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Biomedical subjects

J D Boice

Publications and source records attributed to J D Boice.

At least 163 records · Page 9Linked to original sources

Cancer mortality in a radiation-exposed cohort of Massachusetts tuberculosis patients.

The mortality experience of 13,385 tuberculosis patients treated between 1925 and 1954 in Massachusetts was determined through August 1986. Among 6,285 patients examined by X-ray fluoroscopy an average of 77 times during lung collapse therapy and followed for up to 50 yr (average = 25 yr), no increase in the total number of cancer deaths occurred [standardized mortality ratio (SMR) = 1.05, n = 424]. In contrast, the 7,100 patients treated by other means were at significant risk of dying from cancer (SMR = 1.3), especially of sites linked to cigarette smoking and alcohol use. Among the irradiated patients, estimates of mean radiation doses to the breast, lung, esophagus, and active bone marrow were 0.75, 0.84, 0.80, and 0.09 Gy, respectively. Cancers of the breast (SMR = 1.4, n = 62) and esophagus (SMR = 2.1, n = 14) were significantly increased. The risk of esophageal cancer, however, decreased with time since exposure. Lung cancer (SMR = 0.8, n = 69) and leukemia (SMR = 1.2, n = 17) were not elevated. Despite a wide range of doses to the lung, reaching over 8 Gy, there was no evidence of a dose response. Lung cancer risk also did not vary by time since exposure or age at exposure. Adjustment for smoking and the amount of lung tissue at risk did not appreciably modify these findings. These data suggest that frequent exposures to low doses of radiation over a period of several years increase the occurrence of cancer of the breast. When compared with studies of atomic bomb survivors, however, the fractionated exposures experienced by this cohort appear less effective in causing lung cancer than single exposures of the same total dose.

Adult↗

Breast cancer in women with scoliosis exposed to multiple diagnostic x rays.

Although exposure to ionizing radiation is a recognized risk factor for breast cancer, the potential hazard from low-dose, fractionated exposures during early breast development has not been thoroughly evaluated. Women with scoliosis represent a valuable population for studying this issue because they are exposed to multiple diagnostic x rays during childhood and adolescence, times when the breast may be highly sensitive to the carcinogenic effects of radiation. A study was conducted of 1,030 women with scoliosis who were seen at four Minneapolis area medical facilities between 1935 and 1965. The average age at diagnosis was 12.3 years; 60% of the women had idiopathic scoliosis. Individual x-ray films were counted and the number per patient ranged from 0 to 618 films (mean, 41.5). On average, the x-ray exposures were given over an 8.7-year period. Ninety percent of the women were located, of whom over 92% responded to a mail questionnaire or telephone interview. The average period of observation was 26 years. Overall, 11 cases of breast cancer were reported, compared with six expected (standardized incidence ratio = 1.82, 90% confidence interval = 1.0-3.0). Excess risk increased with time since exposure and was highest among those followed for more than 30 years (standardized incidence ratio = 2.4). Risk also increased with the number of x rays and with the estimated radiation dose to the breast (mean, 13 rad). These data suggest that frequent exposure to low-level diagnostic radiation during childhood or adolescence may increase the risk of breast cancer.

Adult↗

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Adult↗

Cancer among epileptic patients exposed to anticonvulsant drugs.

Cancer incidence among 8,004 patients hospitalized for epilepsy between 1933 and 1962 in the Filadelfia treatment community in Denmark was compared to that of the general population. Patients received powerful and prolonged treatment with phenobarbital, phenytoin, and other anticonvulsants. This new survey extends the follow-up from 1976 through 1984. Among 7,864 patients with epilepsy not known to have received radioactive Thorotrast, record linkage with national cancer incidence files identified 789 cancers, compared to 664 expected [relative risk (RR) = 1.19; 95% confidence interval = 1.11-1.27]. Significant risks were found for cancers of the brain and central nervous system (RR = 5.7; n = 118) and the lung (RR = 1.4; n = 106). The excess numbers of brain cancer were concentrated within 10 years of hospitalization (RR = 20.7; n = 80) and decreased significantly over time, which suggests that brain tumors account for the seizure disorder and are not due to phenobarbital exposure as suggested by some epidemiologic studies. No overall risk was apparent when brain cancers were excluded (RR = 1.03). Because bladder cancer was significantly decreased (RR = 0.6; n = 18), the excess risk of lung cancer may not have been related to the "anecdotal" heavy smoking reported among confined groups of epileptic patients in the early years of the study period. The incidence of malignant melanoma was also significantly low (RR = 0.5; n = 7), which suggested limited exposure to sunlight among confined patients. The risk of non-Hodgkin's lymphoma was increased, but not significantly (RR = 1.4; n = 16), which is interesting in view of previous reports suggesting an association with phenytoin. Overall, these data provide little evidence that phenobarbital and phenytoin are carcinogenic to humans, but the excess risks of lung cancer and non-Hodgkin's lymphoma among epileptic patients in our study deserve further evaluation.

