Use and abuse of mathematical models: an illustration from the 2001 foot and mouth disease epidemic in the United Kingdom

Foot and mouth disease (FMD) is a major threat, not only to countries whose economies rely on agricultural exports, but also to industrialised countries that maintain a healthy domestic livestock industry by eliminating major infectious diseases from their livestock populations. Traditional methods of controlling diseases such as FMD require the rapid detection and slaughter of infected animals, and any susceptible animals with which they may have been in contact, either directly or indirectly. During the 2001 epidemic of FMD in the United Kingdom (UK), this approach was supplemented by a culling policy driven by unvalidated predictive models. The epidemic and its control resulted in the death of approximately ten million animals, public disgust with the magnitude of the slaughter, and political resolve to adopt alternative options, notably including vaccination, to control any future epidemics. The UK experience provides a salutary warning of how models can be abused in the interests of scientific opportunism.

Endocrine disrupters and human health: Could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research

In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of. data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health. Copyright (C) 2004 John Wiley Sons, Ltd.

Estimated intake of dietary phytoestrogens in Australian women and evaluation of correlates of phytoestrogen intake

The role of dietary phytoestrogens in health has been of continued interest and debate, but available data on the distribution of intake in the Australian diet is scarce. Therefore, we aimed to estimate phytoestrogen consumption in Australian women, describe the pattern of intake and identify correlates of high phytoestrogen intake. Study participants were 2078 control women (18-79 y) from two population-based case-control studies on gyneacological cancers (2002-2007). Dietary information was obtained using a 135-item semiquantitative FFQ and intakes of isoflavones, lignans, enterolignans and coumestans, including their individual components, were estimated using a database of phytoestrogen content in food developed in the UK. Median total intake (energy-adjusted) of phytoestrogens was 1.29 mg/d, of isoflavones 611 μg/d, of lignans 639 μg/d, of enterolignans 21μg/d and of coumestrol 8 μg/d. Both isoflavone and lignan intake were strongly skewed towards higher values and positively correlated with age. Women consumed on average 2 serves of soy foods/week. Compared to low phytoestrogen consumers (≤1.29 mg/d, median split), high phytoestrogen consumers (>1.29 mg/d) were slightly older, less likely to be smokers, had a higher educational and physical activity level, lower BMI, lower intake of dietary fat, and higher intake of fibre, selected micronutrient and soy food (all p<0.03). The daily intake of phytoestrogens in Australian women with predominantly Caucasian ethnicity is approximately 1 mg, similar to other Western populations, but considerably lower than among Asian women. However, those with a relatively high phytoestrogen diet seem to have healthier lifestyle and more favourable dietary profile compared to others.

'Score it upon my taille': the use (and abuse) of tallies by the medieval Exchequer

The paper traces the evolution of the tally from a receipt for cash payments into the treasury, to proof of payments made by royal officials outside of the treasury and finally to an assignment of revenue to be paid out by royal officials. Each of these processes is illustrated by examples drawn from the Exchequer records and explains their significance for royal finance and for historians working on the Exchequer records.

Sexual abuse in childhood and postoperative depression in women with breast cancer who opt for immediate reconstruction after mastectomy

INTRODUCTION Breast reconstruction is routinely offered to women who undergo mastectomy for breast cancer. However, patient-reported outcomes are mixed. Child abuse has enduring effects on adults’ well-being and body image. As part of a study into damaging effects of abuse on adjustment to breast cancer, we examined: (i) whether women with history of abuse would be more likely than other women to opt for reconstruction; and (ii) whether mood problems in women opting for reconstruction can be explained by greater prevalence of abuse. PATIENTS AND METHODS We recruited 355 women within 2-4 days after surgery for primary breast cancer; 104 had mastectomy alone and 29 opted for reconstruction. Using standardised questionnaires, women self-reported emotional distress and recollections of childhood sexual abuse. Self-report of distress was repeated 12 months later. RESULTS Women who had reconstruction were younger than those who did not. Controlling for this, they reported greater prevalence of abuse and more distress than those having mastectomy alone. They were also more depressed postoperatively, and this effect remained significant after controlling for abuse. CONCLUSIONS One interpretation of these findings is that history of abuse influences women's decisions about responding to the threat of mastectomy, but it is premature to draw inferences for practice until the findings are replicated. If they are replicated, it will be important to recognise increased vulnerability of some patients who choose reconstruction. Studying the characteristics and needs of women who opt for immediate reconstruction and examining the implications for women's adjustment should be a priority for research.

Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women

Context: Evidence is limited on the effects of different patterns of use of postmenopausal hormone therapy on fracture incidence and particularly on the effects of ceasing use. Objective: To investigate the effect of different patterns of hormone therapy use on fracture incidence. Design, Setting, and Participants: Prospective study of 138737 postmenopausal women aged 50 to 69 years recruited from the UK general population in 19961998 (the Million Women Study) and followed up for 1.9 to 3.9 years (average, 2.8 years) for fracture incidence. Main Outcome Measure: Adjusted relative risk (RR) for incident fracture (except fracture of the fingers, toes, and ribs) in hormone therapy users compared with never users at baseline. Results: A total of 5197 women (3.7%) reported 1 or more fractures, 79% resulting from falls. Current users of hormone therapy at baseline had a significantly reduced incidence of fracture (RR, 0.62; 95% confidence interval [CI], 0.58-0.66; P<.001). This protection was evident soon after hormone therapy began, and the RR decreased with increasing duration of use (P=.001). Among current users at baseline the RR of fracture did not vary significantly according to whether estrogen-only, estrogen-progestin, or other types of hormones were used (RR [95% CI], 0.64 [0.58-0.71], 0.58 [0.53-0.64], and 0.67 [0.56-0.80], respectively; P=19), nor did it vary significantly according to estrogen dose or estrogen or progestin constituents. The RR associated with current use of hormone therapy did not vary significantly according to 11 personal characteristics of study participants, including their age at menopause, body mass index, and physical activity. Past users of hormone therapy at baseline experienced no significant protection against fractures (RR, 1.07; 95% CI, 0.99-1.15); incidence rates returned to those of never-users within about a year of ceasing use. Conclusions: All types of hormone therapy studied confer substantial protection against fracture while they are used. This protection appears rapidly after use commences and wears off rapidly after use ceases. The older women are, the greater is their absolute reduction in fracture incidence while using hormone therapy.

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial complince (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (sem 2.0) % at baseline and 15.5 (sem 1.1) % after isoflavone treatment compared with 12.4 (sem 1.0) % after placebo treatment (P=0.03). NOx increased from 27.7 (sem 2.7) to 31.1 (sem 3.2) mu m after isoflavones treatment compared with 25.4 (sem 1.5) to 20.4 (sem 1.1) mu m after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.

Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones

Background: The incidence of cardiovascular diseases increases after menopause, and soy consumption is suggested to inhibit disease development. Objective: The objective was to identify biomarkers of response to a dietary supplementation with an isoflavone extract in postmenopausal women by proteome analysis of peripheral blood mononuclear cells. Design: The study with healthy postmenopausal woman was performed in a placebo-controlled sequential design. Peripheral mononuclear blood cells were collected from 10 volunteers after 8 wk of receiving daily 2 placebo cereal bars and after a subsequent 8 wk of intervention with 2 cereal bars each providing 25 mg of isoflavones. The proteome of the cells was visualized after 2-dimensional gel electrophoresis, and peptide mass fingerprinting served to identify proteins that by the intervention displayed altered protein concentrations. Results: Twenty-nine proteins were identified that showed significantly altered expression in the mononuclear blood cells under the soy-isoflavone intervention, including a variety of proteins involved in an antiinflammatory response. Heat shock protein 70 or a lymphocyte-specific protein phosphatase and proteins that promote increased fibrinolysis, such as a-enolase, were found at increased intensities, whereas those that mediate adhesion, migration, and proliferation of vascular smooth muscle cells, such as galectin-1, were found at reduced intensities after soy extract consumption. Conclusion: Protcome analysis identified in vivo markers that respond to a dietary intervention with isoflavone-enriched soy extract in postmenopausal women. The nature of the proteins identified suggests that soy isoflavones may increase the anti inflammatory response in blood mononuclear cells that might contribute to the atherosclerosis-preventive activities of a soy-rich diet.

Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women

Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat-carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5.7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0.006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral) was significantly lower after lunch than after breakfast for all four test meals (P=0.019) following the same rank order (SFA < n-6 PUFA < n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with 'carry-over' effects for the next meal.

The effect of the daily intake of inulin on fasting lipid, insulin and glucose concentrations in middle-aged men and women

The present study was carried out to examine the effect of the daily intake of 10 g inulin on fasting blood lipid, glucose and insulin levels in healthy middle-aged men and women with moderately raised total plasma cholesterol (TC) and triacylglycerol (TAG) levels. This study was a doubleblind randomized placebo-controlled parallel study in which fifty-four middle-aged subjects received either inulin or placebo for a period of 8 weeks. Fasting blood samples were collected before the supplementation period (baseline samples 1 and 2, separated by 1 week) and at weeks 4 and 8, with a follow-up at week 12. Compared with baseline values, insulin concentrations were significantly lower at 4 weeks (P,0×01) in the inulin group. There was a trend for TAG values, compared with baseline, to be lower in the inulin group at 8 weeks (P,0×08) returning to baseline concentrations at week 12. On comparison of the inulin and placebo groups, the fasting TAG responses over the 8-week test period were shown to be significantly different (P,0×05, repeated measures ANOVA), which was largely due to lower plasma TAG levels in the inulin group at week 8. The percentage change in TAG levels in the inulin group during the 8-week study was shown to correlate with the initial TAG level of the subjects (rs -0×499, P = 0×004). We therefore conclude that the daily addition of 10 g inulin to the diet significantly reduced fasting insulin concentrations during the 8-week test period and resulted in lower plasma TAG levels, particularly in subjects in whom fasting TAG levels were greater than 1×5 mmol/l. These data support findings from animal studies that fructans influence the formation and/or degradation of TAG-rich lipoprotein particles, and the insulin data are also consistent with recent studies showing attenuation of insulin levels in fructan-treated rats.