Shared and genetically distinct Zea mays transcriptome responses to ongoing and past low temperature exposure.

BACKGROUND: Cold temperatures and their alleviation affect many plant traits including the abundance of protein coding gene transcripts. Transcript level changes that occur in response to cold temperatures and their alleviation are shared or vary across genotypes. In this study we identify individual transcripts and groups of functionally related transcripts that consistently respond to cold and its alleviation. Genes that respond differently to temperature changes across genotypes may have limited functional importance. We investigate if these genes share functions, and if their genotype-specific gene expression levels change in magnitude or rank across temperatures. RESULTS: We estimate transcript abundances from over 22,000 genes in two unrelated Zea mays inbred lines during and after cold temperature exposure. Genotype and temperature contribute to many genes' abundances. Past cold exposure affects many fewer genes. Genes up-regulated in cold encode many cytokinin glucoside biosynthesis enzymes, transcription factors, signalling molecules, and proteins involved in diverse environmental responses. After cold exposure, protease inhibitors and cuticular wax genes are newly up-regulated, and environmentally responsive genes continue to be up-regulated. Genes down-regulated in response to cold include many photosynthesis, translation, and DNA replication associated genes. After cold exposure, DNA replication and translation genes are still preferentially downregulated. Lignin and suberin biosynthesis are newly down-regulated. DNA replication, reactive oxygen species response, and anthocyanin biosynthesis genes have strong, genotype-specific temperature responses. The ranks of genotypes' transcript abundances often change across temperatures. CONCLUSIONS: We report a large, core transcriptome response to cold and the alleviation of cold. In cold, many of the core suite of genes are up or downregulated to control plant growth and photosynthesis and limit cellular damage. In recovery, core responses are in part to prepare for future stress. Functionally related genes are consistently and greatly up-regulated in a single genotype in response to cold or its alleviation, suggesting positive selection has driven genotype-specific temperature responses in maize.

The effects of crop attributes, selection, and recombination on Canadian bread wheat molecular variation.

Cultivated germplasm provides an opportunity to investigate how crop agronomic traits, selection for major genes, and differences in crossing-over rates drive patterns of allelic variation. To identify how these factors correlated with allelic variation within a collection of cultivated bread wheat (Triticum aestivum L.), we generated genotypes for 388 accessions grown in Canada over the past 170 yr using filtered single nucleotide polymorphism (SNP) calls from an Illumina Wheat iSelect 90K SNP-array. Entries' breeding program, era of release, grain texture, kernel color, and growth habit contributed to allelic differentiation. Allelic diversity and linkage disequilibrium (LD) of markers flanking some major loci known to affect traits such as gluten strength, growth habit, and grain color were consistent with selective sweeps. Nonetheless, some flanking markers of major loci had low LD and high allelic diversity. Positive selection may have acted upon homoeologous genes that had significant enrichment for the gene ontology terms 'response-to-auxin' and 'response-to-wounding.' Long regions of LD, spanning approximately one-third the length of entire chromosomes, were associated with many pericentromeric regions. These regions were also characterized by low diversity. Enhancing recombination across these regions could generate novel allele combinations to accelerate Canadian wheat improvement.

Preference in random assignment: implications for the interpretation of randomized trials.

Random assignment to a preferred experimental condition can increase service engagement and enhance outcomes, while assignment to a less-preferred condition can discourage service receipt and limit outcome attainment. We examined randomized trials for one prominent psychiatric rehabilitation intervention, supported employment, to gauge how often assignment preference might have complicated the interpretation of findings. Condition descriptions, and greater early attrition from services-as-usual comparison conditions, suggest that many study enrollees favored assignment to new rapid-job-placement supported employment, but no study took this possibility into account. Reviews of trials in other service fields are needed to determine whether this design problem is widespread.

Transforming Dissatisfaction with Services into Self-Determination: A Social Psychological Perspective on Community Program Effectiveness.

A field study of supported employment for adults with mental illness (N=174) provided an experimental test of cognitive dissonance theory. We predicted that most work-interested individuals randomly assigned to a non-preferred program would reject services and lower their work aspirations. However, individuals who chose to pursue employment through a non-preferred program were expected to resolve this dissonance through favorable service evaluations and strong efforts to succeed at work. Significant work interest-by-service preference interactions supported these predictions. Over two years, participants interested in employment who obtained work through a non-preferred program stayed employed a median of 362 days versus 108 days for those assigned to a preferred program, and participants who obtained work through a non-preferred program had higher service satisfaction.

