The Lived Experience of Informal Caregivers of People Who Have Severe Mental Illness and Coexisting Long-Term Conditions: A Qualitative Study.

BACKGROUND: People with severe mental illness (SMI) experience higher rates and poorer outcomes of physical long-term conditions (LTCs). The management of SMI and LTCs is highly complex and many people with SMI rely on informal carers for support, which may lead to high levels of caregiver burden, and caregiver burnout. Caregiver burnout can result in poor health outcomes for informal carers and a reduction in the quality of care they are able to provide. Therefore, it is important to understand the caring experience to identify and address factors that contribute to burden and burnout. METHODS: This paper reports a secondary qualitative analysis of semistructured interviews and focus groups conducted with informal carers of people who have coexisting SMI and LTCs. We recruited 12 informal carers in England between December 2018 and April 2019. The transcripts were coded and analysed thematically. RESULTS: We identified two overarching themes and five subthemes. The themes included 'Fighting on all fronts: Mounting strain between demands and resources', which described the challenge of providing care in the context of coexisting SMI and LTCs, and 'Safekeeping: The necessity of chronic hypervigilance', which captured how informal carers' roles were defined by managing high-risk situations, leading to hypervigilance and paternalistic approaches to care. CONCLUSION: The experience of informal carers for people with SMI and coexisting LTCs is marked by limited access to support and the management of significant risk, which could contribute to high caregiver burden. Further primary research is needed to understand how the experiences of the caregiver role for people with SMI and LTCs influence caregiver burden. PATIENT OR PUBLIC CONTRIBUTION: Our PPI panel DIAMONDS Voice provided guidance on this study from conception, design and development of interview guides and recruitment materials to final write-up. DIAMONDS Voice consists of service users and carers who have experience of SMI and LTCs. Three carer members reviewed the final manuscript, and two are credited as authors.

The lived experience of severe mental illness and long-term conditions: a qualitative exploration of service user, carer, and healthcare professional perspectives on self-managing co-existing mental and physical conditions.

BACKGROUND: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. METHODS: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. RESULTS: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. CONCLUSION: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities.

Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations.

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.

Genome-wide association study of behavioural and psychiatric features in human prion disease.

Prion diseases are rare neurodegenerative conditions causing highly variable clinical syndromes, which often include prominent neuropsychiatric symptoms. We have recently carried out a clinical study of behavioural and psychiatric symptoms in a large prospective cohort of patients with prion disease in the United Kingdom, allowing us to operationalise specific behavioural/psychiatric phenotypes as traits in human prion disease. Here, we report exploratory genome-wide association analysis on 170 of these patients and 5200 UK controls, looking for single-nucleotide polymorphisms (SNPs) associated with three behavioural/psychiatric phenotypes in the context of prion disease. We also specifically examined a selection of candidate SNPs that have shown genome-wide association with psychiatric conditions in previously published studies, and the codon 129 polymorphism of the prion protein gene, which is known to modify various aspects of the phenotype of prion disease. No SNPs reached genome-wide significance, and there was no evidence of altered burden of known psychiatric risk alleles in relevant prion cases. SNPs showing suggestive evidence of association (P<10(-5)) included several lying near genes previously implicated in association studies of other psychiatric and neurodegenerative diseases. These include ANK3, SORL1 and a region of chromosome 6p containing several genes implicated in schizophrenia and bipolar disorder. We would encourage others to acquire phenotype data in independent cohorts of patients with prion disease as well as other neurodegenerative and neuropsychiatric conditions, to allow meta-analysis that may shed clearer light on the biological basis of these complex disease manifestations, and the diseases themselves.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance.The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in 5 years.

Explicit review of risperidone long-acting injection prescribing practice.

