Trends in the incidence and survival of multiple myeloma in South East England 1985-2004.

BACKGROUND: Multiple myeloma is an uncommon cancer with a poor prognosis. Its incidence is expected to increase due to ageing populations and better diagnosis, and new treatments have been developed to improve survival. Our objective was to investigate trends in the epidemiology and survival of multiple myeloma for South East England. METHODS: Data on 15,010 patients diagnosed with multiple myeloma between 1985 and 2004 was extracted from the Thames Cancer Registry database. We calculated the yearly age-standardised incidence rates for males and females and age-specific incidence rates in 10-year age groups for both sexes combined. We also explored geographical variation in incidence across primary care trusts. We then used period analysis to calculate trends in 1- and 5-year relative survival over the 15 years 1990-2004, comparing survival by sex and by age group 59 years and below versus 60 years and above. Finally, we investigated 5-year relative survival for the period 2000-2004 by socio-economic deprivation, assigning patients to quintiles of deprivation using the Income Domain of the Index of Multiple Deprivation 2004 based on postcode of residence. RESULTS: The incidence of multiple myeloma was higher in males than in females and in patients over 70, throughout the period 1985-2004. No obvious geographical pattern of incidence by primary care trust emerged. The 1- and 5-year relative survival of male and female patients increased in both age groups and was statistically significant in males aged over 60. There was a tendency for better survival in patients resident in the most affluent areas, but this did not reach statistical significance. CONCLUSIONS: The trends in incidence of multiple myeloma in males and females are similar to that reported from other western populations. Relative survival was higher for younger patients although we found significant improvements in 1-year relative survival for male patients over 60 years old. The improved survival demonstrated for patients of all ages is likely to reflect increased detection, earlier diagnosis and the introduction of new treatments. Future studies should investigate the influence of ethnicity on incidence and survival, and the effect of specific treatments on survival and quality of life

Differences in breast cancer hormone receptor status in ethnic groups: a London population.

BACKGROUND: Triple negative breast cancer (TNBC) is associated with different ethnic groups in the United States (US), however this has not previously been examined in a population-based study within the United Kingdom (UK). METHODS: Electronic pathology reports from the North East London Cancer Network (NELCN) on women diagnosed with breast cancer between 2005 and 2007 were collated. The statuses of oestrogen receptor, progesterone receptor and HER-2 were extracted. Women were classified as having TNBC if all three receptor statuses were negative, and as not having TNBC if at least one receptor was positive or borderline. Logistic regression was used to quantify the association between TNBC and ethnicity, adjusting for age, year of diagnosis and socioeconomic deprivation. Overall survival in different ethnic groups was examined using Cox regression, adjusting as appropriate for age, stage of disease, triple negative status, year of diagnosis, socioeconomic deprivation and recorded treatment. RESULTS: There were 2417 women resident in NELCN diagnosed with breast cancer between 2005 and 2007, and TNBC status was determined for 1228 (51%) women. Overall, of women who had their TNBC status determined, 128 (10%) were diagnosed with TNBC. Compared with White women, Black (odds ratio [OR]=2.81, p<0.001) and South Asian (OR=1.80, p=0.044) women with breast cancer were more likely to have TNBC. Black women had a worse age-adjusted survival than White women (hazard ratio [HR]=2.05, p<0.001). This was attenuated by further adjustment for stage of disease (1.52, p=0.032) and triple negative status (1.31, p=0.175). CONCLUSION: Better methods of early detection may need to be developed in addition to more effective systemic treatment in order to improve outcomes for women with TNBC

Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.

The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection.National Institutes of Health (Grant IDs: R37AI054503, R01 AI076327, 5T32HD007233, 5F30HL110455), Wellcome Trust, National Institute of Health Research Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.chom.2016.07.00

