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Biomedical subjects

M Zion

Publications and source records attributed to M Zion.

At least 19 recordsLinked to original sources

Determinants of bone mass and bone size in a large cohort of physically active young adult men.

The determinants of bone mineral density (BMD) at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years) entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA). Peripheral-quantitative computed tomography (pQCT) was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159). Mean BMD at all sites was approximately one standard deviation above young normal (p < 0.05). African Americans had significantly higher hip, spine and heel BMD and greater tibial mineral content and cortical thickness than Caucasians and Asians. In Caucasians (n = 653), weight was a significant determinant of BMD at every skeletal site. Prior exercise levels and milk intake positively related to bone density and size, while caffeine had a negative impact. There was an apparent interaction between milk and exercise in BMD at the heel, spine, hip and tibial mineral content and cortical thickness. Our data confirm the importance of race, body size, milk intake and duration of weekly exercise as determinants of BMD and bone size.

Journal Article↗

Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature.

INTRODUCTION: Estrogen therapy (ET), tamoxifen and raloxifene are associated with a two- to three-fold increased risk of venous thrombosis (VT); however, the mechanisms by which each drug increases venous thrombosis propensity are not fully understood. The objectives of this investigation were to compare the effects of these three treatments on hemostasis in a head to head randomized placebo-controlled trial. PATIENTS/METHODS: Ninety-four postmenopausal women were assigned to receive oral estrogen (conjugated equine estrogen [CEE] 0.625 mg, n=23), tamoxifen 20 mg (n=24), raloxifene 60 mg (n=24) or placebo (n=23) daily for 6 months. Blood samples were analyzed for procoagulant factors (prothrombin, factors VII [fVII], VIII [fVIII], IX [fIX] and XI [fXI], D-dimer and von Willebrand factor [vWf]), anticoagulant factors (antithrombin [AT], total and free protein S, protein C and activated protein C [APC] resistance) and fibrinolytic factors (thrombin activatable fibrinolysis inhibitor [TAFI] and plasminogen activator inhibitor-1 [PAI-1]), at baseline and at 6 months of treatment. RESULTS: Estrogen increased factor VII and D-dimer, and decreased antithrombin, total and free protein S and PAI-1. Changes with tamoxifen were distinct from estrogen with increases in factors VIII, IX, vWf and free protein S, and decreases in AT, total protein S, protein C and plasminogen activator inhibitor-1. Raloxifene produced similar effects as tamoxifen, but did not increase factor IX or decrease protein C. CONCLUSIONS: Estrogen, tamoxifen and raloxifene affected hemostasis favoring procoagulation and impairing anticoagulation. The biochemical effects of the selective estrogen receptor modulators (SERMs) were distinct from those of estrogen and differed only subtly from each other.

Biomarkers↗

Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia.

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.

Adolescent↗

Long-term prognosis of patients after a Q wave compared with a non-Q wave first acute myocardial infarction. Data from the SPRINT Registry.

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Between August 1981 and July 1983, 5839 consecutive myocardial infarction patients were hospitalized in 13 coronary care units in Israel. The present study examines 10 year survival among 4037 consecutive patients with a first myocardial infarction with either Q or non-Q waves. Demographic and medical data were collected from hospital records, and 1 year clinical follow-up was complete for 99% of hospital survivors. Mortality follow-up was extended to June 1992 (mean 10 years of follow-up). RESULTS: Five hundred and eighty patients (14%) had first myocardial infarctions of the non-Q wave type and 3457 of the Q wave type. Hospital mortality was significantly higher in patients with a Q wave (10%) than those with a non-Q wave myocardial infarction (7%) (P < 0.05). One year post-discharge, non-fatal reinfarction and mortality rates were comparable in patients with Q wave (4% and 7%) and non-Q wave myocardial infarctions (4% and 7% respectively). Similarly, 5 to 10 year post-discharge mortality rates were equally high in patients with a non-Q wave (26% and 44%) as in those with a first episode of a Q wave myocardial infarction (22% and 40% respectively). CONCLUSIONS: Patients with a first non-Q wave acute myocardial infarction exhibited relatively better in-hospital survival than counterparts with a first Q wave infarction, but the advantage did not persist after discharge. Patients with a non-Q wave infarction deserve particular attention as their post-discharge mortality risk is similar to counterparts with a first Q wave myocardial infarction.

