STMD is established. The aerodynamic, hydrodynamic and seismic loading models are derived. Soil effects and damage are considered. The National Renewable Energy Lab monopile 5MW baseline wind turbine model is employed to examine the performance of the STMD. A passive tuned mass damper (TMD) is utilized for comparison. Through numerical simulation, it is found that before damage occurs, the wind and wave induced response is more dominant than the earthquake induced response. With damage presence in the tower and the foundation, the nacelle and the tower response is increased dramatically and the natural frequency is decreased considerably. As a result, the passive TMD with fixed parameters becomes off-tuned and loses its effectiveness. In comparison, the STMD retuned in real-time demonstrates consistent effectiveness in controlling the dynamic response of the monopile offshore wind turbines under multi-hazards and damage with a smaller stroke.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•An analytical model of an offshore wind turbine with a three dimensional pendulum tuned mass damper has been established.•The optimum design formula of the three dimensional pendulum tuned mass ...damper is proposed.•The pendulum damper outperforms dual linear tuned mass dampers in mitigating the bi-directional vibration of the nacelle.
Offshore wind turbines suffer from excessive bi-directional vibrations due to wind-wave misalignment and vortex induced vibrations. However, most of existing research focus on unidirectional vibration attenuation which is inadequate for real applications. The present paper proposes a three dimensional pendulum tuned mass damper (3d-PTMD) to mitigate the tower and nacelle dynamic response in the fore-aft and side-side directions. An analytical model of the wind turbine coupled with the 3d-PTMD is established wherein the interaction between the blades, the tower and the 3d-PTMD is modeled. Aerodynamic loading is computed using the Blade Element Momentum method where the Prandtls tip loss factor and the Glauert correction are considered. JONSWAP spectrum is adopted to generate wave data. Wave loading is computed using Morisons equation in collaboration with the strip theory. Via a numerical search approach, the design formula of the 3d-PTMD is obtained and examined on a National Renewable Energy Lab (NREL) monopile 5 MW baseline wind turbine model under misaligned wind, wave and seismic loading. Dual linear tuned mass dampers (TMDs) deployed in the fore-aft and side-side directions are utilized for comparison. It is found that the 3d-PTMD with a mass ratio of 2% can improve the mitigation of the root mean square and peak response by around 10% when compared with the dual linear TMDs in controlling the bi-directional vibration of the offshore wind turbines under misaligned wind, wave and seismic loading.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a ...T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin−Sca-1+c-kit+/loCD25+CD127+) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1−/− mice, but not in Rag2−/−Il2rg−/− mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1−/− mice whereas adoptive transfer of LNH cells enabled Rag2−/−Il2rg−/− mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.
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► Lung natural helper cells produce large amounts of Th2 cell-type cytokines ► Protease allergen stimulates lung natural helper cells ► Stroma-derived cytokines stimulate lung natural helper cells ► Th2 cell-type cytokines from lung natural helper cells induce T cell-independent asthma
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Chronic opioid use imposes a substantial burden in terms of morbidity and economic costs. Whether opioid-naive patients undergoing surgery are at increased risk for chronic opioid use is ...unknown, as are the potential risk factors for chronic opioid use following surgery. OBJECTIVE: To characterize the risk of chronic opioid use among opioid-naive patients following 1 of 11 surgical procedures compared with nonsurgical patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of administrative health claims to determine the association between chronic opioid use and surgery among privately insured patients between January 1, 2001, and December 31, 2013. The data concluded 11 surgical procedures (total knee arthroplasty TKA, total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery FESS, cataract surgery, transurethral prostate resection TURP, and simple mastectomy). Multivariable logistic regression analysis was performed to control for possible confounders, including sex, age, preoperative history of depression, psychosis, drug or alcohol abuse, and preoperatice use of benzodiazepines, antipsychotics, and antidepressants. EXPOSURES: One of the 11 study surgical procedures. MAIN OUTCOMES AND MEASURES: Chronic opioid use, defined as having filled 10 or more prescriptions or more than 120 days’ supply of an opioid in the first year after surgery, excluding the first 90 postoperative days. For nonsurgical patients, chronic opioid use was defined as having filled 10 or more prescriptions or more than 120 days’ supply following a randomly assigned “surgery date.” RESULTS: The study included 641 941 opioid-naive surgical patients (169 666 men; mean SD age, 44.0 12.8 years), and 18 011 137 opioid-naive nonsurgical patients (8 849 107 men; mean SD age, 42.4 12.6 years). Among the surgical patients, the incidence of chronic opioid in the first preoperative year ranged from 0.119% for Cesarean delivery (95% CI, 0.104%-0.134%) to 1.41% for TKA (95% CI, 1.29%-1.53%) The baseline incidence of chronic opioid use among the nonsurgical patients was 0.136% (95% CI, 0.134%-0.137%). Except for cataract surgery, laparoscopic appendectomy, FESS, and TURP, all of the surgical procedures were associated with an increased risk of chronic opioid use, with odds ratios ranging from 1.28 (95% CI, 1.12-1.46) for cesarean delivery to 5.10 (95% CI, 4.67-5.58) for TKA. Male sex, age older than 50 years, and preoperative history of drug abuse, alcohol abuse, depression, benzodiazepine use, or antidepressant use were associated with chronic opioid use among surgical patients. CONCLUSIONS AND RELEVANCE: In opioid-naive patients, many surgical procedures are associated with an increased risk of chronic opioid use in the postoperative period. A certain subset of patients (eg, men, elderly patients) may be particularly vulnerable.