WHAT IS KNOWN AND OBJECTIVE: Long-acting injectable (LAI) antipsychotics are recommended for those people with a preference for this form of treatment and those who experience negative outcomes due to non-adherence with oral medication. LAI antipsychotics have been associated with improved outcomes and lower treatment discontinuation rates when compared with oral formulations. Risperidone long-acting injection (RLAI) treatment is effective and well-tolerated in clinical trials. The aim of this study was to review RLAI prescribing practice and compare prescribing to best practice recommendations (including indication, initiation, dose and co-prescribing) for adults receiving care from five clinical practice settings of New Zealand. METHODS: Patients starting publicly funded RLAI between 1 October 2005 and 31 October 2006 in five mental health services were included in the study. Data were retrospectively collected for 443 patients 1 year pre- and post-RLAI initiation at seven cross-sectional time-points (12, 6 and 3 months before; initiation; and 3, 6 and 12 months after). Patient characteristics (gender, age, ethnicity), DSM-IV-TR diagnosis, duration of mental illness, mental health act utilization, treatment setting and antipsychotic treatment (reasons for starting RLAI) were obtained from patient records. RESULTS AND DISCUSSION: The patients were mostly male (64,3%), of European background (42.9%) with a medium age of 34. In line with treatment recommendations, most had a diagnosis of schizophrenia or related psychoses, a history of medication adherence problems and previously been prescribed oral risperidone (72%). Treatment initiation also reflected recommended guidance; most were started on 25 mg/2 weeks (81.9%) and had treatment crossover (93.3%) until RLAI stabilized. For 58.3% of the group who continued for ≥ 12 months, mean fortnightly doses increased from 36.2 mg (3 months) to 41.3 mg (12 months); within the licensed range of 25-50 mg/2 weeks. Areas differing from recommended practice included high rates of antipsychotic co-prescribing at three cross-sectional time-points and ongoing at 12 months (12.3%). Patients prescribed higher RLAI starting doses were more likely to be prescribed higher doses 12 months later. WHAT IS NEW AND CONCLUSION: To our knowledge this is the largest multi-site explicit review of RLAI use in real world clinical practice. The review found that clinicians were using RLAI in clinical practice predominantly in accordance with best practice recommendations. However, high rates of antipsychotic co-prescribing with RLAI were identified which differ from practice reported in other small reviews of RLAI use and local studies of antipsychotic prescribing. We have demonstrated that clinical audit of practice is a powerful tool to identify areas of potentially poor practice, such as ongoing high rates of antipsychotic co-prescription cross-sectionally and 12 months after RLAI initiation and that this is an area of practice requiring further evaluation. Feedback to clinicians and stakeholders followed by re-audit of practice is needed in order to complete the audit cycle.

Hands-free administration of subjective workload scales: acceptability in a surgical training environment.

INTRODUCTION: Subjective workload measures are usually administered in a visual-manual format, either electronically or by paper and pencil. However, vocal responses to spoken queries may sometimes be preferable, for example when experimental manipulations require continuous manual responding or when participants have certain sensory/motor impairments. In the present study, we evaluated the acceptability of the hands-free administration of two subjective workload questionnaires - the NASA Task Load Index (NASA-TLX) and the Multiple Resources Questionnaire (MRQ) - in a surgical training environment where manual responding is often constrained. METHOD: Sixty-four undergraduates performed fifteen 90-s trials of laparoscopic training tasks (five replications of 3 tasks - cannulation, ring transfer, and rope manipulation). Half of the participants provided workload ratings using a traditional paper-and-pencil version of the NASA-TLX and MRQ; the remainder used a vocal (hands-free) version of the questionnaires. A follow-up experiment extended the evaluation of the hands-free version to actual medical students in a Minimally Invasive Surgery (MIS) training facility. RESULTS: The NASA-TLX was scored in 2 ways - (1) the traditional procedure using participant-specific weights to combine its 6 subscales, and (2) a simplified procedure - the NASA Raw Task Load Index (NASA-RTLX) - using the unweighted mean of the subscale scores. Comparison of the scores obtained from the hands-free and written administration conditions yielded coefficients of equivalence of r=0.85 (NASA-TLX) and r=0.81 (NASA-RTLX). Equivalence estimates for the individual subscales ranged from r=0.78 ("mental demand") to r=0.31 ("effort"). Both administration formats and scoring methods were equally sensitive to task and repetition effects. For the MRQ, the coefficient of equivalence for the hands-free and written versions was r=0.96 when tested on undergraduates. However, the sensitivity of the hands-free MRQ to task demands (η(partial)(2)=0.138) was substantially less than that for the written version (η(partial)(2)=0.252). This potential shortcoming of the hands-free MRQ did not seem to generalize to medical students who showed robust task effects when using the hands-free MRQ (η(partial)(2)=0.396). A detailed analysis of the MRQ subscales also revealed differences that may be attributable to a "spillover" effect in which participants' judgments about the demands of completing the questionnaires contaminated their judgments about the primary surgical training tasks. CONCLUSION: Vocal versions of the NASA-TLX are acceptable alternatives to standard written formats when researchers wish to obtain global workload estimates. However, care should be used when interpreting the individual subscales if the object is to make comparisons between studies or conditions that use different administration modalities. For the MRQ, the vocal version was less sensitive to experimental manipulations than its written counterpart; however, when medical students rather than undergraduates used the vocal version, the instrument's sensitivity increased well beyond that obtained with any other combination of administration modality and instrument in this study. Thus, the vocal version of the MRQ may be an acceptable workload assessment technique for selected populations, and it may even be a suitable substitute for the NASA-TLX.

