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Biomedical subjects

M J Stampfer

Publications and source records attributed to M J Stampfer.

At least 55 records · Page 3Linked to original sources

Dietary fat intake and risk of type 2 diabetes in women.

BACKGROUND: The long-term relations between specific types of dietary fat and risk of type 2 diabetes remain unclear. OBJECTIVE: Our objective was to examine the relations between dietary fat intakes and the risk of type 2 diabetes. DESIGN: We prospectively followed 84204 women aged 34-59 y with no diabetes, cardiovascular disease, or cancer in 1980. Detailed dietary information was assessed at baseline and updated in 1984, 1986, and 1990 by using validated questionnaires. Relative risks of type 2 diabetes were obtained from pooled logistic models adjusted for nondietary and dietary covariates. RESULTS: During 14 y of follow-up, 2507 incident cases of type 2 diabetes were documented. Total fat intake, compared with equivalent energy intake from carbohydrates, was not associated with risk of type 2 diabetes; for a 5% increase in total energy from fat, the relative risk (RR) was 0.98 (95% CI: 0.94, 1.02). Intakes of saturated or monounsaturated fatty acids were also not significantly associated with the risk of diabetes. However, for a 5% increase in energy from polyunsaturated fat, the RR was 0.63 (0.53, 0.76; P < 0.0001) and for a 2% increase in energy from trans fatty acids the RR was 1.39 (1.15, 1.67; P = 0.0006). We estimated that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk (RR: 0.60; 95% CI: 0.48, 0.75). CONCLUSIONS: These data suggest that total fat and saturated and monounsaturated fatty acid intakes are not associated with risk of type 2 diabetes in women, but that trans fatty acids increase and polyunsaturated fatty acids reduce risk. Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially.

Adult↗

Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study.

BACKGROUND: A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive. OBJECTIVE: We investigated the association between dairy product and calcium intakes and prostate cancer risk in the Physicians' Health Study, a cohort of male US physicians. DESIGN: At baseline, the men answered abbreviated dietary questionnaires. During 11 y of follow-up, we documented 1012 incident cases of prostate cancer among 20885 men. We estimated dairy calcium intake on the basis of consumption of 5 major dairy products and used logistic regression to estimate relative risk. RESULTS: At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)(2)D(3) concentrations than did those consuming < or =150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL); P = 0.005]. Compared with men consuming < or =0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 (95% CI: 1.04, 1.71) after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming < or =150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer (95% CI: 1.08, 1.63). CONCLUSIONS: These results support the hypothesis that dairy products and calcium are associated with a greater risk of prostate cancer.

Calcium, Dietary↗

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Alcohol Drinking↗

Electric blanket or mattress cover use and breast cancer incidence in women 50-79 years of age.

Previous research has demonstrated inconsistent associations between electromagnetic radiation, especially from electric blanket use, and breast cancer. Breast cancer risk according to electric blanket or mattress cover use was examined as part of a multicenter population-based case-control study. Breast cancer patients 50-79 years of age (N = 1949) were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from the period June 1994 to July 1995. Women of similar age were randomly selected from population lists as controls. Information regarding electric blanket and mattress cover use and breast cancer risk factors was obtained through telephone interviews. After adjustment for age, body mass index, and other breast cancer risk factors, the risk of breast cancer was similar among ever-users (relative risk = 0.93; 95% confidence interval = 0.82-1.06) and lower among current users than among never-users (relative risk = 0.79; 95% confidence interval = 0.66-0.95). There was no evidence of a dose-response relation with increasing number of months that electric blankets had been used. This study provides evidence against a positive association between electric blanket or mattress cover use and breast cancer.

Aged↗

Physical activity and mortality: a prospective study among women.

