Effectiveness of resistance training and associated program characteristics in patients at risk for type 2 diabetes:a systematic review and meta-analysis

BACKGROUND: Resistance training (RT) is an effective intervention for glycemic control and cardiometabolic health in individuals with type 2 diabetes (T2D). However, the use of RT in individuals at risk for T2D to prevent or delay the onset of T2D, and RT program characteristics that are most effective are still unknown. The purpose of this review is to determine the effects of RT on cardiometabolic risk factors in those at risk for T2D and to examine RT program characteristics associated with intervention effectiveness. METHODS: PubMed, Cochrane, Web of Science, and Embase databases were systematically searched for published controlled trials that compared cardiometabolic outcomes in adults with cardiometabolic risk for those that underwent an RT intervention with those that did not. A systematic review and meta-analysis was conducted to determine the effect of RT on glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), body fat percentage (BF%), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG). Additional analyses examined effects of intervention duration and dietary intervention on FPG and TG. RESULTS: Fourteen trials with 668 participants were included. For RT compared to controls, the standardized mean difference (SMD) was −1.064 for HbA1c (95% confidence interval [CI] −1.802 to −0.327; p=0.005), −0.99 for FPG (95% CI −1.798 to −0.183; p=0.016), −0.933 for TC (95% CI −1.66 to −0.206; p=0.012), −0.840 for BF% (95% CI −1.429 to −0.251; p=0.005), −0.693 for HDL (95% CI −1.230 to −0.156; p=0.011), −1.03 for LDL (95% CI −2.03 to −0.050; p=0.039), and −0.705 for TG (95% CI −1.132 to −0.279; p=0.001). CONCLUSIONS: RT is beneficial for improving glycemic control, BF%, and blood lipids in those at risk for diabetes. The addition of a dietary component did not result in larger reductions in FPG and TG than RT alone. PROSPERO REGISTRATION ID: CRD42019122217 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40798-021-00321-x

Therapeutic Targeting of Glioblastoma and the Interactions with Its Microenvironment

Glioblastoma (GBM) is the most common primary malignant brain tumour, and it confers a dismal prognosis despite intensive multimodal treatments. Whilst historically, research has focussed on the evolution of GBM tumour cells themselves, there is growing recognition of the importance of studying the tumour microenvironment (TME). Improved characterisation of the interaction between GBM cells and the TME has led to a better understanding of therapeutic resistance and the identification of potential targets to block these escape mechanisms. This review describes the network of cells within the TME and proposes treatment strategies for simultaneously targeting GBM cells, the surrounding immune cells, and the crosstalk between them

NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials

BACKGROUND HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP. METHODS Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2-12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment. RESULTS Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2-12 was -27.0% versus -15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (-27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2. CONCLUSIONS A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated. TRIAL REGISTRATION C107 = NCT00064623; C119 = NCT00321672

Control-Flow Integrity for Real-Time Embedded Systems

Attacks on real-time embedded systems can endanger lives and critical infrastructure. Despite this, techniques for securing embedded systems software have not been widely studied. Many existing security techniques for general-purpose computers rely on assumptions that do not hold in the embedded case. This paper focuses on one such technique, control-flow integrity (CFI), that has been vetted as an effective countermeasure against control-flow hijacking attacks on general-purpose computing systems. Without the process isolation and fine-grained memory protections provided by a general-purpose computer with a rich operating system, CFI cannot provide any security guarantees. This work proposes RECFISH, a system for providing CFI guarantees on ARM Cortex-R devices running minimal real-time operating systems. We provide techniques for protecting runtime structures, isolating processes, and instrumenting compiled ARM binaries with CFI protection. We empirically evaluate RECFISH and its performance implications for real-time systems. Our results suggest RECFISH can be directly applied to binaries without compromising real-time performance; in a test of over six million realistic task systems running FreeRTOS, 85% were still schedulable after adding RECFISH

First Remote Sensing Observations of Trifluoromethane (HFC-23) in the Upper Troposphere and Lower Stratosphere

This work reports the first remote sensing measurements of atmospheric HFC-23 (CHF3) using solar occultation measurements made by the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and the Jet Propulsion Laboratory Mark IV (MkIV) balloon interferometer. A total of 8809 ACE occultations measured between 2004 and 2010 have been processed, along with 24 MkIV occultations measured between 1989 and 2007. ACE data (yearly averages over the 10-25 km altitude range) in the tropics/subtropics (40°S-40°N) reveal a trend of 4.0 ± 1.6% per year in the growth of HFC-23 for 2004-2009 (or 3.9 ± 1.2% per year for 2004-2010), slightly smaller than surface measurements from Cape Grim air archive samples over the same time period (4.7 ± 0.3% per year). The northern midlatitude and high-latitude MkIV data (averaged over the 10-25 km altitude range) indicate a growth rate of 5.8 ± 0.3% per year over the period 1989-2007 (5.3 ± 0.4% per year for just the midlatitude data), similar to the Cape Grim surface trend of 5.7 ± 0.1% per year over the same period. The absolute HFC-23 volume mixing ratios measured by ACE and MkIV in the upper troposphere/lower stratosphere are in good agreement (\u3c5% bias) with each other but are ∼30% larger than ground-based measurements. The source of this bias has not been definitively ascertained; however, spectroscopic errors are the most likely cause. Copyright 2012 by the American Geophysical Union

Reduction of neurovascular damage resulting from microelectrode insertion into the cerebral cortex using

