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Aquifers provide integral freshwater resources and host ecosystems of largely uncharacterized, truncated endemic microorganisms. In recent history, many aquifers have become increasingly contaminated from various anthropogenic sources. To better understand the impacts of nitrogen contamination on native groundwater ecosystems, 16S rRNA sequencing of the groundwater microbial communities was carried out. Samples were taken from an aquifer known to be contaminated with nitrogen from multiple sources, including fertilizers and wastewater treatment plant effluents. In total, two primary contaminants were identified: NH4+ (<0.1–3.7–26 mg L−1 NH4+ min-median-max), and NO3− (<0.01–18–150 mg L−1 NO3− min-median-max). These contaminants were found to be associated with a decrease/increase in microbial species richness within affected groundwater for NH4+/NO3−, respectively. Important phyla were identified, including Proteobacteria, which had the highest abundance within samples unaffected by NH4+ (36–81% NH4+ unaffected, 4–33% NH4+ affected), and Planctomycetes (0.05–10% NH4+ unaffected, 43–72% NH4+ affected), which had the highest abundance within the NH4+ affected samples, likely due to its ability to perform anaerobic ammonia oxidation (ANAMMOX). Planctomycetes were identified as a potential indicator for the presence of NH4+ contamination. The analysis and characterization of sequencing data alongside physicochemical data showed potential to increase the depth of our understanding of contaminant behavior and fate within a contaminated aquifer using this type of data and analysis.

Inhibition of the proteasome with Bortezomib as well as inhibition of Polo-like-kinase-1 (PLK-1) has been shown to be effective in many solid tumour models and also in squamous cell carcinoma of the head and neck (SCCHN) cell lines. For the first time, we systematically examined the antitumour effect of Bortezomib in combination with BI2536 in SCCHN in an in vitro study. Dose escalation studies were performed with nine SCCHN cell lines using Bortezomib and BI2536 as single agent and combination treatments. Growth-inhibitory and pro-apoptotic effects were measured quantitatively using cytohistology and Human Apoptose Array kit. The combination of Bortezomib and BI2536 showed significant anti-proliferative and apoptotic activity in all SCCHN cell lines investigated (P=0.008) compared to both the untreated control group and Bortezomib alone. A combination treatment regime consisting of the proteasome inhibitor, Bortezomib, and the inhibitor of PLK-1, BI2536, leads to an enhanced anti-proliferative and apoptotic effect in SCCHN cell lines, compared to single agent treatment with Bortezomib alone.

Objective The objective of this prospective, single-subject, repeated measures study was to evaluate the audiological benefit and patient satisfaction with an adhesive, pressure-free bone conduction hearing system (ADHEAR; MED-EL, Innsbruck, Austria) in patients who underwent middle ear surgery with transient hearing loss due to auditory canal tamponade. Methods Eleven adult subjects suffering from transient conductive hearing loss were enrolled in the study and followed up to 3 weeks after middle ear surgery. Bone and air conduction thresholds were measured pre and postoperatively to evaluate eligibility for enrollment. Postoperative unaided and aided sound-field thresholds, as well as speech tests in quiet and noise were compared to confirm hearing improvement with the hearing system. To determine patient satisfaction, the SSQ12 and a system-specific quality of life questionnaire was administered to all subjects. Results Speech perception for monosyllables in quiet improved by 46%, with statistical significance for the ADHEAR system compared to the unaided condition after one week. The functional hearing gain improved by 19 dB. Speech perception in noise with the device was − 6.7 dB SNR on average, with a statistically significant improvement of 2.7 dB SNR. The results of the questionnaire showed a high level of patient satisfaction and subjective hearing improvement. No serious skin reactions or other severe complications occurred. Conclusion As long as the auditory canal is blocked due to tamponade, patients benefit from hearing rehabilitation. This adhesive hearing system is a safe and effective device to treat transient conductive hearing loss and may considerably improve treatment for patients even with short-term hearing loss.

