A Study of Fluorescent Nanoparticles: Quantum Dots and Silica Dots

Optical techniques have here been employed for the study of two types of nanoscopic fluorescent probes, quantum dots and silica dots. Basic characterization of these fluorescent nanoparticles? photophysics and their capabilities have been explored utilizing the following techniques: fluorescence correlation spectroscopy, FCS, time resolved single photon counting lifetime decay measurements, and steady state absorbance, emission, and excitation measurements. The unique properties of QDs, unmatched by any available organic fluorophore, have the potential to allow the development of FRET-based nanoscale biosensors. Unambiguous assignment of a quenching mechanism between partners as FRET may only occur through the measurement of the rate of transfer from the donor to the acceptor, this rate manifests itself as a negative amplitude component in the overall lifetime decay of the accepting partner. Two experimental regimes were executed in an attempt to identify the presence of FRET between fluorescent donor semi-conductor quantum dots surrounded by streptavidin with peak emission at 525nm (525-CdSe-ZnS QD-streptavidin) and biocytin dye acceptors chosen to have varying degrees of absorption overlap with the 525-CdSe-ZnS QD-streptavidin emission. Significant quenching of the donor, along with the acceptor, was seen when the donor was bound to the acceptor, signifying some form of energy transfer. The degree of donor quenching, illustrated by the decrease in average lifetime, corresponded with the loading ratio of the acceptor?the more acceptors present, the larger the quenching. An unambiguous assignment of the rate of transfer of excited state energy from the donor to the acceptor, signified by a negative amplitude component in the lifetime decay of the acceptor, was not accomplished. Organic fluorescent dyes encapsulated in silica to create nanoscopic core-shell particles for use in biological applications have presented an interesting alternative to semiconductor fluorescent probes. In this experiment, an expanded core-shell morphology was surrounded by increasingly thicker layers of the siliceous shell to determine if this could control the photophysical properties of the nanoparticles. Sixteen nanoparticles were synthesized, all of distinct sizes and their photophysical properties investigated. No correlation between the thickness of the silica shell and the brightness of the particle was found. However, as the size of the particle increased the siliceous shell acted as a protective coating from potential quenchers for the TRITC dye in the center allowing molecules to stay in the triplet state for longer periods of time.Watt Webb Frank Wise Jim Alexander IRG-Ne

Kaposi's Sarcoma in Uganda: Geographic and Ethnic Distribution

Over the quinquennium 1964-68 the crude annual incidence of Kaposi's sarcoma in Uganda per million of the population was 7·9 overall, 14·6 for males and 1·1 for females. Statistical analysis indicates that the disease is most prevalent in highland areas to the west and among the indigenous Bantu tribes. There was no correlation with the distribution of squamous cell carcinoma of the lower leg, and Kaposi's sarcoma was not seen in an Indian or European during the period under review

Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy

Background: Although breast cancer risk is greater in users of estrogen-progestin than estrogen-only formulations of menopausal hormonal therapy, reports on their effects have been somewhat inconsistent. We investigated whether the timing of these therapies affected breast cancer incidence. Methods: A total of 1 129 025 postmenopausal UK women provided prospective information on hormonal therapy use and other factors relevant for breast cancer risk. We used Cox regression to estimate adjusted relative risks (RRs) of breast cancer in hormonal therapy users vs never users and calculated standardized incidence rates. All statistical tests were two-sided. Results: During 4.05 million woman-years of follow-up, 15 759 incident breast cancers occurred, with 7107 in current users of hormonal therapy. Breast cancer incidence was increased in current users of hormonal therapy, returning to that of never users a few years after use had ceased. The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap (Pheterogeneity <. 001, for both estrogen-only and estrogen-progestin formulations). Among current users of estrogen-only formulations, there was little or no increase in risk if use began 5 years or more after menopause (RR = 1.05, 95% confidence interval [CI] = 0.89 to 1.24), but risk was statistically significantly increased if use began before or less than 5 years after menopause (RR = 1.43, 95% CI = 1.35 to 1.51). A similar pattern was observed among current users of estrogen-progestin formulations (RR = 1.53, 95% CI = 1.38 to 1.70, and RR = 2.04, 95% CI = 1.95 to 2.14, respectively). At 50-59 years of age, annual standardized incidence rates for breast cancer were 0.30% (95% CI = 0.29% to 0.31%) among never users of hormone therapy and 0.43% (95% CI = 0.42% to 0.45%) and 0.61% (95% CI = 0.59% to 0.64%), respectively, among current users of estrogen-only and estrogen-progestin formulations who began use less than 5 years after menopause. Conclusions: There was substantial heterogeneity in breast cancer risk among current users of hormonal therapy. Risks were greater among users of estrogen-progestin than estrogen-only formulations and if hormonal therapy started at around the time of menopause than later

