Concordance Of Changes Research Articles

Comparing patient-reported outcomes measurement information system® (PROMIS®)-16 domain scores with the PROMIS-29 and 5-item PROMIS cognitive function scores.

This study evaluates the interpretability of Patient-Reported Outcomes Measurement Information System® (PROMIS®)-16 profile domain scores (physical function, ability to participate in social roles and activities, anxiety, depression, sleep disturbance, pain interference, cognitive function - abilities, and fatigue) compared to the PROMIS-29 scores and a 5-item PROMIS cognitive function score. The study aims to provide insights into using these measures in clinical and research settings. Analyses were conducted using data from 4130 adults from a nationally representative, probability-based internet panel between September and October 2022. A subset of 1256 individuals with back pain was followed up at six months. We compared the PROMIS-16 profile with the corresponding domain scores from the PROMIS-29 and a custom five-item cognitive function measure. We evaluated (1) reliability through inter-item correlations within each domain and (2) criterion validity by comparing PROMIS-16 profile with the corresponding longer PROMIS measures: (a) standardized mean differences in domain scores, (b) correlations, and (c) concordance of change (i.e., got worse, stayed the same, got better) among those with back pain from baseline to six months later using the reliable change index. We report the Kappa coefficient of agreement and the frequency and percentage of participants with concordant classifications. Inter-item correlations for the PROMIS-16 domains ranged from 0.65 in cognitive function to 0.92 in pain interference. Standardized mean differences between PROMIS-16 and the scores for the corresponding longer PROMIS domains were minimal (< 0.2). Correlations among the corresponding domain scores ranged from 0.82 for sleep disturbance to 0.98 for pain interference. The percentage of concordance in change groups ranged from 63% for sleep disturbance to 88% for pain interference. Except for sleep disturbance, the change groups derived from the PROMIS-16 showed moderate to substantial agreement with scores estimated from the longer PROMIS measures (Kappa coefficients ≥ 0.41). The PROMIS-16 domain scores perform similarly to the longer PROMIS measures and can be interpreted in the same way. This similarity indicates that PROMIS-16 can be useful for research as a brief health-related quality-of-life profile measure.

P.053 Efficacy of lemborexant in adults with insomnia is supported by improvements in both objective and subjective measures

Background: Improvements in sleep-onset, maintenance, and daytime functioning, are all important outcomes for the treatment of insomnia. These improvements are usually assessed by objective or patient-reported (subjective) measures or both. Some sleep-promoting drugs do not report consistently aligned subjective and objective outcomes. Therefore, we examined concordance in change from baseline (CFB) in sleep parameters (objective/subjective measures) and daytime functioning (subjective measures) in the clinical program of lemborexant (LEM), a dual-orexin receptor antagonist. Methods: Study E2006-G000-304 (NCT02783729), a 1-month, placebo (PBO)- and active-controlled (zolpidem; not discussed here) study, and Study E2006-G000-303 (NCT02952820), a 12-month, randomized, PBO-controlled study (first 6-months), evaluated the efficacy/safety of LEM 5mg (LEM5) and LEM 10mg (LEM10) in subjects with insomnia disorder. The primary/secondary endpoints in both studies included multiple objective/subjective sleep parameters and patient-reported measures, which were assessed for concordance. Results: In both studies, statistically significant improvements with LEM5/LEM10 were reported in multiple objective and patient-reported measures versus PBO, showing a concordance of results, with observed improvements continuing through 12 months. LEM was well tolerated; most treatment-emergent adverse events were mild/moderate. Conclusions: When deciding which sleep agent to prescribe, it is important that improvement can be demonstrated in both objective and patient-reported measures. LEM treatment showed concordance among observed measures.

Concordance in PTSD symptom change between DSM-5 versions of the Clinician-Administered PTSD Scale (CAPS-5) and PTSD Checklist (PCL-5).