OBJECTIVES: This study examined the association between recreational physical activity and mortality in middle-aged and older women and the possibility that physical activity serves as an important marker of health. METHODS: Analyses were conducted among participants in the Nurses' Health Study. Levels of physical activity were assessed by questionnaire in 1980 and updated every 2 to 4 years. RESULTS: Levels of physical activity were inversely associated with mortality risk; however, each activity level above the reference level had approximately the same level of risk reduction (20%-30%). The inverse association was stronger for cardiovascular deaths than for cancer deaths and was strongest for respiratory deaths. Women who died of noncardiovascular, noncancer causes were more likely to have reported that poor health limited their physical activity than were women who died of other causes or who remained alive. CONCLUSIONS: Part of the link between physical activity and mortality risk is probably spurious and difficult to remove analytically; however, on the basis of epidemiologic evidence, much of the health benefit of activity is real.

Adult↗

A prospective study of drinking patterns in relation to risk of type 2 diabetes among men.

Using data from a 12-year prospective study, we determined the importance of the pattern of alcohol consumption as a risk factor for type 2 diabetes in a cohort of 46,892 U.S. male health professionals who completed biennial postal questionnaires. Overall, 1,571 new cases of type 2 diabetes were documented. Compared with zero alcohol consumption, consumption of 15-29 g/day of alcohol was associated with a 36% lower risk of diabetes (RR = 0.64; 95% CI 0.53-0.77). This inverse association between moderate consumption and diabetes remained if light drinkers rather than abstainers were used as the reference group (RR = 0.60, CI 0.50-0.73). There were few heavy drinkers, but the inverse association persisted to those drinking >/=50 g/day of alcohol (RR = 0.60, CI 0.43-0.84). Frequency of consumption was inversely associated with diabetes. Consumption of alcohol on at least 5 days/week provided the greatest protection, even when less than one drink per drinking day was consumed (RR = 0.48, CI 0.27-0.86). Compared with infrequent drinkers, for each additional day per week that alcohol was consumed, risk was reduced by 7% (95% CI 3-10%) after controlling for average daily consumption. There were similar and independent inverse associations for beer, liquor, and white wine. Our findings suggested that frequent alcohol consumption conveys the greatest protection against type 2 diabetes, even if the level of consumption per drinking day is low. Beverage choice did not alter risk.

Adult↗

The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer.

The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men and women. We prospectively assessed the association between the A2 allele of CYP17 and prostate cancer risk among 590 cases and 782 controls in a case-control study nested within the Physicians' Health Study cohort. We also evaluated associations between CYP17 genotype and plasma steroid hormones among controls and the potential interaction between CYP17 and SRD5A2 V89L polymorphisms in relationship with prostate cancer risk and circulating steroid hormone levels. We observed a borderline significant association between the A2 allele and prostate cancer risk (odds ratio, 1.23; 95% confidence interval, 0.99-1.54), however, we did not observe evidence of a gene-dosage effect (versus A1/A1 genotype: A1/A2 genotype; odds ratio, 1.26; 95% confidence interval, 0.99-1.59; A2/A2 genotype: odds ratio, 1.17; 95% confidence interval, 0.85-1.61). The A2 allele was not overrepresented among cases with advanced prostate cancer. Among controls, carriers of the A2 allele had steroid hormone levels similar to noncarriers. We also found no evidence of a gene-gene interaction between CYP17 and SRD5A2 V89L polymorphisms on prostate cancer risk or endogenous steroid hormone levels. These results suggest that CYP17 genotype may possibly confer a small increased susceptibility to prostate cancer but is not a strong predictor of endogenous steroid hormone levels in men.

Adult↗

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.

Adult↗

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

Adult↗

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. METHODS AND RESULTS: We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P:=0.04), apoCIII in VLDL+LDL (RR 2.3, P:=0.04), and apoE in HDL (RR 1.8, P:=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P:=0.03), was not related to coronary events (RR 1.3, P:=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. CONCLUSIONS: The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.

Apolipoprotein C-III↗

Whole grain consumption and risk of ischemic stroke in women: A prospective study.