Penetrating neural probe technologies allow investigators to record electrical signals in the brain. The implantation of probes causes acute tissue damage, partially due to vasculature disruption during probe implantation. This trauma can cause abnormal electrophysiological responses and temporary increases in neurotransmitter levels, and perpetuate chronic immune responses. A significant challenge for investigators is to examine neurovascular features below the surface of the brain in vivo. The objective of this study was to investigate localized bleeding resulting from inserting microscale neural probes into the cortex using two-photon microscopy (TPM) and to explore an approach to minimize blood vessel disruption through insertion methods and probe design. 3D TPM images of cortical neurovasculature were obtained from mice and used to select preferred insertion positions for probe insertion to reduce neurovasculature damage. There was an 82.8 ± 14.3% reduction in neurovascular damage for probes inserted in regions devoid of major (>5 µm) sub-surface vessels. Also, the deviation of surface vessels from the vector normal to the surface as a function of depth and vessel diameter was measured and characterized. 68% of the major vessels were found to deviate less than 49 µm from their surface origin up to a depth of 500 µm. Inserting probes more than 49 µm from major surface vessels can reduce the chances of severing major sub-surface neurovasculature without using TPM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85401/1/7_4_046011.pd

Modelling Marek's Disease Virus (MDV) infection: parameter estimates for mortality rate and infectiousness

Background: Marek's disease virus (MDV) is an economically important oncogenic herpesvirus of poultry. Since the 1960s, increasingly virulent strains have caused continued poultry industry production losses worldwide. To understand the mechanisms of this virulence evolution and to evaluate the epidemiological consequences of putative control strategies, it is imperative to understand how virulence is defined and how this correlates with host mortality and infectiousness during MDV infection. We present a mathematical approach to quantify key epidemiological parameters. Host lifespan, virus latent periods and host viral shedding rates were estimated for unvaccinated and vaccinated birds, infected with one of three MDV strains. The strains had previously been pathotyped to assign virulence scores according to pathogenicity of strains in hosts. Results: Our analyses show that strains of higher virulence have a higher viral shedding rate, and more rapidly kill hosts. Vaccination enhances host life expectancy but does not significantly reduce the shedding rate of the virus. While the primary latent period of the virus does not vary with challenge strain nor vaccine treatment of host, the time until the maximum viral shedding rate is increased with vaccination. Conclusions: Our approach provides the tools necessary for a formal analysis of the evolution of virulence in MDV, and potentially simpler and cheaper approaches to comparing the virulence of MDV strains

Final Report DE-EE0005380: Assessment of Offshore Wind Farm Effects on Sea Surface, Subsurface and Airborne Electronic Systems

Offshore wind energy is a valuable resource that can provide a significant boost to the US renewable energy portfolio. A current constraint to the development of offshore wind farms is the potential for interference to be caused by large wind farms on existing electronic and acoustical equipment such as radar and sonar systems for surveillance, navigation and communications. The US Department of Energy funded this study as an objective assessment of possible interference to various types of equipment operating in the marine environment where offshore wind farms could be installed. The objective of this project was to conduct a baseline evaluation of electromagnetic and acoustical challenges to sea surface, subsurface and airborne electronic systems presented by offshore wind farms. To accomplish this goal, the following tasks were carried out: (1) survey electronic systems that can potentially be impacted by large offshore wind farms, and identify impact assessment studies and research and development activities both within and outside the US, (2) engage key stakeholders to identify their possible concerns and operating requirements, (3) conduct first-principle modeling on the interactions of electromagnetic signals with, and the radiation of underwater acoustic signals from, offshore wind farms to evaluate the effect of such interactions on electronic systems, and (4) provide impact assessments, recommend mitigation methods, prioritize future research directions, and disseminate project findings. This report provides a detailed description of the methodologies used to carry out the study, key findings of the study, and a list of recommendations derived based the findings

Coupled land use and ecological models reveal emergence and feedbacks in socio-ecological systems

Acknowledgements: This work was supported by an EPSRC Doctoral Training Centre grant (EP/G03690X/1). Supplementary material (Appendix ECOG‐04039 at ). Appendix 1.Peer reviewedPublisher PD

Dynamical Mass Constraints on Low-Mass Pre-Main-Sequence Stellar Evolutionary Tracks: An Eclipsing Binary in Orion with a 1.0 Msun Primary and an 0.7 Msun Secondary

We report the discovery of a double-lined, spectroscopic, eclipsing binary in the Orion star-forming region. We analyze the system spectroscopically and photometrically to empirically determine precise, distance-independent masses, radii, effective temperatures, and luminosities for both components. The measured masses for the primary and secondary, accurate to ~1%, are 1.01 Msun and 0.73 Msun, respectively; thus the primary is a definitive pre-main-sequence solar analog, and the secondary is the lowest-mass star yet discovered among pre-main-sequence eclipsing binary systems. We use these fundamental measurements to test the predictions of pre-main-sequence stellar evolutionary tracks. None of the models we examined correctly predict the masses of the two components simultaneously, and we implicate differences between the theoretical and empirical effective temperature scales for this failing. All of the models predict the observed slope of the mass-radius relationship reasonably well, though the observations tend to favor models with low convection efficiencies. Indeed, considering our newly determined mass measurements together with other dynamical mass measurements of pre-main-sequence stars in the literature, as well as measurements of Li abundances in these stars, we show that the data strongly favor evolutionary models with inefficient convection in the stellar interior, even though such models cannot reproduce the properties of the present-day Sun.Comment: Accepted by Ap