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B W Brown

Publications and source records attributed to B W Brown.

At least 55 records · Page 3Linked to original sources

Designing a cost-effective clinical trial.

Researchers and administrators must decide which clinical trials are worth doing and how many subjects are needed for a trial. We calculated sample size considering the costs of implementing the results of the trial and the trial costs using (1) Neyman-Pearson methods and (2) a Bayesian cost-benefit method. We illustrate these methods in a clinical trial sponsored by the National Institutes of Health that compares two levels of blood urea nitrogen clearance by haemodialysis for patients with end-stage renal disease. When applied to evaluations of research proposals, these methods may help researchers to decide whether to begin a study, and, if so, how many subjects to enrol in it. These methods should be especially useful for large studies intended to inform health policy.

Bayes Theorem↗

Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin's lymphoma.

High-dose chemotherapy with or without radiotherapy followed by autologous transplantation of hematopoietic progenitor cells is an effective treatment for patients with high-risk or relapsed non-Hodgkin's lymphoma. Chemotherapy and/or hematopoietic growth factors have been used to mobilize progenitor cells in the peripheral blood for transplantation. However, the mobilized blood cell products have been found to be frequently contaminated with tumor cells, and techniques have not been developed to purge tumor cells from these products. In addition, the minimum number of hematopoietic progenitor cells required for engraftment has not yet been fully elucidated. We treated 21 patients with a single infusion of cyclophosphamide (4 g/m2) followed by daily administration of granulocyte colony-stimulating factor (G-CSF). After recovery of the white blood cell count, a single 3-hour apheresis collection was performed. The apheresis product was then applied to a discontinuous Percoll gradient. The low-density fractions resulting from this separation procedure were enriched for CD34+ progenitor cells (total cell yield, 19.5%; CD34+ cell recovery, 81.2%). These enriched cellular products were treated with a panel of anti-B cell or anti-T cell monoclonal antibodies and complement in an effort to remove residual tumor cells. After treatment of the patient with myeloablative therapies, the enriched and purged cells were reinfused. Hematologic recovery was rapid, with median neutrophil engraftment in 10 days [absolute neutrophil count (ANC), greater than 0.5 x 10(9)/L] and 11 days (ANC, greater than 1.0 x 10(9)/L). Median platelet transfusion independence required 13 days. The rapidity of multilineage engraftment correlated with the number of CD34+ cells per kilogram that were infused. Patients who received more than 2 x 10(6) CD34+ cells per kilogram had rapid hematologic engraftment, whereas those patients transplanted with less than 2 x 10(6) CD34+ cells per kilogram had slower platelet recovery. Modeling studies using a lymphoma cell line with a t(14; 18) chromosomal translocation demonstrated the successful removal of tumor cells assayed using the polymerase chain reaction (PCR) after the processing and purging. Four of the 21 patients had PCR-detectable lymphoma cells in the bone marrow and peripheral blood; however, the enriched and purged blood products reinfused in all four did not contain detectable tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

"Quilty" revisited: a 10-year perspective.

The goals of this study were to better define Quilty lesions, facilitating differentiation from other endocardial infiltrates; to correlate Quilty lesions with clinical parameters; and to assess whether classification into Quilty A (noninvasive lesions) and Quilty B (invasive lesions) had clinical utility. Two hundred seventeen adults who received transplants between 1981 and 1987 and 22 children who received transplants between 1981 and 1989 were studied. Allograft survival for over 1 year was the selection criterion. Clinical, angiographic, and biopsy data were reviewed up to 1992, obtaining a minimum follow up of 5 years for adults and 3 years for children. All 7,439 endomyocardial biopsy cases were allotted an International Society for Heart and Lung Transplantation (ISHLT) grade for rejection, and Quilty was classified as Quilty A or B. Quilty was correlated with transplant recipient age and gender, cytomegalovirus and Epstein-Barr virus (EBV) infection, treatment protocols, allograft rejection, graft vascular disease (GVD), and lymphoma. Immunohistochemistry was performed to determine Quilty cell composition. Quilty incidence was 49.77% in adults and 68.18% in children, and did not appear to be influenced by cyclosporine dosage. Quilty showed no gender variation nor association with cytomegalovirus (CMV) or EBV infection or lymphoma. A total of 74.04% of adults developed Quilty within the first year posttransplant and 81.48% had multiple Quilty-positive biopsies. One hundred eight of 217 Quilty-positive adults had 456 Quilty-positive endomyocardial biopsies, 82.24% of which were associated with an ISHLT grade of 0 or I, and only 12.28% being associated with a grade III rejection. Histological division into Quilty A and Quilty B did not appear to have clinical significance. Graft vascular disease appears to have decreased significantly more in Quilty-positive patients. Although our findings in children were similar to those in the adults, we were unable to draw definite conclusions, the number of children being too small to permit valid statistical correlations.

