Concomitant t(8;21) and trisomy 4 in a patient with Acute Myeloid Leukemia (AML)

The t(8;21)(q22;q22) is a frequently occurring aberration in acute myeloid leukemia (AML) (18-20%) and usually correlate with French-America-British (FAB) M2 subtype. Several studies showed that patients carrying this abnormality demonstrated good response to standard chemotherapy but also have a high incidence of disease relapse. Trisomy 4 is a rare and specific chromosomal abnormality occurring in AML M2 or M4 of the FAB subtypes. We report a case of a 33-year-old female with an apparently clinical and hematologic diagnosis of acute promyelocytic leukemia (APL) in whom cytogenetic analysis revealed an abnormal karyotype with trisomy 4, in addition to t(8;21). Trisomy 4 and t(8;21) in a patient with AML is rare. The significance of t(8;21) with trisomy 4 in AML are unclear but patients bearing this abnormality are associated with a poor prognosis

Scaling of hysteresis dispersion in a model spin system

2001-2002 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Utilization of glucose, blood pressure, and lipid lowering medications among people with type II diabetes in the United States, 1999-2010

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Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Mechanical, tribological, and stress analyses of ion-beam-deposited boron-rich boron nitride films with increasing N content

Author name used in this publication: C. L. ChoyVersion of RecordPublishe

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract.

Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases

Tensile strength of zinc oxide films measured by a microbridge method

Author name used in this publication: C. L. Choy2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Relationship between the microstructure and nanoindentation hardness of thermally evaporated and magnetron-sputtered electrochromic tungsten oxide films

Author name used in this publication: G. K. H. PangAuthor name used in this publication: C. L. Choy2000-2001 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Early Pregnancy-Associated Plasma Protein A Concentrations are Associated with Third Trimester Insulin Sensitivity

Context: First or early second trimester pregnancy-associated plasma protein-A (PAPP-A) concentrations have previously been shown to be lower in women who subsequently develop gestational diabetes (GDM) and gestational hypertension. Objective: We therefore sought to investigate why circulating PAPP-A concentrations are related to the subsequent risk of GDM and gestational hypertension. Patients, Design and Setting: We measured serum PAPP-A concentrations around week 15 of pregnancy and related these to indices derived from week 28 oral glucose tolerance tests (OGTT) and blood pressures across pregnancy in the Cambridge Baby Growth Study cohort. Results: Increased PAPP-A concentrations were associated with reduced GDM risk (odds ratio 0.623 (0.453, 0.856), P=3.5 x 10$^{-3}$, n=777) and reduced mean arterial blood pressures (β=-0.202– -0.177, P=1.7–6.9 x 10$^{-3}$, n=347–355). They were also negatively associated with week 28 fasting (β=-0.149, P=6.6 x 10$^{-4}$, n=777) and 60 minute (β=-0.188, P=1.5 x 10-5, n=777) OGTT glucose concentrations. These associations were underpinned by the strong associations between increased week 15 PAPP-A concentrations and decreased week 28 insulin resistance (HOMA IR: β=-0.319, P=1.7 x 10$^{-13}$, n=768), and increased insulin secretion relative to insulin sensitivity (insulin disposition index: β=0.202, P=6.5 x 10$^{-6}$, n=731). Conclusions: These results suggest that links between PAPP-A concentrations in early pregnancy and subsequent glucose concentrations and blood pressures may be mediated by changes in insulin sensitivity (and secretion).Most of the endocrine measurements described in this study were funded by the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, U.K.) (RG1644). Core funding for the Cambridge Baby Growth Study has come from the Medical Research Council (7500001180); European Union Framework 5 (QLK4-1999-01422); the Mothercare Charitable Foundation (RG54608); Newlife Foundation for Disabled Children (07/20) and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants.

STUDY QUESTION: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent. LIMITATIONS, REASONS FOR CAUTION: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.European Union (Framework V programme), World Cancer Research Fund International, Medical Research Council (UK), Newlife Foundation for Disabled Children, Evelyn Trust, Mothercare Group Foundation, Mead Johnson Nutrition, National Institute for Health Research Cambridge Comprehensive Biomedical Research CentreThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford University Press