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) versions of the Clinician-Administered PTSD Scale (CAPS-5) and PTSD Checklist (PCL-5) are widely used PTSD measures. Researchers and clinicians routinely use both measures in tandem to quantify symptom change, despite substantive instrumentation differences beyond administration modality, and absent a theoretical rationale or differential hypotheses for the two measures. The degree to which these measures provide comparable estimates of symptom change is unknown. This study examined concordance in change between CAPS-5 and PCL-5 scores over time. Participants were male veterans (N = 198) randomly assigned to one of two group PTSD treatments. We administered both the CAPS-5 and PCL-5 at baseline, midtreatment, immediately posttreatment, and 3-, 6-, and 12-month posttreatment. Results indicated that CAPS-5 and PCL-5 scores changed over time in a similar manner, as evidenced by generally parallel repeated-measures effect sizes, highly correlated slopes of change (r = .878), and similar associations with improvements in measures of depression and psychosocial functioning. However, the two measures did not produce identical estimates of symptom change. Estimates of symptom improvement were somewhat less concordant at posttreatment follow-up assessments; by the 12-month posttreatment assessment, changes in CAPS-5 scores from baseline indicated somewhat greater symptom improvement than changes in PCL-5 scores (CAPS-5 ESsg = -0.67, PCL-5 ESsg = -0.53). Collectively, results indicate that CAPS-5 and PCL-5 scores produce similar but not identical estimates of PTSD symptom change. Thus, although PCL-5 scores closely approximate symptom change estimated by CAPS-5 scores, the two measures are not interchangeable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Bedside monitoring of lung volume available for gas exchange

BackgroundBedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lung injury. We propose here a novel operator-independent technique, enabled by a fibre optic oxygen sensor, to quantify the lung volume available for gas exchange. We hypothesised that the continuous measurement of arterial partial pressure of oxygen (PaO2) decline during a breath-holding manoeuvre could be used to estimate lung volume in a single-compartment physiological model of the respiratory system.MethodsThirteen pigs with a saline lavage lung injury model and six control pigs were studied under general anaesthesia during mechanical ventilation. Lung volumes were measured by simultaneous PaO2 rate of decline (VPaO2) and whole-lung computed tomography scan (VCT) during apnoea at different positive end-expiratory and end-inspiratory pressures.ResultsA total of 146 volume measurements was completed (range 134 to 1869 mL). A linear correlation between VCT and VPaO2 was found both in control (slope = 0.9, R2 = 0.88) and in saline-lavaged pigs (slope = 0.64, R2 = 0.70). The bias from Bland–Altman analysis for the agreement between the VCT and VPaO2 was − 84 mL (limits of agreement ± 301 mL) in control and + 2 mL (LoA ± 406 mL) in saline-lavaged pigs. The concordance for changes in lung volume, quantified with polar plot analysis, was − 4º (LoA ± 19°) in control and − 9° (LoA ± 33°) in saline-lavaged pigs.ConclusionBedside measurement of PaO2 rate of decline during apnoea is a potential approach for estimation of lung volume changes associated with different levels of airway pressure.

Fluctuating Asymmetry, Developmental Noise and Developmental Stability: Future Prospects for the Population Developmental Biology Approach

Developmental noise—which level may vary within a certain backlash allowed by natural selection—is a reflection of the state of a developing system or developmental stability. Phenotypic variations inside the genetically determined norm observed in case of fluctuating asymmetry provide a unique opportunity for evaluating this form of ontogenetic variability. Low levels of developmental noise for the biologic system under study is observed under certain conditions, while its increase acts as a measure of stress. The concordance of changes in developmental stability with changes in other parameters of developmental homeostasis indicates the significance of fluctuating asymmetry estimates. All this determines the future prospects of the study of fluctuating asymmetry not only for developmental biology, but also for population biology. The study of developmental stability may act as the basis of an approach of population developmental biology to assess the nature of the phenotypic diversity and the state of natural populations under various impacts and during evolutionary transformations.

