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Before age 35, Holman hit over 0.500 at the University of California Los Angeles (UCLA); was recruited by professional baseball; led the Association of Interns and Medical Students and the International Union of Students in Denmark; had his passport confiscated; was stripped of a prestigious internship; shadowed by the Federal Bureau of Investigation ; grilled before a Senate committee on subversive activities; made a major medical discovery; and was recruited to be the new Chief of Medicine at Stanford. Holman was involved in building a leading academic institution. He expanded what medical students and graduates learned and what they researched. Holman saw the collision course between the technological capacity to do more and the growing expectations of the public. Moreover, he anticipated the monetization of health care and how it would widen the gap between what we know and what we practice in health care. He reinvented himself in population health. In contrast to reductionist laboratory-based research, his work embraced complexity and made action researchable and research action-oriented. Some innovations did not survive as originally conceived, but their ethos became mainstream. These included evidence-based management, shared physician-patient decision-making, self-management, critical evaluation of medical technology and diagnostics, and chronic disease management. Through the rise of the twentieth century American biomedical medicine, medical education, and slow-motion health care delivery crises that still occur, Holman changed the debate in a time when the funding, the people, the technology, and the need made all things seem possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Microalgae are considered to be a very promising class of raw material for carotenoid production. In this study, melatonin (MLT), a widely used plant growth regulator, was added to the autotrophic medium of Dunaliella bardawil to explore its effects on the growth and pigment accumulation of Dunaliella bardawil. The results showed that the induction of exogenous MLT alone was not beneficial to the growth and pigment accumulation of Dunaliella bardawil, and the higher the concentration, the more obvious the inhibitory effect on the algal cells. Therefore, a strategy to promote carotenoid accumulation in Dunaliella bardawil by combining exogenous MLT and light induction was carried out. Under 4500 LUX light intensity, the content of zeaxanthin was significantly increased under exogenous MLT induction. In the 200 μg/mL, 300 μg/mL, and 400 μg/mL MLT-treated groups, the zeaxanthin single-cell content in the 300 μg/mL-treated group was as high as 0.38 ng/mL (0.17 ng/mL in the control group), which was 1.24-fold higher compared to the control. Under 9500 LUX light intensity, all carotenoids showed an increasing trend in all experimental groups, except for zeaxanthin, which showed a decreasing trend. The effect of 300 μg/mL showed the most obvious in the 200 μg/mL,300 μg/mL, and 400 μg/mL MLT treatment groups, where the lutein, α-carotene and β-carotene contents were 1.24, 1.14 and 1.31 times higher than those of the control group, respectively. Overall, exogenous MLT at high light intensities had a significant effect on pigment accumulation in Dunaliella bardawil., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dunaliella bardawil, a unicellular green alga, can accumulate a large amount of lutein and β-carotene under stresses. Using chemical inducers combined with abiotic stress to promote the accumulation of high value-added products such as lipids and carotenoids in microalgae has attracted more and more attention. In this study, creatinine was added into autotrophic medium to investigate its effects on the growth, chlorophyll content, and the ingredients and content of carotenoids in D. bardawil. The results showed that creatinine alone could significantly increase the biomass, chlorophyll and carotenoid contents of D. bardawil, among which the contents of lutein and β-carotene were further increased, while the content of zeaxanthin was decreased. In order to further improve the content of the two carotenoids, different light intensities combined with creatinine have been adopted. Under 6.589 W/m 2 light intensity, creatinine could effectively increase the production of lutein, zeaxanthin, α-carotene and β-carotene. Compared with the control, the content of lutein increased by 46 % and the content of β-carotene increased by 77 % when the concentration of creatinine was 500 μg/mL. In conclusion, creatinine can effectively improve the production lutein and β-carotene in D. bardawil, which is more conducive under lower light intensity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The halophilic green alga Dunaliella bardawil has been used for commercial production of natural β-carotene by large-scale outdoor cultivation, which often suffers from heat stress especially at noon in hot summers. In this study, the effects of heat stress on cell growth, pigment contents, and activities of antioxidant system in D. bardawil were studied, and RNA-seq experiment was conducted to analyze the transcriptional response to heat stress (42 °C for 2 h) in D. bardawil. High temperature (42 °C) for short time treatment (≤3 h) did not severely affect the cell growth and pigment accumulation of D. bardawil. Multiple genes encoding heat shock proteins for protein folding and antioxidant enzymes against toxic reactive oxygen species were substantially up-regulated significantly under heat stress. D. bardawil cells tended to shift from aerobic to glycolytic metabolism for energy production to increase survival chances under heat stress. Furthermore, the enrichment of ascorbate-glutathione cycle, up-regulation of genes responsible for chloroplast membranes, and changes in lipid characteristics like carbon chain length and unsaturation degree could play a vital role in achieving thermotolerance of D. bardawil. Taken together, this study improved our understanding of the molecular mechanisms of heat stress responses in D. bardawil., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The halophilic green alga Dunaliella bardawil FACHB-847 is rich in lutein and α-carotene, which has great potential for carotenoid production in open ponds. In this study, genes encoding lycopene β- and ε-cyclases (DbLcyB and DbLcyE) from D. bardawil FACHB-847 were functionally identified by genetic complementation in E. coli. The bifunctional DbLcyB not only catalyzed the formation of both mono- and bi-cyclic β-rings with a major β-cyclase activity, but also possessed a weak ε-cyclase activity. In contrast, DbLcyE preferred to convert lycopene into monocyclic δ-carotene, and possessed a weak β-monocyclase activity. Lutein and α-carotene were the prominent carotenoids in D. bardawil FACHB-847, which was in agreement with the result of genetic complementation of co-expression of DbLcyB and DbLcyE in E. coli with α-carotene as the prominent product. The bifunctional DbLcyB and DbLcyE may contribute to the high accumulation of α-carotene in D. bardawil FACHB-847. Interestingly, the accumulation of lutein in D. bardawil FACHB-847 was more sensitive to salt stress, while the accumulation of β-carotene in D. salina CCAP 19/18 was induced by salt stress. In brief, the production of different carotenoid compositions from these two Dunaliella species can be induced by different growth conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glycerol-3-phosphate (G3P) is the important precursors for triacylglycerol synthesis, while glycerol-3-phosphate dehydrogenase (GPDH) determines the formation of G3P. In this study, two GDPH genes, Dtgdp1 and Dtgdp2 were isolated and identified from Dunaliella tertiolecta. The full-length Dtgdp1 and Dtgdp2 CDS were 2016 bp and 2094 bp, which encoded two putative protein sequences of 671 and 697 amino acids with predicted molecular weights of 73.64 kDa and 76.73 kDa, respectively. DtGDP1 and DtGDP2 both had a close relationship with those of algal and higher plants. DtGDP1 shared two conserved superfamily (A1 and A2) and four signature motifs (I-IV), and the DtGDP2 showed six signature domains (from motif I to VI) and DAO_C conserved family. Our previous work showed that the triethylamine intervention could greatly increase the triacylglycerol content (up to 80%) of D. tertiolecta. This study aims to investigate the effect of triethylamine on GPDH expression. Results showed that, when treated by triethylamine at 100 ppm and 150 ppm, the expression levels of Dtgdp1 and Dtgpd2 were increased to 5.121- and 56.964-fold compared with the control, respectively. Triethylamine seemed to enhance lipid metabolic flow by inducing the expressions of Dtgdp1 and Dtgdp2 to increase the lipid content, which provides a new insight into the desired pathway of lipid synthesis in algae through genetic engineering., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A two-step strategy was employed to culture Dunaliella tertiolecta, an oleaginous unicellular green alga, combined by the salt stress and sodium azide intervention, to observe their effects on its lipid accumulation. When the algae cultured at different salt concentrations reached the logarithmic growth phase, sodium azide was added. The results showed that the addition of sodium azide significantly increased the lipid content and had no significant effect on cell biomass. The lipid yield and single cell lipid content under 50 μM sodium azide increased by 10.4% and 21.7%. Under the two-step culture condition, combining of the treatment of 50 μM sodium azide and 2.5 M salt stress, the total lipid productivity and single-cell lipid content were 10% and 70.5% higher than that of the control. It seemed that sodium azide and salinity might have a synergistic effect on the lipid accumulation of D. tertiolecta. It can be concluded that sodium azide is an effective inducer of lipid accumulation in D. tertiolecta, and two-stage cultivation is a feasible way to improve lipid accumulation in microalgae., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of the study was to describe the research environment of scientists in health services and policy research in China., Study Design: Study was conducted during the 2016 Westlake Youth Forum with grantees of China Medical Board and key informants. Mixed methods used anonymous, survey of grantees, semistructured open-ended interviews with randomly selected awardees, convenience samples of extramural reviewers, and senior scientists with research experience in China., Results: Among 51 awardees, 34 responded fully. Fifty percent were women, averaged 42 years; 88% had PhD/MD and 10 years from their advanced degree. Most had overseas research training (94%); 32% held overseas degrees. Their mean salary, $24,000, barely qualifying as middle class in China. Their confidence using analytical techniques were variable. Their interaction with those using their work seemed nascent. Interviewees echo young researchers elsewhere: lack of mentors, statistical consultation, collaborators, and help to run the gauntlet of requirements in doing research., Conclusion: China's health has improved dramatically since 1949. As the ecology of disease change, expectations increase, and services grow, the expertise to evaluate and improve health care needs to expand. This requires recognition of their importance and a concerted effort to recruit, nurture, and sustain this cadre., (Copyright © 2019 Elsevier Inc. All rights reserved.)

HBscFv-IFNγ, a fusion protein constructed by fusing γ-interferon (IFNγ) with an antibody fragment HBscFv for the purpose of targeted delivery of the cytokine IFNγ, was designed in order to enhance its therapeutic efficacy through increasing its hepatoma localization. HBscFv and IFNγ were connected into HBscFv-IFNγ by the linker (Gly 4 Ser) 3 , and then the multicopy recombinant plasmids pPICZαA/(HBscFv-IFNγ) 1,2,4 were constructed and transformed into Komagatella (Pichia) pastoris X33. The engineering strain X4, which had much higher copy number and could secretively express HBscFv-IFNγ, was screened from transformed X33 by qPCR. Results from SDS-PAGE, Western blotting and ELISA indicated that HBscFv-IFNγ displayed an excellent immunoreaction against HBsAg. The culture supernatant of X4 was purified by 14F7 affinity chromatography to obtain the fusion protein HBscFv-IFNγ in a purity of 95-98%. The HBscFv-IFNγ was able to bind 27.9% HBsAg in the serum of HBV transgenic mice, showing that the antibody of HBscFv-IFNγ has high binding affinity against HBsAg. The expressing of the recombinant HBscFv-IFNγ in P. pastoris provides a promising and inexpensive diagnostic reagent for preventing HBV infection., (Copyright © 2017. Published by Elsevier Inc.)