Adolescent↗

Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in ewes.

Groups of Merino ewe lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and were studied over the following 2 years to determine the long-term effects on reproductive development, function and hormone concentrations. At least 60% of the GnRH-immunized ewes in either treatment group did not experience oestrus and possessed small uteri and small ovaries that lacked follicular development. Growth rates of immunized and control ewes were similar throughout the study. Compared with the increase in plasma LH and FSH concentrations with age in control ewes, the concentrations of these hormones in immunized animals were lower and remained relatively constant from 46 to 90 weeks of age. Plasma FSH concentrations were particularly suppressed in immunized ewes and were significantly (P < 0.05) lower than the control values of 61 and 90 weeks of age. LH release after injection of 1 microgram GnRH at 90 weeks of age was either absent or suppressed in immunized ewes compared with controls. The findings suggest that the lack of GnRH stimulation and consequent deprivation of gonadotrophins, early in the life of ewes, may result in some degree of permanent impairment of hypothalamic and/or pituitary function.

Animals↗

Running and the development of disability with age.

OBJECTIVE: To determine, by longitudinal study, whether regular vigorous running activity is associated with accelerated, unchanged, or postponed development of disability with increasing age. STUDY DESIGN: 8-year prospective, longitudinal study with yearly assessments. PARTICIPANTS: 451 members of a runners' club and 330 community controls who were initially 50 to 72 years old (also characterized as "ever-runners" [n = 534] and "never-runners" [n = 247], respectively). MEASUREMENTS: The dependent variable was disability as assessed by the Health Assessment Questionnaire and separately validated in these participant cohorts. Covariates included age, sex, body mass index, comorbid conditions, education level, smoking history, alcohol intake, mean blood pressure, initial disability level, family history of arthritis, and radiologic evidence of osteoarthritis of the knee in a subsample. RESULTS: Initially, the runners were leaner, reported joint symptoms less frequently, took fewer medications, had fewer medical problems, and had fewer instances of and less severe disability, suggesting either that the average previous 12 years of running had improved health or that self-selection bias was present. After 8 years of longitudinal study, the differences in initial disability levels (0.026 compared with 0.079; P < 0.001) had steadily increased to 0.071 for runners compared with 0.242 for controls (P < 0.001). The difference was consistent for men and women. The rate of development of disability was several times lower in the runners' club members than in community controls; this difference persisted after adjusting for age, sex, body mass, baseline disability, smoking history, history of arthritis, or other comorbid conditions (slopes of progression of disability for the years 1984 to 1992, after adjusting for covariates: men in the runners' club, 0.004 [SE, 0.002]; community controls, 0.012 [SE, 0.002]; women in the runners' club, 0.009 [SE, 0.005]; community controls, 0.027 [SE, 0.004]; P < 0.002 for both sets of comparisons). In addition to differences in disability, there were significant differences in mortality between the runners' club members (1.49%) and community controls (7.09%) (P < 0.001). These differences remained significant after adjusting for age, sex, body mass, comorbid conditions, education level, smoking history, alcohol intake, and mean blood pressure (P < 0.002, conditional risk ratio for community controls compared with the runners, 4.27; 95% CI, 1.78 to 10.26). CONCLUSIONS: Older persons who engage in vigorous running and other aerobic activities have lower mortality and slower development of disability than do members of the general population. This association is probably related to increased aerobic activity, strength, fitness, and increased organ reserve rather than to an effect of postponed osteoarthritis development.

Aging↗

A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation.

Anemia is a universal finding in patients undergoing autologous bone marrow transplantation (BMT). Effective therapies to increase the number of autologous red blood cells could result in a lower morbidity and mortality associated with red blood cell transfusions. We examined whether the addition of erythropoietin (Epo) to intensive therapy supported by progenitor cell transplantation and granulocyte colony-stimulating factor (G-CSF) would result in a lower requirement for red blood cell transfusions. Thirty-five patients with lymphoma were randomized to receive Epo versus placebo. Epo (600 U/kg three times per week) or placebo was begun 3 weeks before administration of high-dose therapy. Epo was held during the week of the preparatory regimen, and restarted on the day after BMT. All patients also received G-CSF following BMT. No significant differences were noted between the two groups in terms of patient characteristics at pretreatment or post-BMT evaluation. There were no differences in the total number of red blood cell units transfused (median Epo: 8 v placebo: 6, P = .22) nor the number of platelet transfusions given (median Epo: 12 v placebo 5, P = .14). Engraftment of granulocytes (absolute neutrophil count > or = 500/microL) occurred in a median of 12 days (range, 9 to 33) for the patients receiving Epo and G-CSF, compared with a median of 10 days (range, 8 to 22) for those receiving placebo and G-CSF (P = .70). Likewise, there were no differences in the time to platelet count > or = 20,000/microL without further transfusions with a median of 22 days (range, 15 to 150+) for those receiving Epo and G-CSF compared with a median of 20 days (range, 11 to 54) for those patients receiving placebo and G-CSF (P = .28). The combination of G-CSF and Epo as administered in this study appears to be safe but does not result in an improvement in the total number of red blood cell transfusions or total number of single donor platelet units transfused.

Adult↗

Accuracy of family history of cancer obtained through interviews with relatives of patients with childhood sarcoma.

The purpose of this study was to determine the accuracy of reporting of invasive cancer by relatives for family studies. First, we attempted to evaluate whether a lower than expected cancer rate found in second-degree relatives of children with soft-tissue sarcoma was a result of underreporting. Second, we evaluated the accuracy of reported cancer in two data sets by comparing reported cancer information with documentation by medical records and death certificates. We obtained medical histories from a primary informant, usually the proband's parent, on 346 first- and 784 second-degree relatives of 68 childhood and adolescent soft-tissue sarcoma patients. To investigate underreporting by the primary informant we conducted an individual interview with each adult relative or proxy. Primary informants reported 22 cancers in first-degree relatives, all confirmed as invasive cancer, and 71 cancers in second-degree relatives with 50 of 67 for which documentation confirmed as invasive. Of 715 individual informants contacted, 15 additional cancers were reported, including 5 confirmed as invasive. The number of first-degree relatives with confirmed invasive cancers was within the expected range; however, the number of cancers in second-degree relatives was below the expected range (observed/expected = 0.51 (54/105.5) 95% confidence interval (CI) = 0.39-0.67). Thus, the lower than expected number of cancers in second-degree relatives was not attributable to underreporting by a single informant or inability to obtain documentation. The overreporting of 25 cancers (24.5%) in second-degree relatives, indicates the need to document all reported cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A review of nutritional influences on reproduction in boars, bulls and rams.

In this paper, nutritional influences on reproduction in boars, bulls and rams during prepubertal life and in the adult is reviewed. Reproductive functions in young animals appear to be more susceptible to dietary restrictions of energy and protein than in the adult and severe feed restriction may even result in permanent damage to gonadal and neural tissue. Whilst restricted feed intake in adult animals can reduce androgen secretion and semen quality, such effects are temporal as re-feeding previously underfed adult animals usually restores reproductive function. There is now considerable evidence suggesting that the influence of nutrition on reproductive processes is mediated via effects of dietary constituents on the hypothalamic-pituitary axis, although there is some indication that dietary changes may affect the testis directly. That some nutritional regimes imposed on animals can alter volume of ejaculates and androgen activity without necessarily affecting spermatogenesis, suggests that certain constituents of the diet can differentially affect the production and/or the release of LH and FSH.