Adolescent↗

Breast cancer after multiple chest fluoroscopies: second follow-up of Massachusetts women with tuberculosis.

A second follow-up was conducted of 1742 women with tuberculosis who were treated in one of two sanatoria in Massachusetts between 1930 and 1956. One hospital treated only children under the age of 17. Patient follow-up was extended from 1975 through 1980, and an additional 18 breast cancers were identified from hospital records, death certificates, and responses to a mailed questionnaire. Vital status was established for 97% of the subjects. Among 1044 women who were examined an average of 101 times with X-ray fluoroscopies during lung collapse therapy, 55 breast cancers were observed in contrast to 35.8 expected, based on incidence rates from the general population. No excess was found for 698 women treated by other means (19 observed versus 22.8 expected). Excess breast cancer risk did not appear until 15 years after initial exposure and was present at the end of 50 years of observation. Risk appeared to decrease with increasing age at exposure. Estimates of radiation dose to the breast for individuals (mean = 96 rad) were based on the most current information for the numbers of fluoroscopies, reconstruction of exposure conditions, and absorbed dose calculations. The relation between dose and breast cancer risk was consistent with linearity up to 400 rads (4 Gy). For 10-year survivors, the absolute excess risk was 5.5/1 million woman-year-rad, the excess relative risk per rad was 0.73%, and the relative risk at 100 rad was 1.7. These data indicate that a woman's lifetime risk of breast cancer is influenced by events occurring in early reproductive life, that low-dose fractionated exposures are as effective as single exposures of the same total dose in inducing breast cancer, and that risk of radiogenic breast cancer persists for many years, and perhaps for life.

Adolescent↗

Estrogen and androgen levels in women treated with radiation for cervical cancer--possible influence on breast cancer risk.

In 1984-1985, estrogen and androgen levels in blood sera were measured in 320 women who had been treated for cervical cancer in the early 1960s. Study subjects were from US clinics in Baltimore, Maryland; Boston and Norfolk, Massachusetts; Buffalo, New York; Houston, Texas; and San Juan, Puerto Rico. These clinics had participated in a larger international follow-up study of cervical cancer in which a 20-30% reduction in breast cancer risk was linked to prior pelvic irradiation, even when treatment occurred after menopause. Overall, the 203 irradiated and 117 nonirradiated women had similar mean levels of estradiol, estrone, androstenedione, and testosterone. However, there appeared to be negative, albeit inconsistent, trends for androstenedione, testosterone, and estrone, suggesting that the irradiated women had lower levels of these hormones when compared with the nonirradiated women. These differences did not reach the level of statistical significance. While chance could partially explain these findings, it is plausible that the frequently observed protective association of breast cancer with pelvic irradiation could be due in part to a decrease in steroid hormones that is secondary, perhaps, to adrenal irradiation.

Adult↗

Mortality and career radiation doses for workers at a commercial nuclear power plant: feasibility study.

Career radiation doses for 8,961 male workers at the Calvert Cliffs Nuclear Power Plant (CCNPP) were determined for both utility (n = 4,960) and contractor (n = 4,001) employees. Workers were followed from the time of first employment at CCNPP (including plant construction) to the end of 1984 (mean follow-up = 5.4 y). Plant operation began in 1975. The mean duration of employment was 1.9 y at CCNPP and 3.1 y in the nuclear industry. Career radiation doses were determined from dosimetry records kept by the utility company and the U.S. Nuclear Regulatory Commission (NRC). For all exposed workers, the average career dose was 21 mSv and was higher for contractor (30 mSv) than utility (13 mSv) workers. Career doses were also higher among those employed in the nuclear industry for greater than or equal to 15 y (111 mSv) and among workers classified as health physicists (56 mSv). Cumulative doses of greater than or equal to 50 mSv were received by 12% of the workers; the maximum career dose reported was 470 mSv. The availability of social security numbers for practically all employees facilitated record-linkage methods to determine mortality; 161 deaths were identified. On average the workers experienced mortality from all causes that was 15% less than that of the general population of the U.S., probably due to healthier members of the population being selected for employment. Our investigation demonstrates that historical information is available from which career doses could be constructed and that, in principle, it is feasible to conduct epidemiologic studies of nuclear power plant workers in the U.S. Although difficult, the approach taken could prove useful until such time as a comprehensive registry of U.S. radiation workers is established.