Maximising engagement, motivation and long term change in a Structured Intensive Education Programme in Diabetes for children, young people and their families: Child and Adolescent Structured Competencies Approach to Diabetes Education (CASCADE).

BACKGROUND: This trial aims to evaluate effective delivery and cost effectiveness of an innovative structured psycho-educational programme (CASCADE) for young people and their families living with diabetes. The increase in numbers of people being diagnosed with diabetes is posing a challenge for both the UK and the rest of the world. The peak age for diagnosis is between 10 and 14 years of age. There is clear evidence that improved diabetes control from diagnosis in childhood can reduce the incidence and progression of long-term complications. However, despite the development of improved insulin regimens and delivery methods, the overall metabolic control in children and adolescents has improved little in the UK in the past decade. Therefore there is a need for novel interventions and health delivery mechanisms aimed at young people and their families to help improve control and reduce complications, illness burden and costs to the NHS. METHODS/DESIGN: The CASCADE trial is a multi-centre randomised control trial with 26 clinics randomised to control or intervention groups, with 572 children and young people involved in the study. The intervention will be delivered in 4 group sessions, over a 4 month period. A developmentally appropriate curriculum will be delivered to groups of 3 - 4 families, focusing on achievement of increasing competency in self-management of diabetes. The control group will receive standard care from their clinical team, usually consisting of regular 3-monthly clinic visits and telephone contact as required with the clinical nurse specialist and consultant. The primary outcomes of the trial will be change in HbA1c between baseline and 12 months and 24 months post recruitment. Secondary outcomes will include measures related to the economic evaluation, psychosocial outcomes, outcomes related to management of diabetes outcomes, and adherence to the intervention. DISCUSSION: The trial will be run by independent research and service delivery teams and supervised by a trial steering committee. A data monitoring and ethics committee has been put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The trial will be conducted according to the principles of MRC Good Clinical Practice (GCP) Guidelines and CTRU Phase III Trial Standard Operating procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52537669

Comparison of various characteristics of women who do and do not attend for breast cancer screening

BACKGROUND: Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. METHODS: Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared. RESULTS: Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders. CONCLUSION: Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications

Hormone replacement therapy and false positive recall in the Million Women Study: patterns of use, hormonal constituents and consistency of effect

INTRODUCTION: Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall. METHODS: A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome. RESULTS: Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics. CONCLUSION: Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening

Breast cancer histological classification: agreement between the Office for National Statistics and the National Health Service Breast Screening Programme

INTRODUCTION: Epidemiological studies rely on data supplied by central cancer registration sources to be timely, accurate and complete. Validation studies of such data at a national level are limited. Data collected for the Million Women Study was used to compare the level of agreement between the Office for National Statistics (ONS) and the National Health Service Breast Screening Programme (NHSBSP) in the recording of incident screen-detected breast cancer histology between 1996 and 2001. METHODS: 1.3 million women aged 50 to 64 years were recruited into the Million Women Study cohort via the NHSBSP. Incident screen-detected breast cancer histologies were notified separately by the ONS and NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly coded to allow for comparison in terms of cancer invasiveness and morphology. The statistical outcome measures are percentage agreement and the kappa statistic. RESULTS: A total of 5,886 incident screen-detected breast cancers were available for analysis. Of the 5,886 screen-detected cancers reported by the ONS and NHSBSP, 5,684 (96.6%, κ = 0.9) agreed in terms of the degree of invasiveness. Of the 5,458 cancers that had been assigned a specific morphology code, there was exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, κ = 0.8). CONCLUSION: There is an excellent level of agreement between the ONS and NHSBSP in the recording of the histology of screen-detected breast cancer. From these results it is not possible to comment on which source of data is the more or less accurate, although the differences are very small

Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry-based national study

BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. ----- METHODS: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. ----- RESULTS: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. ----- CONCLUSIONS: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia