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SummaryWe performed a meta-analysis of relevant studies to quantify the magnitude of the association between proton pump inhibitors (PPIs) and risk of hip fracture. Patients with PPIs had a greater risk of hip fracture than those without PPI therapy (RR 1.20, 95% CI 1.14–1.28, p < 0.0001). These results could be taken into consideration with caution, and patients should also be concerned about the inappropriate use of PPIs.IntroductionProton pump inhibitors (PPIs) are generally considered as first-line medicine with great safety profile, commonly prescribed for gastroesophageal reflux disease (GERD) and peptic ulcer disease. However, several epidemiological studies documented that long-term use of PPIs may be associated with an increased risk of hip fracture. Although, the optimal magnitude of the hip fracture risk is still undetermined. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between PPIs and risk of hip fracture.MethodsWe collected relevant articles using MEDLINE, EMBASE, Google Scholar, and Web of Science from January 1, 1990, to March 31, 2018. We included only the large (n ≥ 500) observational studies with a follow-up duration of at least one year in which the hip fracture patients were identified by a standard procedure. Two of the authors extracted data from each included study independently according to a standardized protocol.ResultsA total of 24 observational studies with 2,103,800 participants (319,568 hip fracture patients) met all the eligibility criteria. Patients with PPIs had a greater risk of hip fracture than those without PPI therapy (RR 1.20, 95% CI 1.14–1.28, p < 0.0001). An increased association was also observed in both low and medium doses of PPI taken and hip fracture risk (RR 1.17, 95% CI 1.05–1.29, p = 0.002; RR 1.28, 95% CI 1.14–1.44, p < 0.0001), but it appeared to be even greater among the patients with higher dose (RR 1.30, 95% CI 1.20–1.40, p < 0.0001). Moreover, the overall pooled risk ratios were 1.20 (95% CI 1.15–1.25, p < 0.0001) and 1.24 (95% CI 1.10–1.40, p < 0.0001) for the patients with short- and long-term PPI therapy, respectively, compared with PPI non-users.ConclusionOur results suggest that PPI use is significantly associated with an increased risk of hip fracture development, which is not observed in H2RA exposure. Physicians should, therefore, exercise caution when considering a long-term PPI treatment to their patients who already have an elevated risk of hip fracture. In addition, patients should be concerned about the inappropriate use of PPIs; if necessary, then, they should continue to receive it with a clear indication.

Condensed matter physics has been driven forward by significant experimental and theoretical progress in the study and understanding of equilibrium phase transitions based on symmetry and topology. However, nonequilibrium phase transitions have remained a challenge, in part due to their complexity in theoretical descriptions and the additional experimental difficulties in systematically controlling systems out of equilibrium. Here, we study a one-dimensional chain of 72 microwave cavities, each coupled to a superconducting qubit, and coherently drive the system into a nonequilibrium steady state. We find experimental evidence for a dissipative phase transition in the system in which the steady state changes dramatically as the mean photon number is increased. Near the boundary between the two observed phases, the system demonstrates bistability, with characteristic switching times as long as 60 ms—far longer than any of the intrinsic rates known for the system. This experiment demonstrates the power of circuit QED systems for studying nonequilibrium condensed matter physics and paves the way for future experiments exploring nonequilbrium physics with many-body quantum optics.

This study investigates the intraseasonal variability of tropical cyclones (TCs) by systematically examining the two major components of the intraseasonal oscillation (ISO), the 30–60-day Madden–Julian oscillation (MJO) and the 10–20-day quasi-biweekly oscillation (QBWO). Results suggest that these two ISO modes exhibit different origins, spatial scales, and propagation characteristics, which result in distinctive TC modulation in the western North Pacific Ocean (WNP). The northeastward-propagating MJO predominantly controls the basinwide TC frequency. The significant increase (reduction) in cyclogenesis in the convective (nonconvective) phase is found to be associated with the concomitant strengthening (weakening) of the monsoon trough. In addition, the large contrast in TC frequency also results in a significant difference in daily accumulated cyclone energy (ACE) between the convective and nonconvective MJO phases. The northwestward-propagating QBWO, in contrast, is characterized by alternating signals of positive and negative convection. It leads to the opposite TC modulation in the WNP1 (°8–30°N, 120°–150°E) and WNP2 (0°–30°N, 150°E–180°) regions and results in a northwestward shift in TC genesis locations, which in turn causes substantial differences in intensity distribution and daily ACE for different QBWO phases. Finally, a brief examination of the dual mode situation suggests that the QBWO generally exerts modulation upon the background MJO, and the modulation seems to vary under different MJO conditions.

Background There are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy. Patients and methods Multi-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies. Results In total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2–53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (r s  = 0.15, p  < 0.05-r s  = 0.48 p  < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN. Conclusion The historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.