Aged↗

Early risk stratification of patients with a first inferior wall acute myocardial infarction. SPRINT Study Group.

A prognostic index based on admission characteristics of patients with inferior acute myocardial infarction was developed to predict mortality and other major complications during hospitalization. The study sample included 1841 consecutive patients with a first inferior wall acute myocardial infarction, hospitalized in 13 out of 21 operating coronary care units in Israel. Age, angina in the past, congestive heart failure and blood glucose level > 180 mg/dl were independently associated with higher in-hospital mortality and morbidity. The prognostic weights of these risk factors were determined in a study group which comprised two thirds of the patients (n = 1210) who were randomly selected from the 1841 participants. A prognostic score (range, 0-15) was calculated as the sum of the prognostic weights of the above four risk factors for each patient. These scores were determined in both the study group and in a validation group (the remaining one third of the patients, n = 592). In-hospital mortality in the study group ranged from no death for 102 patients with a prognostic score of 0, to a 37% mortality rate in 106 patients whose prognostic score was > 8. Accordingly, the study group was divided into groups of low-risk (score 0-5), intermediate-risk (score 6-8) and high-risk (score > 8), with in-hospital mortality of 3, 13 and 37%, respectively. In-hospital mortality among patients in the validation group determined to be at low-, intermediate- and high-risk was 3, 13 and 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The predictive value of admission heart rate on mortality in patients with acute myocardial infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial.

The purpose of this study was to assess the predictive value of admission heart rate (HR) for in-hospital and 1 year post-discharge mortality in a large cohort of patients hospitalized for acute myocardial infarction (MI). Data were derived from the SPRINT-2 secondary prevention study population, and included 1044 patients (aged 50-79), hospitalized in 14 coronary care units in Israel with acute MI in the years 1985-1986, before the beginning of thrombolytic therapy in acute MI. Demographic, historical and medical data were collected for each patient. All deaths during initial hospitalization and 1 year post-discharge were recorded. In-hospital mortality was 5.2% for 294 patients with HR < 70 beats/min, 9.5% for 532 patients with HR 70-89 beats/min, and 15.1% for 323 patients with HR > or = 90 beats/min (p < 0.01). One year post-discharge mortality was 4.3% for patients with HR < 70 beats/min, 8.7% for patients with HR 70-80 beats/min and 11.8% for patients with HR > or = 90 beats/min (p < 0.01). An increasing trend of mortality with higher HR was confined to patients with mild CHF (p = 0.02) and likely to patients with absent CHF (p = 0.06), but this post hoc observation requires confirmation in larger groups. The combination of high admission HR (> or = 90 beats/min) and a systolic blood pressure < 120 mmHg was a powerful predictor of in-hospital mortality. Multivariate analysis showed that admission HR was an independent risk factor for in-hospital and 1 year post-discharge mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Progressive de novo DNA methylation at the bcr-abl locus in the course of chronic myelogenous leukemia.

