Increasing productivity by matching farming system management and genotype in water-limited environments.

Improvements in water productivity and yield arise from interactions between varieties (G) and their management (M). Most G×M interactions considered by breeders and physiologists focus on in-crop management (e.g. sowing time, plant density, N management). However, opportunities exist to capture more water and use it more effectively that involve judicious management of prior crops and fallows (e.g. crop sequence, weed control, residue management). The dry-land wheat production system of southern Australia, augmented by simulation studies, is used to demonstrate the relative impacts and interactions of a range of pre-crop and in-crop management decisions on water productivity. A specific case study reveals how a novel genetic trait, long coleoptiles that enable deeper sowing, can interact with different management options to increase the water-limited yield of wheat from 1.6 t ha(-1) to 4.5 t ha(-1), reflecting the experience of leading growers. Understanding such interactions will be necessary to capture benefits from new varieties within the farming systems of the future.

Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behavior.

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes.

Effects of nonaqueous phase liquids on the washing of soil in the presence of nonionic surfactants.

The removal of malathion from soil by surfactant washing was investigated under various physical-chemical states of the malathion. Three distinctive phases (without nonaqueous phase liquids (NAPL), with NAPL, and the transitional zone of NAPL) were found to be important for a better understanding of the washing process. When there is no NAPL in the system, the washing process is less dependent on the surfactant dose if the applied surfactant concentration is above the critical micelle concentration. The existence of a sorption site boundary, which for the determination of different washing mechanisms, was identified. In the presence of NAPL, the washing performance is generally independent of the organic content (f(oc)) of the soils but is dominated by the concentration of the surfactant used, due to the lesser resistance for mass transfer in NAPL. If the formation of NAPL is marginal, a two-stage washing pattern is observed, which has been quantified by the term 'unit extraction'. For this two-stage system, a mathematical model was derived based on the observed initial unit extraction and final extraction capacity, which eventually resulted in a practical design equation with the use of primary parameters such as f(oc) and surfactant dose.

Prescription of perioperative analgesics by UK small animal veterinary surgeons in 2013.

Data from a survey conducted in 1996-1997 suggested a low level of perioperative analgesic administration to cats and dogs in the UK. In order to evaluate current practice and attitudes with regards to perioperative analgesic prescription, a cross-sectional survey of UK practising small animal veterinary surgeons was undertaken in spring 2013. Four thousand one hundred paper questionnaires were distributed and the survey was made available online. Seven hundred and twenty valid responses were received and analysed. All respondents had access to at least one non-steroidal anti-inflammatory drug (NSAID) and one opioid within their practice. Respondents considered analgesic efficacy, and degree of intraoperative pain, the most important factors governing their selection of NSAID and opioid analgesics. Perioperative NSAIDs were administered by approximately 98 per cent of respondents to dogs and cats undergoing neutering. Multimodal (opioid+NSAID) analgesia was prescribed by the majority of respondents. Neutering was considered more painful in dogs than in cats, and lower rates of opioid and postdischarge NSAID prescription were reported for cats. Orthopaedic, abdominal and dental surgeries were considered equally painful in dogs and cats. Local analgesic techniques were not commonly used. Analgesic prescription has increased since previous surveys, which should translate to improved animal welfare.

Adaptation of iron absorption in men consuming diets with high or low iron bioavailability.

BACKGROUND: Short-term measurements of iron absorption are substantially influenced by dietary bioavailability of iron, yet bioavailability negligibly affects serum ferritin in longer, controlled trials. OBJECTIVE: Our objective was to test the hypothesis that in men fed diets with high or low iron bioavailability, iron absorption adapts to homeostatically maintain body iron stores. DESIGN: Heme- and nonheme-iron absorption from whole diets were measured in 31 healthy men at 0 and 10 wk while the men consumed weighed, 2-d repeating diets with either high or low iron bioavailability for 12 wk. The diets with high and low iron bioavailability contained, respectively, 14.4 and 15.3 mg nonheme Fe/d and 1.8 and 0.1 mg heme Fe/d and had different contents of meat, ascorbic acid, whole grains, legumes, and tea. RESULTS: Adaptation occurred with nonheme- but not with heme-iron absorption. Total iron absorption decreased from 0.96 to 0.69 mg/d (P < 0.05) and increased from 0.12 to 0.17 mg/d (P < 0.05) after 10 wk of the high- and low-bioavailability diets, respectively. This partial adaptation reduced the difference in iron bioavailability between the diets from 8- to 4-fold. Serum ferritin was insensitive to diet but fecal ferritin was substantially lower with the low- than the high-bioavailability diet. Erythrocyte incorporation of absorbed iron was inversely associated with serum ferritin. CONCLUSIONS: Iron-replete men partially adapted to dietary iron bioavailability and iron absorption from a high-bioavailability diet was reduced to approximately 0.7 mg Fe/d. Short-term measurements of absorption overestimate differences in iron bioavailability between diets.

Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food.

BACKGROUND: Results of cross-sectional studies suggest that in healthy people, iron absorption adapts to meet physiologic needs and stabilize iron stores, but this has not been adequately tested in longitudinal studies. OBJECTIVE: We tested whether heme- and nonheme-iron absorption decrease in response to increased iron intake and whether iron stores reach a steady state. DESIGN: In a randomized, placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and women (n = 57) were measured before and after 12 wk of supplementation with 50 mg Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during supplementation and for 6 mo thereafter. RESULTS: Initially, both heme- and nonheme-iron absorption were inversely associated with serum ferritin concentration. Volunteers who took iron supplements, even those with serum ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week 12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef-based meal. Serum ferritin concentration was slightly but significantly higher after iron supplementation than after placebo (difference = 13 microg/L). This higher ferritin concentration persisted for >/=6 mo after supplementation, except in subjects with low iron stores, whose serum ferritin returned to baseline within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during supplementation. CONCLUSIONS: Healthy individuals, even those with low iron stores, had reduced nonheme-iron absorption from food in response to iron supplementation. Despite this partial adaptation, iron stores were greater after iron supplementation than after placebo and this difference was sustained, except in individuals with the lowest iron stores.

Apparent copper absorption from a vegetarian diet.

BACKGROUND: Vegetarian diets often contain more copper than do nonvegetarian diets, but observations of decreased plasma copper associated with vegetarian diets suggest that these diets have lower copper bioavailability than do nonvegetarian diets. OBJECTIVE: Our objective was to determine apparent copper absorption from controlled lactoovovegetarian and nonvegetarian diets. DESIGN: Eighteen women aged 20-43 y consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each in a randomized, crossover design. The lactoovovegetarian and nonvegetarian diets provided 1.45 and 0.94 mg Cu, 38 and 16 g dietary fiber, and 1584 and 518 mg phytic acid, respectively, per 9.2 MJ (2200 kcal). After the women had been consuming each diet for 4 wk, their apparent copper absorption was determined by measuring the fecal excretion of the 65Cu stable isotope, extrinsically added to the entire menu as 65CuCl2. RESULTS: Plasma copper and ceruloplasmin were not affected by diet. The efficiency of apparent copper absorption from the lactoovovegetarian diet was less (33%) than that from the nonvegetarian diet (42%) (pooled SD: 9%; P < 0.05). However, because the lactoovovegetarian diet contained approximately 50% more copper, the total apparent copper absorption from the lactoovovegetarian diet (0.48 mg/d) was greater than that from the nonvegetarian diet (0.40 mg/d) (pooled SD: 0.09 mg; P < 0.05). CONCLUSION: Although copper was less efficiently absorbed from a vegetarian diet than from a nonvegetarian diet, total apparent copper absorption was greater from the vegetarian diet because of its greater copper content.

Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk.

BACKGROUND: The characteristics of vegetarian diets suggest that these diets would have lower dietary iron bioavailability than nonvegetarian diets, but there is no evidence of iron deficiency in vegetarians. OBJECTIVE: We evaluated the responsiveness of serum and fecal ferritin to differences in iron absorption from controlled lactoovovegetarian and nonvegetarian diets. DESIGN: Twenty-one women aged 20-42 y with serum ferritin concentrations from 6 to 149 microg/L consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each (crossover design). The diets differed substantially in meat and phytic acid contents. Nonheme-iron absorption was measured from the whole diets after 4 wk by using extrinsic 59Fe and whole-body counting. Ferritin in extracts of fecal composites and in serum was measured by enzyme-linked immunosorbent assay the last 2 wk of each diet. RESULTS: Nonheme-iron absorption was less from the lactoovovegetarian diet than from the nonvegetarian diet (1.1% compared with 3.8%; P < 0.01; n = 10). Diet did not affect hemoglobin, transferrin saturation, erythrocyte protoporphyrin, or serum ferritin. Substantially less fecal ferritin was excreted with the lactoovovegetarian diet than with the nonvegetarian diet (1.1 compared with 6.0 microg/d, respectively; P < 0.01; n = 21). CONCLUSIONS: This research indicates 1) 70% lower nonheme-iron absorption from a lactoovovegetarian diet than from a nonvegetarian diet; 2) an associated decrease in fecal ferritin excretion, suggesting partial physiologic adaptation to increase the efficiency of iron absorption; and 3) an insensitivity of blood iron indexes, including serum ferritin, to substantial differences in dietary iron absorption for 8 wk.

