Publications by authors named "Jim Smith"

Serious crime modelling typically needs to be undertaken securely behind a firewall where police knowledge and capabilities remain undisclosed. Data informing an ongoing incident are often sparse; a large proportion of relevant data only come to light after the incident culminates or after police intervene-by which point it is too late to make use of the data to aid real-time decision-making for the incident in question. Much of the data that available to the police to support real-time decision-making are highly confidential and cannot be shared with academics, and are therefore missing to them.

View Article and Find Full Text PDF

The analysis of system reliability has often benefited from graphical tools such as fault trees and Bayesian networks. In this article, instead of conventional graphical tools, we apply a probabilistic graphical model called the chain event graph (CEG) to represent the failures and processes of deterioration of a system. The CEG is derived from an event tree and can flexibly represent the unfolding of asymmetric processes.

View Article and Find Full Text PDF
Article Synopsis
  • Cutaneous melanoma is increasing globally at a faster rate than other cancers, with metastasis being the leading cause of death in patients, highlighting the need for a better understanding of this process and new treatment options.
  • Recent research indicates that epigenetic factors play a significant role in melanoma progression, revealing a mechanism where high DNA methylation can paradoxically activate certain genes instead of silencing them as previously thought.
  • The study used a new CRISPR-based system to manipulate DNA methylation in melanoma cells, demonstrating effective changes in gene expression and providing insights into the role of specific genes in the IFN pathway signalling, challenging traditional views on DNA methylation.
View Article and Find Full Text PDF

Introduction: Trusted research environments (TREs) provide secure access to very sensitive data for research. All TREs operate manual checks on outputs to ensure there is no residual disclosure risk. Machine learning (ML) models require very large amount of data; if this data is personal, the TRE is a well-established data management solution.

View Article and Find Full Text PDF
Article Synopsis
  • - Prostate cancer is a common cancer affecting men, with treatment-induced de novo neuroendocrine prostate cancer (t-NEPC) occurring in up to 25% of patients after androgen deprivation therapy, which leads to a much worse prognosis.
  • - Key genetic mutations such as TP53, RB1, and MYCN contribute to the transition from prostate adenocarcinoma (PRAD) to t-NEPC, along with various epigenetic changes that enhance cellular plasticity.
  • - Current challenges in diagnosing NEPC include the absence of reliable biomarkers; however, advancements in liquid biopsy techniques to analyze circulating tumor cells and ctDNA could soon allow for non-invasive monitoring and better treatment strategies.
View Article and Find Full Text PDF

The wastewater release from the Fukushima Daiichi nuclear plant is expected to have negligible effects on people and the ocean.

View Article and Find Full Text PDF

Recent studies apparently finding deleterious effects of radiation exposure on cataract formation in birds and voles living near Chernobyl represent a major challenge to current radiation protection regulations. This study conducted an integrated assessment of radiation exposure on cataractogenesis using the most advanced technologies available to assess the cataract status of lenses extracted from fish caught at both Chernobyl in Ukraine and Fukushima in Japan. It was hypothesised that these novel data would reveal positive correlations between radiation dose and early indicators of cataract formation.

View Article and Find Full Text PDF

Introduction: Artificial intelligence (AI) applications in healthcare and medicine have increased in recent years. To enable access to personal data, Trusted Research Environments (TREs) (otherwise known as Safe Havens) provide safe and secure environments in which researchers can access sensitive personal data and develop AI (in particular machine learning (ML)) models. However, currently few TREs support the training of ML models in part due to a gap in the practical decision-making guidance for TREs in handling model disclosure.

View Article and Find Full Text PDF

Neuroendocrine neoplasms (NENs) are a group of rare, heterogeneous tumors of neuroendocrine cell origin, affecting a range of different organs. The clinical management of NENs poses significant challenges, as tumors are often diagnosed at an advanced stage where overall survival remains poor with current treatment regimens. In addition, a host of complex and often unique molecular changes underpin the pathobiology of each NEN subtype.

View Article and Find Full Text PDF

Spinal muscular atrophy with lower extremity dominant (SMALED) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in lower limbs muscle weakness and paralysis. Mutations in DYNC1H1, which encodes BICD2, a multifunctional adaptor for microtubule motor proteins, cause the disorder. Here, we generated four induced pluripotent stem cell (iPSC) lines from patients with SMALED.

View Article and Find Full Text PDF

The Chernobyl Exclusion Zone (CEZ) contains the vast majority of radionuclides released by the accident in nuclear fuel particle form. We present and analyze groundwater measurements collected from the monitoring network in CEZ covering key aquifers over 35 years since the accident. These new data, together with a comprehensive analysis of historical data shows that Sr remains mobile in the subsurface environment, while groundwater concentrations of Cs, Pu isotopes and Am are relatively low, and are not of radiological concern.

View Article and Find Full Text PDF

Despite being recognized as a major global health issue, older adult abuse (OAA) remains largely undetected and under-reported. Most OAA assessment tools fail to capture true prevalence. Follow up of patients where abuse exposure is not easily determined is a necessity.

View Article and Find Full Text PDF

Objectives: To explore the impacts of the 2020 New Zealand COVID-19 lockdown on peer-led Steady as You Go (SAYGO) fall prevention exercise classes and members, and to develop recommendations for mitigating impacts during future lockdowns.