De novo methylation of CpG islands is a rare event in mammalian cells. It has been observed in the course of developmental processes, such as X chromosome inactivation and genomic imprinting. The methylation of DNA, an important factor in the epigenetic control of gene expression, may also be involved in tumorigenesis. After the t(9;22) chromosomal translocation and generation of the Philadelphia chromosome, the initiating event in chronic myelogenous leukemia (CML), most of the abl coding sequence is fused to the 5' region of the bcr gene. Expression of the hybrid bcr-abl gene is, therefore, regulated by the bcr promoter. In most cases of CML, one of the two abl promoters (Pa) is nested within the bcr-abl transcriptional unit and should be able to transcribe the type Ia 6-kb normal abl mRNA from the Philadelphia chromosome. However, we have found that the 6-kb transcript is present only in CML cell lines containing a normal abl allele and that the apparent inactivation of the nested Pa promoter is associated with allele-specific methylation. Furthermore, we have noticed that the Pa promoter is contained within a CpG island and undergoes progressive de novo methylation in the course of the disease. This is attested to by the fact that DNA samples from CML patients that are methylation-free at the time of diagnosis invariably become methylated in advanced CML. Since tumor progression in CML cannot always be inferred from the clinical presentation, assessment of de novo CpG methylation may prove to be of critical value in management of the disease. It could herald blastic transformation at a stage when bone marrow transplantation, the only potentially curative therapeutic procedure in CML, is still effective.

Animals↗

Short- and long-term prognosis of patients with a first acute myocardial infarction with concomitant peripheral vascular disease. SPRINT Study Group.

PURPOSE: The aim of the study was to assess the prevalence and the prognostic impact of concomitant peripheral vascular disease (PVD) in patients developing acute myocardial infarction (AMI). PATIENTS AND METHODS: Four thousand two hundred fifty-eight consecutive patients with a first AMI hospitalized in 13 of 21 operating coronary care units in Israel were screened. Anamnestic, demographic, and medical data were collected from hospitalization charts, and all patients were followed clinically 1 year after discharge and up to 7 years (mean: 5.5 years) for mortality. RESULTS: The prevalence of clinically diagnosed PVD in patients with a first AMI was 6.3% (269 of 4,258), with no difference between men and women. Patients with PVD were older (66.2 years) and included more hypertensive subjects (47.2%), diabetic persons (26.4%), and individuals with a previous history of cerebrovascular accident (CVA) (11.5%) in comparison to counterparts without PVD (61.7 years; 39.4%, 19.9%, and 3.3%, respectively; p < 0.01 for each). On admission to the coronary care units, 36.5% of patients with PVD were in Killip class II, III, or IV versus only 18.0% in the reference group (p < 0.001). During hospitalization, patients with PVD exhibited a significantly higher rate of paroxysmal atrial fibrillation (17.5%), advanced atrioventricular block (15.2%), and cardiogenic shock (11.9%) in comparison to patients without PVD (11.9%, 10.2%, and 5.3%, respectively; p < 0.01 for each). After adjustment for age, gender, hypertension, history of angina, diabetes mellitus, history of CVA, site of infarction, and congestive heart failure on admission, the odds ratio for in-hospital mortality associated with PVD was 1.37 (90% confidence interval 1.01 to 1.83). There was no independent contribution of PVD to long-term (mean: 5.5 years) postdischarge mortality; the odds ratio was 1.02. CONCLUSION: PVD in patients with a first AMI independently increases the risk of in-hospital death but does not affect long-term mortality in survivors.

Aged↗

Prognosis of early versus late ventricular fibrillation complicating acute myocardial infarction.

Earlier studies have suggested that patients exhibiting late (> 24 h) ventricular fibrillation during acute myocardial infarction had a poorer outcome in comparison to myocardial infarction patients with early (< 24 h) ventricular fibrillation. Between August 1981 and July 1983, 5839 consecutive patients with acute myocardial infarction were hospitalized in 13 out of 21 operating coronary care units in Israel. Demographic and medical data were collected from hospitalization charts and during 1 year of follow-up. Mortality assessment was done for 99% of hospital survivors up to mid-1988 (mean, 5.5 years). The incidence of ventricular fibrillation in the SPRINT Registry was 6% (371/5839). Patients with ventricular fibrillation in the setting of cardiogenic shock (n = 107) were excluded from analysis. Patients with late ventricular fibrillation (n = 109; 41%) were older and had a more complicated hospital course than patients with early ventricular fibrillation (n = 155; 59%). In-hospital and 1-year post-discharge mortality were significantly higher in patients with late ventricular fibrillation (63% and 17%) as compared to patients with early ventricular fibrillation (26% and 4%, respectively; P < 0.05 for each). This difference vanished 5 years after hospital discharge. After multiple logistic regression analysis late occurrence of ventricular fibrillation emerged as an independent predictor of increased in-hospital mortality (Odds ratio, 4.29; 95% confidence interval, 2.11-8.74) but not for subsequent death. Patients with late ventricular fibrillation during the hospital course of acute myocardial infarction had a poorer immediate and subsequent outcome in comparison to patients with early ventricular fibrillation.