Evidence for an elders' advantage in the naive product usability judgments of older and younger adults.

OBJECTIVE: To determine whose naive judgments of consumer product usability are more accurate--those of younger or older adults. Accuracy is here defined as judgments compatible with results from performance-based usability tests. BACKGROUND: Older adults may be better able to predict usability problems than younger adults, making them particularly good participants in studies contributing to the user-centered design of products. This advantage, if present, may stem from older adults' motivation for more usable products or from their experience adapting their own environments to meet their changing physical, cognitive, and sensory needs. METHOD: Sixty older participants (ages 65-75 years) and 60 younger ones (ages 18-22 years) evaluated illustrations of consumer products on specific criteria (e.g., readability, learnability, or error rates). They either rated a single design for each product or ranked six alternative designs. They also explained their choices, indicated which features were most critical for usability, and selected usability-enhancing modifications. RESULTS: Although there was no reliable age difference in the amount of usability information provided in the open-ended explanations, older adults were more accurate at ranking alternative designs, selecting the most usability-critical features, and selecting usability-enhancing modifications (all ps < .05). CONCLUSION: The usability judgments of older adults are more accurate than those of younger adults when these judgments are solicited in a fixed-alternative, but not open-ended, format. APPLICATION: Because older adults are more discerning about potential product usability problems, they may be particularly valuable as research participants in early-stage design research (prior to the availability of working prototypes).

Assessing mental workload during laparoscopic surgery.

Although the use of performance efficiency measures (speed, movement economy, errors) and ergonomic assessments are relatively well established, the evaluation of cognitive outcomes is rare. This report makes the case for assessment strategies that include mental workload measures as a way to improve training scenarios and training/operating environments. These mental workload measures can be crucially important in determining the difference between well-intentioned but subtly distracting technologies and true breakthroughs that will enhance performance and reduce stress.

Daclizumab: a review of its use in the management of organ transplantation.

UNLABELLED: The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in solid organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. When added to standard triple immunosuppression regimens, daclizumab significantly reduces the rate of acute rejection at 1 year in renal transplantation by 36% and there are indications that it may be effective in other solid organ transplantations. Three-year outcomes of two phase III clinical trials in renal transplantation indicate similar values for graft and patient survival between daclizumab and placebo when given in addition to triple immunosuppression; however, these pivotal trials were not designed with sufficient power to demonstrate any statistical significance. The addition of daclizumab induction shows potential in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without increasing the rate of acute graft rejection or adverse effects in renal and liver transplantation. Preliminary reports indicate that daclizumab may also be a useful agent in delayed graft function and graft versus host disease (GVHD). Further investigation of its efficacy in these groups and in children is needed. Data from clinical trials show daclizumab to be well tolerated in solid organ transplantation. It does not increase the incidence of infection, including cytomegalovirus infection, when compared with placebo or no induction groups. Preliminary comparative data with muromonab CD3 indicate that daclizumab may be associated with a lower rate of infectious complications and similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been proven to reduce acute rejection in renal transplant recipients when given in addition to traditional baseline immunosuppression. It has shown potential to reduce acute rejection in other solid organ transplants; however, well designed, randomised studies are required to confirm this. Clinical experience from trials to date indicate that daclizumab has a tolerability profile similar to placebo with no significant effect on the incidence of infection. The relative efficacy and tolerability of daclizumab compared with other induction agents has yet to be defined. Available data suggest that daclizumab may allow the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may have potential in the treatment of GVHD.

Rate of intrachain contact formation in an unfolded protein: temperature and denaturant effects.

