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"Williams, Melanie"
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Female Stars of British Cinema
Female Stars of British Cinema uses case studies of seven female stars whose careers span the 1940s to the present day - Jean Kent, Diana Dors, Rita Tushingham, Glenda Jackson, Helena Bonham Carter, Emily Lloyd, and Judi Dench - to explore how British star femininities have developed over time.
The potential of residual clinical Group B Streptococcus swabs for assessing the vaginorectal microbiome in late pregnancy
2024
The maternal pregnancy microbiome (including genitourinary and gut) has been linked to important pregnancy/birth and later childhood health outcomes. However, such sampling as part of large population cohort studies is logistically and financially challenging. Many countries routinely collect vaginal or vaginal-rectal swabs in late pregnancy for Group B Streptococcus (GBS) screening, but their utility for population-based research is still unclear. As part of planning for the Generation Victoria population-based cohort study beginning in pregnancy, we assessed the utility and reliability of residual clinical GBS vaginal/vaginal-rectal swabs for generating late pregnancy microbiome data. We carried out a two-phased pilot study. Phase one assessed the level of microbial diversity apparent in ‘residual’ clinical vaginal/vaginal-rectal swabs post clinical testing and storage for 7–10 days at 4 °C (routine clinical practice). Phase two directly assessed the impact of storage time and temperature on the microbial composition of vaginal/vaginal-rectal swabs collected specifically for research purposes. The microbiota composition in the ‘residual’ clinical swabs aligned with published studies. The ‘research’ swabs, stored at 4 °C for up to ten days, showed minimal changes in microbiota profile, compared to swabs examined on the day of collection. In contrast, significant variation in diversity was seen in swabs stored at room temperature for up to 48 h. Residual clinical material from swabs collected primarily for GBS screening in late pregnancy represent a reliable and abundant source of material for assessing the late pregnancy maternal microbiome for research purposes. This represents a low-burden opportunity for population-representative pregnancy studies to assess the potential of late pregnancy microbiome for prediction and understanding maternal and child health outcomes.
Journal Article
Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex
2011
Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.
Journal Article
CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit
by
Mash, Deborah C
,
Richie, Christopher T
,
Spivak, Charles E
in
Brain research
,
Cell culture
,
Cell Line
2017
Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies.
Journal Article
Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study
by
Aguilar, Christine
,
Williams, Melanie
,
Mesa, Ruben
in
Cancer in children
,
Care and treatment
,
Evaluation
2023
This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas. The population-based cohort study used Texas Cancer Registry data (1995–2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses. The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0–19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15–19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01–1.26] for all cancer types. Comparing to patients diagnosed at ages 1–4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36–2.09), at 10–14 year (HR: 1.42, 95% CI: 1.20–1.68), or at 15–19 years (HR: 1.40, 95% CI: 1.20–1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer. South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age<1 year or 10–19 years were also associated with decreased childhood cancer survival. Despite advances in treatment, Hispanic patients lag significantly behind NHW patients. Further cohort studies in South Texas are warranted to identify additional factors affecting survival and to develop interventional strategies.
Journal Article
Correction: Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study
2024
[This corrects the article DOI: 10.1371/journal.pone.0278354.].
Journal Article
Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study
by
Aguilar, Christine
,
Williams, Melanie
,
Mesa, Ruben
in
Acute lymphoblastic leukemia
,
Age groups
,
Analysis
2023
This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas. The population-based cohort study used Texas Cancer Registry data (1995–2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses. The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0–19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15–19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01–1.26] for all cancer types. Comparing to patients diagnosed at ages 1–4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36–2.09), at 10–14 year (HR: 1.42, 95% CI: 1.20–1.68), or at 15–19 years (HR: 1.40, 95% CI: 1.20–1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer. South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age<1 year or 10–19 years were also associated with decreased childhood cancer survival. Despite advances in treatment, Hispanic patients lag significantly behind NHW patients. Further cohort studies in South Texas are warranted to identify additional factors affecting survival and to develop interventional strategies.
Journal Article
Breastfeeding practices and associations with pregnancy, maternal and infant characteristics in Australia: a cross-sectional study
2023
Background
Exclusive breastfeeding to six months of age is a major global public health priority. Several characteristics are known to be associated with early cessation of breastfeeding, however, limited evidence exists regarding whether women’s reported reasons for cessation are associated with maternal, pregnancy and infant characteristics. The aims of this study were to: i) describe women’s reported intention to breastfeed and their subsequent breastfeeding practices; ii) describe women’s reported reasons for breastfeeding cessation prior to the infant being five months of age; and iii) examine associations between these factors and maternal, pregnancy and infant characteristics.
Methods
Telephone and online surveys were conducted between October 2019 and April 2020 with 536 women who had given birth in the previous eight to 21 weeks at four public maternity services in Australia.
Results
The majority of women intended to (94%), and did, initiate (95%) breastfeeding. At the time the survey was conducted, 57% of women were exclusively breastfeeding. Women who: had less than University level education, had a pre-pregnancy BMI in the overweight or obese category, and who smoked tobacco at the time of the survey had lower odds of exclusively breastfeeding. The most common self-reported reasons for breastfeeding cessation were breastfeeding challenges (47%) and low milk supply (40%). Women aged 26–35 years and 36 + years had greater odds of reporting breastfeeding cessation due to low milk supply (OR = 2.92, 95% CI: 1.11, 7.66; OR = 5.57, 95% CI: 1.70, 18.29) compared to women aged 18–25 years. While women who had completed a TAFE certificate or diploma had lower odds of reporting this as a reason for breastfeeding cessation (OR = 0.28; 95% CI: 0.11, 0.73) compared to women who had University level education. There were no other significant associations found between characteristics and reasons for ceasing breastfeeding.
Conclusions
The most common reasons for breastfeeding cessation may be modifiable through the provision of breastfeeding support in the early postpartum period, with such support being tailored to women’s age and level of education. Such support should aim to increase women's self-efficacy in breastfeeding, and be provided from the antenatal period and throughout the first six months postpartum.
Journal Article
The burden of Legionnaires' disease in New Zealand (LegiNZ): a national surveillance study
2019
Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand.
LegiNZ was a national surveillance study done over 1-year in which active case-finding was used to maximise the identification of cases of Legionnaires' disease in hospitals. Respiratory specimens from patients of any age with pneumonia, who could provide an eligible lower respiratory specimen, admitted to one of 20 participating hospitals, covering a catchment area of 96% of New Zealand's population, were routinely tested for legionella by PCR. Additional cases of Legionnaires' disease in hospital were identified through mandatory notification.
Between May 21, 2015, and May 20, 2016, 5622 eligible specimens from 4862 patients were tested by PCR. From these, 197 cases of Legionnaires' disease were detected. An additional 41 cases were identified from notification data, giving 238 cases requiring hospitalisation. The overall incidence of Legionnaires' disease cases in hospital in the study area was 5·4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases.
The rate of notified disease during the study period was three-times the average over the preceding 3 years. Active case-finding through systematic PCR testing better clarified the regional epidemiology of Legionnaires' disease and uncovered an otherwise hidden burden of disease. These data inform local Legionnaires' disease testing strategies, allow targeted antibiotic therapy, and help identify outbreaks and effective prevention strategies. The same approach might have similar benefits if applied elsewhere in the world.
Health Research Council of New Zealand.
Journal Article