Nitrogen contamination is ubiquitous across the globe; as a result of this, the need to understand and predict the extent and effects of nitrogen contamination on microbial ecosystems is increasingly important. This paper utilises a dataset that provides a rare opportunity to observe varying contamination conditions in a single aquifer and understand the differences between potential background bores and two different types of contamination spread across the other bores. Using physicochemical and microbiological community analysis, this paper aims to determine the impacts of the two contaminants, nitrate and ammonia, on the microbial communities and the differences between polluted and physicochemical background bores. Total nitrogen (N) varied by a factor of over 2000 between bores, ranging from 0.07 to 155 mg L−1. Nitrate (NO3−) concentrations ranged from 150 to <0.01 mg L−1; ammonium (NH4+) concentrations ranged from 26 to <0.1 mg L−1. MANOVA analysis confirmed an overall significant relationship (p = 0.0052) between N variables and the physicochemical data (or status) of the three areas of contamination dubbed ‘contamination zones’. The contamination zones were defined by no known presence of contamination in the uncontaminated bores, the presence of NO3− contamination and the presence of NO3− and NH4+ contamination. PERMANOVA analysis confirmed that there was an overall significant difference in the microbial communities between the three contamination zones (p = 0.0002); however, the presence of NH4+ had a significant effect (p = 0.0012). In general, the nitrate-contaminated bores showed a decrease in the abundance of individual OTUs. We further confirmed that NH4+ contamination had a significant relationship with an increased percentage of abundance occupied by the Planctomycetota phylum (specifically the Candidatus Brocadia genus). It was found that one of the two background bores (BS-004) was likely also representative of natural microbial background, and another (BS-002) showed characteristics that may be representative of past or intermittent contamination. This paper demonstrates a possible way to determine the microbial background and discusses the potential uses for this information.

Inhibition of the Polo-like-kinase-1 (PLK1) has been shown to be effective in a number of solid tumor models. In this in vitro study, we examined the antitumor effect of BI2536, a small molecule inhibitor of PLK1, in squamous cell carcinoma of the head and neck (SCCHN) cell lines. Dose escalation studies were performed with nine SCCHN cell lines using BI2536. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptosis Array Kit. BI2536 demonstrated a significant antiproliferative and apoptotic activity in all nine SCCHN cell lines investigated (p<0.009). Our results indicate that inhibition of PLK1 by BI2536 leads to an antiproliferative and apoptotic effect in SCCHN cell lines. In vivo and in the clinical setting, the application of BI2536 may support the antitumoral activity of conventional drugs that are in current use and could decrease the systemic toxicity of these drugs.

Inhibition of the polo-like-kinase-1 (PLK-1) has been shown to be effective in several haematological and solid tumor models. In this systemic in vitro study, the antitumor effect of BI2536, a small molecule inhibitor of PLK-1, in combination with cisplatin and docetaxel was examined in nine squamous cell carcinoma cell lines, most of which had a head and neck origin (SCCHN). Dose escalation studies were conducted with nine SCCHN cell lines using BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptose Array kit. BI2536 in combination with cisplatin and docetaxel showed a markedly higher antiproliferative and apoptotic activity in the SCCHN cell lines investigated (P≤0.008), compared with single agent cisplatin or docetaxel alone. The findings of this study showed that the addition of PLK-1-inhibitor BI2536 to conventional chemotherapeutic drugs led to a statistically higher antiproliferative and apoptotic effect in SCCHN cell lines compared with cisplatin or docetaxel alone. Inaugurating BI2536 in the clinical setting might enhance the antitumoral activity of conventional drugs, possibly leading to less toxic side effects of cancer therapy.

SYRUP of senega is one of the most troublesome syrups which the pharmacist has to deal with, owing to the separation of pectin compounds and its liability to crystallize and gelatinize.