Concordance for changes in allergic asthma domain variables after short-term corticosteroid therapy

BackgroundAsthma is a complex syndrome with multiple domains including symptoms, lung function, asthma control, and airway inflammation. A study of Fenom PRO™, a novel monitor for exhaled nitric oxide (FeNO), provided an opportunity to look at concordance/discordance (C/D) for changes in multiple asthma domains over a 2-week period after corticosteroid therapy.MethodsNon-steroid-treated adults and children with uncontrolled asthma had asthma domain measures, (FeNO), forced expired volume in 1 s (FEV1), the 6-item Asthma Control Questionnaire scores (ACQ6), and daily asthma symptoms, assessed before and after a 2-week course of corticosteroids. Asthma symptoms were assessed using a custom novel twice-daily symptom scale (ASX). C/D bidirectional changes in all domains were calculated around both the zero point, and around the minimal important difference (MID) in relevant subjects.ResultsThere was a highly significant fall in mean FeNO of 51.7% over 2 weeks (p < 0.0001) accompanied by significant improvements in mean FEV1, ACQ6 and ASX scores. However, C/D between individual domains varied considerably between subjects. The C/D between parameters for any change around zero for the combined adults and pediatric population was best for FeNO and ACQ6, 79.3/20.7% while FEV1 was more discordant than other parameters in general. When considering changes around the minimal important difference (MID) in a subset, the level of concordance increased in general, with FeNO and ACQ6 demonstrating a C/D of 93.5/6.6%.ConclusionThis data demonstrates that the concordance between changes in the asthma domains is often substantially less than 100%. Reasons for this may include different time courses for change of the separate domains, the degree of abnormality for each domain at baseline, as well as intrinsic limitations of each parameter.

Concordance of changes in the extracellular DNA of blood plasma and DNA of tumor tissue using the example of EGFR gene mutations in patients with non-small cell lung cancer

Concordance of changes in the extracellular DNA of blood plasma and DNA of tumor tissue using the example of EGFR gene mutations in patients with non-small cell lung cancer

Abstract P1-02-06: Serial monitoring of circulating tumor DNA in patients with metastatic breast cancer

Abstract Background: For patients with MBC, there is currently no evidence that changing therapy on the basis of biomarker results improves outcome. Clinical benefit of treatment is defined as complete response, objective response, or stable disease as determined by RECIST criteria on radiological evaluation. Serial measurements of serum biomarkers such as CA2729 and CTCs have proven unsuccessful in predicting clinical benefit. Circulating tumor DNA(ctDNA) has emerged as a potential biomarker that may predict response to therapy or progression of disease. The present retrospective study was conducted to evaluate the relationship between change in ctDNA with clinical benefit determined by clinical and radiological evaluations of patients with MBC patients. Methods: We conducted a retrospective, single-institutional study to determine if serial monitoring of ctDNA allele frequency levels predict clinical benefit of a treatment. 55 patients with measurable MBC who had serial monitoring of ctDNA between August 2014 and May 2016 were included. The median age was 55.9 (27–94) years). Clinical outcomes were determined as per standard guidelines. The analysis was performed on all cases that had serial measurements of ctDNA with no change in therapy in between and the repeat blood draw was done within 30 days of repeat radiographic evaluation. The dataset contained 125 observations from 48 unique patients. The relationship between the change in ctDNA and clinical benefit was analyzed using a generalized linear model with a random subject effect to account for the intrapatient dependence occurring from obtaining multiple evaluations from the same patient. A logit link function was used akin to logistic regression and a compound symmetric correlation structure was assumed. Results: 68.8% of the cases were hormone receptor-positive, 18.8% HER2-positive, and 27.1% TNBC. The treatments received were 58.4% hormonal therapy, 31.2% chemotherapy, 26.4% included anti-HER2 therapy, 2 cases were on targeted therapy, and 1 case was not on any treatment. Three patients had stage 4 disease in complete remission. ctDNA analysis was repeated on average 4 days prior to radiological evaluation. The average time between repeat assessments was 108.5 days. 93% of the patients had a genomic alteration detected at some point during their course of disease. The most common mutations detected were TP53 41.7%, PIK3CA 35.4%, ESR1 18.8%, and ERBB2 amplifications 6.3%. A dichotomized change in ctDNA is a significant predictor of clinical benefit (p &amp;lt; 0.0001). The intrapatient correlation is estimated to be 0.273 for the transformed variable. The model yields a predicted probability of clinical benefit of 26.9% when the increase in ctDNA is greater than or equal to 0.5 and when the increase in ctDNA is less than 0.5, the a predicted probability of clinical benefit is 78.4%. The concordance of change in ctDNA and change in CA 27-29 was 76.2%. Conclusions: Serial evaluation of serum ctDNA may be useful to evaluate molecular response to treatment which may correlate with clinical benefit and potentially guide treatment decisions. Early indication that a chosen therapy is not effective may lead to avoidance of overtreatment and initiation of an alternative regimen. Further, prospective studies are needed. Citation Format: Patel A, Mukherjee A, Hwang D, Ensor J, Patel TA, Chang JC, Rodriguez AA. Serial monitoring of circulating tumor DNA in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-06.

