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"Fitzgerald, Terence D"
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GPRC5D-Targeted CAR T Cells for Myeloma
In an early-phase study involving 17 patients with highly refractory multiple myeloma, CAR T-cell therapy with specificity for a G protein–coupled receptor that is expressed on myeloma cells produced a response in 71% of the patients.
Journal Article
PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia
IntroductionTraumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology.Methods and analysisPRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites.Ethics and disseminationEthics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient’s behalf if they lack capacity. Study findings will be disseminated by peer-review publications.Trial registration numberNCT05855252.
Journal Article
Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease
Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13–q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (
P
=0.0017). Re-sequencing of eight prioritised candidate genes in the region in six selected individuals identified 15 SNPs segregating with the IBD haplotype, located within the
ITGA2
gene. Three of these polymorphisms were selected for genotyping in an independent Tasmanian data set comprising 127 cases with familial prostate cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with prostate cancer risk: rs3212649 (OR=1.67 (1.07–2.6),
P
=0.0009) and rs1126643 (OR=1.52 (1.01–2.28),
P
=0.0088). Significant association was observed in both familial and sporadic prostate cancer. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by
in vivo
and
in vitro
studies, supports a role for
ITGA2
in tumour development.
Journal Article
Formal approaches to function in grammar : in honor of Eloise Jelinek
The contributions making up this volume in honor of Eloise Jelinek are written from a formalist perspective that deals with stereotypically functionalist questions about language. Jelinek's pioneering work in formalist syntax has shown that autonomous syntax need not exist in a vacuum. Her work has highlighted the importance of incorporating the effects of discourse and information structure on the syntactic representation. This book aims to invoke Jelinek's work either in substance or spirit. The focus is on Jelinek's influential Pronominal Argument Hypothesis as an \"non-configurational\" language; the influence of discourse-related interface phenomena on syntactic structure; the syntactic analysis of the grammaticalization; interactions between morphology, phonology and phonetics; and foundational issues about the link between formal grammar and function of language, as well as the methodological issues underlying the different approaches to linguistics.
eBook