Methods: Semi-structured phone interviews were conducted with 20 SAYGO program participants and managers following the first COVID-19 lockdown in New Zealand. Interviews were audio-recorded, transcribed verbatim and analysed using the General Inductive Approach.

View Article and Find Full Text PDF

DNA methylation is an epigenetic modification with an established role in both normal cellular function and mammalian disease. Despite well-characterized associations between aberrant DNA methylation changes and gene expression, evidence for a causal relationship in this context has been difficult to obtain. Early techniques for interrogating the role of DNA methylation in the regulation of gene transcription lack specificity and, where more specific techniques such and ZNFs and TALEs have been developed, they are limited by their extensive cost and labor requirements.

View Article and Find Full Text PDF

Bisulfite sequencing is the "gold-standard" technique for DNA methylation analysis. By combining bisulfite sequencing with high-throughput, next-generation sequencing technology, we can document methylation from many thousands of individual reads (equivalent to alleles or "cells"), for multiple target regions and from many samples simultaneously. Here, we describe a next-generation bisulfite-sequencing assay for targeted DNA methylation analysis which offers scope for the simultaneous interrogation of multiple genomic loci across numerous samples.

View Article and Find Full Text PDF

Despite the development of novel therapeutic approaches and improved clinical management, survival from metastatic disease remains poor. Indeed, metastasis accounts for the vast majority of cancer-related deaths. The metastatic cascade comprises a complex range of molecular events that cannot be explained by genetic aberrations alone; dynamic, epigenetic regulatory mechanisms are now being implicated as key drivers of successful metastasis.

View Article and Find Full Text PDF

DNA methylation is a key epigenetic modification implicated in the pathogenesis of numerous human diseases, including cancer development and metastasis. Gene promoter methylation changes are widely associated with transcriptional deregulation and disease progression. The advent of CRISPR-based technologies has provided a powerful toolkit for locus-specific manipulation of the epigenome.

View Article and Find Full Text PDF

The 2011 Tohoku earthquake-tsunami and the subsequent nuclear accident at the Fukushima Dai-ichi Nuclear Power Station (FDNPS) led to large-scale radionuclide contamination of the marine and freshwater environment. Monitoring studies of marine food products in the Fukushima region have generally demonstrated a declining trend in radiocaesium concentrations. However, the accumulation and elimination of radiocaesium and potential biological effects remain poorly understood for freshwater biota inhabiting highly contaminated areas at Fukushima.

View Article and Find Full Text PDF

Graph-based causal inference has recently been successfully applied to explore system reliability and to predict failures in order to improve systems. One popular causal analysis following Pearl and Spirtes et al. to study causal relationships embedded in a system is to use a Bayesian network (BN).

View Article and Find Full Text PDF

Fish have been highly exposed to radiation in freshwater systems after the Chernobyl Nuclear Power Plant (NPP) accident in 1986 and in freshwater and marine systems after the more recent Fukushima NPP accident in 2011. In the years after the accident, the radioactivity levels rapidly declined due to radioactive decay and environmental processes, but chronic lower dose exposures persisted. To gain insights into the long-term effects of environmental low dose radiation on fish ovaries development, a high-throughput transcriptomic approach including a de novo assembly was applied to different gonad phenotypes of female perch: developed gonads from reference lakes, developed/irradiated from medium contaminated lake, and both developed/irradiated and undeveloped from more highly contaminated lakes.

View Article and Find Full Text PDF

Strontium-90 (Sr) is the major long-lived radionuclide derived from the Chernobyl accident, and is still being detected in the heavily contaminated catchments of the Chernobyl Exclusion Zone. This study examines the long-term decrease in the dissolved-phase Sr concentration and the concentration-discharge (Sr-Q) relationship in stream water since the accident. We show that the slow decline in Sr follows a double-exponential function, and that there is a clear relationship between Sr and Q.

View Article and Find Full Text PDF

DNA methylation is a stable epigenetic modification that contributes to the spatiotemporal regulation of gene expression. The manner in which DNA methylation contributes to transcriptional control is dependent on the biological context, including physiological state and the properties of the DNA itself. Classically, dense promoter DNA methylation is associated with transcriptional repression.

View Article and Find Full Text PDF

The Chernobyl and Fukushima nuclear power plant (NPP) accidents that occurred in 1986 and 2011 respectively have led to many years of chronic radiation exposure of wildlife. However, controversies remain on the dose threshold above which an impact on animal health occurs. Fish have been highly exposed immediately after both accidents in freshwater systems around Chernobyl and in freshwater and marine systems around Fukushima.

View Article and Find Full Text PDF

A review is presented of data on solid-liquid distribution coefficients (Kd-s) of the main radiologically important radionuclides of the Chernobyl release within geological deposits at the Chernobyl Nuclear Power Plant (ChNPP) Site. The Kd values for Sr, Cs and Pu for Quaternary sandy deposits that form sedimentary cover at Chernobyl fall within the range of parameters reported in international sorption databases. In agreement with general knowledge on radionuclide geochemical behavior and affinity to soils, Kd-s increase in the sequence: Sr < Cs < Pu.

View Article and Find Full Text PDF