The collagen/chitosan/hydroxyapatite (COL/CS/HA) composite microspheres with a good spherical form and a high dispersity were successfully obtained using an in-situ synthesis method. The FT-IR and XRD results revealed that the inorganic phase in the microspheres was crystalline HA containing carbonate ions. The morphology of the composite microspheres was dependent on the HA content, and a more desirable morphology was achieved when 20 wt.% HA was contained. The composite microspheres exhibited a narrow particle distribution, most of which ranged from 5 to 10 μm. In addition, the needle-like HA nano-particles were uniformly distributed in the composite microspheres, and their crystallinity and crystal size decreased with the HA content., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Trimeresurus mucrosquamatus (TM) is one of majorities of snake envenomation with necrotic and hemorrhagic toxin in Taiwan. In this study, chickens were used as an alternative animal model for immunization with TM venom. Using phage display technology to process four rounds of panning, selected single chain variable fragments (scFv) could specifically recognize TM venom proteins, which were later identified as a group of homogeneous venom serine protease. The specific scFv antibodies showed various inhibitory effects on sheep RBC lysis induced by TM venom using an indirect hemolytic assay in vitro. In addition, the survival times of mice were extended to certain degrees when treated with these scFv antibodies individually or in a combination. To elucidate the inhibitory mechanism, we used molecular modeling to build up the serine protease structure to simulate the possible interactions with scFv antibodies. The results suggested that the CDR-loop of the scFv antibodies (3S10 or 4S1) might bind at the 99-loop of venom serine protease so as to affect substrate access due to the partial collapse of the subsite S2 and the partial movement of the subsite S4. It is hoped these chicken-derived antibodies could be applied to develop diagnostic and therapeutic agents against snakebites., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Clinical trials in many diseases are experiencing more difficulties in achieving sufficient or timely enrollment of participants; anecdotal reports from trials of novel therapies for systemic lupus erythematosus (SLE) seem to be facing the same challenges. General factors associated with this trend include the growth of the contract research industry, increasing oversight, and high-profile accounts of scientific misconduct and fraud in research. Complicated protocols that increase participant burden, overly restrictive entry criteria, the fear of an SLE flare may also affect enrollment in SLE trials., (Published by Elsevier Inc.)

Objective: Test the efficacy of educational interventions to reduce literacy barriers and enhance health outcomes among patients with inflammatory arthritis., Methods: The intervention consisted of plain language information materials and/or two individualized sessions with an arthritis educator. Randomization was stratified by education level. Principal outcomes included adherence to treatments, self-efficacy, satisfaction with care, and appointment keeping. Secondary outcomes included health status and mental health. Data were collected at baseline, six, and twelve months post., Results: Of the 127 patients, half had education beyond high school and three quarters had disease duration greater than five years. There were no differences in the primary outcome measures between the groups. In mixed models controlling for baseline score and demographic factors, the intervention group showed improvement in mental health score at six and twelve months (3.0 and 3.7 points, respectively), while the control group showed diminished scores (-4.5 and -2.6 points, respectively) (p=0.03 and 0.01)., Conclusion: While the intervention appears to have had no effect on primary outcomes, further studies with continued attention to literacy are warranted. Study site and disease duration must be considered as participants in this study had higher than average health literacy and had established diagnoses for years prior to this study., Practice Implications: The study offers insight into an application of many of the protocols currently recommended to ameliorate effects of limited literacy.

Objective: To estimate the minimal clinically important difference (MCID) of seven measures of fatigue in rheumatoid arthritis., Study Design and Setting: A cross-sectional study design based on interindividual comparisons was used. Six to eight subjects participated in a single meeting and completed seven fatigue questionnaires (nine sessions were organized and 61 subjects participated). After completion of the questionnaires, the subjects had five one-on-one 10-minute conversations with different people in the group to discuss their fatigue. After each conversation, each patient compared their fatigue to their conversational partners on a global rating. Ratings were compared to the scores of the fatigue measures to estimate the MCID. Both nonparametric and linear regression analyses were used., Results: Nonparametric estimates for the MCID relative to "little more fatigue" tended to be smaller than those for "little less fatigue." The global MCIDs estimated by linear regression were: Fatigue Severity Scale, 20.2; Vitality scale of the MOS-SF36, 14.8; Multidimensional Assessment of Fatigue, 18.7; Multidimensional Fatigue Inventory, 16.6; Functional Assessment of Chronic Illness Therapy-Fatigue, 15.9; Chalder Fatigue Scale, 9.9; 10-point numerical Rating Scale, 19.7, for normalized scores (0-100). The standardized MCIDs for the seven measures were roughly similar (0.67-0.76)., Conclusion: These estimates of MCID will help to interpret changes observed in a fatigue score and will be critical in estimating sample size requirements.