Androgens↗

Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in rams.

Groups of Merino ram lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and studied over the following 2 years to determine the long-term effects of such immunization on reproductive development, function and hormone concentrations. The treatment was equally effective in suppressing reproductive function and hormones when given at either time. Growth rates of immunized and controls rams were similar throughout the study. Prepubertal immunization delayed testicular growth until the rams were at least 27 weeks of age and some rams had subnormally sized testes even at 115 weeks of age. After peripubertal immunization, the mass of the testes declined and remained regressed until the rams were from 51 to 90 weeks old. There was a significant correlation between total testicular mass at 115 weeks of age and duration (weeks) of suppression of testicular growth (prepubertal, r = -0.7375; peripubertal, r = -0.7132, P < 0.001). Prepubertal immunization markedly delayed separation of the penis from the prepuce. The immunized rams did not display sexual activity until their total testicular mass reached at least 70 g. In control and immunized rams with testicular mass > 100 g, the semen did not differ in the percentage of spermatozoa that were unstained (live), of normal morphology, or showed progressive movement. Compared with the increase in plasma LH and FSH concentrations with age in control rams, the concentrations of these hormones in the immunized animals were lower and remained relatively constant from 46 to 90 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Noncancer deaths in white adult cancer patients.

BACKGROUND: The cancer-specific death rate is a commonly used indicator in the assessment of progress against cancer. However, since the cause of death is often not substantiated and complete medical information is lacking, the validity of cancer-specific mortality rates is being questioned. PURPOSE: We investigated the validity of the cancer-specific death rate by examining noncancer deaths of cancer patients in a large patient population. METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program on cancer patients diagnosed between 1973 and 1987, with follow-up complete through December 1987. The SEER database consists of 1.2 million records from nine population-based registries covering nine geographic regions of the United States. Rates of noncancer deaths in the U.S. population were obtained from the National Center for Health Statistics. Cancer mortality rates were subtracted from overall mortality rates to obtain noncancer death rates by sex and the 5-year age group for each calendar year. Excluded from the study were patients of races other than White and those diagnosed at age 85 years or more due to absence of noncancer death rate comparisons. Also excluded were cancer cases discovered at autopsy and in persons less than 20 years of age. The statistical analysis employed a log-linear model. RESULTS: The ratio of patient-to-general-population noncancer death rates, as calculated by dividing the number of patient noncancer deaths per year by the number found in the matched U.S. population data and referred to as the noncancer relative hazard, is considered significant with values greater than 1 for those with all cancers combined and for the common solid tumors examined. Of the 12 leading causes of death other than cancer in the patient population, the most common causes were circulatory and respiratory failures. The noncancer relative risk of death decreased rapidly after diagnosis and also decreased with the patient's age at diagnosis. It increased slightly with the calendar year of diagnosis. CONCLUSIONS: Because more noncancer deaths occurred shortly after diagnosis, it appears that this excess was caused by treatment of the cancer. Generally, cancer-specific death rates underestimate the mortality associated with a diagnosis of cancer. Therefore, because the degree of underestimation changes with time, an examination solely of cancer-caused mortality in assessing progress against the disease is incomplete.

Adult↗

Double beta-lactam regimen compared to an aminoglycoside/beta-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients.

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C +/- T), both agents being administered only if the initial granulocyte count was below 200/microliters, or ceftazidime plus piperacillin (C + P). The overall response rate was 71% (39 of 60 for C +/- T and 45 of 58 for C + P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C + P regimen (P = 0.06), there was no difference in response for patients with bacteremia and profound (< 100/microliters) sustained granulocytopenia. The double beta-lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced excellent serum bactericidal levels (C +/- T geometric mean peak 1:170; C + P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C + P and in 6 of 89 trials in the C +/- T group (P = 0.19). The incidence of secondary infections in patients with profound (< 100/microliters) sustained granulocytopenia was lower in the C +/- T group (P = 0.04). Alimentary canal anaerobic flora preservation with C +/- T, and suppression with C + P, was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A computer program for designing clinical trials with arbitrary survival curves and group sequential testing.

We present a program, mhghseq, for designing a clinical trial to compare two treatments. For a user-specified hypothesis and a user-specified alternative, mhghseq finds the number of subjects required to achieve a given size and power. It permits each treatment to have an arbitrary survival curve and it allows for group sequential testing. It provides solutions for small samples as well as for large samples. There may be a follow-up period after accrual is completed. Tests may be one or two-sided, either the log-rank or the Gehan test may be used, and either of two commonly used boundary forms--the O'Brien-Fleming or Pocock boundary forms--may be specified. Although mhghseq relies primarily on simulation to produce results, the large sample sequential boundary for the log-rank test optionally may be computed with an algorithm given here that is different from ones used in the past for this purpose.

Computer Simulation↗

Hodgkin's disease: study of treatment intensities and incidences of second malignancies.

BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non-Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non-Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage.

Actuarial Analysis↗

Calculating the probability of rare events: why settle for an approximation?

OBJECTIVE: Health services researchers often need to compute the probability of observing a certain number of events when only a few such events are expected. Our objective is to show that the standard approaches (Poisson, binomial, and normal approximations) are inappropriate in such instances, and to suggest an alternative. DATA SOURCES: Patients undergoing cholecystectomy (34,234) in 465 California hospitals in 1983 are used to demonstrate the biases arising from various methods of calculating the probability of observing a given number of deaths in each hospital. Similar data from other procedures and diagnoses with lower and higher mortality rates are also used for illustration. STUDY DESIGN: The computational methods to derive probabilities using the Poisson, normal, simulation, and exact probabilities are discussed. Using a previously developed risk factor model, the probability of observing the actual number of deaths (or more) is calculated given the expectation of death for each patient in each hospital. Results for the four methods are compared, showing the types of random and systematic errors in the Poisson, normal, and simulation approaches. DATA COLLECTION: Routinely collected hospital discharge abstract data were provided by the California Office of Statewide Planning and Development. PRINCIPAL FINDINGS: The Poisson and normal approximations are often biased substantially in calculating upper-tail p-values, especially when the expected number of adverse outcomes is less than five. Simulations allow unbiased calculations, and the degree of random error can be made arbitrarily small given enough trials. Exact calculations using a simple recursive algorithm can be done very efficiently on either a mainframe or personal computer. For example, the whole set of cholecystectomy patients can be assessed in less than 90 seconds on a Macintosh. CONCLUSIONS: Calculating the probability of observing a small number of events using standard approaches may result in substantial errors. The availability of a simple and inexpensive method of calculating these probabilities exactly can avoid these errors.

Bias↗

Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas.

BACKGROUND: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. METHODS: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. RESULTS: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. CONCLUSIONS: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

Adult↗

Evidence for a programmed life span in a colonial protochordate.

The variety of theories that have attempted to define the mechanisms of aging and life span can be broadly divided into two alternative but nonexclusive viewpoints. The first stipulates that random changes of cellular and molecular structures lead to death following progressive "wear and tear." The second argues that life span is, at least in part, genetically programmed, and therefore aging may also result from time-dependent intrinsic processes. Here we demonstrate that ramets (clonal replicates) experimentally separated from colonies of the acidian protochordate Botryllus schlosseri died months after their separation, almost simultaneously with their parent colony and sibling ramets. In addition, in experimentally joined chimeras between ramets of senescent and nonsenescent colonies, elements from different parent colonies displayed parent-colony-specific timing of mortality. Thus, the senescent phenotype was simultaneously expressed both in chimeras and in unfused ramets of the parent colony that was undergoing senescence, whereas control ramets from the other partner survived. These findings provide experimental evidence for a heritable basis underlying mortality in protochordates, unlinked to reproductive effort and other life history traits of this species.

Aging↗