A longitudinal study of changes and associations in dental fear in parent/adolescent dyads.

Dental fear seems to fluctuate, but concordance of changes in dental fears between parent/adolescent dyads has not been reported. To study longitudinally the associations between adolescent and parental dental fears and their changes. Adolescents and parents reported their dental fear independently of each other when adolescents were between 11-12 and 15-16-year-olds. Eight hundred and seventeen eligible parent/adolescent dyads were included in the analyses. Dental fear was measured with a single question using five response alternatives. Associations between adolescent and parental dental fears and their changes were analysed using χ2 tests and correlation coefficients. Prevalence of dental fear remained rather similar during the study. There was a positive association between adolescent and parental dental fears in early adolescence (P < 0.001) but at middle adolescence only among parent/girl dyads (P = 0.007 for girls, P = 0.341 for boys). Changes in dental fear among parent/adolescent dyads did not correlate statistically significantly. Difference between girls' and boys' change in dental fear was statistically significant (P = 0.001). Dental fear increased more often among girls than among boys. Boys had stable low/no dental fear more often than girls did. Adolescents' and parents' dental fears seemingly change independently of each other.

Stable marital relationship protects men from oral and genital HPV infections

Human papillomavirus (HPV) infections are associated with sexual behavior. Changes in the sexual habits of couples and their impact on male genital and oral HPV infections were determined during 7 years of follow-up (FU). At baseline and 7 years FU, urethral, semen/penile, and oral samples were collected from 46 men and cervical and oral samples of their spouses for HPV DNA detection. Demographic data and risk factors of spouses were recorded by questionnaire at both time points and analyzed for concordance. HPV genotyping was done with the Multimetrix® kit. At baseline, 29.5 % of the male genital and 11 % of their oral samples tested positive. Incident genital HPV infection was found in 23 % and oral infection in 10.9 % of men. Genotype-specific persistence was detected in one man (HPV53) in genital samples. Moderate to almost perfect concordance of changes in sexual habits during FU among spouses were found. Changing partners [p = 0.028; odds ratio (OR) = 15; 95 % confidence interval (CI) 1.355-166.054] and marital status (p = 0.001; 95 % CI 0.000-0.002) increased the risk of incident genital HPV infections. The overall outcome of genital HPV disease in men was linked to the frequency of sexual intercourse (p = 0.023; 95 % CI 0.019-0.026) and changes in marital status (p = 0.022; 95 % CI 0.019-0.026), while oral HPV infections were associated with the number of sexual partners (p = 0.047; 95 % CI 0.041-0.052). Taken together, asymptomatic genital HPV infections among the men were common. The risk of incident genital HPV infections increased among men reporting a change of sexual partner during FU, implicating that a stable marital relationship protects against oral and genital HPV infection.