CONTEXT: Although increased intake of grain products has been recommended to prevent cardiovascular disease (CVD), prospective data examining the relation of whole grain intake to risk of ischemic stroke are sparse, especially among women. OBJECTIVE: To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus, coronary heart disease, stroke, or other CVDs in 1984, who completed detailed food frequency questionnaires (FFQs) in 1984, 1986, 1990, and 1994, and were followed up for 12 years as part of the Nurses' Health Study. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, confirmed by medical records, by quintile of whole grain intake according to FFQ responses. RESULTS: During 861,900 person-years of follow-up, 352 confirmed incident cases of ischemic stroke occurred. We observed an inverse association between whole grain intake and ischemic stroke risk. The age-adjusted relative risks (RRs) from the lowest to highest quintiles of whole grain intake were 1.00 (referent), 0.68 (95% confidence interval [CI], 0.49-0.94), 0.69 (95% CI, 0.51-0.95), 0.49 (95% CI, 0.35-0.69), and 0.57 (95% CI, 0.42-0.78; P =.003 for trend). Adjustment for smoking modestly attenuated this association (RR comparing extreme quintiles, 0.64; 95% CI, 0.47-0.89). This inverse association remained essentially unchanged with further adjustment for known CVD risk factors, including saturated fat and transfatty acid intake (multivariate-adjusted RR comparing extreme quintiles, 0.69; 95% CI, 0.50-0.98). The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked, did not drink alcohol, did not exercise regularly, or who did not use postmenopausal hormones. No significant association was observed between total grain intake and risk of ischemic stroke. CONCLUSIONS: In this cohort, higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women, independent of known CVD risk factors. These prospective data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke.

Adult↗

Seven-year changes in alcohol consumption and subsequent risk of cardiovascular disease in men.

BACKGROUND: Few studies have examined whether changes in alcohol consumption influence future cardiovascular risk. OBJECTIVE: To examine whether 7-year changes in alcohol consumption are associated with the subsequent risk of cardiovascular disease (CVD). METHODS: We prospectively followed up 18,455 men aged 40 to 84 years from the Physicians' Health Study with no history of CVD or cancer. Alcohol consumption was reported on the baseline and the 7-year questionnaires; follow-up for this analysis began after the 7-year questionnaire (median follow-up, 5.8 years). There were 1091 CVD cases, including myocardial infarction, angina pectoris, revascularization, stroke, and CVD-related death. RESULTS: Among men initially consuming 1 drink per week or less (n=7360), those with moderate increases (>1 to <6 drinks per week) in alcohol consumption had a borderline significant (P=.05) 29% reduced risk of CVD compared with men with no changes (-1 to 1 drink per week). Among men initially consuming greater than 1 to 6 drinks per week (n=6612), those with moderate increases had a nonsignificant (P=.32) 15% decrease in CVD risk compared with men with no changes. Finally, among men initially consuming 1 drink per day or more (n=4483), those who increased intake had a 63% increased risk of CVD compared with men with no changes. CONCLUSIONS: These prospective data suggest that, among men with initially low alcohol consumption (</=1 drink per week), a subsequent moderate increase in alcohol consumption may lower their CVD risk. The possible reduction in CVD risk from increasing alcohol intake did not extend to men initially consuming greater than 1 drink per week. Given the potential risks and benefits associated with alcohol consumption, physician counseling of patients must be individualized in the context of the primary prevention of CVD.

Adult↗

Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women.

