Trajectories in mammographic breast screening participation in middle-age overweight and obese women: A retrospective cohort study using linked data.

OBJECTIVES: Despite the established benefits and availability of mammographic breast screening, participation rates remain suboptimal. Women with higher BMIs may not screen regularly, despite being at increased risk of postmenopausal breast cancer and worse outcomes. This study investigated the association between prospective changes in BMI and longitudinal adherence to mammographic screening among women with overweight or obesity. METHODS: Retrospective cohort study of women (N = 2822) participating in the Australian Longitudinal Study on Women's Health with an average follow-up of 20 years, with screening participation enumerated via BreastScreen NSW, Australia clinical records over the period 1996-2016. Association between BMI and subsequent adherence to screening was investigated in a series of marginal structural models, incorporating a time variant/invariant socio-demographic, clinical, and health behaviour confounders. Models were also stratified by a proxy measure of socio-economic status (education). RESULTS: Participants with overweight/obesity were less adherent to mammography screening, compared to healthy/underweight participants (OR=1.29, 95 % CI=1.07, 1.55). The association between overweight/obesity and non-adherence was higher among those who ever had private health insurance (OR=1.30, 95 % CI=1.05, 1.61) compared to those who never had private health insurance and among those with lower educational background (OR=1.38, 95 % CI=1.08, 1.75) compared to those with higher educational background. CONCLUSIONS: Long-term impacts on screening participation exist among women with higher BMI, who are less likely to participate in routinely organised breast screening. Women with a higher BMI should be a focus of efforts to improve breast screening participation, particularly given their increased risk of breast cancer and association of higher BMI with worse breast cancer outcomes among older women.

Co-design of an intervention to optimize mammographic screening participation in women with obesity and/or physical disabilities.

BACKGROUND: Mammographic breast screening/rescreening rates are suboptimal for women with obesity and/or physical disabilities. This study describes development of an intervention framework targeting obesity- and disability-related barriers to improve participation. METHODS: Mixed methods combined a systematic review with first-person perspectives to optimise screening engagement among women with obesity and/or physical disabilities. Phase 1 (systematic review) was conducted following the PRISMA framework. Phase 2 involved in-depth interviews with n = 8 women with lived experience of obesity and/or physical disabilities. An inductive coding approach was applied to the data which was then combined with Phase 1 results to develop the intervention framework. RESULTS: Six studies were included in the systematic review. Tailored education based on individual risk increased willingness to undergo mammographic screening. Recommendations to improve the screening experience included partnerships with consumers, targeted messaging, and enhanced professional development for breast screening staff. Participants also identified strategies to improve the uptake of screening and the experience itself. CONCLUSION: Development and evaluation of interventions informed by frameworks like the one developed in this study are needed to improve engagement in screening to promote regular participation among women with physical disabilities and/or obesity. IMPLICATIONS FOR PRACTICE: Successful implementation of practice interventions co-designed by women with obesity and/or physical disabilities are likely to improve their breast screening participation. Enhanced training of radiographers aimed at upskilling in empathetic communication around required manoeuvring and potentially longer screening times for clients with obesity and/or physical disabilities may encourage more positive client practitioner interactions. Client information aimed at women with obesity should include information on how to prepare for the appointment and explain there may be equipment limitations compromising imaging which may not be completed at an initial appointment.

Development and validation of measures to evaluate adolescents' knowledge about human papillomavirus (HPV), involvement in HPV vaccine decision-making, self-efficacy to receive the vaccine and fear and anxiety.