Aged↗

Immediate and long-term prognostic significance of a first anterior versus first inferior wall Q-wave acute myocardial infarction. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

Of 3,981 patients with a first Q-wave acute myocardial infarction (AMI), 1,929 (48%) had an anterior and 1,724 (43%) an inferior wall AMI. These 2 groups were well-matched with respect to age, gender and relevant history. The in-hospital mortality rate was 18%, and the 1- and 5-year post-discharge mortality rates were 9 and 25%, respectively, in patients with anterior wall AMI compared with the corresponding rates of 11, 6 and 19% in those with inferior wall AMI (p < 0.0001 for each category). The frequency of recurrent nonfatal AMI in the year after the index AMI was 8% in the patients with anterior wall AMI compared with 4% in those with inferior wall AMI (p < 0.0001). By multiple logistic regression analysis of events, anterior wall AMI was an independent predictor of in-hospital mortality only. The findings indicate that the anatomic location of a Q-wave AMI influences immediate and short-term survival of patients with a first Q-wave AMI.

Aged↗

Predictors and long-term prognostic significance of recurrent infarction in the year after a first myocardial infarction. SPRINT Study Group.

This study was undertaken to examine whether clinical factors predict reinfarction within 1 year of a first acute myocardial infarction (AMI) and to quantify the subsequent influence of reinfarction on long-term mortality. Data from 3,695 patients with a first AMI included in the Secondary Prevention Reinfarction Israeli Nifedipine Trial Registry were analyzed. The 1-year reinfarction incidence was 6.0% (220 of 3,695) and in-hospital mortality during reinfarction was 31%. Patients with reinfarction were older (63.0 vs 60.8 years) at entry. The independent clinical predictors for 1-year reinfarction were (adjusted relative odds): peripheral vascular disease (2.12), anterior location of the first AMI (1.62), angina before the first AMI (1.53), congestive heart failure on admission (1.34), diabetes (1.33), systemic hypertension (1.28) and age increment (1.13). One-year reinfarction rate increased from 4.0% in patients with 0 or 1 risk factor to 23.3% in patients with 5 to 6 risk factors (p < 0.0001). Patients with reinfarction had significantly increased 1- and 5-year mortality compared with those who had no reinfarction (11.8 vs 5.3% and 40.1 vs 20.3%, respectively, p < 0.001). Recurrent AMI within 1 year was the most powerful predictor of long-term (mean 5.5 years) total mortality (adjusted relative risk = 4.76).

Age Factors↗

[Prognosis of acute myocardial infarction in the elderly. SPRINT Study Group].

In countries with aging populations acute myocardial infarction (MI) in the elderly is increasing rapidly and hospital and long-term mortality remain high. During 1981-83, 5839 consecutive patients with acute MI were hospitalized in 13 coronary care units in Israel. Of these, 653 (11%) were older than 75 years, 41% were women, and 70% had a first MI. The hospital mortality in these very elderly patients was 35%. The mortality rates 1 and 5 years postdischarge were 24% and 55%, respectively. In view of this high risk and the promising results obtained elsewhere with thrombolysis, particularly in the elderly, this treatment should be routinely considered in elderly patients with acute MI when there are no specific contraindications.