Adult↗

Estimating Rn-induced lung cancer in the United States.

The proportion of lung cancer deaths attributable to Rn among residents of single-family homes in the U.S. (approximately 70% of the housing stock) is estimated using the log-normal distribution of Rn concentrations proposed by Nero et al. (1986) and the risk model developed by the National Academy of Sciences' BEIR IV Committee. The risk model, together with the exposure distribution, predicts that approximately 14% of lung cancer deaths among such residents (about 13,300 deaths per year, or 10% of all U.S. lung cancer deaths) may be due to indoor Rn exposure. The 95% confidence interval is 7%-25%, or approximately 6600 to 24,000 lung cancer deaths. These estimated attributable risks due to Rn are similar for males and females and for smokers and nonsmokers, but higher baseline risks of lung cancer result in much larger absolute numbers of Rn-attributable cancers among males (approximately 9000) and among smokers (approximately 11,000). Because of the apparent skewness of the exposure distribution, most of the contribution to the attributable risks arises from exposure rates below 148 Bq m-3 (4 pCi L-1), i.e., below the EPA "action level." As a result, if all exposure rates that exceed 148 Bq m-3 (approximately 8% of homes) were eliminated, the models predict that the total annual lung cancer burden in the U.S. would drop by 4-5%, or by about 3800 lung cancer deaths, in contrast to a maximum reduction of 14% if all indoor Rn exposure above the 1st percentile were eliminated.

Air Pollutants↗

Leukemia risk following radiotherapy for breast cancer.

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

Aged↗

Thyroid neoplasia following low-dose radiation in childhood.

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.

Adolescent↗

Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix.

An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints. The higher radiation dose and the concentration of that dose in a smaller area of the body appear to be responsible for the lower rate of persistent aberrations observed in cervical cancer patients.

Bone Marrow↗

Tumors of the brain and nervous system after radiotherapy in childhood.

We investigated the relation between radiotherapy in childhood for tinea capitis and the later development of tumors of the brain and nervous system among 10,834 patients treated between 1948 and 1960 in Israel. Benign and malignant tumors were identified from the pathology records of all Israeli hospitals and from Israeli national cancer and death registries. Doses of radiation to the neural tissue were retrospectively estimated for each patient (mean, 1.5 Gy). Sixty neural tumors developed in the patients exposed as children, and the 30-year cumulative risk (+/- SE) was 0.8 +/- 0.2 percent. The incidence of tumors was 1.8 per 10,000 persons per year. The estimated relative risk as compared with that for 10,834 matched general-population controls and 5392 siblings who had not been irradiated was 6.9 (95 percent confidence interval, 4.1 to 11.6) for all tumors and 8.4 (confidence interval, 4.8 to 14.8) when the analysis was restricted to neural tumors of the head and neck. Increased risks were apparent for meningiomas (relative risk, 9.5; n = 19), gliomas (relative risk, 2.6; n = 7), nerve-sheath tumors (relative risk, 18.8; n = 25), and other neural tumors (relative risk, 3.4; n = 9). A strong dose--response relation was found, with the relative risk approaching 20 after estimated doses of approximately 2.5 Gy. Our study confirms that radiation doses on the order of 1 to 2 Gy can significantly increase the risk of neural tumors.

Adolescent↗

Cancer among medical diagnostic x-ray workers in China.

Cancer incidence among 27,011 diagnostic x-ray workers was compared to that of 25,782 other medical specialists employed between 1950 and 1980 in China. X-ray workers had a 50% higher risk of developing cancer than the other specialists [relative risk (RR) = 1.5; 95% CI = 1.3-1.7]. Leukemia was strongly linked to radiation work (RR = 3.5, n = 30). Cancers of the breast (RR = 1.4, n = 11), thyroid (RR = 2.1, n = 7), and skin (RR = 1.5, n = 6) were increased among x-ray workers employed for 10 or more years. High risks of cancers of the esophagus (RR = 3.5, n = 15) and liver (RR = 2.4, n = 48) were not consistent with a radiation effect since risk did not vary by duration of employment. This finding suggested that some differences might exist between groups of hospital workers in social class, alcohol intake, dietary habits, and other risk factors. No excess lung cancer (RR = 0.9, n = 22) or multiple myeloma (n = 0) was observed. Significant excesses of leukemia and cancers of the breast and thyroid occurred among x-ray workers first employed prior to 1960 when radiation exposures in China were high. In fact, it was not uncommon for employees to be given time off from x-ray work because their wbc count was severely depressed. These data indicated that repeated exposure to x-rays over many years can increase the risk of leukemia and several other tumors but apparently not that of lung cancer.