Supported employment outcomes of a randomized controlled trial of ACT and clubhouse models.

OBJECTIVE: In a randomized controlled trial, a vocationally integrated program of assertive community treatment (ACT) was compared with a certified clubhouse in the delivery of supported employment services. METHODS: Employment rates, total work hours, and earnings for 121 adults with serious mental illness interested in work were compared with published benchmark figures for exemplary supported employment programs. The two programs were then compared on service engagement, retention, and employment outcomes in regression analyses that controlled for background characteristics, program preference, and vocational service receipt. RESULTS: Outcomes for 63 ACT and 58 clubhouse participants met or exceeded most published outcomes for specialized supported employment teams. Compared with the clubhouse program, the ACT program had significantly (p<.05) better service engagement (ACT, 98 percent; clubhouse, 74 percent) and retention (ACT, 79 percent; clubhouse, 58 percent) over 24 months, but there was no significant difference in employment rates (ACT, 64 percent; clubhouse, 47 percent). Compared with ACT participants, clubhouse participants worked significantly longer (median of 199 days versus 98 days) for more total hours (median of 494 hours versus 234 hours) and earned more (median of $3,456 versus $1,252 total earnings). Better work performance by clubhouse participants was partially attributable to higher pay. CONCLUSIONS: Vocationally integrated ACT and certified clubhouses can achieve employment outcomes similar to those of exemplary supported employment teams. Certified clubhouses can effectively provide supported employment along with other rehabilitative services, and the ACT program can ensure continuous integration of supported employment with clinical care.

Impact of referral source and study applicants' preference for randomly assigned service on research enrollment, service engagement, and evaluative outcomes.

OBJECTIVE: The inability to blind research participants to their experimental conditions is the Achilles' heel of mental health services research. When one experimental condition receives more disappointed participants, or more satisfied participants, research findings can be biased in spite of random assignment. The authors explored the potential for research participants' preference for one experimental program over another to compromise the generalizability and validity of randomized controlled service evaluations as well as cross-study comparisons. METHOD: Three Cox regression analyses measured the impact of applicants' service assignment preference on research project enrollment, engagement in assigned services, and a service-related outcome, competitive employment. RESULTS: A stated service preference, referral by an agency with a low level of continuity in outpatient care, and willingness to switch from current services were significant positive predictors of research enrollment. Match to service assignment preference was a significant positive predictor of service engagement, and mismatch to assignment preference was a significant negative predictor of both service engagement and employment outcome. CONCLUSIONS: Referral source type and service assignment preference should be routinely measured and statistically controlled for in all studies of mental health service effectiveness to provide a sound empirical base for evidence-based practice.

Effectiveness and cost of risperidone and olanzapine for schizophrenia: a systematic review.

Risperidone and olanzapine are novel antipsychotic medications that compete as first-line agents in treating patients with schizophrenia. The objective of this paper is to review the available evidence regarding the effectiveness and cost of risperidone versus olanzapine. We reviewed both randomised and peer-reviewed non-randomised head-to-head (olanzapine versus risperidone) studies in populations with schizophrenia. The studies were selected through a MEDLINE search. Risperidone and olanzapine provide control of positive, negative and global symptoms of schizophrenia. Each drug has a distinct adverse effect profile. Five randomised trials comparing risperidone with olanzapine suggested grossly similar efficacy in the first 2 months of treatment, with some results indicating advantages for olanzapine over the longer term. Only two of the trials included measures of service utilisation. One had 28-week follow-up, and the other followed patients for 12 months but had small sample sizes. Both experimental and naturalistic studies indicated that the acquisition cost of olanzapine is about 50% greater than for risperidone at dose levels commonly used for the treatment of schizophrenia. The only experiment with 12-month total treatment cost data found essentially equivalent costs for patients assigned to olanzapine or risperidone, showing that there are circumstances where total cost is similar in spite of the higher drug acquisition cost of olanzapine. Most retrospective studies also reported comparable total cost. Few studies gave enough information to evaluate cost effectiveness. The clear difference in acquisition cost of these two medications was rarely reflected in overall treatment cost in the studies we reviewed. Overall, our review of the literature highlights that there is inadequate evidence to distinguish the relative total cost of care associated with risperidone versus olanzapine, although accumulating evidence suggests the difference is small. This population-based conclusion does not indicate which medication is more costly or more cost effective for a particular patient; this depends on each patient's response to each medication.

Trends in use of antidepressants, lithium, and anticonvulsants in Kaiser Permanente-insured youths, 1994-2003.

In view of the current controversy regarding the use of antidepressants in children and adolescents, we examined trends from 1994 to 2003 in the use of antidepressants, lithium, and anticonvulsants by enrollees, aged 5-17 years, of Kaiser Permanente in Northern California. We found that the use of antidepressants more than doubled from 9.4 per 1000 enrollees to 21.3 per 1000. Most of this increase is associated with selective serotonin reuptake inhibitors (SSRIs), which increased from 4.6 to 14.5 per 1000. The use of tricyclic antidepressants (TCAs) decreased markedly, while the increase of other newer antidepressants rose from 1.3 to 6.5 per 1000. The use of anticonvulsants nearly doubled, from 3.5 to 6.9 per 1000, while lithium use was relatively stable at a rate of nearly 1 per 1000. Use of SSRIs, newer antidepressants, and anticonvulsants increased in boys as well as girls in each of three age groups: 5-9, 10-14, and 15-17 years. An increasing percentage of the antidepressant users had a diagnosis of depression, and an increasing percentage of anticonvulsant users had a diagnosis of bipolar disorder. Although the safety and efficacy of antidepressants in youths needs to be more firmly established, these findings may reflect progress in the diagnosis and treatment of mental illness.

Skating to where the puck is going to be: a plan for clinical trials and translation research in mood disorders.

As part of the National Institute of Mental Health Strategic Plan for Mood Disorders Research effort, the Clinical Trials and Translation Workgroup was asked to define priorities for clinical trials in mood disorders and for research on how best to translate the results of such research to clinical practice settings. Through two face-to-face meetings and a series of conference calls, we established priorities based on the literature to date and what was known about research currently in progress in this area. We defined five areas of priority that cut across developmental stages, while noting that research on adult mood disorders was at a more advanced stage in each of these areas than research on child or geriatric disorders. The five areas of priority are: 1) maximizing the effectiveness and cost-effectiveness of initial (acute) treatments for mood disorders already known to be efficacious in selected populations and settings when they are applied across all populations and care settings; 2) learning what further treatments or services are most likely to reduce symptoms and improve functioning when the first treatment is delivered well, but the mood disorder does not remit or show adequate improvement; 3) learning what treatments or services are most cost-effective in preventing recurrence or relapse and maintaining optimal functioning after a patient's mood disorder has remitted or responded maximally to treatment; 4) developing and validating clinical, psychosocial, biological, or other markers that predict: a) which treatments are most effective, b) course of illness, c) risk of adverse events/tolerability and acceptability for individual patients or well-defined subgroups of patients; 5) developing clinical trial designs and methods that result in lower research costs and greater generalizability earlier in the treatment development and testing process. A rationale for the importance of each of these priorities is provided.

The heterogeneity of schizophrenia in disease states.

PREVIOUS PRESENTATION: Some of the contents of this paper have been previously presented at the 16th Annual Meeting of the International Society for Technology Assessment in Health Care June 20, 2000 in the Hague, Netherlands and at the 21st Annual Meeting of the Society for Medical Decision Making as a poster on October 3, 1999 in Reno, NV. BACKGROUND: Studies of schizophrenia treatment often oversimplify the array of health outcomes among patients. Our objective was to derive a set of disease states for schizophrenia using the Positive and Negative Symptom Assessment Scale (PANSS) that captured the heterogeneity of symptom responses. METHODS: Using data from a 1-year clinical trial that collected PANSS scores and costs on schizophrenic patients (N=663), we conducted a k-means cluster analyses on PANSS scores for items in five factor domains. Results of the cluster analysis were compared with a conceptual framework of disease states developed by an expert panel. Final disease states were defined by combining our conceptual framework with the empirical results. We tested its utility by examining the influence of disease state on treatment costs and prognosis. RESULTS: Analyses led to an eight-state framework with varying levels of positive, negative, and cognitive impairment. The extent of hostile/aggressive symptoms and mood disorders correlated with severity of disease states. Direct treatment costs for schizophrenia vary significantly across disease states (F=27.47, df=7, p<0.0001), and disease state at baseline was among the most important predictors of treatment outcomes. CONCLUSION: The disease states we describe offer a useful paradigm for understanding the links between symptom profiles and outcomes.

