Qualified method for the estimation of di-18:1 bis(monoacylglycero)phosphate in urine, a noninvasive biomarker to monitor drug-induced phospholipidosis

Aim: Our objective was to develop and qualify a bioanalytical method for the estimation of di-18:1-bis(monoacylglycero)phosphate (di-18:1 BMP) as a urinary biomarker for the assessment of drug-induced phospholipidosis and demonstrate its application in a preclinical study. Methodology/results: di-18:1 BMP was extracted by liquid–liquid extraction using n-butanol and analyzed by LC–MS/MS. The qualified method was selective, precise, robust and accurate across the linearity range (0.2–250 ng/ml). Qualified method was then used to assess chloroquine-induced phospholipidosis in rats dosed at 120 mg/kg for 5 days. A fivefold increase in di-18:1 BMP was observed on Day 5 compared with predose. Conclusion: Di-18:1 BMP can be used as a noninvasive biomarker to assess/screen compounds that could cause drug-induced phospholipidosis in rats.

TweTriS: Twenty trillion-atom simulation

Significant improvements are presented for the molecular dynamics code ls1 mardyn — a linked cell-based code for simulating a large number of small, rigid molecules with application areas in chemical engineering. The changes consist of a redesign of the SIMD vectorization via wrappers, MPI improvements and a software redesign to allow memory-efficient execution with the production trunk to increase portability and extensibility. Two novel, memory-efficient OpenMP schemes for the linked cell-based force calculation are presented, which are able to retain Newton’s third law optimization. Comparisons to well-optimized Verlet list-based codes, such as LAMMPS and GROMACS, demonstrate the viability of the linked cell-based approach. The present version of ls1 mardyn is used to run simulations on entire supercomputers, maximizing the number of sampled atoms. Compared to the preceding version of ls1 mardyn on the entire set of 9216 nodes of SuperMUC, Phase 1, 27% more atoms are simulated. Weak scaling performance is increased by up to 40% and strong scaling performance by up to more than 220%. On Hazel Hen, strong scaling efficiency of up to 81% and 189 billion molecule updates per second is attained, when scaling from 8 to 7168 nodes. Moreover, a total of 20 trillion atoms is simulated at up to 88% weak scaling efficiency running at up to 1.33 PFLOPS. This represents a fivefold increase in terms of the number of atoms simulated to date.

Firearms, alcohol and crime: convictions for driving under the influence (DUI) and other alcohol-related crimes and risk for future criminal activity among authorised purchasers of handguns

Firearm violence frequently involves alcohol, but there are no studies of misuse of alcohol and risk for future violence among firearm owners. We examined the association between prior convictions for alcohol-related crimes, chiefly driving under the influence (DUI), and risk of subsequent arrest among 4066 individuals who purchased handguns in California in 1977. During follow-up through 1991, 32.8% of those with prior alcohol-related convictions and 5.7% of those with no prior criminal history were arrested for a violent or firearm-related crime; 15.9% and 2.7%, respectively, were arrested for murder, rape, robbery or aggravated assault. Prior alcohol-related convictions were associated with a fourfold to fivefold increase in risk of incident arrest for a violent or firearm-related crime, a relative increase greater than that seen for age, sex or prior violence. Prior convictions for alcohol-related crime may be an important predictor of risk for future criminal activity among purchasers of firearms.

A solution-based approach to composite dielectric films of surface functionalized CaCu3Ti4O12 and P(VDF-HFP)

Composite thin films of surface functionalized CaCu3Ti4O12 prepared by spin-coating show a fivefold increase of the relative permittivity compared to the pure P(VDF-HFP) polymer.

Table of Contents & Editorial

The field of yoga therapy is growing at a phenomenal rate. An estimated 1,000 yoga therapy studies have been published since 2000. This represents a nearly fivefold increase since the previous decade. The benefits of yoga as therapy are no secret to the millions of yoga practitioners in the East who have embraced its rich traditions for thousands of years, yet in the West yoga therapy remains relatively novel and, for some, enigmatic. The field of yoga therapy is faced with the necessary task of defining itself to inculcate an understanding of its benefits for individuals regardless of their age or ability level.

Osteosarcoma: Evolution of Treatment Paradigms

This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success.