Exploring the impact of traumatic injury on mortality: An analysis of the certified cause of death within one year of serious injury in the Scottish population.

Background: Few studies effectively quantify the long-term incidence of death following injury. The absence of detailed mortality and underlying cause of death data results in limited understanding and a potential underestimation of the consequences at a population level. This study takes a nationwide approach to identify the one-year mortality following injury in Scotland, evaluating survivorship in relation to pre-existing comorbidities and incidental causes of death.

Use of protracted CPAP as supportive treatment for COVID-19 pneumonitis and associated outcomes: a national cohort study.

Background: Continuous positive airway pressure (CPAP) has been increasingly deployed to manage patients with COVID-19 and acute respiratory failure, often for protracted periods. However, concerns about protracted CPAP have been raised. This study aimed to examine the use of CPAP for patients with COVID-19 and the outcomes after protracted use.

Prevalence, characteristics, and longer-term outcomes of patients with persistent critical illness attributable to COVID-19 in Scotland: a national cohort study.

Background: Patients with COVID-19 can require critical care for prolonged periods. Patients with persistent critical Illness can have complex recovery trajectories, but this has not been studied for patients with COVID-19. We examined the prevalence, risk factors, and long-term outcomes of critically ill patients with COVID-19 and persistent critical illness.

Low-input Nucleus Isolation and Multiplexing with Barcoded Antibodies of Mouse Sympathetic Ganglia for Single-nucleus RNA Sequencing.

The cardiac autonomic nervous system is crucial in controlling cardiac function, such as heart rate and cardiac contractility, and is divided into sympathetic and parasympathetic branches. Normally, there is a balance between these two branches to maintain homeostasis. However, cardiac disease states such as myocardial infarction, heart failure, and hypertension can induce the remodeling of cells involved in cardiac innervation, which is associated with an adverse clinical outcome.

Influence of socioeconomic deprivation on interventions and outcomes for patients admitted with COVID-19 to critical care units in Scotland: A national cohort study.

Background: Coronavirus disease 2019 (COVID-19) can lead to significant respiratory failure with between 14% and 18% of hospitalised patients requiring critical care admission. This study describes the impact of socioeconomic deprivation on 30-day survival following critical care admission for COVID-19, and the impact of the COVID-19 pandemic on critical care capacity in Scotland.

Methods: This cohort study used linked national hospital records including ICU, virology testing and national death records to identify and describe patients with COVID-19 admitted to critical care units in Scotland.

The effectiveness of quality control samples in pharmaceutical bioanalysis.

The use of quality control (QC) samples in bioanalysis is well established and consistent with regulatory guidance. However, a systematic evaluation of whether QC samples serve the intended purpose of improving data quality has not been undertaken. The Translational and ADME Sciences Leadership Group (TALG) of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) conducted an evaluation to assess whether closer agreement is observed when comparing pharmacokinetic data from two passed runs, than when comparing data from failed and passed (retest) runs.

Regional variation in the incidence rate and sex ratio of multiple sclerosis in Scotland 2010-2017: findings from the Scottish Multiple Sclerosis Register.

Background: Fifteen regional studies published over the last six decades surveying prevalence, mortality and hospital admissions have suggested that Scotland is amongst the highest risk nations for multiple sclerosis (MS) in the world. However, substantial intranational variation in rates (between regions) has been described in numerous countries, including in the only previous Scottish national survey, which used hospital admission data, to address this issue. Against this backdrop, the Scottish Multiple Sclerosis Register (SMSR) was established in 2010 to prospectively collect nationally comprehensive incidence data and to allow for regional comparisons.

Fasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury.

Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations.

A phase II trial evaluating the effects and intra-tumoral penetration of bortezomib in patients with recurrent malignant gliomas.

One resistance mechanism in malignant gliomas (MG) involves nuclear factor-κB (NF-κB) activation. Bortezomib prevents proteasomal degradation of NF-κB inhibitor α (NFKBIA), an endogenous regulator of NF-κB signaling, thereby limiting the effects of NF-κB on tumor survival and resistance. A presurgical phase II trial of bortezomib in recurrent MG was performed to determine drug concentration in tumor tissue and effects on NFKBIA.

Automated non-stepwise preparation of bioanalytical calibration standards and quality controls using an ultra-low volume digitizing liquid dispenser.

Rationale: Stepwise preparation of calibration standards and quality controls (QCs) is one of the most routine and laborious steps in bioanalysis. An alternative non-contact dispenser using low picoliter digitized dispensing technology is evaluated for its application in non-stepwise preparation of calibration curve and QCs in bioanalysis.

Methods: Fluorescein was initially used to assess the accuracy and precision of dispense volumes with fluorescent measurement.

A phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children's Oncology Group study.

Purpose: A phase 1 study to determine the maximum-tolerated dose, dose-limiting toxicity, pharmacokinetics, and biological effects of bortezomib in children with recurrent/refractory leukemia.

Experimental Design: Bortezomib was administered twice weekly for 2 consecutive weeks at either 1.3 or 1.

Impact of differential recovery in bioanalysis: the example of bortezomib in whole blood.

A key assumption in pharmaceutical bioanalysis is that spiked standards mimic incurred samples in every analytical aspect. Although deviations from this assumption have been reported in terms of the difference in ion suppression or metabolite interference, the difference of extraction recovery and its impact has been rarely reported and is often characterized as unlikely. In this work, we demonstrated the presence and significance of differential recovery using a real-world example: the assay of bortezomib in whole blood.