This study investigates how tropical cyclone (TC) tracks and landfalls are modulated by the two major components of the intraseasonal oscillation (ISO), the 30–60-day Madden–Julian oscillation (MJO) and the 10–20-day quasi-biweekly oscillation (QBWO). In the convective phases of the MJO (phases 7 + 8 and 1 + 2), the western North Pacific Ocean (WNP) is mainly clustered with westward- and northwestward-moving TCs. The strong easterlies (southeasterlies) in the southern flank of the subtropical high lead to an increase in TC activity and landfalls in the Philippines and Vietnam (China and Japan) in phase 7 + 8 (phase 1 + 2). In the nonconvective phases (phases 3 + 4 and 5 + 6), TCs change from the original straight-moving type to the recurving type, such that the tendency for landfalls is significantly reduced. The QBWO, on the other hand, has a significant influence on TC landfalls in the Philippines and Japan. The strengthening of the subtropical high in phase 1 + 2 favors the development of westward-moving TCs and results in an increase in landfalls in the Philippines, while in phase 3 + 4 (phase 5 + 6), there is an increase (decrease) in TC activity and landfalls in Japan because of changes in genesis locations and large-scale circulations. The results herein suggest that both the MJO and QBWO exert distinctive impacts on TCs in the WNP.

Lithium-ion batteries (LIBs) are widely used in electrical vehicles (EVs), but safety issues with LIBs still occur frequently. State of charge (SOC) and state of health (SOH) are two crucial parameters for describing the state of LIBs. However, due to inconsistencies that may occur among hundreds to thousands of battery cells connected in series and parallel in the battery pack, these parameters can be difficult to estimate accurately. To address this problem, this paper proposes a joint SOC and SOH estimation method based on the nonlinear state space reconstruction (NSSR) and long short-term memory (LSTM) neural network. An experiment testbed was set up to measure the SOC and SOH of battery packs under different criteria and configurations, and thousands of charging/discharging cycles were recorded. The joint estimation algorithms were validated using testbed data, and the errors for SOC and SOH estimation were found to be within 2.5% and 1.3%, respectively, which is smaller than the errors obtained using traditional Ah-Integral and LSTM-only algorithms.

This study examines persistent and short-lived heavy precipitation events (PHPEs and SHPEs, respectively) in South China during summer (July–September) 1975–2009 in association with large-scale circulation and moisture processes at different timescales. Compared to SHPEs, PHPEs are characterized by long-lasting enhanced convection and cyclonic moisture circulation as well as strengthened moisture convergence over South China. Examination of environmental variables at different timescales suggests that intraseasonal and synoptic components play a deterministic role in regulating the overall changes in convection and moisture convergence, while the low-frequency background state plays only a marginal role. Further analysis of the moisture divergence terms also reveals that the overall changes in moisture divergence during PHPEs and SHPEs stem primarily from variations in the intraseasonal and synoptic wind fields rather than in the humidity fields. Overall, it is found that the location and strength of the intraseasonal oscillation (ISO) and the synoptic disturbances play a decisive role in controlling the severity and duration of rainfall events over South China. The synchronization and persistence of the enhanced convection and moisture circulation of the ISO and synoptic disturbances jointly contribute to prolonged heavy precipitation over South China, while the weakening and asynchrony of the associated convection and moisture circulation at different timescales result in rainfall events of weaker intensity and shorter duration.

High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL -negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV; n =89), essential thrombocythemia (ET; n =57), primary myelofibrosis (PMF; n =60), post-PV MF ( n =14), post-ET MF ( n =7) and blast phase PV/ET/MF ( n =12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% ( P =0.50). Mutant TET2 was detected in ∼17 and ∼7% of JAK2 V617F-positive and -negative cases, respectively ( P =0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients ( P <0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted ( P =0.05). We conclude that TET2 mutations occur in both JAK2 V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.

Summary This study is a prospective cluster-randomized controlled clinical trial involving 710 elderly subjects to investigate the long-term effects of low-magnitude high-frequency vibration (LMHFV) on fall and fracture rates, muscle performance, and bone quality. The results confirmed that LMHFV is effective in reducing fall incidence and enhancing muscle performance in the elderly. Introduction Falls are direct causes of fragility fracture in the elderly. LMHFV has been shown to improve muscle function and bone quality. This study is to investigate the efficacy of LMHFV in preventing fall and fractures among the elderly in the community. Methods A cluster-randomized controlled trial was conducted with 710 postmenopausal females over 60 years. A total of 364 participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18 months; 346 participants served as control. Fall or fracture rate was taken as the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9, and 18 months. Results With an average of 66.0 % compliance in the vibration group, 18.6 % of 334 vibration group subjects reported fall or fracture incidences compared with 28.7 % of 327 in the control (adjusted HR = 0.56, p  = 0.001). The fracture rate of vibration and control groups were 1.1 and 2.3 % respectively ( p  = 0.171). Significant improvements were found in reaction time, movement velocity, and maximum excursion of balancing ability assessment, and also the quadriceps muscle strength ( p  < 0.001). No significant differences were found in the overall change of BMD. Minimal adverse effects were documented. Conclusion LMHFV is effective in fall prevention with improved muscle strength and balancing ability in the elderly. We recommend its use in the community as an effective fall prevention program and to decrease related injuries.