Rigidity in Gender‐Typed Behaviors in Early Childhood: A Longitudinal Study of Ethnic Minority Children

A key prediction of cognitive theories of gender development concerns developmental trajectories in the relative strength or rigidity of gender typing. To examine these trajectories in early childhood, 229 children (African American, Mexican American, and Dominican American) were followed annually from age 3 to 5years, and gender-stereotypical appearance, dress-up play, toy play, and sex segregation were examined. High gender-typing was found across ethnic groups, and most behaviors increased in rigidity, especially from age 3 to 4years. In addressing controversy surrounding the stability and structure of gender-typing it was found that from year to year, most behaviors showed moderately stable individual differences. Behaviors were uncorrelated within age but showed more concordance in change across time, suggesting that aspects of gender-typing are multidimensional, but still show coherence.

Concordance of Changes in Metabolic Pathways Based on Plasma Metabolomics and Skeletal Muscle Transcriptomics in Type 1 Diabetes

Insulin regulates many cellular processes, but the full impact of insulin deficiency on cellular functions remains to be defined. Applying a mass spectrometry–based nontargeted metabolomics approach, we report here alterations of 330 plasma metabolites representing 33 metabolic pathways during an 8-h insulin deprivation in type 1 diabetic individuals. These pathways included those known to be affected by insulin such as glucose, amino acid and lipid metabolism, Krebs cycle, and immune responses and those hitherto unknown to be altered including prostaglandin, arachidonic acid, leukotrienes, neurotransmitters, nucleotides, and anti-inflammatory responses. A significant concordance of metabolome and skeletal muscle transcriptome–based pathways supports an assumption that plasma metabolites are chemical fingerprints of cellular events. Although insulin treatment normalized plasma glucose and many other metabolites, there were 71 metabolites and 24 pathways that differed between nondiabetes and insulin-treated type 1 diabetes. Confirmation of many known pathways altered by insulin using a single blood test offers confidence in the current approach. Future research needs to be focused on newly discovered pathways affected by insulin deficiency and systemic insulin treatment to determine whether they contribute to the high morbidity and mortality in T1D despite insulin treatment.

Dynamic Variability of Isometric Action Tremor in Precision Pinching

Evolutionary development of isometric force impulse frequencies, power, and the directional concordance of changes in oscillatory tremor during performance of a two-digit force regulation task was examined. Analyses compared a patient group having tremor confounding volitional force regulation with a control group having no neuropathological diagnosis. Dependent variables for tremor varied temporally and spatially, both within individual trials and across trials, across individuals, across groups, and between digits. Particularly striking findings were magnitude increases during approaches to cue markers and shifts in the concordance phase from pinching toward rigid sway patterns as the magnitude increased. Magnitudes were significantly different among trace line segments of the task and were characterized by differences in relative force required and by the task progress with respect to cue markers for beginning, reversing force change direction, or task termination. The main systematic differences occurred during cue marker approach and were independent of trial sequence order.

Serum Heavy/Light Chain and Free Light Chain Measurements Provide Prognostic Information, Allow Creation of a Prognostic Model and Identify Clonal Changes (clonal tiding) Through the Course of Multiple Myeloma (MM)