The effect on diagnostic rates of assigning patients to ethnically focused inpatient psychiatric units.

OBJECTIVE: The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three psychiatric inpatient units that provided culturally appropriate treatment to those groups would affect rates of diagnosis of various psychiatric disorders. METHODS: Retrospective administrative data for 5,983 inpatients at a large urban community hospital with several ethnically focused units were examined. The data represented 10,645 admissions between 1989 and 1996. Chi square analyses and Stuart-Maxwell tests of symmetry and homogeneity were used to assess the relationship between matching patients to ethnically focused units and the rates of major psychiatric illnesses among Asian, black, and Latino patients compared with whites. RESULTS: Ethnic differences in diagnostic rates were consistent with the results of previous studies. Black patients had more diagnoses of psychotic disorders and fewer diagnoses of affective disorders than other ethnic minorities or whites, and Latino patients had more nonspecific diagnoses. Matching inpatients to ethnically focused units did not have a marked effect on patterns of diagnoses among black patients, but an association was observed for Latino patients, particularly those who had only one admission. No significant diagnostic differences were found between Asian patients and whites, irrespective of whether the Asian patients had been ethnically matched to a specialty focus unit. CONCLUSIONS: The effect of referring inpatients with serious mental illnesses to an ethnically focused psychiatric unit varied by ethnic group, probably because each specialty unit functioned differently, depending on the needs of its particular patient population.

The effect on treatment outcomes of assigning patients to ethnically focused inpatient psychiatric units.

OBJECTIVE: The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three ethnically focused psychiatric inpatient units would affect treatment outcome. METHODS: Retrospective administrative data for 5,983 inpatients at a large urban community hospital with several ethnically focused units were examined. The data represented 10,645 admissions between 1989 and 1996. Cox proportional-hazards models, logistic and multinomial regressions, and chi square analyses were used to assess the relationship between matching patients to ethnically focused units and time to rehospitalization, referral destination on discharge, and length of stay for Asian, black, and Latino patients. RESULTS: Ethnic matching status was strongly associated with referral destination for Asian and Latino patients but not for black patients. Asian and Latino patients who had been treated on the appropriate ethnically focused units were more frequently sent to outpatient or residential treatment (71 to 73 percent of discharges) than unmatched patients, black patients, and white patients (44 to 49 percent of discharges), who more frequently refused follow-up or were sent to locked facilities. No association was found between matching status and time to rehospitalization or length of stay for any ethnic group. CONCLUSIONS: Matching inpatients to ethnically focused psychiatric units was related to referral destination at discharge. Matched patients were more likely than unmatched patients to accept referral to postdischarge treatment, which has been shown previously to reduce readmission rates. Among persons with serious mental illness, matching patients to ethnically focused units may be important for enhancing communication and trust as a means of improving participation in ongoing treatment programs.

Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness.

OBJECTIVES: This study examined Medicaid claims forms to determine the prevalence, severity, and co-occurrence of physical illness within a representative sample of persons with serious mental illness (N=147). METHODS: Representativeness of health problems in the study sample was established through comparison with a larger sample of persons with serious mental illness enrolled in Medicaid within the same state. Standardized annual costs were then assigned to Medicaid claims diagnoses, and individual health problem severity was measured as the sum of estimated treatment costs for diagnosed conditions. RESULTS: Seventy-four percent of the study sample (N=109) had been given a diagnosis of at least one chronic health problem, and 50 percent (N=73) had been given a diagnosis of two or more chronic health problems. Of the 14 chronic health conditions surveyed, chronic pulmonary illness was the most prevalent (31 percent incidence) and the most comorbid. Persons with chronic pulmonary illness were second only to those with infectious diseases in average annual cost of treatment ($8,277). Also, 50 percent or more of participants in eight other diagnostic categories had chronic pulmonary illness. A regression analysis identified age, obesity, and substance use disorders as significant predictors of individual health problem severity. CONCLUSIONS: Risk adjustment for physical health is essential when setting performance standards or cost expectations for mental health treatment. Excluding persons with chronic health problems from mental health service evaluations restricts generalizability of research findings and may promote interventions that are inappropriate for many persons with serious mental illness.