This article discusses the clinimetrics of disease activity and organ damage, and response criteria using systemic lupus erythematosus as a paradigm. Similar considerations apply to the other systemic rheumatic illnesses. Clinically relevant and psychometrically tested measures of disease states aid the conduct of clinical studies and trials that are more rigorous, efficient, and relevant to patients' concerns. These same measures used in clinical trials will likely improve clinical outcomes if they are used in the monitoring and titration of therapy in patients who have these disorders. For this use to really occur, clinical trials will have to demonstrate treatments that alter these therapies in a meaningful way and the measures or modifications of them will need to meet the desiderata of techniques that can be used in practice.

In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority.

The authors studied the relative contributions of psychological characteristics and rheumatoid arthritis (RA) morbidity to RA symptoms and medication side effects. Thirty-one consecutive patients attending an RA clinic completed self-report questionnaires and diaries assessing RA symptoms and somatic style, a constellation of beliefs, attitudes, and concerns about disease and health. After 3 months, the patients were assessed for RA symptoms and self-reported medication side effects. At inception, RA symptoms were associated with several components of somatic style. At 3-month follow-up, changes in RA symptoms and the incidence of medication side effects were predicted by somatic style variables measured at inception. The symptoms of RA and the side effects of RA pharmacotherapy are prospectively predicted by somatic style as well as by the severity and extent of RA.

Patients' preferences for specific health outcomes in carpal tunnel syndrome (CTS) and their association with demographic factors and satisfaction with the results of surgery after 6 months were evaluated. Two hundred fifty subjects with CTS and enrolled in a prospective community-based cohort study in Maine completed a preference questionnaire before surgery. Patients were asked to specify the single most important reason they decided to undergo surgery and to rate the importance of improvement in 10 areas, including lessening of specific symptoms and improvement in specific functional states related to CTS. The single most important reason for CTS patients to have surgery was relief of night pain (37%), followed by relief of numbness (21%) and relief of daytime pain (13%). When patients were asked to rate the importance of obtaining relief from specific symptoms and improvement in specific functional states, relief of numbness received the highest rating, with 94% of the patients answering that it was extremely or very important. Workers' compensation recipients, patients with less than a college level of education, and patients with more severe symptoms and functional impairment at baseline assigned higher importance to symptom relief and functional improvement. Controlling for other predictors, higher preference for improved strength was associated with lower satisfaction with the results of the surgery at 6 months. Most CTS patients undergoing surgery have realistic preferences for health outcomes that are influenced by demographic and clinical characteristics; however, physicians should pay attention to unrealistic preferences that might influence patients' satisfaction with surgical results.

The objective of this study was to analyze the problem of interpreting change scores of ordinal health status measures for clinical research or practice. Methods used included exploration of the generation of change scores in the physical ability scale of the SF-36, one of the most widely used generic health status instruments. Resulting data are presented as the ranking of items according to baseline score; a percentage of patients with severe difficulty and Rasch analysis provided the same rank order of item difficulty. On the interval scale provided by the Rasch model a concentration of items reflecting moderate difficulty occurred. This "inflates" numerical gains for patients with moderate disability compared to patients with very severe or minor physical disability. Calibration of change scores using patient perception of the level of change in function showed important variation of numerical gains with baseline. We conclude that numerically equal gains may differ in their meaning depending on baseline health status. It is recommended that distribution of baseline health status measures and distribution of responders by baseline status be reported in evaluative studies.

The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference [RD] [95% CI] = -2.9 [-3.8 to -2.1] [p = 0.001]) and morning stiffness (RD [95% CI] = -25.9 [-44.3 to -7.5] [p < 0.01]) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an interaction term between site and treatment again confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data.

The objective of this study was to compare the relative responsiveness of a condition-specific spinal stenosis measure and two generic health status measures for outcome assessment of surgery for degenerative lumbar spinal stenosis, and to examine whether responsiveness statistics and measures of the ability to distinguish clinically important improvement rank the instruments consistently. Physical function and symptom severity scales of the spinal stenosis measure were compared to the Sickness Impact Profile (SIP) and the Roland scale, which is derived from the SIP. Responsiveness was calculated with the standardized response mean, the effect size, and Guyatt's responsiveness statistic. The discriminative ability of the instruments to distinguish patients who improved from those who did not was assessed using satisfaction with surgery as an external criterion. Minimal clinically relevant improvement was estimated using patient satisfaction as the external criterion. All responsiveness statistics revealed the same order of responsiveness; the physical function scale (SRM = 1.07) and symptom severity scales (SRM = 0.96) were more responsive than the Roland scale (SRM = 0.77) which was only slightly more responsive than the SIP (SRM = 0.69). Strikingly, the physical dimension of the SIP (SRM = 0.62) was even less responsive than the global SIP. The shape of and the area under the ROC curves showed that the physical function and symptom severity scales discriminate better between satisfied and unsatisfied patients than the Roland scale and SIP. The sensitivity to detect clinically important changes was somewhat lower at the ends of the scales, especially for the SIP and the Roland scale. Statistical approaches that assess the ability to distinguish clinically important changes and overall responsiveness statistics ranked the measures consistently. On the basis of these findings, we suggest that a condition-specific spinal stenosis measure is preferable as the primary end point in evaluative studies of degenerative lumbar spinal stenosis.

To develop a technique to screen populations for potential connective tissue disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or Sjögren's syndrome and to 340 randomly selected control subjects. The response rate after four mailings was 71% for case subjects and 54% for control subjects. Test-retest reliability for detection of any CTD was 0.82. Sensitivity for specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%; negative predictive value was 99.7%. The CTD Screening Questionnaire has high sensitivity and specificity for screening large populations.

Improved diagnosis and treatment have reduced mortality from SLE and present us with an opportunity to consider SLE in finer distinctions than alive or dead. Although much has been learned about SLE without a gold standard of disease activity or a universally agreed-upon definition of SLE activity, standardization of one or more measures would greatly enhance our ability to compare results from different centers and to communicate more precisely. It is unlikely that any of the existing measures or any ones to be developed will completely satisfy everyone's needs but it is pointless to proliferate new ones without testing their metric properties. Some differences in concept are desirable, particularly for investigators who have specialized interests or insights, but each should meet criteria of reliability and validity and have explicit definitions of terms, rules for their ascertainment, and the time period covered. Moreover, agreement on minimum essential elements of any SLE activity measure and their operational definitions would be a boon. SLE activity is one dimension in the disease pathway of lupus and implies a continuous phenomena that is potentially reversible. Organ damage, another point in the path of causation, connotes irreversible disease. We recommend that minimum essential elements be based on their frequency of occurrence, biological sensibleness, and the likelihood that degrees of activity can be rated reliably to show a change in a clinical state. The rating should be independent of whether a therapy is employed. Since activity is always considered with severity, the two dimensions could be recognized in the scale. Severity can be used to expand a scale's gradations if a symptom or sign is present. Severity could be rated by the need to treat with immunosuppressive agents, the need to follow the patient more closely, or the functional or prognostic consequences of the manifestation. For every organ system clinical judgment should be used to decide whether and how the scale should be constructed. For instance, in skin manifestations one could construct a scale by describing the extent of the lesion over the body and whether the lesion has potential for scarring, i.e., involving the dermis. However, the presence of, rather than the number of, cytoid bodies might be the only thing that is clinically important in rating the eye.(ABSTRACT TRUNCATED AT 400 WORDS)