Aged↗

Early administration of nifedipine in suspected acute myocardial infarction. The Secondary Prevention Reinfarction Israel Nifedipine Trial 2 Study.

BACKGROUND: The administration of nifedipine, 30 mg/d, between 7 and 22 days after hospitalization for an acute myocardial infarction (Secondary Prevention Reinfarction Israel Nifedipine Trial study) showed no effect on subsequent mortality and morbidity. Since a possible indication of benefit was observed in patients with a second- or higher-order infarction, a second trial was conducted with a higher dose (60 mg/d), early administration (usually within 3 hours of hospital admission), and in high-risk patients only. METHODS: A total of 1358 men and women with suspected acute myocardial infarction (MI), judged not to require calcium antagonist therapy, were randomized to receive nifedipine, 60 mg/d, or placebo between November 1985 and July 1986. Study medication was discontinued in 352 patients because they did not exhibit study criteria for MI or lacked high-risk criteria, or because they decided to discontinue the study. Thus, the treated high-risk group included 1006 patients, of whom 826 were successfully titrated to the target dose of 60 mg/d and were treated for up to 6 months. RESULTS: In the 1006 patients, mortality was 18.7% among those randomized to nifedipine and 15.6% in the patients randomized to placebo. This reflected an increased mortality of 7.8% as compared with 5.5% during the first 6 days in the nifedipine and placebo groups, respectively (adjusted mortality odds ratio by logistic regression, 1.60; 95% confidence interval, 0.86 to 3.00). Among the 826 patients who continued treatment, mortality was equal in the nifedipine (9.3%) and placebo (9.5%) groups. No differences in the rates of nonfatal MI (5.1% and 4.2% in the nifedipine and placebo groups, respectively), hospitalization due to unstable angina, and frequency of chest pain reported during follow-up were observed. An increased rate of sudden death (4.9%) in the placebo group in comparison with the nifedipine group (2.3%) was not statistically significant on post hoc testing, nor was an effect of nifedipine demonstrable in post hoc analyses by congestive heart failure status of randomized patients. CONCLUSION: Nifedipine as a prophylactic treatment in patients immediately after acute MI or in survivors recovering 1 week or longer after acute MI appears ineffective. Early routine administration of nifedipine in acute MI, other than to patients in whom it may be specifically indicated (eg, those with Prinzmetal's variant angina or severe hypertension) may be hazardous and seems to be contraindicated.

Aged↗

Complete atrioventricular block complicating inferior acute wall myocardial infarction: short- and long-term prognosis.

The incidence of complete atrioventricular block (AVB) in a large group of patients with Q-wave inferior acute myocardial infarction (AMI) was 251 (11%) of 2273 patients. This incidence was significantly higher in women (14%) and patients > 70 years old (15%) than in men and patients < 70 years old (10% and 9%, respectively). Patients with complete AVB exhibited more serious arrhythmic and mechanical complications during hospitalization and included more patients with very high enzyme levels than their counterparts without AVB. The in-hospital mortality rate was 92 (37%) of 251 patients with complete AVB versus 200 (11%) of 1890 in those without AVB (p < 0.0001). After adjustment for age, gender, and important anamnestic, medical, and enzymatic findings, complete AVB emerged as an independent predictor of in-hospital mortality, yielding an odds ratio of 2.0 (90% confidence interval 1.12 to 3.57). The long-term (5-year) mortality rate in hospital survivors was slightly but not significantly higher in patients with complete AVB (28%) during hospitalization than in their counterparts with no AVB (23%). In view of these data, patients with inferior AMI in whom complete AVB develops are at increased risk and may benefit from urgent revascularization; the postdischarge management of survivors with complete AVB should be no different from that of patients without AVB.

Aged↗

Circadian variation and possible external triggers of onset of myocardial infarction. SPRINT Study Group.