Policy Points Dissemination of Choosing Wisely guidelines alone is unlikely to reduce the use of low‐value health services. Interventions by health systems to implement Choosing Wisely guidelines can reduce the use of low‐value services. Multicomponent interventions targeting clinicians are currently the most effective types of interventions. Context Choosing Wisely aims to reduce the use of unnecessary, low‐value medical services through development of recommendations related to service utilization. Despite the creation and dissemination of these recommendations, evidence shows low‐value services are still prevalent. This paper synthesizes literature on interventions designed to reduce medical care identified as low value by Choosing Wisely and evaluates which intervention characteristics are most effective. Methods We searched peer‐reviewed and gray literature from the inception of Choosing Wisely in 2012 through June 2019 to identify interventions in the United States motivated by or using Choosing Wisely recommendations. We also included studies measuring the impact of Choosing Wisely on its own, without interventions. We developed a coding guide and established coding agreement. We coded all included articles for types of services targeted, components of each intervention, results of the intervention, study type, and, where applicable, study quality. We measured the success rate of interventions, using chi‐squared tests or Wald tests to compare across interventions. Findings We reviewed 131 articles. Eighty‐eight percent of interventions focused on clinicians only; 48% included multiple components. Compared with dissemination of Choosing Wisely recommendations only, active interventions were more likely to generate intended results (65% vs 13%, p < 0.001) and, among those, interventions with multiple components were more successful than those with one component (77% vs 47%, p = 0.002). The type of services targeted did not matter for success. Clinician‐based interventions were more effective than consumer‐based, though there is a dearth of studies on consumer‐based interventions. Only 17% of studies included a control arm. Conclusions Interventions built on the Choosing Wisely recommendations can be effective at changing practice patterns to reduce the use of low‐value care. Interventions are more effective when targeting clinicians and using more than one component. There is a need for high‐quality studies that include active controls.

Understanding the factors governing the stability of fault slip is a crucial problem in fault mechanics 1 , 2 – 3 . The importance of fault geometry and roughness on fault-slip behaviour has been highlighted in recent lab experiments 4 , 5 , 6 – 7 and numerical models 8 , 9 , 10 – 11 , and emerging evidence suggests that large-scale complexities in fault networks have a vital role in the fault-rupture process 12 , 13 , 14 , 15 , 16 , 17 – 18 . Here we present a new perspective on fault creep by investigating the link between fault-network geometry and surface creep rates in California, USA. Our analysis reveals that fault groups exhibiting creeping behaviour show smaller misalignment in their fault-network geometry. The observation indicates that the surface fault traces of creeping regions tend to be simple, whereas locked regions tend to be more complex. We propose that the presence of complex fault-network geometries results in geometric locking that promotes stick-slip behaviour characterized by earthquakes, whereas simpler geometries facilitate smooth fault creep. Our findings challenge traditional hypotheses on the physical origins of fault creep explained primarily in terms of fault friction 19 , 20 – 21 and demonstrate the potential for a new framework in which large-scale earthquake frictional behaviour is determined by a combination of geometric factors and rheological yielding properties. Analysis of some of the main fault zones in California shows that the presence of complex earthquake fault-network geometries results in geometric locking that promotes stick-slip behaviour, whereas simpler geometries lead to smooth fault creep.

Understanding the generation of damaging, high‐frequency ground motions during earthquakes is essential both for fundamental science and for effective hazard preparation. Various theories exist regarding the origin of high‐frequency ground motions, including the standard paradigm linked to slip heterogeneity on the rupture plane, and alternative perspectives associated with fault complexity. To assess these competing hypotheses, we measure ground motion amplitudes in different frequency bands for 3 ≤ M ≤ 5.8 earthquakes in Southern California and compare them to empirical ground motion models. We utilize a Bayesian inference technique called the Integrated Nested Laplace Approximation (INLA) to identify earthquake source regions that produce higher or lower ground motions than expected. Our analysis reveals a strong correlation between fault complexity measurements and the high‐frequency ground motion event terms identified by INLA. These findings suggest that earthquakes on complex faults (or fault networks) lead to stronger‐than‐expected ground motions at high frequencies. Plain Language Summary An important and unresolved question in earthquake science is how damaging, rapid ground shaking is generated during an earthquake. Various ideas currently exist to explain the cause of such ground motions, with the standard view attributing strong ground motion to frictional variations on the fault plane that ruptures during an earthquake. However, recent studies have also indicated that geometric complexities within fault networks may likewise influence the strong ground shaking. To help resolve this conundrum, we analyzed the ground motions produced by earthquakes in Southern California to assess the dependence of these ground motions to the complex fault networks on which the earthquakes occur. Our findings indicate that complex fault network systems have a substantial influence on how damaging earthquake ground shaking could be. These results have broad implications for our understanding of the physics of earthquakes and have important implications for earthquake hazards. Key Points We investigate the influence of fault network complexity on the high‐frequency ground motions of earthquakes in California We observe a strong correlation between fault complexity and residual ground motions at high frequencies The correlation is frequency‐dependent, with stronger correlations observed at frequencies above 2 Hz