We have measured the effect of temperature and denaturant concentration on the rate of intrachain diffusion in an unfolded protein. After photodissociating a ligand from the heme iron of unfolded horse cytochrome c, we use transient optical absorption spectroscopy to measure the time scale of the diffusive motions that bring the heme, located at His18, into contact with its native ligand, Met80. Measuring the rate at which this 62 residue intrachain loop forms under both folding and unfolding conditions, we find a significant effect of denaturant on the chain dynamics. The diffusion of the chain accelerates as denaturant concentration decreases, with the contact formation rate approaching a value near approximately 6x10(5) s(-1) in the absence of denaturant. This result agrees well with an extrapolation from recent loop formation measurements in short synthetic peptides. The temperature dependence of the rate of contact formation indicates an Arrhenius activation barrier, Ea approximately 20 kJ/mol, at high denaturant concentrations, comparable to what is expected from solvent viscosity effects alone. Although Ea increases by several kBT as denaturant concentration decreases, the overall rate of diffusion nevertheless increases. These results indicate that inter-residue energetic interactions do not control conformational diffusion in unfolded states, even under folding conditions.

Rabeprazole: an update of its use in acid-related disorders.

UNLABELLED: Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION: Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.

Effect of centralized intake on outcomes of substance abuse treatment.

OBJECTIVE: State governments are exploring the potential of various forms of case management to control the costs of substance abuse treatment programs. This report describes an experimental program in one Iowa county in which clients are assessed and referred elsewhere if treatment is needed. Outcomes of clients in that county are compared with those of clients served elsewhere in the state. METHODS: All claims submitted by provider agencies to the Iowa Department of Public Health for substance abuse treatment of eligible clients in 1994 were analyzed to test the effect of the experimental intake-and-referral program on clients' utilization of outpatient treatment, rate of treatment completion, and rate of abstention at discharge from treatment. RESULTS: In the county with the experimental program, 27 percent of clients recommended for treatment actually attended, compared with 48 percent in other counties. Clients who used the experimental program were also less likely to complete treatment. These differences persisted after adjusting for baseline differences in client characteristics. CONCLUSIONS: Lower utilization arising from failure to attend recommended treatment may reduce treatment costs but is not the intended outcome of the intake-and-referral program. Failure to complete treatment also is an adverse outcome. Outcomes of various types of case management programs should be carefully evaluated before statewide implementation is considered.

The Fungicide Phosphonate Disrupts the Phosphate-Starvation Response in Brassica nigra Seedlings.

The development of Brassica nigra seedlings over 20 d of growth was disrupted by the fungicide phosphonate (Phi) in a manner inversely correlated with nutritional inorganic phosphate (Pi) levels. The growth of Pi-sufficient (1.25 mM Pi) seedlings was suppressed when 10, but not 5, mM Phi was added to the nutrient medium. In contrast, the fresh weights and root:shoot ratios of Pi-limited (0.15 mM) seedlings were significantly reduced at 1.5 mM Phi, and they progressively declined to about 40% of control values as medium Phi concentration was increased to 10 mM. Intracellular Pi levels generally decreased in Phi-treated seedlings, and Phi accumulated in leaves and roots to levels up to 6- and 16-fold that of Pi in Pi-sufficient and Pi-limited plants, respectively. Extractable activities of the Pi-starvation-inducible enzymes phosphoenolpyruvate phosphatase and inorganic pyrophosphate-dependent phosphofructokinase were unaltered in Pi-sufficient seedlings grown on 5 or 10 mM Phi. However, when Pi-limited seedlings were grown on 1.5 to 10 mM Phi (a) the induction of phosphoenolpyruvate phosphatase and inorganic pyrophosphate-dependent phosphofructokinase activities by Pi limitation was reduced by 40 to 90%, whereas (b) soluble protein concentrations and the activities of the ATP-dependent phosphofructokinase and pyruvate kinase were unaffacted. It is concluded that Phi specifically interrupts processes involved in regulation of the Pi-starvation response in B. nigra.

Bromodeoxyuridine/DNA analysis of replication in CHO cells after exposure to UV light.

The effects of ultraviolet light on cellular DNA replication were evaluated in an asynchronous Chinese hamster ovary cell population. BrdUrd incorporation was measured as a function of cell-cycle position, using an antibody against bromodeoxyuridine (BrdUrd) and dual parameter flow cytometric analysis. After exposure to UV light, there was an immediate reduction (approximately 50%) of BrdUrd incorporation in S phase cells, with most of the cells of the population being affected to a similar degree. At 5 h after UV, a population of cells with increased BrdUrd appeared as cells that were in G1 phase at the time of irradiation entered S phase with apparently increased rates of DNA synthesis. For 8 h after UV exposure, incorporation of BrdUrd by the original S phase cells remained constant, whereas a significant portion of original G1 cells possessed rates of BrdUrd incorporation surpassing even those of control cells. Maturation rates of DNA synthesized immediately before or after exposure to UV light, measured by alkaline elution, were similar. Therefore, DNA synthesis measured in the short pulse by anti-BrdUrd fluorescence after exposure to UV light was representative of genomic replication. Anti-BrdUrd measurements after DNA damage provide quantitative and qualitative information of cellular rates of DNA synthesis especially in instances where perturbation of cell-cycle progression is a dominant feature of the damage. In this study, striking differences of subsequent DNA synthesis rates between cells in G1 or S phase at the time of exposure were revealed.

Choosing specifiers: an evaluation of the basic tasks model of graphical perception.

Effect sizes obtained from 39 experiments were used to evaluate the predictions of the basic tasks model of graphical efficacy. This model predicts that performance will be attenuated with graphical displays as a function of the particular specifier, or visual dimension, used to code data values. In this review the basic tasks model predicted performance more accurately than did Tufte's data-ink principle. In addition, variability in effect sizes across studies revealed that the model was more successful at predicting performance in local (focusing) tasks than in global information synthesis tasks. Furthermore, the model was better at predicting performance in tasks requiring the use of physically present rather than remembered graphs. Further differences in effect sizes resulted from variability in the exact specifiers used in experimental graphs. Minimal differences were obtained among graphs that used position, length, or angle as specifiers. However, graphs that used area or volume to represent quantitative values were associated with consistently worse performance than found with other formats.

A cell cycle analysis of growth-related genes expressed during T lymphocyte maturation.

Fetal liver or bone marrow-derived T lymphocyte precursors undergo extensive, developmentally regulated proliferation in response to inductive signals from the thymic microenvironment. We have used neonatal mouse thymocytes size-separated by centrifugal elutriation to study the cell cycle stage-specific expression of several genes associated with cell proliferation. These include genes involved in the biosynthesis of deoxyribonucleotide precursors, such as dihydrofolate reductase (DHFR), thymidylate synthase (TS), and the M1 and M2 subunits of ribonucleotide reductase, as well as c-myc, a cellular oncogene of unknown function. Using nuclear run-on assays, we observed that the transcription rates for these genes, with the exception of TS, are essentially invariant not only throughout the cell cycle in proliferating cells, but also in noncycling (G0) cells. The TS gene showed a transient increase in transcription rate in cells which bordered between a proliferating and nonproliferating status. Studies of an elutriated T cell line, S49.1, yielded similar results, indicating that the process of immortalization has not affected the transcriptional regulation of these genes. Analysis of steady-state mRNA levels using an RNase protection assay demonstrated that the levels of DHFR and TS mRNA accumulate as thymocytes progress through the cell cycle. In contrast, only the M2 subunit of ribonucleotide reductase showed cyclic regulation. Finally, in contrast to cultured cell models, we observed an abrupt fivefold increase in the steady-state level of c-myc mRNA in the transition from G1 to S-phase. We conclude from these studies that the transcriptional regulation of specific genes necessary for cellular proliferation is a minor component of the developmental modulation of the thymocyte cell cycle.

The perceptual interaction of graphical attributes: configurality, stimulus homogeneity, and object integration.

Researchers have proposed that graphical efficacy may be determined, in part, by the nature of the perceptual interactions that exist between attributes used to create graphical displays. One extreme type of interaction is integrality, in which two or more physical dimensions are represented as a single psychological dimension in the observer. An alternative type of interaction is configurality, in which a global emergent dimension is available to the observer in addition to the component attributes. Thirteen stimulus sets, each composed of attributes commonly used in the design of graphs, were submitted to the performance-based diagnostics of integrality and configurality. Analyses suggest a continuum of configurality among the present stimulus sets, with little evidence for integral graphical attributes. The configural pattern of results was more common when two identical dimensions were paired (homogeneous stimuli) than when two different dimensions were paired (heterogeneous stimuli). However, there was no evidence that pairs of dimensions belonging to a single object (object integration) were any more configural than dimensions belonging to different objects. Object integration was, however, consistently related to inefficient performance in tasks requiring the filtering of one of two component dimensions.