Prevalence-Dependent Costs of Parasite Virulence

Costs of parasitism are commonly measured by comparing the performance of infected groups of individuals to that of uninfected control groups. This measure potentially underestimates the cost of parasitism because it ignores indirect costs, which may result from the modification of the competitiveness of the hosts by the parasite. In this context, we used the host-parasite system consisting of the yellow fever mosquito Aedes aegypti and the microsporidian parasite Vavraia culicis to address this question: Do infected individuals exert a more or less intense intraspecific competition than uninfected individuals? Our experimental results show that, indeed, infected hosts incur a direct cost of parasitism: It takes them longer to become adults than uninfected individuals. They also incur an indirect cost, however, which is actually larger than the direct cost: When grown in competition with uninfected individuals they develop even slower. The consequence of this modification of competitiveness is that, in our system, the cost of parasitism is underestimated by the traditional measure. Moreover, because the indirect cost depends on the frequency of interactions between infected and uninfected individuals, our results suggest that the real cost of parasitism, i.e., virulence, is negatively correlated with the prevalence of the parasite. This link between prevalence and virulence may have dynamical consequences, such as reducing the invasion threshold of the parasite, and evolutionary consequences, such as creating a selection pressure maintaining the host's constitutive resistance to the parasite

Estimating attendance for breast cancer screening in ethnic groups in London

BACKGROUND: Breast screening uptake in London is below the Government's target of 70% and we investigate whether ethnicity affects this. Information on the ethnicity for the individual women invited is unavailable, so we use an area-based method similar to that routinely used to derive a geographical measure for socioeconomic deprivation. METHODS: We extracted 742,786 observations on attendance for routine appointments between 2004 and 2007 collected by the London Quality Assurance Reference Centre. Each woman was assigned to a lower super output (LSOA) based on her postcode of residence. The proportions of the ethnic groups within each LSOA are known, so that the likelihood of a woman belonging to White, Black and Asian groups can be assigned. We investigated screening attendance by age group, socioeconomic deprivation using the Index of Deprivation 2004 income quintile, invitation type and breast screening service. Using logistic regression analysis we calculated odds ratios for attendance based on ethnic composition of the population, adjusting for age, socioeconomic status, the invitation type and screening service. RESULTS: The unadjusted attendance odds ratios were high for the White population (OR: 3.34 95% CI [3.26-3.42]) and low for the Black population (0.13 [0.12-0.13]) and the Asian population (0.55 [0.53-0.56]). Multivariate adjustment reduced the differences, but the Black population remained below unity (0.47 [0.44-0.50]); while the White (1.30 [1.26-1.35]) and Asian populations (1.10 [1.05-1.15]) were higher. There was little difference in the attendance between age groups. Attendance was highest for the most affluent group and fell sharply with increasing deprivation. For invitation type, the routine recall was higher than the first call. There were wide variations in the attendance for different ethnic groups between the individual screening services. CONCLUSIONS: Overall breast screening attendance is low in communities with large Black populations, suggesting the need to improve participation of Black women. Variations in attendance for the Asian population require further investigation at an individual screening service level

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics. Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels. Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child\u27s weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample. Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes

Trends in the incidence and survival of multiple myeloma in South East England 1985-2004

Abstract Background Multiple myeloma is an uncommon cancer with a poor prognosis. Its incidence is expected to increase due to ageing populations and better diagnosis, and new treatments have been developed to improve survival. Our objective was to investigate trends in the epidemiology and survival of multiple myeloma for South East England. Methods Data on 15,010 patients diagnosed with multiple myeloma between 1985 and 2004 was extracted from the Thames Cancer Registry database. We calculated the yearly age-standardised incidence rates for males and females and age-specific incidence rates in 10-year age groups for both sexes combined. We also explored geographical variation in incidence across primary care trusts. We then used period analysis to calculate trends in 1- and 5-year relative survival over the 15 years 1990-2004, comparing survival by sex and by age group 59 years and below versus 60 years and above. Finally, we investigated 5-year relative survival for the period 2000-2004 by socio-economic deprivation, assigning patients to quintiles of deprivation using the Income Domain of the Index of Multiple Deprivation 2004 based on postcode of residence. Results The incidence of multiple myeloma was higher in males than in females and in patients over 70, throughout the period 1985-2004. No obvious geographical pattern of incidence by primary care trust emerged. The 1- and 5-year relative survival of male and female patients increased in both age groups and was statistically significant in males aged over 60. There was a tendency for better survival in patients resident in the most affluent areas, but this did not reach statistical significance. Conclusions The trends in incidence of multiple myeloma in males and females are similar to that reported from other western populations. Relative survival was higher for younger patients although we found significant improvements in 1-year relative survival for male patients over 60 years old. The improved survival demonstrated for patients of all ages is likely to reflect increased detection, earlier diagnosis and the introduction of new treatments. Future studies should investigate the influence of ethnicity on incidence and survival, and the effect of specific treatments on survival and quality of life.</p