PURPOSE: To determine whether a circadian pattern in onset of symptoms existed and possible external triggers were implicated in the precipitation of acute myocardial infarction (AMI). PATIENTS AND METHODS: One thousand eight hundred eighteen consecutive patients with AMI hospitalized in 14 of the 21 existing coronary care units in Israel during the study period were assessed. RESULTS: The frequency of onset of symptoms by 6-hour intervals showed a predominant morning peak (6 AM to noon) (32%, p < 0.01) in comparison with the other three 6-hour intervals of the day. The preponderance of the morning peak persisted for subgroup analysis by gender (males 32%, females 31%); age (less than or equal to 65 years--32%; greater than 65 years--33%); diabetes mellitus (present or absent, 32%). However, patients with peripheral vascular disease and those with stroke in the past had a predominant evening peak. Possible external triggers of onset of AMI were present in 10% of patients. Exceptional heavy physical work, violent quarrel at work or at home, and unusual mental stress were the three most frequent possible external triggers reported immediately before or within the 24 hours preceding pain onset. Patients with possible external triggers were more likely to be males (85%) and were somewhat but not significantly younger (63.1 years) in comparison with patients without external triggers (73% and 64.3 years respectively). CONCLUSIONS: In a large group of consecutive patients with AMI, a predominant cyclic morning peak of pain onset was found in comparison with the other hours of the day. Possible external triggers precipitating AMI were involved in a minority of cases, suggesting that endogenous changes occurring in the morning hours are generally responsible for the increased rate of myocardial infarction occurring after awakening.

Aged↗

Frequency and prognosis of stroke/TIA among 4808 survivors of acute myocardial infarction. The SPRINT Study Group.

BACKGROUND AND PURPOSE: Stroke complicating acute myocardial infarction is associated with substantial morbidity and mortality. The purpose of this study was to assess the incidence, predictors, and impact on mortality of stroke/transient ischemic attacks occurring after hospital discharge in a large unselected population of acute myocardial infarction survivors. METHODS: During a secondary prevention study with nifedipine (SPRINT), demographic, anamnestic, and clinical data were collected for 5839 consecutive acute myocardial infarction patients admitted to 13 coronary care units in Israel. Hospital survivors (n = 4808) were followed for a year after their discharge. Mortality was assessed for a mean follow-up of 5.5 years (range, 4.5 to 7 years). RESULTS: One percent (48/4808) of hospital survivors from acute myocardial infarction experienced a stroke/transient ischemic attack in the year after acute myocardial infarction. Thirty-one percent (15 of 48) of events occurred in the first month after hospital discharge. Incidence was higher among older patients (> 70 years; 1.9%), those with anterior site of myocardial infarction (1.35%), a previous history of myocardial infarction (1.8%), hypertension (1.4%), stroke in the past (4.1%), and chronic atrial fibrillation (9%). Multivariate analysis identified the following as independent predictors of stroke/transient ischemic attacks occurring in the year after hospital discharge: chronic atrial fibrillation, older age, history of previous myocardial infarction, anterior myocardial infarction site, serum glutamic oxaloacetic transaminase levels more than four times above upper normal limits, and stroke in the past. The age-adjusted 1-year and long-term mortality rates (4.5 to 7 years; mean, 5.5 years) were significantly higher in patients with (31% and 62%) than in those without stroke/transient ischemic attacks (9% and 31%, respectively; P < .01). CONCLUSIONS: Stroke/transient ischemic attack is a relatively rare (1%) complication in the year after hospital discharge from acute myocardial infarction, though more frequent in the first month. Chronic atrial fibrillation, older age, anterior myocardial infarction site, serum glutamic oxaloacetic transaminase levels more than four times above upper normal limits, past myocardial infarction, and stroke identify high-risk patients. Patients suffering from subsequent stroke/transient ischemic attacks experienced higher mortality than counterparts who remained free from this complication.

Age Factors↗