Association of empathy of nursing staff with reduction of seclusion and restraint in psychiatric inpatient care.

OBJECTIVE: Disruptive behavior leading to seclusion or restraint increases with patients in a high-acuity stage of mental illness who have histories of aggressive behavior. The study examined whether greater nursing staff empathy skills and motivation reduced use of seclusion and restraint and whether empathy training can further this effect. METHODS: In 1,098 nursing shifts in 2 six-month periods one year apart, hierarchical analyses examined the effects of nursing shift and patient characteristics, the effect for each shift of nurses' skill and motivation to use empathy, and whether empathy training reduced use of seclusion and restraint. RESULTS: With controls for shift, patient, and other staffing variables, analyses showed that the presence of more nursing staff with above-average empathy ratings was strongly associated with reduced use of seclusion and restraint but empathy training showed no further benefit. CONCLUSIONS: Recruiting and retaining empathic nursing staff may be the best way to reduce the use of seclusion and restraint.

A four-year retrospective study of Assertive Community Treatment: change to more frequent, briefer client contact.

The authors explored the feasibility of providing frequent, brief client contact as a strategy for reallocating Assertive Community Treatment (ACT) staff time to new clients, while preserving relationships with current clients and ACT program fidelity standards. A retrospective analysis of 4 years of service records for a high-fidelity ACT team revealed gradual increases in staff-client contact frequency, and corresponding decreases in contact duration. During these years, fidelity to ACT standards remained moderately high, and clients' employment and hospitalization outcomes improved.

A web-delivered care management and patient self-management program for recurrent depression: a randomized trial.

OBJECTIVE This study assessed the impact of an Internet-delivered care management and patient self-management program, eCare for Moods, on patients treated for recurrent or chronic depression. METHODS Patients with recurrent or chronic depression were randomly assigned to eCare (N=51) or usual specialty mental health care (N=52). The 12-month eCare program integrates with ongoing depression care, links to patients' electronic medical records, and provides clinicians with panel management and decision support. Participants were interviewed at baseline and six, 12, 18, and 24 months after enrollment. Telephone interviewers blind to treatment used a timeline follow-back method to estimate depression severity on a 6-point scale for each of the 105 study weeks (including the baseline). Differences between groups in weekly severity over two years were examined by generalized estimating equations. RESULTS Participants in eCare experienced more reduction in depressive symptoms (estimate=-.74 on the 6-point scale over two years; 95% confidence interval [CI]=-1.38 to -.09, p=.025) and were less often depressed (-.24 over two years; CI=-.46 to -.03, p=.026). At 24 months, 43% of eCare and 30% of usual-care participants were depression free; the number needed to treat to attain one additional depression-free participant was 8. eCare participants had other favorable outcomes: improved general mental health (p=.002), greater satisfaction with specialty care (p=.003) and with learning new coping skills (p<.001), and more confidence in managing depression (p=.006). CONCLUSIONS Internet-delivered care management can help improve outcomes of patients treated for recurrent or chronic depression.

When programs benefit some people more than others: tests of differential service effectiveness.

Practitioners need to know for whom evidence-based services are most or least effective, but few services research studies provide this information. Using data from a randomized controlled comparison of supported employment findings for two multi-service psychiatric rehabilitation programs, we illustrate and compare procedures for measuring program-by-client characteristic interactions depicting differential program effectiveness, and then illustrate how a significant program-by-client interaction can explain overall program differences in service effectiveness. Interaction analyses based on cluster analysis-identified sample subgroups appear to provide statistically powerful and meaningful hypothesis tests that can aid in the interpretation of main effect findings and help to refine program theory.

Doing the difficult and dangerous: the community program practice scale.

The CPPS uses staff respondents to portray practices and program climate of nonresidential mental health programs. We report psychometric analyses of 1,533 respondents in 165 programs. Confirmatory factor and partial credit analyses identified eight practice and five climate subscales, all of which show adequate psychometric properties. Program types are distinguished better by practices (R (2) values .37 to .52) than by climate (R (2) values .09 to .23), as expected. Multiple discriminant analysis and K-means cluster analysis illustrate how well the CPPS distinguishes program differences. The CPPS offers a promising, economical approach to measuring program practices in clinical trials comparing service programs.