On safety, pharmacokinetics and dosage of bevacizumab in ROP treatment – a review

Off-label intravitreal use of the vascular endothelial growth factor (VEGF) antibody bevacizumab for retinopathy of prematurity (ROP) increases despite lack of studies on safety, pharmacokinetics and dosage in developing individuals. Systemic absorption has been considered negligible. A literature search was performed with emphasis on potential adverse systemic effects in developing individuals

Quantifying similarity of pore-geometry in nanoporous materials

In most applications of nanoporous materials the pore structure is as important as the chemical composition as a determinant of performance. For example, one can alter performance in applications like carbon capture or methane storage by orders of magnitude by only modifying the pore structure. For these applications it is therefore important to identify the optimal pore geometry and use this information to find similar materials. However, the mathematical language and tools to identify materials with similar pore structures, but different composition, has been lacking. We develop a pore recognition approach to quantify similarity of pore structures and classify them using topological data analysis. This allows us to identify materials with similar pore geometries, and to screen for materials that are similar to given top-performing structures. Using methane storage as a case study, we also show that materials can be divided into topologically distinct classes requiring different optimization strategies

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes

Both leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase) are promising targets for the treatment of Parkinson's disease (PD). Evidence suggests that both proteins are involved in biological pathways involving the lysosome. However, studies to date have largely investigated the enzymes in isolation and any relationship between LRRK2 and GCase remains unclear. Both enzymes are highly expressed in peripheral blood monocytes and have been implicated in immune function and inflammation. To facilitate the standardized measurement of these readouts in large cohorts of samples collected from persons with PD across the globe, we developed and optimized a sample collection and processing protocol with parallel flow cytometry assays. Assay parameters were first optimized using healthy control peripheral blood mononuclear cells (PBMCs), and then LRRK2 and GCase activities were measured in immune cells from persons with idiopathic PD (iPD). We tested the ability of this protocol to deliver similar results across institutes across the globe, and named this protocol the Wallings-Hughes Optimized Protocol for PBMC Assessment (WHOPPA). In the application of this protocol, we found increased LRRK2 levels and stimulation-dependent enzymatic activity, and decreased GBA index in classical iPD monocytes, as well as increased cytokine release in PD PBMCs. WHOPPA also demonstrated a strong positive correlation between LRRK2 levels, pRab10 and HLA-DR in classical monocytes from subjects with iPD. These data support a role for the global use of WHOPPA and expression levels of these two PD-associated proteins in immune responses, and provide a robust assay to determine if LRRK2 and GCase activities in monocytes have potential utility as reliable and reproducible biomarkers of disease in larger cohorts of subjects with PD.Copyright © 2022 Wallings, Hughes, Staley, Simon, McFarland, Alcalay, Garrido, Martí, Sarró, Dzamko and Tansey

Quantifying trading behavior in financial markets using Google Trends

Crises in financial markets affect humans worldwide. Detailed market data on trading decisions reflect some of the complex human behavior that has led to these crises. We suggest that massive new data sources resulting from human interaction with the Internet may offer a new perspective on the behavior of market participants in periods of large market movements. By analyzing changes in Google query volumes for search terms related to finance, we find patterns that may be interpreted as “early warning signs” of stock market moves. Our results illustrate the potential that combining extensive behavioral data sets offers for a better understanding of collective human behavior

Photographic investigation of reflected shock phenomena from decigram explosive charges

An investigation of the primary shock front and Mach Y-stem systems was conducted utilizing decigram explosive charges. Distance and arrival time data of the primary shock front was correlated with that of high yield explosions. A good correlation would indicate the feasibility of conducting laboratory scale tests to obtain information on high yield explosions without the expenditure of time and money involved in large scale field tests. The shock front system was also investigated at the time of first formation of the Mach Y-stem. The critical angle of incidence of the primary shock front for the formation of the Y-stem was compared to the theoretical value. Theoretical calculations of the yield of the explosion was also compared to the actual yield. Basic data were obtained from the explosions by photographing the shadow of the shock front system utilizing a Polaroid camera, a microflash unit and a time delay generator. Correlation of the overpressure was excellent for small to moderate distances from the point of explosion, as was the yield comparison. The critical angle of incidence comparison indicated a marked difference between experimental end theoretical values.http://www.archive.org/details/photographicinve00luskLieutenant, United States NavyLieutenant, United States NavyApproved for public release; distribution is unlimited

A global assessment of the impact of climate change on water scarcity

This paper presents a global scale assessment of the impact of climate change on water scarcity. Patterns of climate change from 21 Global Climate Models (GCMs) under four SRES scenarios are applied to a global hydrological model to estimate water resources across 1339 watersheds. The Water Crowding Index (WCI) and the Water Stress Index (WSI) are used to calculate exposure to increases and decreases in global water scarcity due to climate change. 1.6 (WCI) and 2.4 (WSI) billion people are estimated to be currently living within watersheds exposed to water scarcity. Using the WCI, by 2050 under the A1B scenario, 0.5 to 3.1 billion people are exposed to an increase in water scarcity due to climate change (range across 21 GCMs). This represents a higher upper-estimate than previous assessments because scenarios are constructed from a wider range of GCMs. A substantial proportion of the uncertainty in the global-scale effect of climate change on water scarcity is due to uncertainty in the estimates for South Asia and East Asia. Sensitivity to the WCI and WSI thresholds that define water scarcity can be comparable to the sensitivity to climate change pattern. More of the world will see an increase in exposure to water scarcity than a decrease due to climate change but this is not consistent across all climate change patterns. Additionally, investigation of the effects of a set of prescribed global mean temperature change scenarios show rapid increases in water scarcity due to climate change across many regions of the globe, up to 2°C, followed by stabilisation to 4°C