Aims/hypothesis
Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with ...inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS).
Methods
A total of 100 obese women aged 33–51 years with BMI ≥ 28 kg/m
2
and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (
n
= 50) or identical placebo (
n
= 50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes.
Results
At 12 weeks, a total of 92 participants completed this trail. Compared with the placebo group (
n
= 47), histidine supplementation significantly decreased HOMA-IR (−1.09 95% CI −1.49, −0.68), BMI (−0.86 kg/m
2
95% CI −1.55, −0.17), waist circumference (−2.86 cm 95% CI −3.86, −1.86), fat mass (−2.71 kg 95% CI −3.69, −1.73), serum NEFA (−173.26 μmol/l 95% CI −208.57, −137.94), serum inflammatory cytokines (TNF-α, −3.96 pg/ml 95% CI −5.29, −2.62; IL-6, −2.15 pg/ml 95% CI −2.52, −1.78), oxidative stress (superoxide dismutase, 17.84 U/ml 95% CI 15.03, 20.65; glutathione peroxidase, 13.71 nmol/ml 95% CI 9.65, 17.78) and increased serum histidine and adiponectin by 18.23 μmol/l 95% CI 11.74, 24.71 and 2.02 ng/ml 95% CI 0.60, 3.44 in histidine supplementation group (
n
= 45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses
IL6
and
TNF
mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB.
Conclusions/interpretation
Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes.
Trial registration
www.chictr.org/cn/ChiCTR-TRC-11001551
Funding
The study was supported by the National Natural Science Fund of China (No. 81202184, 81130049, 81102112), Heilongjiang Post/doctoral Fund (No. LBN-Z12193) and Key Laboratory of Nutrition and Food Hygiene (Harbin Medical University, Heilongjiang Higher Education Institutions, No. YYKFKT1202).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid ...overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Recent reports have identified a phenomenon by which hypoxia shifts glutamine metabolism from oxidation to reductive carboxylation. We now identify the mechanism by which HIF-1 activation results in ...a dramatic reduction in the activity of the key mitochondrial enzyme complex α ketoglutarate dehydrogenase (αKGDH). HIF-1 activation promotes SIAH2 targeted ubiquitination and proteolysis of the 48 kDa splice variant of the E1 subunit of the αKGDH complex (OGDH2). Knockdown of SIAH2 or mutation of the ubiquitinated lysine residue on OGDH2 (336KA) reverses the hypoxic drop in αKGDH activity, stimulates glutamine oxidation, and reduces glutamine-dependent lipid synthesis. 336KA OGDH2-expressing cells require exogenous lipids or citrate for growth in hypoxia in vitro and fail to grow as model tumors in immunodeficient mice. Reversal of hypoxic mitochondrial function may provide a target for the development of next-generation anticancer agents targeting tumor metabolism.
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•HIF-1 activation reduces mitochondrial OCR while generating anabolic precursors•Hypoxia reduces glutamine oxidation through SIAH2-dependent proteolysis of OGDH2•Active OGDH2 makes cells dependent on exogenous lipids for hypoxic growth•Expression of nondegradable OGDH2 blocks the growth of model tumors
Sun and Denko identify a mechanism by which hypoxia redirects the metabolism of glutamine away from mitochondrial oxidation toward the synthesis of cellular fatty acids in order to support tumor cell proliferation. This work suggests that redirecting the intracellular fate of glutamine may be an effective anticancer therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The process of in situ chemical oxidation (ISCO) by persulfate (S2O82−) can be accelerated by metal ion activation, which more effectively degrades subsurface pollutants by enhancing sulfate radical ...(SO4−) generation. This study compared the results of propachlor degradation by Cu2+ and Fe2+ activated persulfate and revealed differing degradation kinetics and mechanisms between the two types of activation system. The activation of persulfate by Fe2+ ions generally resulted in rapid degradation in the early stage, but was accompanied by a dramatic decrease in efficiency due to the rapid depletion of Fe2+ by the sulfate radicals generated. In contrast, the Cu2+ activated persulfate had a longer lasting degradation effect and a proportionally greater degradation enhancement at elevated Cu2+ concentrations. An optimal Fe2+ concentration should be sought to activate the persulfate, as a high Fe2+ concentration of 2.5mM or above, as was used in this study, may inhibit propachlor degradation due to the competitive consumption of sulfate radicals by the excess Fe2+ ions. Higher temperatures (55°C compared with 30°C) resulted in enhanced metal activation, particularly with the Cu2+ activated system. Furthermore, acidic conditions were found to be more favorable for propachlor degradation by metal activated persulfate. The ecotoxicity of degraded propachlor samples, which was indicated by average well color development (AWCD) for its microbial community activity, was confirmed to be decreased during the degradation processes with these two ions activated persulfate.
► Propachlor can be efficiently degraded by persulfate activated by either Cu2+ or Fe2+ ions. ► Different degradation kinetics was observed in Cu2+ and Fe2+ activated persulfate. ► Reaction conditions influence the activated persulfate differently by Cu2+ and Fe2+. ► The ecotoxicity of propachlor sample was confirmed decreased by Cu2+/Fe2+ activated persulfate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Natural killer (NK) cells are innate lymphocytes that provide critical host defense against pathogens and cancer. Originally heralded for their early and rapid effector activity, NK cells have been ...recognized over the last decade for their ability to undergo adaptive immune processes, including antigen-driven clonal expansion and generation of long-lived memory. This review presents an overview of how NK cells lithely partake in both innate and adaptive responses and how this versatility is manifest in human NK cell-mediated immunity.
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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