OBJECTIVES: We describe the development and validation of measures of human papillomavirus (HPV)/HPV vaccination knowledge, fear/anxiety about vaccination, involvement in HPV vaccine decision-making, and self-efficacy with regard to getting the vaccine, designed to evaluate the efficacy of an intervention to affect these domains (collectively termed the HAVIQ: HPV Adolescent Vaccine Intervention Questionnaire). STUDY DESIGN: Literature search, cognitive interviews and cross-sectional survey. METHODS: A literature search identified existing items that were modified for the present measures. Experts reviewed draft measures for face and content validity. Cognitive interviews with adolescents were also used to assess content validity. Adolescents completed the measures and an internal reliability analysis of each measure was performed. RESULTS: The four experts concurred that the measures had face validity. Cognitive interviews identified items requiring refinement. Content validity was examined with ten experts and was deemed acceptable. There were 1800 adolescents who completed the measures; Cronbach's alpha was >0.6 for three of the four measures. The four final measures are brief, comprising 25 items in total. CONCLUSIONS: The measures are robustly developed and validity-tested. The HAVIQ may be used in research settings to evaluate adolescents' knowledge and experiences of the process of HPV vaccination in a school-based vaccination programme.

Hemoglobin switching in Rana/Xenopus erythroid heterokaryons: factors mediating the metamorphic hemoglobin switch are conserved.

Hemoglobin switching, which occurs in all classes of vertebrates as well as in certain invertebrates, is due to developmental regulation of different globin genes which are typically arranged in clustered families. By fusing erythroid cells of different developmental programs, trans-acting factors that regulate this switch in gene expression have been detected [Ramseyer et al. (1989): Dev Biol 133:262-271]. Adult erythroid cells of one anuran species, Xenopus laevis, were fused with tadpole erythroid cells of another frog, Rana catesbeiana, creating developmental erythroid heterokaryons that synthesize adult Rana globin mRNA and hemoglobins. The results show that factors from adult Xenopus erythroid cells are capable of inducing adult Rana globin gene expression in the Rana tadpole erythroid cell nucleus. We have used the cross-induction of adult Rana hemoglobin synthesis in these adult Xenopus/Rana tadpole erythroid heterokaryons to address two practical questions, answers to which may be helpful in isolating developmental stage-specific globin gene regulatory proteins: 1) Are erythroblasts which are actively expressing globin mRNAs and hemoglobins richer in specific globin-inducing activities than other stages of erythroid cellular differentiation? 2) Do mature, circulating erythrocytes still have the activities necessary to mediate the cross-induction of Hb synthesis? The results reported here show that the answers to both questions are affirmative and show that quiescent, fully differentiated adult erythroid cells are still capable of expressing the trans-activator(s). These findings show that factors which mediate the metamorphic hemoglobin switch are conserved between these two genera of frogs.

Intracellular signals for developmental hemoglobin switching.

We have detected trans-acting factors that regulate developmental hemoglobin switching by fusing erythroid cells of different developmental programs. Adult erythroid cells of one anuran species, Xenopus laevis, were fused with tadpole erythroid cells of another frog, Rana catesbeiana. In a second set of experiments, dimethyl sulfoxide-induced murine erythroleukemia cells, which express only adult mouse globins, were fused with Rana tadpole erythroid cells, which express only embryonic and fetal-like globins. Adult Rana globin gene expression was detected in both sets of transient heterokaryons at 6 hr after fusion. Dot blots and Northern blots of total RNA from the heterokaryons contained material that reacted with an adult Rana alpha-globin probe; newly synthesized adult Rana hemoglobin tetramers were detected with native polyacrylamide gel electrophoresis. These results show that developmental stage-specific transacting factors for globin genes can function across vertebrate classes (mammalia to amphibia) and suggest that the mechanisms that regulate developmental hemoglobin switching are highly conserved.

Erythroid heterokaryons: a system for investigating the functional role of trans-acting factors in developmental hemoglobin switching.

We have shown that erythroid cells from widely divergent species such as amphibians and mammals can be efficiently fused using either calcium phosphate bridges or polyethylene glycol. Transient heterokaryons of adult mouse erythroid (MEL) cells and Rana catesbeiana (bullfrog) tadpole erythroid cells produce adult Rana alpha globin mRNA and adult Rana hemoglobin (Hb) tetramers. Rana tadpole/adult Xenopus erythroid heterokaryons also exhibit this switch to adult Rana globin gene expression. These results indicate that trans-acting factors--and the globin gene regulatory mechanism of which they are a part--are conserved in vertebrate phylogeny. We also wish to know whether the reciprocal Hb switch occurs in each of these two types of heterokaryons, i.e., whether embryonic or fetal globin genes are reactivated in the adult nucleus. Experiments to answer these questions are in progress and are briefly discussed. The influence of stage of erythroid differentiation of the larval and adult donor cells on the cross-inductions is also being explored. These types of experiments should indicate which cells will be the best sources of stimulatory and inhibitory factors that are globin-gene specific. This system may be useful as an in situ assay for the function of purified trans-factors, which could be encapsulated within RBC ghosts and delivered via cell fusion.

