Methylation age acceleration does not predict mortality in schizophrenia.

Schizophrenia (SCZ) is associated with high mortality. DNA methylation levels vary over the life course, and pre-selected combinations of methylation array probes can be used to estimate "methylation age" (mAge). mAge correlates highly with chronological age but when it differs, termed mAge acceleration, it has been previously associated with all-cause mortality. We tested the association between mAge acceleration and mortality in SCZ and controls. We selected 190 SCZ cases and 190 controls from the Sweden Schizophrenia Study. Cases were identified from the Swedish Hospital Discharge Register with ≥5 specialist treatment contacts and ≥5 antipsychotic prescriptions. Controls had no psychotic disorder or antipsychotics. Subjects were selected if they had died or survived during follow-up (2:1 oversampling). Extracted DNA was assayed on the Illumina MethylationEPIC array. mAge was regressed on age at sampling to obtain mAge acceleration. Using Cox proportional hazards regression, the association between mAge acceleration and mortality was tested. After quality control, the following were available: n = 126 SCZ died, 63 SCZ alive, 127 controls died, 62 controls alive. In the primary analyses, we did not find a significant association between mAge acceleration and SCZ mortality (adjusted p > 0.005). Sensitivity analyses excluding SCZ cases with pre-existing cancer demonstrated a significant association between the Hannum mAge acceleration and mortality (hazard ratio = 1.13, 95% confidence interval = 1.04-1.22, p = 0.005). Per our pre-specified criteria, we did not confirm our primary hypothesis that mAge acceleration would predict subsequent mortality in people with SCZ, but we cannot rule out smaller effects or effects in patient subsets

Neutrinoless double beta decay via light neutralinos in R-parity violating supersymmetry

We perform a study of neutrinoless double beta (0νββ) decay mediated by the lightest neutralino of arbitrary mass in the minimal supersymmetric Standard Model (MSSM) under the presence of R-parity violating trilinear interactions. In this scenario, the exchange of the lightest neutralino can result in 0νββ decay of either long-range or short-range behaviour, depending on the neutralino mass. Using nuclear matrix elements calculated in the interacting boson model, we use an interpolation between the long- and short-range behaviours with an approximate formula. The non-observation of 0νββ decay is then used to place constraints on the supersymmetry parameter space, compatible with constraints from collider experiments. We compare these constraints to bounds from pion decays, CKM unitarity and big bang nucleosynthesis

Probes of Heavy Sterile Neutrinos

We review probes of heavy sterile neutrinos, focusing on direct experimental searches and neutrinoless double beta decay. Working in a phenomenological parametrization, we emphasize the importance of the nature of sterile neutrinos in interpreting neutrinoless double beta decay searches. While current constraints on the active-sterile neutrino mixing are already stringent, we highlight planned future efforts that will probe regimes motivated by the lightness of active neutrinos

Magnet-targeted delivery and imaging

Magnetic nanoparticles, in combination with applied magnetic fields, can non-invasively focus delivery of small-molecule drugs and human cells to specific regions of the anatomy. This emerging technology could solve one of the main challenges in therapy development: delivery of a high concentration of the therapeutic agent to the target organ or tissue whilst reducing systemic dosing and off-target side effects. Several challenges, however, must be met before this technology can be applied either effectively or safely in the clinic to augment therapies. Multiple nanoparticle features interact to influence the efficiency of magnet-targeted delivery, and so their design will have a large influence on the success of therapeutic targeting. Iron oxide core size and composition affect the type and strength of magnetism, and thus the amount of force that can be applied by an external magnetic field, while particle behaviour within biological systems can be affected by particle size and coating. Preclinical researchers have investigated the use of magnetic targeting-based therapies across a wide range of conditions, and positive results have been reported for both cell and drug delivery applications. Furthermore, magnetic resonance imaging (MRI) can non-invasively monitor the success of targeted delivery—providing high-resolution anatomical information on particle location in preclinical and clinical contexts. In this chapter, we provide a basic introduction to the physical principles behind magnetic targeting technology, relevant design features of nanoparticles and magnetic targeting devices, an overview of preclinical and clinical applications, and an introduction to imaging magnetic particles in vivo

Predictive Biomarkers of Immune Checkpoint Inhibition in Gastroesophageal Cancers.

Immune checkpoint inhibition has transformed cancer treatment. For gastroesophageal cancer, this class of drugs have demonstrated durable responses and survival benefit in a subgroup of patients, resulting in regulatory approval. However, several recent randomized phase III studies in gastroesophageal cancer have reported negative results, blunting initial enthusiasm. Identification and validation of predictive biomarkers with appropriate patient selection for benefit from immunotherapy is an area of intense research with novel concepts rapidly emerging. In this review we describe the latest immune checkpoint inhibitor trials which have been reported in gastroesophageal cancers with a focus on predictive biomarkers. We also explore novel biomarkers being developed to improve precision oncology for immunotherapy in gastroesophageal cancers

Radio-metal cross-linking of alginate hydrogels for non-invasive in vivo imaging

Alginate hydrogels are cross-linked polymers with high water content, tuneable chemical and material properties, and a range of biomedical applications including drug delivery, tissue engineering, and cell therapy. However, their similarity to soft tissue often renders them undetectable within the body using conventional bio-medical imaging techniques. This leaves much unknown about their behaviour in vivo, posing a challenge to therapy development and validation. To address this, we report a novel, fast, and simple method of incorporating the nuclear imaging radio-metal 111In into the structure of alginate hydrogels by utilising its previously-undescribed capacity as an ionic cross-linking agent. This enabled non-invasive in vivo nuclear imaging of hydrogel delivery and retention across the whole body, over time, and across a range of model therapies including: nasal and oral drug delivery, stem cell transplantation, and cardiac tissue engineering. This information will facilitate the development of novel therapeutic hydrogel formulations, encompassing alginate, across disease categories

Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice

Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is the inefficiency of injection routes to deliver cells to the kidney parenchyma. Systemic injection, such as intravenous injection only delivers a small proportion of cells to the kidney. Whereas direct delivery, such as renal artery injection requires surgical procedures. A minimally invasive renal artery injection was therefore developed to enhance cell delivery to kidney. In this study, luciferase expressing human adipocyte derived stem cells (ADSC) were labelled with gold nanorods (GNR) and injected into the renal artery using ultrasound guidance. The ADSCs were tracked using bioluminescence and photoacoustic imaging serially over 7 days. Imaging confirmed that the majority of signal was within the kidney, indicative of successful injection and that the cells remained viable for 3 days. Histology showed co-localization of GNRs with ADSC staining throughout the kidney with no indication of injury caused by injection. These findings demonstrate that ultrasound-guided renal artery injection is feasible in mice and can successfully deliver a large proportion of cells which are retained within the kidney for 3 days. Therefore, the techniques developed here will be useful for optimising cell therapy in kidney diseases

Search for Nanosecond Near-infrared Transients around 1280 Celestial Objects

Stars and planetary system

Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible