John T. Chang

Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials

Abstract Objective To assess the relative effectiveness of interventions to prevent falls in older adults to either a usual care group or control group. Table 2 Components of multifactorial falls risk assessment Trial Orthostatic blood pressure Vision Balance and gait Drug review Instrumental activities of daily living or activities of daily living Cognitive evaluation Environmental hazards Other Carpenter 1990w4 No No No No Yes No No Fabacher 1994w13 Yes Yes Yes Yes Yes Yes Yes Assessment of hearing and depression Rubenstein 1990w30 Yes Yes Yes Yes Yes Yes Yes Neurological and musculoskeletal examination, laboratory tests, 24 hour heart monitor Tinetti 1994w37 Yes No Yes Yes No No Yes Muscle strength and range of motion Wagner 1994w39 No Yes No Yes No No Yes Hearing, assessment of alcohol misuse, assessment of physical activity Gallagher 1996w15 Yes Yes Yes Yes Yes Yes Yes List of health problems Coleman 1999w7 No No No Yes No No No Self management skills, health assessment Close 1999w6 Yes Yes Yes Yes Yes Yes Yes Affect, carotid sinus studies (if clinical suspicion) McMurdo 2000w21 Yes Yes No Yes No No No Review of lighting in environment Van Haastregt 2000w38 No No No Yes Yes Yes Yes Physical health, psychosocial functioning Millar 1999w24 Yes Yes No Yes No No No Review of lighting in environment Crome 2000w8* Jensen 2002w17 No Yes Yes Yes Yes Yes Yes Hearing, review of lighting in environment, assistive device (for example, cane, walker), review of use of device, and repair of device if needed See table A on bmj.com for details of references. * No specific components stated. Design Systematic review and meta-analyses. Data sources Medline, HealthSTAR, Embase, the Cochrane Library, other health related databases, and the reference lists from review articles and systematic reviews. Data extraction Components of falls intervention: multifactorial falls risk assessment with management programme, exercise, environmental modifications, or education. Results 40 trials were identified. A random effects analysis combining trials with risk ratio data showed a reduction in the risk of falling (risk ratio 0.88, 95% confidence interval 0.82 to 0.95), whereas combining trials with incidence rate data showed a reduction in the monthly rate of falling (incidence rate ratio 0.80, 0.72 to 0.88). The effect of individual components was assessed by meta-regression. A multifactorial falls risk assessment and management programme was the most effective component on risk of falling (0.82, 0.72 to 0.94, number needed to treat 11) and monthly fall rate (0.63, 0.49 to 0.83; 11.8 fewer falls in treatment group per 100 patients per month). Exercise interventions also had a beneficial effect on the risk of falling (0.86, 0.75 to 0.99, number needed to treat 16) and monthly fall rate (0.86, 0.73 to 1.01;2.7). Conclusions Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling.

Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

The Quality of Medical Care Provided to Vulnerable Community-Dwelling Older Patients

Context Many Americans 65 years of age and older are at risk for functional decline, yet we know little about the quality of care for geriatric conditions. Contribution This study used a 13-item survey about functional status to evaluate the care of 420 people 65 years of age and older whom the investigators identified as vulnerable to functional decline. Quality of care was highly variable from condition to condition but was generally better for general medical conditions, such as diabetes, than for geriatric conditions, such as incontinence. Implications Efforts to improve care for vulnerable elders should focus on the geriatric conditions that profoundly influence functional status. The Editors The quality of care among patients 65 years of age and older has not been extensively investigated, and most existing studies have focused on general adult medical conditions. This is surprising, considering that more than 40% of all medical expenditures are for persons 65 years of age and older (1). The most comprehensive study to date of quality of care among older patients evaluated 24 process indicators among U.S. Medicare beneficiaries in all 50 states between 1997 and 1999 (2). Care for acute myocardial infarction, heart failure, stroke, and pneumonia was evaluated by using inpatient medical records. Pneumonia, breast cancer, and diabetes indicators were evaluated by using survey and Medicare claims data. The investigators found that the percentage of patients receiving appropriate care varied widely by measure and state. Several other studies of older patients evaluated cardiovascular conditions, diabetes, or aspects of preventive care and medication use (3-10). No study, however, has assessed the quality of medical care provided for geriatric conditions that profoundly affect the lives of vulnerable older patients. Furthermore, surveys find that older persons often prioritize function and comfort over disease treatment and prolongation of life (11). Quality-of-care measurement for older patients that examines only a few conditions and only indicators aimed at prolonging life yields an incomplete assessment because it ignores other conditions and aspects of care that are of equal or even greater importance to older patients. For this reason, we developed a quality assessment system that assesses more conditions. Together, these conditions account for a majority of all of the care older patients receive (12) and include several geriatric syndromes. We used this quality assessment system to evaluate the care provided to a sample of vulnerable elders at increased risk for death or functional decline. Methods The Assessing Care of Vulnerable Elders (ACOVE) project developed and applied a quality assessment system for vulnerable older persons. The assessment system aimed to develop quality indicators (QIs) that cover the spectrum of care for these patients. Indicators were implemented by using medical record abstraction and patient interview. The ACOVE Quality-of-Care Assessment System The ACOVE investigators developed a system of QIs to cover the most important conditions vulnerable elders encounter in all care venues. This system focused on processes (care behaviors) rather than outcomes for 2 reasons. First, although most agree that outcomes should be adjusted for risk when quality is measured, there is little consensus regarding the best severity measurement system (13). Second, measurement of processes of care is thought to be a more direct assessment of quality than measurement of outcomes (14). The process measures were selected to represent the various domains of care: screening and prevention, diagnosis, treatment, and follow-up. The development of the assessment system was guided by a Policy Advisory Committee, which helped to direct the focus toward practical applications, and by a Clinical Committee, which provided clinical expertise for development and monitored the assembly of the QIs into a comprehensive system (15). The methods for selecting conditions and developing the QIs have been described in detail elsewhere (12, 16). In brief, the Clinical Committee used the criteria of prevalence, impact, effectiveness of prevention or treatment, need for quality improvement, feasibility of measurement, and geriatric niche in a formal group rating process to identify 22 target conditions for quality improvement (12). For each of the 22 conditions, we developed a set of evidence-based QIs for vulnerable elders using a combination of systematic reviews and expert judgment (16). Of 420 proposed QIs, the 2 expert panels, the Clinical Committee, and the American College of Physicians Task Force on Aging accepted 236 as valid indicators; these were assembled into the ACOVE QI set (17). The 236 QIs covered the domains of care as follows: Sixty-one (26%) focused on screening and prevention, 50 (21%) focused on diagnosis, 84 (36%) focused on treatment, and 41 (17%) focused on follow-up and continuity of care. Examples of ACOVE QIs for each condition are presented in Table 1. Table 1. Examples of Assessing Care of Vulnerable Elders Quality Indicators Patients and Data Collection Using the ACOVE QI set, we assessed care provided to seniors who were enrolled in 2 managed care organizations. These patients were defined as vulnerable on the basis of self-report or proxy report on a brief, 13-item screening survey (Vulnerable Elders-13 [VE-13] Survey [18]). Vulnerable elders, identified by this function-based survey, are community-dwelling persons 65 years of age and older who have 4 times the risk for functional decline or death over the next 2 years compared with individuals not identified as vulnerable (18). Each managed care organization, 1 in the northeastern United States and the other in the southwestern United States, had more than 20 000 elderly enrollees and contracted with a network of providers to deliver care. Eligibility criteria included continuous enrollment in the managed care organization for at least 13 months and no out-of-plan care or active treatment for malignant conditions (excluding nonmelanoma skin cancer) during this period. A random sample of 3207 community-dwelling elderly adults was drawn from eligible persons in each managed care organization by using a random-number generator. Vulnerable elders were identified by using the VE-13 Survey as part of a telephone interview. Patients who did not speak English were not eligible to participate. The RAND Institutional Review Board approved the study protocol. Medical Record Review Using administrative data, we identified all inpatient and outpatient medical care received by study participants during the 13-month period of 1 July 1998 to 31 July 1999. Medical records were requested from primary care and specialist providers (including eye care and mental health providers), acute care hospitals, skilled-nursing facilities, home health agencies, and facilities providing outpatient services (for example, physical therapy). Identifying information of patients and providers was removed from the medical records. Trained nurses with previous experience in quality assessment performed medical record abstraction. Abstractors were provided with written abstraction guidelines and real-time consultation with a senior nurse reviewer. The abstractor considered all of a patients records when assessing whether he or she was eligible for and received the indicated care processes. In other words, information on eligibility for a QI could have been derived from 1 record (such as an outpatient note) while the care process was delivered and documented in another setting (for example, inpatient medical record). If the care process was performed in the defined time interval, care was scored as complying with the QI. The senior nurse reviewer also assessed each completed medical record abstraction. Physicians reviewed QIs that required a more detailed level of clinical assessment. Examples include whether the elements of a delirium evaluation had been completed or whether an adequate intervention was performed for hyperlipidemia. An ophthalmologist evaluated selected data elements addressing vision care. Ten percent of all records were reabstracted to evaluate reliability of the abstraction process. Exact agreement on QI eligibility and score was 95%. (For details of abstractor preparation and abstraction materials, see the Appendix.) Quality-of-Care Interview A quality-of-care interview was conducted to ask study participants (or, if participants were incapable of responding, their proxies) about aspects of their care that might not be captured in the medical record (for example, physicianpatient counseling). On the basis of conditions and medications reported during the interview, patients were asked about specific processes of care they had received. Patients were also asked about care preferences that might affect the applicability of QIs. In addition, the interview included demographic questions and functional status items. The quality-of-care interview was conducted by telephone between August and October 2000 and required, on average, 44 minutes to complete. Statistical Analysis Of the 236 QIs, we were able to evaluate 207 using chart abstraction (n = 185 [89%]) or interview (n = 22 [11%]). Interview was used to score QIs for data elements that we did not collect from the medical record. A QI was scored for a patient if he or she satisfied the IF statement of the QI and thus was eligible to receive the specified care process (Table 1). A score of 1 was awarded if the care process was carried out, and a score of 0 was assigned if it was not. For QIs that included several triggering events, a score between 0 and 1 was possible. If the medical record indicated that the patient declined the care process, the QI was considered to be passed (the care was credited in both the numerator and the denominator of the indicator score). On the other hand, if the patient had a pre

The Quality of Pharmacologic Care for Vulnerable Older Patients

Context Prescription and management of medications are important issues for older adults. Contribution Among elders enrolled in two managed care organizations, most quality problems were related to failure to prescribe indicated medications; failure to monitor medications; and failure to provide medication along with proper documentation and education in concert with other physicians. Implications Prescribing inappropriate medications for older adults is less of an issue than other aspects of drug therapy. Quality improvement efforts should focus on avoiding errors of omission in prescribing indicated medications, monitoring, patient education, and follow-up. The Editors Pharmacotherapy is an essential component of medical treatment for older patients, but medications are also responsible for many adverse events in this group. Ninety percent of people 65 years of age or older take at least one medication (1). This age group, which represents only 13% of the population, accounts for one third of all prescription drug expenditures in the United States (2). Many older persons take multiple drugs for the treatment of several conditions, which increases the chance of adverse drug reactions, drugdrug interactions, and drugdisease interactions. The frequency of adverse drug events in elderly outpatients ranges from 10% to 35%, depending on the setting (3-5). Recognizing the magnitude of medication-related issues, panels of geriatric experts rate medication problems among the most important quality-of-care problems for older patients (6-8). Reflecting the severity and frequency of adverse drug events in older patients, many investigations have focused on the appropriateness of medication prescribing to elderly persons. Implicit review mechanisms include the Medication Appropriateness Index, which consists of 10 medication characteristics (including indication, effectiveness, and dosage) that a trained pharmacist reviewer can judge as appropriate, marginally appropriate, or inappropriate. An application of the Medication Appropriateness Index to elderly veterans taking 5 or more prescription medications found that 74% had at least 1 inappropriate aspect to their prescriptions (9, 10). Reviews using explicit criteria usually focus on medications that should be avoided in the care of older patients. The list of medications to avoid, which was developed by Beers and colleagues on the basis of a formal consensus of geriatric experts (11-13), has been applied to various groups of patients, revealing a high prevalence of inappropriate drug use (14-20). In addition, explicit criteria about drugdrug interactions, treatment duration, and drug contraindications were created by Tamblyn and colleagues and applied to medications prescribed to older patients in Canada (21). They found that more than half of older patients took at least one high-risk medication. Health policy efforts, on the other hand, have focused predominantly on finding ways to pay for the medication needed by older patients. Proposals aim to improve access to pharmacologic care but do not strive to develop mechanisms to evaluate or improve the quality of medication management for older patients. Improvement in access to medications without quality assurance may result in a mere increase in care without change in outcomes. To provide a more comprehensive evaluation of the quality of pharmacologic care for older patients, we systematically evaluated medication management for a sample of older patients by taking advantage of a set of explicit process of care quality indicators developed and implemented in the Assessing Care of Vulnerable Elders (ACOVE) project (22). Whereas the earlier ACOVE analysis described overall quality of care and compared care quality for geriatric and medical conditions, this study focuses on pharmacologic care and identifies improvement needs in medication management. Our quality evaluation covered the continuum of pharmacologic care, from recognizing the indications for medications to choosing medication, prescribing appropriately, educating and documenting, and monitoring after prescribing. Methods The ACOVE project developed a set of explicit quality indicators to evaluate the care provided to vulnerable older persons (22-24). The system focuses on processes of care within the domains of prevention, diagnosis, treatment, and follow-up and covers the spectrum of care contained in 22 conditions that are important in the care of older patients (7). The methods for selecting conditions and developing the quality indicators are described in detail elsewhere (7, 23). Methods included systematic literature reviews and multiple layers of expert judgment (23). The literature review resulted in proposal of candidate quality indicators, which were reviewed by an expert panel that rated each of the proposed quality indicators for validity and feasibility. This set was modified and approved by a clinical committee of national geriatric experts and by the American College of Physicians Task Force on Aging (24). From the final ACOVE set of quality indicators, 43 quality indicators (Table 1 and Appendix Table) that pertained to pharmacologic care and had more than 5 eligible patients are included in this analysis. Table 1. Medication Quality Indicators, Number of Eligible Patients, and Pass Rates Patients and Data Collection We assessed care provided to older persons who were enrolled in 2 managed care organizations. Each managed care organization, one in the U.S. Northeast and the other in the Southwest, had more than 20 000 senior enrollees and contracted with a network of providers to deliver care. A random sample of community-dwelling persons 65 years of age or older was drawn from enrollees in each managed care organization. Eligibility criteria included continuous enrollment in the managed care organization for at least 13 months, no out-of-plan care, and no active treatment for malignant conditions (excluding nonmelanoma skin cancer) during the period. In addition, persons who did not speak English were excluded because our interview instruments were not available in other languages. Among the enrollees, we targeted vulnerable elders, defined as persons 65 years of age and older who are at increased risk for death or functional decline. Vulnerable elders were identified on the basis of self-report (or proxy report) by using a brief screening survey (the Vulnerable Elders-13 [VE-13] Survey [25]) administered by telephone. The RAND Institutional Review Board approved the study protocol. Data were derived mainly from abstracting medical records. For participating patients, we identified all inpatient and outpatient medical records during the 13-month period of 1 July 1998 to 31 July 1999. These medical records were abstracted by trained nurses with experience in quality assessment. The abstractor considered all of a patients medical records when assessing whether a patient was eligible for and received the indicated care processes. Information on eligibility for a quality indicator could be derived from one medical record (such as a primary care physician starting an appropriate antidepressant) and the care process delivered and documented from records in another setting (such as a psychiatric consultant escalating the antidepressant dosage in response to lack of improvement). A senior nurse-reviewer assessed each completed medical record abstract, and physician overreaders reviewed quality indicators that required a clinical assessment, such as whether there was follow-up to newly started long-term therapy with a medication or whether newly started therapy with a highly anticholinergic drug had acceptable alternatives. We evaluated inter-rater reliability by re-abstracting a random sample of 10% of the medical records. These records contained 698 quality indicators; 97% had identical eligibility and 95% demonstrated identical eligibility and score. Details of study enrollment and data collection can be found elsewhere (22). Because some aspects of care might not be adequately captured in the medical record (for example, patient education about medications), these data were supplemented by a quality-of-care interview with study participants (or, if necessary, their proxies). During the interview, patients were asked to list all of their medications. On the basis of conditions and medications reported during the interview, patients were asked about specific processes of care they had received. The interview was conducted by telephone between August and October 2000. To minimize recall bias, we asked about most recent care when implementing quality indicators that may include multiple events (for example, education about newly started therapy with a medication). Information was obtained from medical records for 37 quality indicators and from the patient interview for 6 quality indicators. For 4 quality indicators reported previously by using medical record data (22), we used interview data in this analysis because subsequent evaluation revealed that interview data on information transfer quality indicators yielded higher pass rates that were aligned with a priori hypotheses and provided more conservative estimates of quality of care. Statistical Analysis A quality indicator was scored for a patient if he or she met the eligibility criteria to receive the specified care process. The quality indicator was passed if the care process was implemented for the patient. If the medical record indicated that the patient declined the care process, the quality indicator was considered to be passed. On the other hand, if the patient had a prespecified contraindication to the care process (such as a patient with asthma who otherwise was eligible to receive a -blocker after a myocardial infarction), the patient was considered ineligible for the quality indicator. Quality scores were calculated as the proportion of eligible patients who received indicated care. I

A gp130-Src-YAP module links inflammation to epithelial regeneration

Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members, the expression of which is elevated in many diseases including inflammatory bowel diseases and colorectal cancer. Here we show in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signalling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signalling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.

CpG Oligonucleotides Are Potent Adjuvants for the Activation of Autoreactive Encephalitogenic T Cells In Vivo

The mechanism of action of microbial adjuvants in promoting the differentiation of autoimmune effector cells remains to be elucidated. We demonstrate that CpG-containing oligodeoxynucleotides (ODN) can completely substitute for heat-killed mycobacteria in the priming of encephalitogenic myelin-reactive T cells in vivo. The adjuvanticity of the CpG ODN was secondary to their direct ability to induce IL-12 or to act synergistically with endogenous IL-12 to promote Th1 differentiation and encephalitogenicity. T cells primed in the absence of CpG with Ag and IFA alone appeared to be in a transitional state and had not undergone differentiation along a conventional Th pathway. Unlike Th2 cells, they expressed low levels of the IL-12Rβ2 subunit and retained the ability to differentiate into encephalitogenic effectors when reactivated in vitro under Th1-polarizing conditions. These results support the use of CpG ODN as adjuvants but also suggest that they could potentially trigger autoimmune disease in a susceptible individual.

The costimulatory effect of IL-18 on the induction of antigen-specific IFN-γ production by resting T cells is IL-12 dependent and is mediated by up-regulation of the IL-12 receptor β2 subunit

IL‐18 was originally described as a cytokine which induced IFN‐γ production by established Th1 cells in an IL‐12‐independent manner. However, subsequent studies demonstrated that exogenous IL‐18 in the absence of IL‐12 failed to drive Th1 differentiation of naive cells and induced IFN‐γ from established Th1 cells only in combination with IL‐12. We have examined the role of endogenous IL‐18 in controlling Th1 lineage commitment. When naive TCR‐transgenic T cells were stimulated with antigen, anti‐IL‐18 antibodies resulted in partial inhibition of IFN‐γ production, but did not inhibit Th1 differentiation. To distinguish whether the inhibitory effect of anti‐IL‐18 antibodies was mediated directly by blocking IFN‐γ production or indirectly by blocking IL‐12Rβ2 up‐regulation, naive T cells from IL‐12 − / − mice were stimulated with anti‐CD3 and IL‐18. These cells failed to produce IFN‐γ, but markedly up‐regulated IL‐12Rβ2 expression. We propose that the major effect of IL‐18 on Th1 development is mediated by up‐regulation of IL‐12Rβ2 expression, thereby enhancing IL‐12‐mediated signaling. The enhancement of IL‐12Rβ2 expression by IL‐18 may be particularly important for the differentiation of foreign antigen‐ or autoantigen‐specific Th1 cells when the stimulatory concentration of IL‐12 in the microenvironment is just below the threshold required for Th1 development.

Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells

Protective immunity against Leishmania major generated by DNA encoding the LACK (Leishmania homologue of receptor for activated C kinase) Ag has been shown to be more durable than vaccination with LACK protein plus IL-12. One mechanism to account for this may be the selective ability of DNA vaccination to induce CD8+ IFN-γ-producing T cells. In this regard, we previously reported that depletion of CD8+ T cells in LACK DNA-vaccinated mice abrogated protection when infectious challenge was done 2 wk postvaccination. In this study, we extend these findings to study the mechanism by which CD8+ T cells induced by LACK DNA vaccination mediate both short- and long-term protective immunity against L. major. Mice vaccinated with LACK DNA and depleted of CD8+ T cells at the time of vaccination or infection were unable to control infection when challenge was done 2 or 12 wk postvaccination. Remarkably, it was noted that depletion of CD8+ T cells in LACK DNA-vaccinated mice was associated with a striking decrease in the frequency of LACK-specific CD4+ IFN-γ-producing T cells both before and after infection. Moreover, data are presented to suggest a mechanism by which CD8+ T cells exert this regulatory role. Taken together, these data provide additional insight into how Th1 cells are generated and sustained in vivo and suggest a potentially novel immunoregulatory role for CD8+ T cells following DNA vaccination.

Multimorbidity is associated with better quality of care among vulnerable elders

Background: Older patients with multiple chronic conditions may be at higher risk of receiving poorer overall quality of care compared with those with single or no chronic conditions. Possible reasons include competing guidelines for individual conditions, burden of numerous recommendations, and difficulty implementing treatments for multiple conditions. Objectives: We sought to determine whether coexisting combinations of 8 common chronic conditions (hypertension, coronary artery disease, chronic obstructive pulmonary disease, osteoarthritis, diabetes mellitus, depression, osteoporosis, and having atrial fibrillation or congestive heart failure) are associated with overall quality of care among vulnerable older patients. Materials and Methods: Using an observational cohort study, we enrolled 372 community-dwelling persons 65 years of age or older who were at increased risk for death or functional decline within 2 years. We included (1) a comprehensive measure (% of quality indicators satisfied) of quality of medical and geriatric care that accounted for patient preference and appropriateness in light of limited life expectancy and advanced dementia, and (2) a measure of multimorbidity, either as a simple count of conditions or as a combination of specific conditions. Results: Multimorbidity was associated with greaer overall quality scores: mean proportion of quality indicators satisfied increased from 47% for elders with none of the prespecified conditions to 59% for those with 5 or 6 conditions (P < 0.0001), after controlling for number of office visits. Patients with greater multimorbidity also received care that was better than would be expected based on the specific set of quality indicators they triggered. Conclusions: Among older persons at increased risk of death or functional decline, multimorbidity results in better, rather than worse, quality of care.

Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division

Polarized segregation of proteins in T cells is thought to play a role in diverse cellular functions including signal transduction, migration, and directed secretion of cytokines. Persistence of this polarization can result in asymmetric segregation of fate-determining proteins during cell division, which may enable a T cell to generate diverse progeny. Here, we provide evidence that a lineage-determining transcription factor, T-bet, underwent asymmetric organization in activated T cells preparing to divide and that it was unequally partitioned into the two daughter cells. This unequal acquisition of T-bet appeared to result from its asymmetric destruction during mitosis by virtue of concomitant asymmetric segregation of the proteasome. These results suggest a mechanism by which a cell may unequally localize cellular activities during division, thereby imparting disparity in the abundance of cell fate regulators in the daughter cells.