Formation of transient polykaryons by fusion of erythrocytes of different developmental programs.

We report here two methods of fusing erythroid cells from bullfrogs (Rana catesbeiana), using polyethylene glycol or calcium phosphate, which yield masses of polykaryons in which the cytoplasms and nuclei of tadpole and adult frog erythroid cells are intermixed. The masses of fused cells carry out protein synthesis in culture, including the assembly of normal hemoglobin (Hb) tetramers. In these polykaryons there is reactivation of the expression of specific Hbs that have previously been "turned off" in vivo as the result of either a developmental Hb switch or normal cellular differentiation and RBC maturation. For example, the products of fusion of tadpole erythroblasts with adult frog mature RBCs synthesize adult Hb, whereas neither cell population alone does so. Recent experiments have taken advantage of a Hb-expression polymorphism that we discovered in this species, such that some tadpoles have greatly reduced expression of one of the larval Hbs (Hb Td-4). Fusion of erythroblasts from such tadpoles with RBC from frogs that had expressed Hb Td-4 when they were tadpoles produces polykaryons that synthesize Hb Td-4, indicating there is a trans factor that stimulates Td-4 expression. Heterospecific erythroid cell polykaryons can be constructed in an analogous manner, facilitating the study of trans-acting factors that regulate specific globin gene expression during development.

Hemoglobin switching across vertebrate classes: exchange of developmental signals by cell fusion.

Our aim is to obtain evidence for trans-acting factors that regulate developmental hemoglobin (Hb) switching. Our approach is to fuse erythroid cells that have different developmental programs, allowing the trans-acting factors from the adult cell to have access to the nucleus of the fetal or embryonic cell and vice-versa. After cell fusion, the heteropolykaryons are cultured for six hours, and globin gene expression is assayed at two levels: (1) at the level of mRNAs on dot blots hybridized with globin-specific cDNA probes, and (2) at the level of fully-formed Hb tetramers separated by native polyacrylamide gel electrophoresis (PAGE). Since the donor erythroid cells are from different species, it is easy to determine which globin gene products are from which nucleus. And since there is no nuclear fusion for at least twelve hours, the Hb switching that occurs is due to regulation in trans. Our results show that developmental Hb switching occurs in mouse-frog erythroid cell polykaryons. When DMSO-induced murine erythroleukemia (MEL) cells (which express only adult mouse Hbs) are fused with Rana tadpole RBCs (which express only embryonic and fetal-like Hbs), the resultant heteropolykaryons express adult frog globin mRNA and adult frog Hbs. We conclude that there are developmental stage-specific trans-acting factors for Hb switching, that trans-acting factors from adult mouse erythroid cells can induce expression of adult frog globin genes in a tadpole RBC nucleus, and that Hb switching mechanisms are conserved across vertebrate classes.

Management of combined segment disease.

Eighty-five of 148 inflow procedures were performed for combined segment disease. Our study shows that aortofemoral bypass is clinically and functionally superior to axillofemoral bypass in limbs with combined segment disease and hemodynamic criteria for limb salvage. The results of these two procedures are comparable for claudicant limbs. A derivative of segmental plethysmography, the predictive index, can select preoperatively those limbs that will fail to respond to aortofemoral bypass alone. Finally, either in limbs selected for aortofemoral bypass with both ischemic tissue lesions and a predictive index greater than 0.2 or in limbs selected for axillofemoral bypass with ischemic tissue lesions alone, a synchronous procedure can be performed with relatively low morbidity and excellent early functional results.