Zonal flow generation through four wave interaction in reduced models of fusion plasma turbulence

In tokamaks, turbulence is a key contributor to cross field transport. However, it is also responsible for the spontaneous generation of large scale structures such as zonal ows. These are of relevance to fusion plasmas as they can create transport barriers which aid plasma confinement. The interaction between drift waves and zonal ows can be investigated using reduced models such as the Hasegawa- Mima and Hasegawa-Wakatani equations. A four-wave truncated model is developed for the Extended-Hasegawa-Mima (EHM) equation. This produces a set of four ordinary differential equations (ODEs) that are used to investigate the modulational instability (MI), a mechanism by which drift waves can produce a zonal ow. These equations are linearised to produce a dispersion relation for the MI which is used to produce a set of maps of the linear growth rate of the MI. These show how additional modes become unstable as the gyroradius is increased. The truncated model and dispersion relation are then compared to measurements taken from simulations of the full EHM partial differential equation (PDE) which has been seeded with an appropriate initial condition. Good agreement is found when the pump wave has no component in the direction of the density gradient. A similar truncated model is derived for the Extended-Hasegawa-Wakatani (EHW) equations. As the EHW system has separate equations for density and potential this leads to a set of eight ODEs. The linearisation technique used for the EHM system cannot be applied here. Instead, approximations based on the built in EHW instability are made to calculate a linear growth rate for the zonal ow using the ODEs describing it. These analytical predictions are then compared to a full PDE simulation of the system, which is initialised using random noise. It is found that for particular sets of waves the ODEs provide a good prediction of the linear growth rate. A driving term is added to the EHM equation to reproduce the effect of the built in instability of the EHW equations. This causes a drift wave spectrum to grow when full EHW PDE simulations are seeded with random noise. The four-wave ODE model is updated to include this driving. The ODE model again produces good predictions for the growth rate of the zonal flow

Making It Last: Storage Time and Temperature Have Differential Impacts on Metabolite Profiles of Airway Samples from Cystic Fibrosis Patients.

Metabolites of human or microbial origin have the potential to be important biomarkers of the disease state in cystic fibrosis (CF). Clinical sample collection and storage conditions may impact metabolite abundances with clinical relevance. We measured the change in metabolite composition based on untargeted gas chromatography-mass spectrometry (GC-MS) when CF sputum samples were stored at 4°C, -20°C, or -80°C with one or two freeze-thaw cycles. Daily measurements were taken for 1 week and then weekly for 4 weeks (4°C) and 8 weeks (-20°C). The metabolites in samples stored at -20°C maintained abundances similar to those found at-80°C over the course of 8 weeks (average change in Bray-Curtis distance, 0.06 ± 0.04) and were also stable after one or two freeze-thaw cycles. However, the metabolite profiles of samples stored at 4°C shifted after 1 day and continued to change over the course of 4 weeks (average change in Bray-Curtis distance, 0.31 ± 0.12). The abundances of several amino acids and other metabolites increased with time of storage at 4°C but remained constant at -20°C. Storage temperature was a significant factor driving the metabolite composition (permutational multivariate analysis of variance: r2 = 0.32 to 0.49, P < 0.001). CF sputum samples stored at -20°C at the time of sampling maintain a relatively stable untargeted GC-MS profile. Samples should be frozen on the day of collection, as more than 1 day at 4°C impacts the global composition of the metabolites in the sample. IMPORTANCE Metabolomics has great potential for uncovering biomarkers of the disease state in CF and many other contexts. However, sample storage timing and temperature may alter the abundance of clinically relevant metabolites. To assess whether existing samples are stable and to direct future study design, we conducted untargeted GC-MS metabolomic analysis of CF sputum samples after one or two freeze-thaw cycles and storage at 4°C and -20°C for 4 to 8 weeks. Overall, storage at -20°C and freeze-thaw cycles had little impact on metabolite profiles; however, storage at 4°C shifted metabolite abundances significantly. GC-MS profiling will aid in our understanding of the CF lung, but care should be taken in studies using sputum samples to ensure that samples are properly stored

Portfolio Concentration and Investment Performance

This study examines the relationship between investment performance and concentration in active equity portfolios. Active management is dependent on the success of two important components in the investment process – stock selection skill and portfolio management. Our study documents a positive relationship between fund performance and portfolio concentration. The relationship is stronger for stocks in which active managers hold overweight positions, as well as for stocks outside the largest 50 stocks listed on the Australian Stock Exchange (ASX). We find more concentrated funds tend to be those implementing growth styles, having smaller aggregate assets under management, being institutions which are not affiliated with a bank or life-office entity, whose funds experience past period outflows, and who are benchmarked to narrower indexes than the S&P/ASX 300

Clustering of solutions in the random satisfiability problem

Using elementary rigorous methods we prove the existence of a clustered phase in the random $K$-SAT problem, for $K\geq 8$. In this phase the solutions are grouped into clusters which are far away from each other. The results are in agreement with previous predictions of the cavity method and give a rigorous confirmation to one of its main building blocks. It can be generalized to other systems of both physical and computational interest.Comment: 4 pages, 1 figur

Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients

Background: Previous studies have not demonstrated a consistent association between potentially inappropriate medicines (PIMs) in older patients as defined by Beers criteria and avoidable adverse drug events (ADEs). This study aimed to assess whether PIMs defined by new STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) criteria are significantly associated with ADEs in older people with acute illness. Methods: We prospectively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval. Potentially inappropriate medicines were defined by both Beers and STOPP criteria. Adverse drug events were defined by World Health Organization- Uppsala Monitoring Centre criteria and verified by a local expert consensus panel, which also assessed whether ADEs were causal or contributory to current hospitalization. Hallas criteria defined ADE avoidability. We compared the proportions of patients taking Beers criteria PIMs and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission. Results: A total of 329 ADEs were detected in 158 of 600 patients (26.3%); 219 of 329 ADEs (66.6%) were considered causal or contributory to admission. Of the 219 ADEs, 151(68.9%) considered causal or contributory to admission were avoidable or potentially avoidable. After adjusting for age, sex, comorbidity, dementia, baseline activities of daily living function, and number of medications, the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed (odds ratio, 1.847; 95% confidence interval [CI], 1.506-2.264;P<.001);prescription of Beers criteria PIMs did not significantly increase ADE risk (odds ratio, 1.276; 95% CI, 0.945-1.722; P=.11). Conclusion: STOPP criteria PIMs, unlike Beers criteria PIMs, are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization

Adipose depot gene expression identifies intelectin-1 as potential mediator of the metabolic response to cancer and cachexia

Background Cancer cachexia is a poorly understood metabolic consequence of cancer. During cachexia, different adipose depots demonstrate differential wasting rates. Animal models suggest adipose tissue may be a key driver of muscle wasting through fat–muscle crosstalk, but human studies in this area are lacking. We performed global gene expression profiling of visceral (VAT) and subcutaneous (SAT) adipose from weight stable and cachectic cancer patients and healthy controls. Methods Cachexia was defined as >2% weight loss plus low computed tomography‐muscularity. Biopsies of SAT and VAT were taken from patients undergoing resection for oesophago‐gastric cancer, and healthy controls (n = 16 and 8 respectively). RNA was isolated and reverse transcribed. cDNA was hybridised to the Affymetrix Clariom S microarray and data analysed using R/Bioconductor. Differential expression of genes was assessed using empirical Bayes and moderated‐t‐statistic approaches. Category enrichment analysis was used with a tissue‐specific background to examine the biological context of differentially expressed genes. Selected differentially regulated genes were validated by qPCR. Enzyme‐linked immunosorbent assay (ELISA) for intelectin‐1 was performed on all VAT samples. The previously‐described cohort plus 12 additional patients from each group also had plasma I = intelectin‐1 ELISA carried out. Results In VAT vs. SAT comparisons, there were 2101, 1722, and 1659 significantly regulated genes in the cachectic, weight stable, and control groups, respectively. There were 2200 significantly regulated genes from VAT in cachectic patients compared with controls. Genes involving inflammation were enriched in cancer and control VAT vs. SAT, although different genes contributed to enrichment in each group. Energy metabolism, fat browning (e.g. uncoupling protein 1), and adipogenesis genes were down‐regulated in cancer VAT (P = 0.043, P = 5.4 × 10−6 and P = 1 × 10−6 respectively). The gene showing the largest difference in expression was ITLN1, the gene that encodes for intelectin‐1 (false discovery rate‐corrected P = 0.0001), a novel adipocytokine associated with weight loss in other contexts. Conclusions SAT and VAT have unique gene expression signatures in cancer and cachexia. VAT is metabolically active in cancer, and intelectin‐1 may be a target for therapeutic manipulation. VAT may play a fundamental role in cachexia, but the down‐regulation of energy metabolism genes implies a limited role for fat browning in cachectic patients, in contrast to pre‐clinical models