Publications by authors named "Thomas Bird"

Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are the most common forms of early-onset dementia. Unlike AD, FTD begins with behavioral changes before the development of cognitive impairment. Dominantly inherited mutations in MAPT, the microtubule-associated protein tau gene, give rise to cases of FTD and parkinsonism linked to chromosome 17.

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Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer-related mortality worldwide. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulate progressive driver mutations, with hepatocytes the most likely cell of origin.

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Objective: To develop expert consensus on the optimal testing pathway for oesophago-gastric (OG) cancer care.

Methods And Analysis: The process followed a modified Delphi methodology to develop consensus on the optimal testing pathway for OG cancer care. In November 2023, a review of available literature on the topic of OG cancer was conducted.

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Background: Huntington disease (HD) is a genetic neurodegenerative disorder. Given the focus on motor manifestations, nonmotor symptoms are frequently underappreciated in clinical evaluations, despite frequently contributing to primary functional impairment.

Recent Findings: A diagnosis of motor-onset as the definition of manifest symptoms misrepresents the complex nature of HD presentation.

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Introduction: We investigated whether the cerebellum develops neuropathology that correlates with well-accepted Alzheimer's disease (AD) neuropathological markers and cognitive status.

Methods: We studied cerebellar cytoarchitecture in a cohort (N = 30) of brain donors. In a larger cohort (N = 605), we queried whether the weight of the contents of the posterior fossa (PF), which contains primarily cerebellum, correlated with dementia status.

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Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure.

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Background & Aims: Only a handful of countries are on target to achieve elimination of HCV by 2030. People experiencing homelessness (PEH) remain an important HCV reservoir. The END C study evaluated clinical, patient reported, and health economic outcomes of a decentralised integrated model.

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Hereditary spastic paraplegia (HSP) with thin corpus callosum can be due to a variety of genetic causes, the most common of which are biallelic variants in SPG11 (HSP11). Only six cases of neuropathologic examination of HSP11 have been reported. Here we present neuropathological findings in another case of HSP11 with novel mutation (homozygous c.

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Article Synopsis
  • - This study assessed the cost-effectiveness of four different surveillance methods for hepatocellular carcinoma (HCC) in the UK, which included various combinations of biomarker assays and ultrasound techniques.
  • - A detailed Markov model was created using Excel to simulate patient outcomes based on life-years and quality-adjusted life-years (QALYs), ultimately revealing that the GAAD method was the most cost-effective approach, while GAAD combined with ultrasound proved to be the most clinically effective.
  • - The findings suggest that, given current costs and low HCC rates in the UK, either the GAAD strategy alone or in combination with ultrasound offers the best balance of cost-effectiveness, although further evaluations of the GAAD + ultrasound strategy's performance are
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Background: Measures are needed to address recruitment and retention problems in general practice. A good team climate (relational processes of team working) can mitigate the effects of pressured work environments, but little is known about it in British general practice.

Aim: To assess team climate, explore practice characteristics and workforce combinations associated with favourable team climates, and analyse associations between practice team climate and job satisfaction, intention to remain in post, burnout and measures of practice performance.

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A number of post-mortem studies conducted in transplanted Huntington's disease (HD) patients from various trials have reported the presence of pathological and misfolded proteins, in particular mutant huntingtin (mHtt) and phosphorylated tau neuropil threads, in the healthy grafted tissue. Here, we extended these observations with histological analysis of post-mortem tissue from three additional HD patients who had received similar striatal allografts from the fetal tissue transplantation trial conducted in Los Angeles in 1998. Immunohistochemical staining was performed using anti-mHtt antibodies, EM48 and MW7, as well as anti-hyperphosphorylated tau antibodies, AT8 and CP13.

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Article Synopsis
  • Frontotemporal dementia (FTD) and Alzheimer's disease are key types of early-onset dementia linked to mutations in the tau gene, particularly in cases known as FTDP-17.
  • Researchers used electron cryo-microscopy to analyze tau filaments from brains of individuals with specific mutations (V337M and R406W), finding that both mutations produced tau structures resembling those seen in Alzheimer's disease.
  • The study discovered variations in filament structures, including paired helical and straight filaments, and identified a new assembly pattern of tau filaments in patients with the V337M mutation that suggests an enhanced rate of filament formation.
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Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26) that integrates reporters for complementary imaging modalities, flfluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression.

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Article Synopsis
  • The study investigates early Alzheimer's disease changes in the brains of people with Down syndrome and those with genetic variants linked to Alzheimer's, aiming to better understand disease development and improve prevention strategies.
  • Using cross-sectional data from two cohort studies, researchers analyzed tau protein spread and its relationship with amyloid accumulation in participants aged 25 and older.
  • Findings revealed significant differences in the pattern and timing of tau accumulation in the two groups, suggesting implications for early intervention and clinical trials targeting Alzheimer's pathology.
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The SORL1 gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

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Loss-of-function variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are responsible for a spectrum of neurodegenerative disorders. In the homozygous state, they cause severe pathologies with early onset dementia, such as Nasu-Hakola disease and behavioural variants of frontotemporal dementia (FTD), whereas heterozygous variants increase the risk of late-onset Alzheimer's disease (AD) and FTD. For over half of TREM2 variants found in families with recessive early onset dementia, the defect occurs at the transcript level via premature termination codons or aberrant splicing.

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The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that the hominid-specific gene LRRC37B encodes a receptor expressed in human cortical pyramidal neurons (CPNs) and selectively localized to the axon initial segment (AIS), the subcellular compartment triggering action potentials. Ectopic expression of LRRC37B in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs.

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Although lung cancer claims more lives than any other cancer in the United States, screening is severely underutilized, with <6% of eligible patients screened nationally in 2021 versus 76% for breast cancer and 67% for colorectal cancer. This article describes an effort to identify key reasons for the underutilization of lung cancer screening in a rural population and to develop interventions to address these barriers suitable for both a large health system and local community clinics. Data were generated from 26 stakeholder interviews (clinicians, clinical staff, and eligible patients), a review of key systems (Electronic Health Record and billing records), and feedback on the feasibility of several potential interventions by health care system staff.

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Background: NOTCH3 is the causative gene for autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) which is associated with both stroke and dementia. When CADASIL presents primarily as dementia it can be difficult to distinguish from Alzheimer's disease (AD) at both the clinical and neuropathological levels.

Methods: We performed exome sequencing of several affected individuals from a large family affected with AD.

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Article Synopsis
  • - The study addresses the issue of limited ancestral diversity in genome-wide association studies (GWAS), which makes it hard to find genetic risk variants in non-European ancestry groups, focusing on Alzheimer's Disease (AD).
  • - Researchers analyzed a multi-ancestry GWAS dataset within the Alzheimer's Disease Genetics Consortium (ADGC) involving individuals from various ancestries, identifying 13 shared risk loci and 3 ancestry-specific loci, highlighting the benefits of diverse samples.
  • - The findings underscore the importance of including underrepresented populations in genetic research, suggesting that even smaller sample sizes can lead to the discovery of novel genetic variants related to AD and implicating specific biological pathways like amyloid regulation and neuronal development.
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The gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

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Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34).

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