Effect of ascorbic acid on apparent iron absorption by women with low iron stores.

The effect of ascorbic acid supplementation on apparent iron absorption was tested in women with low iron stores. For 10 wk, 25 healthy nonpregnant women, aged 20-45 y with low serum ferritin (3.5-17.7 micrograms/L), consumed either a diet with predicted poorly bioavailable iron or a typical Western diet, classified according to dietary meat and ascorbic acid contents. Meals were supplemented with ascorbic acid (500 mg, three times a day) for 5 of the 10 wk, in a double-blind, crossover design. Ascorbic acid did not affect most biochemical indexes of iron status, the biological half-life of 59Fe, or apparent iron absorption (diet-feces) from either diet, but slightly increased serum ferritin (11.9 vs 10.7 micrograms/L, P < 0.06) when data from both diets were combined. These results support other evidence that ascorbic acid has less effect on iron bioavailability than has been predicted from tests with single meals.

Severe or marginal iron deficiency affects spontaneous physical activity in rats.

The influence of dietary iron on spontaneous activity was investigated in growing rats. Male rats weighing 97 +/- 10 g fed diets containing 4.6 (deficient), 19.9 (marginal), and 108.4 (adequate) mg Fe/kg diet for 8 wks had hemoglobin values of 52 +/- 6, 152 +/- 4, and 159 +/- 6 g/L, and liver nonheme iron concentrations of 0.79 +/- 0.24, 1.36 +/- 0.39, and 4.58 +/- 0.62 mumol/g, respectively. Body weights were affected only at the lowest iron intake. Diurnal activity was not reversed by iron status; all animals were more active during the dark cycle than the light cycle. Iron deficiency resulted in less time and frequency of horizontal, vertical, and stereotypic movements; less distance moved; and less frequent rotations. Movement speed of iron-deficient rats was faster during early iron deficiency. In the light, rats with marginal iron nutriture were generally more active than were iron-deficient or iron-adequate animals. In the dark, activity generally decreased with each reduction in dietary iron.

Zinc absorption, mineral balance, and blood lipids in women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk.

Zinc absorption, mineral balance, and blood lipid concentrations were measured in 21 women aged 33 +/- 7 y (range: 20-42 y) consuming controlled lactoovovegetarian and nonvegetarian diets for 8 wk each in a crossover design. The lactoovovegetarian and nonvegetarian diets, respectively, provided (by analysis) 973 and 995 mg Ca, 1.8 and 1.3 mg Cu, 367 and 260 mg Mg, 5.9 and 2.5 mg Mn, 1457 and 1667 mg P, 9.1 and 11.1 mg Zn, and (by calculation) 40 and 16 g dietary fiber, 2.5 and 0.8 mmol phytic acid, molar ratios of phytate to Zn of 14 and 5, and millimolar ratios of (phytate x Ca) to Zn of 344 and 111. Dietary zinc absorption was measured by extrinsic isotopic labeling and whole-body counting. Plasma cholesterol, cholesterol fractions, and lipoproteins were reduced 7-12% with the lactoovovegetarian diet, consistent with predictions based on dietary cholesterol and fat. Blood pressure was unaffected. Calcium, copper, magnesium, and phosphorus balances were not different between diets; manganese balance tended to be greater with the lactoovovegetarian diet (P < 0.07). The lactoovovegetarian diet was associated with a 21% reduction in absorptive efficiency that, together with a 14% reduction in dietary zinc, reduced the amount of zinc absorbed by 35% (2.4 compared with 3.7 mg/d) and reduced plasma zinc by 5% within the normal range. Zinc balance was maintained with both diets. Although there is a greater risk of zinc deficiency in persons consuming lactoovovegetarian compared with omnivorous diets, with inclusion of whole grains and legumes zinc requirements can be met and zinc balance maintained.

Ethanol metabolism in postmenopausal women fed a diet marginal in zinc.

Five postmenopausal women aged 50-63 y were fed a diet of mixed Western foods that supplied an average of 2.6 mg zinc/d for 6 mo. Plasma zinc did not change significantly during Zn depletion but increased slightly when Zn was fed. Zn content of blood cellular components and activities of Zn-containing enzymes were not affected by Zn intake. Ethanol tolerance tests performed at the end of control, middle of depletion, end of depletion, and end of repletion showed a change in ethanol metabolism at the end of the low-Zn intake period that was corrected within 1 mo with Zn supplementation. These data suggest that there are homeostatic mechanisms that maintain circulating levels of Zn. Zn and activity of Zn enzymes in tissues may be decreased before changes in circulating Zn levels are seen. Functional indices of Zn biochemistry, such as ethanol metabolism, may be more sensitive indicators of Zn stores and nutriture than circulating Zn.