Adult↗

The joint effect of risk factors on endometrial cancer.

The joint effect of risk factors on endometrial cancer was examined by applying general statistical models to the data of a hospital-based case-control study conducted in Copenhagen, Denmark. The analysis included 149 cases of histologically confirmed adenocarcinoma of the endometrium and 154 age-matched controls with cervical cancer. Information on risk factors derived from the medical records. Estrogen use and body mass were found to be the main predictors of endometrial cancer risk. In the model proposed, women who ever used non-contraceptive estrogens had a 10-fold increased risk irrespective of their weight and height. Among non-users of estrogen, the risk of endometrial cancer rose with increasing body mass, the largest showing a five-fold increased risk. These data provide further evidence of the significant role that excess estrogens play, whether exogenous from replacement therapy or endogenous from enhanced androgen conversion, in the etiology of endometrial cancer.

Adenocarcinoma↗

Mortality after radiotherapy for ringworm of the scalp.

The mortality experience of 10,834 children treated with x-rays for ringworm of the scalp between 1948 and 1960, 10,834 matched comparison subjects, and 5,392 siblings was evaluated over an average follow-up period of 26 years. Mortality was ascertained by linking unique personal identification numbers of study subjects with the national death registry. Radiotherapy in childhood was associated with an increased risk of death due to tumors of the head and neck (relative risk (RR) = 3) and leukemia (RR = 2.3). No other causes of death were significantly elevated after irradiation. The excess of brain tumors (average intracranial dose = 150 rads) confirms that the central nervous system of the child is sensitive to the induction of cancers by radiation. The bone marrow dose averaged over the entire body was approximately 30 rad, and the estimated risk coefficient of 0.9 excess leukemias per million per year per rad is consistent with other studies of whole-body exposure. A significant excess of bone and soft tissue sarcomas (RR = 9) was also observed. The pattern of cancer risk over time was bimodal; an early peak due to excess leukemias occurred within a few years of exposure, whereas excesses of solid tumors were most apparent after about 15 years. Despite the excess of cancers among exposed persons, over 50% of the deaths in the entire study population were from external events, mainly accidents or events related to military service. An estimate of the total impact of radiogenic cancer after childhood irradiation will require additional years of observation since the population irradiated is just now entering the age ranges normally associated with high cancer risk.

Brain Neoplasms↗

Carcinogenesis--a synopsis of human experience with external exposure in medicine.

Studies in the 1980s of medically irradiated populations have increased our knowledge of radiation carcinogenesis. (1) Investigations of prenatal x-ray exposures, especially in twins, provide evidence that very low doses of ionizing radiation may cause cancer in humans. (2) Fractionated doses appear as effective as single exposures of the same total dose in causing breast cancer, but seem less effective for lung cancer. (3) Excess breast cancers can occur among women exposed under age 10, indicating that the immature breast is susceptible to the carcinogenic action of radiation. (4) Moderate doses on the order of 1 Gy to the brains of children can cause tumors later in life; moderately high doses to the skin can cause cancer when followed by frequent exposure to ultraviolet light. (5) Radiotherapy for cervical cancer can increase the rate of subsequent leukemia with the best fitting dose-response functions including a negative exponential term to account for cell-killing. (6) Low-dose exposures of about 10 cGy may increase the risk of thyroid cancer. (7) Second cancers following radiotherapy for a variety of cancers occur primarily among long-term survivors. (8) Radiotherapy may not significantly increase the risk of leukemia following childhood cancer, whereas chemotherapy with alkylating agents is a major risk factor. (9) Bone cancer occurs after high-dose radiotherapy for childhood cancer, but children with retinoblastoma are not more susceptible to radiation-induced disease than children with other malignancies. (10) High-dose external beam therapy can cause thyroid cancer, whereas high-dose radioactive 131I may not. (11) Studies of cervical cancer patients indicate that the risk of radiation-induced second malignancies follows a time-response model consistent with a constant multiplication of the underlying background incidence, i.e. a relative risk model seems to hold for projecting risks forward in time.

Adult↗

Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study.

The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease.

Breast Neoplasms↗