BACKGROUND: Previous studies have found concurrent declines in blood pressure, serum cholesterol levels, and the incidence of and mortality from coronary disease. However, the effects of changes in diet and lifestyle on trends in coronary disease are largely unknown. METHODS: We followed 85,941 women who were 34 to 59 years old and had no previously diagnosed cardiovascular disease or cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle variables were assessed at base line and updated during follow-up. RESULTS: After adjustment for the effect of age, the incidence of coronary disease declined by 31 percent from the two-year period 1980-1982 to the two-year period 1992-1994. From 1980 to 1992, the proportion of participants currently smoking declined by 41 percent, the proportion of postmenopausal women using hormone therapy increased by 175 percent, and the prevalence of overweight, defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or more, increased by 38 percent. During the study period, diet improved substantially. Statistically, changes in these variables--when considered simultaneously--explained a 21 percent decline in the incidence of coronary disease, representing 68 percent of the overall decline from 1980-1982 to 1992-1994. Taken individually, the reduction in smoking explained a 13 percent decline in the incidence of coronary disease; improvement in diet explained a 16 percent decline; and increase in postmenopausal hormone use explained a 9 percent decline. On the other hand, the increase in body-mass index explained an 8 percent increase in the incidence of coronary disease. CONCLUSIONS: Reduction in smoking, improvement in diet, and an increase in postmenopausal hormone use accounted for much of the decline in the incidence of coronary disease in this group of women. An increasing prevalence of obesity, however, appears to have slowed the decline in the incidence of coronary disease.

Adult↗

Adiposity and mortality in men.

The relation between measures of adiposity and mortality has been a controversial topic. The authors examined prospectively the relation between several measures of adiposity and risks of overall and cause-specific mortality in 39,756 US men aged 40-75 years. During 10 years of follow-up (1986-1996), 1,972 deaths (747 from cancer, 423 from cardiovascular disease, and 802 from other causes) were documented. An elevated risk of death among the leanest men was partly accounted for by excess mortality during early follow-up and high mortality among those with a history of recent weight loss. After exclusion of men with substantial recent weight loss and deaths occurring during the first 4 years of follow-up, overall and cardiovascular disease mortality among men aged <65 years increased linearly with greater body mass index (BMI) (weight (kg)/height (m)2); multivariate relative risks for overall mortality were 1.0 (referent) for a BMI of <23, 1.21 for a BMI of 23-24.9, 1.19 for a BMI of 25-26.9, 1.39 for a BMI of 27-29.9, and 1.97 for a BMI of >30 (test for trend: p< 0.001). Among men aged > or =65 years, there were no significant relations between BMI and overall, cardiovascular disease, or cancer mortality risk. However, waist circumference strongly predicted risk of death from cardiovascular disease among the older men. These findings indicated that the relation between body fat and mortality was influenced by reverse causation and varied by age.

Adipose Tissue↗

Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus.

BACKGROUND: Moderate alcohol consumption is associated with reduced risk for coronary heart disease (CHD) in generally healthy populations. We assessed prospectively the association between moderate alcohol intake and CHD risk in women with type 2 diabetes mellitus, a group at high risk for cardiovascular disease. METHODS AND RESULTS: We studied women in the Nurses' Health Study who reported a diagnosis of diabetes mellitus at >/=30 years of age. During 39 092 person-years of follow-up from 1980 to 1994, there were 295 CHD events documented among this population, including 194 cases of nonfatal myocardial infarction and 101 cases of fatal CHD. Odds ratios derived from logistic regression were used to estimate relative risks (RRs) for CHD as a function of usual alcohol intake, with adjustment for potential confounders. Compared with diabetic women reporting no alcohol intake, the age-adjusted RR for nonfatal or fatal CHD among diabetic women reporting usual intake of 0.1 to 4.9 g (<0.5 drinks) of alcohol daily was 0.74 (95% CI 0.56 to 0.98), and among those reporting usual intake >/=5 g/d, it was 0.48 (95% CI 0.32 to 0.72) (P for trend <0.0001). Inverse associations between alcohol intake and CHD risk remained significant in multivariate analysis adjusting for several other coronary risk factors (0.1 to 4. 9 g/d: RR 0.72 [95% CI 0.54 to 0.96]; >/=5 g/d: RR 0.45 [0.29 to 0.68]). CONCLUSIONS: Although potential risks of alcohol consumption must be considered, these data suggest that moderate alcohol consumption is associated with reduced CHD risk in women with diabetes and should not be routinely discouraged.

Adult↗