Bioavailability in humans of zinc from beef: intrinsic vs extrinsic labels.

Beef is a concentrated source of zinc. However, the bioavailability of Zn from beef has not been clearly established. It is also unclear whether there is a difference in absorption between intrinsic and extrinsic Zn. To address these questions, a calf was labeled with 65ZnCl2 and the meat was used as a source of intrinsically labeled beef. Twelve subjects were given a meal containing 100 g beef labeled either intrinsically or extrinsically with 65ZnCl2. Gamma-ray emissions, as determined by whole-body counting, were used to calculate Zn absorption. Absorption values were 20.9 +/- 5.5% from the extrinsic meal and 26.4 +/- 10.6% from the intrinsic meal, a difference that was not statistically significant (p greater than 0.05). Zn absorption was thus much less than the 40% assumed in establishing the 1980 Recommended Dietary Allowance for Zn. These results also indicate that extrinsic labels of Zn are valid markers of zinc absorption in beef.

High- versus low-meat diets: effects on zinc absorption, iron status, and calcium, copper, iron, magnesium, manganese, nitrogen, phosphorus, and zinc balance in postmenopausal women.

The effects of three diets--high meat (HM), low meat (LM), or low meat with mineral supplements (LS)--on zinc absorption, elemental balance, and related clinical indexes were investigated in a metabolic study of 14 women aged 51-70 y. The women ate each of the three diets for 7 wk in random order. Lean beef, chicken, ham, and tuna in the HM diet replaced foods with a low mineral content in the LM diet. The LS diet was similar to the HM diet in K, P, Fe, Mg, and Zn contents. Compared with the other diets, the HM diet increased zinc absorption and retention, and slightly increased urinary zinc. Nitrogen and calcium balances and urinary calcium were not different for the HM and LM diets. Iron balance was not different for the HM and LS diets with similar iron content, but the HM diet was unexpectedly associated with lower iron status (higher iron-binding capacity and lower ferritin than LM and LS diets). These results indicate that 0.8 g protein/kg body wt meets protein requirements in older women, and that high meat consumption increases zinc retention without compromising calcium status and may reduce indexes of iron status, in contrast with iron absorption results from studies with radiolabeled test meals.

Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women.

The effect of ascorbic acid on iron retention from a diet with predicted low iron bioavailability (containing minimal meat and ascorbic acid) was investigated in iron-depleted premenopausal women. Eleven women were depleted of storage iron (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 d) and phlebotomy. They then consumed a diet containing 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid three times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent iron absorption (balance method) [38 +/- 2% (means +/- SEM) vs 27 +/- 2%]. Ascorbic acid also improved hemoglobin, erythrocyte protoporphyrins, and serum iron but not hematocrit, serum ferritin, iron-binding capacity, or transferrin saturation. In iron-depleted women consuming a diet with predicted poor iron availability, ascorbic acid supplementation enhanced body iron retention for 5.5 wk.

Cancer-related behavior of vitamin supplement users.

Epidemiological studies suggest that certain vitamin supplements may reduce the risk of some cancers. However, observational studies can be compromised by confounding, because supplement use is related to other factors that affect cancer risk. The purpose of this paper is to identify cancer-related behaviors that could confound studies of the associations between vitamin supplement use and cancer risk. Data are from a random digit dial survey to monitor cancer risk behavior in adults in Washington State (n = 1449). Unconditional logistic regression was used to examine whether regular supplement users were more likely to practice other cancer-related behaviors than nonusers, after adjustment for age, education, and smoking. Among women, supplement users were more likely to have had a sigmoidoscopy [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.2-4.5], hemoccult (OR, 2.3; CI, 1.5-3.5), or mammogram (OR, 1.5; CI, 1.0-2.1) in the past 2 years. Among men, supplement users were twice as likely to have had a prostate-specific antigen test (OR, 2.2; CI, 1.3-3.7) and to regularly take aspirin (OR, 1.7; CI, 1.1-2.6). Supplement users were statistically significantly more likely to exercise regularly, eat four or more servings of fruits and vegetables per day, follow a low-fat diet pattern, and believe in a connection between diet and cancer. The association was especially strong for fruits and vegetables (women, OR, 1.9; and CI, 1.3-2.6; men, OR, 2.4; CI, 1.6-3.8). Those investigating the benefits and risks of vitamin and mineral supplements need to be aware of the lifestyle characteristics of supplement users to assess the potential for bias in their studies.

Coupling transport and biodegradation of VOCs in surface and subsurface soils.

Volatile organic chemicals present at Superfund sites preferentially partition into the soil gas and may be available for microbial degradation. A simple mass transfer model for biodegradation for volatile substrates has been developed for the aerobic decomposition of aromatic and aliphatic hydrocarbons. The mass transfer analysis calculates diffusive fluxes from soil gas through water and membrane films and into the cell. This model predicts an extreme sensitivity of potential biodegradation rates to the air-water partition coefficients of the compounds. Aromatic hydrocarbons are removed rapidly while the aliphatic hydrocarbons are much slower by orders of magnitude. Furthermore, oxygen transfer is likely to limit aromatic hydrocarbon degradation rates. The model presents results that cast doubt on the practicality of using methane or propane for the co-metabolic destruction of trichloroethylene in a gas phase bioreactor. Toluene as a primary substrate has better mass transfer characteristics to achieve more efficient trichloroethylene degradation. Hence, in sites where these contaminants coexist, bioremediation could be improved.

Metabolism, toxicokinetics and hemoglobin adduct formation in rats following subacute and subchronic acrylamide dosing.

Long-term, low-dose (subchronic) oral acrylamide (ACR) exposure produces peripheral nerve axon degeneration, whereas irreversible axon injury is not a component of short-term, higher dose (subacute) i.p. intoxication [Toxicol Appl Pharmacol 1998;151:211]. It is possible that this differential axonopathic expression is a product of exposure-dependent differences in ACR biotransformation and/or tissue distribution. Therefore, we determined the toxicokinetics and metabolism of ACR following subchronic oral (2.8 mM in drinking water for 34 days) or subacute i.p. (50 mg/kg per day for 11 days) administration to rats. Both dosing regimens produced moderate levels of behavioral neurotoxicity and, for each, ACR was rapidly absorbed from the site of administration and evenly distributed to tissues. Peak ACR plasma concentrations and tissue levels were directly related to corresponding daily dosing rates (20 or 50 mg/kg per day). During subchronic oral dosing a larger proportion (30%) of plasma ACR was converted to the epoxide metabolite glycidamide (GLY) than was observed following subacute i.p. intoxication (8%). This subchronic effect was not specifically related to changes in enzyme activities involved in GLY formation (cytochrome P450 2E1) ormetabolism (epoxide hydrolases). Both ACR and GLY formed hemoglobin adducts during subacute and subchronic dosing, the absolute quantity of which did not change as a function of neurotoxicant exposure. Compared to subacute i.p. exposure, the subchronic schedule produced approximately 30% less ACR adducts but two-fold more GLY adducts. GLY has been considered to be an active ACR metabolite and might mediate axon degeneration during subchronic ACR administration. However, corresponding peak GLY plasma concentrations were relatively low and previous studies have shown that GLY is only a weak neurotoxicant. Our study did not reveal other toxicokinetic idiosyncrasies that might be a basis for subchronic induction of irreversible axon damage. Consequently the mechanism of axon degeneration does not appear to involve route- or rate-dependent differences in metabolism or disposition.

Coping with health threat: social influence processes in reactions to medical test results.

In a laboratory experiment, undergraduate subjects tested positive for an enzyme deficiency they believed to be a risk factor for pancreatic disorders. All Ss were tested with a confederate who received a positive or negative test result. For half the Ss, the confederate expressed a minimizing appraisal of the deficiency's seriousness. Although Ss' concern about the test result was significantly reduced by what the confederate said, behavioral intentions were determined by the confederate's diagnostic status. The effect of the confederate's diagnostic status on intentions was mediated by Ss' perceptions of the deficiency's prevalence. The results support Leventhal's self-regulation theory and demonstrate that the opinions and health characteristics of comparison others have differential effects on cognitive, emotional, and behavioral aspects of coping with a health threat.

Women's health initiative. Why now? What is it? What's new?

Studies collectively named the Women's Health Initiative (WHI) are currently enrolling 164,500 postmenopausal women in several overlapping clinical trials and an observational study. The overall goals of WHI are to understand the determinants of postmenopausal women's health and to evaluate the efficacy of practical interventions in preventing the major causes of morbidity and mortality in older women. This article reviews the research leading to the WHI studies; describes the study designs and protocols, with an emphasis on what's new about WHI from a psychological perspective; and outlines the major psychosocial hypotheses under investigation and the major challenges WHI presents to psychological science.