Abstract▪2883▪This icon denotes a clinically relevant abstractIn MM, increasing evidence indicates progressive clonal evolution A novel polyclonal immunoassay specific for the different light chain types of intact immunoglobulins (Ig) (heavy/light chain assays; HLC) and the serum free light chain (FLC) test enable measurement of changes in the production of clone specific Ig and of the non-involved polyclonal Ig of the same isotype. By calculating the HLCratio the relationship between clonal and non clonal plasma cells can be assessed. Here we evaluate the prognostic value of the HLCratio, construct a two tiered prognostic model employing the HLC and FLC tests, and use these assays to analyze the clonal tide in patients (pts) with MM.103 previously untreated pts with MM were enrolled (35 IgGκ, 17 IgGλ, 29 IgAκ, 22 IgAλ). ISS stage I: 39 (38%), stage II: 42 (41%), stage III: 22 (21%) pts. Median age: 66years (range 32–86). 82 pts with a minimum of 5 serum samples were followed for a median of 36 mos (range: 57 days -133 mos).Serum FLC and HLC (IgGk/IgGl, IgAk/IgAl) measurements were made using polyclonal antisera assays (Freelite™, Binding Site, Birmingham, UK. and, Hevylite™, Binding Site, Birmingham, UK). Serum protein electrophoresis and immunofixation were conducted on a SEBIA Hydrasys II platform. Survival analysis was performed using the SPSS v 18 programme.Median survival of the entire pt cohort was 53.6 mos. When pts were stratified according to their presentation HLCratios being moderately abnormal (0.022 −45; n=51) or highly abnormal (<0.022 or >45; n=52), survival was significantly shorter in those with highly abnormal ratios (median 32.1 mos vs. median not reached, HR: 2.07, CI 1.15 – 3.75, p=0.016). The survival rates at 5 years were 33.4% for the former and 58.9% for the latter group (p=0.01). For pts with a highly abnormal FLCratio (<0.1 or >30) a statistically non-significant tendency for shorter survival was noted (40.8 mos vs. median not reached, HR: 1.72, CI: 0.93 – 3.17, p=0.08) compared to those with less abnormal FLC ratios (0.1 − 30). A risk stratification prognostic model with highly abnormal HLC and FLC ratios as risk factors at presentation was developed. Overall survival was significantly different between pts with both, highly abnormal HLC and FLC ratios, or only one, or none of these risk factors (p=0.01). The median was not reached in pts with 0 or 1 risk factor and was 29.2 mos in those with 2 risk factors. The respective five year survival rates were 67.4%, 50.0%, and 23.3% (0 risk factor, HR: 1, 1 vs. 0 risk factor, HR: 1.76 CI: 0.71 – 4.33, p=0.22, 2 vs. 0 risk factor, HR: 3.69, CI: 1.45 – 9.44 for 2 risk factors, p=0.006, figure 1). [Display omitted] The comparison of FLC and HLC values over the follow up period revealed concordance of changes in 75 pts (91.5%). In 1 pt after 78 days a >50% reduction in dFLC (and FLCratio) indicated a partial response, whereas HLCratios (and IgGk concentrations) showed no response; this indicates the existence of clones with different sensitivity to myeloma therapy. FLC escape was noted in 1 pt with increasingly abnormal free FLC values while HLCratios remained stable. In 4 pts, increasingly abnormal HLCratios at the same time as FLC values were stable or normalising indicated outgrowth of clones producing intact Ig only. One additional pt showed an increasingly abnormal HLCratio due to subtle suppression of the polyclonal Ig while the monoclonal concentration remained constant. Conclusion:Highly abnormal HLCratio correlates with shorter survival and a risk-stratification model combining HLC and FLCratio revealed marked discriminative power. Monitoring pts with FLC and HLC assays showed significant changes in clonal protein production as an indication of a major clonal tide in about 10% of myeloma pts. Disclosures:Faint:The Binding Site Ltd.: Employment. Bradwell:The Binding Site Ltd.: Consultancy, Equity Ownership, Patents & Royalties. Young:The Binding Site Ltd.: Employment. Harding:The Binding Site Group Ltd: Employment.

Comparison of non-calibrated pulse-contour analysis with continuous thermodilution for cardiac output assessment in patients with induced hypothermia after cardiac arrest

Aim Induced mild hypothermia after cardiac arrest interferes with clinical assessment of the cardiovascular status of patients. In this situation, non-invasive cardiac output measurement could be useful. Unfortunately, arterial pulse contour is altered by temperature, and the performance of devices using arterial blood pressure contour analysis to derive cardiac output may be insufficient. Methods Mild hypothermia (32–34 °C) was induced in eight patients after out-of-hospital cardiac arrest and successful resuscitation. Cardiac output (CO) was measured simultaneously by continuous thermodilution using a pulmonary artery catheter and a cardiac output monitor (Vigilance II, Edwards Lifesciences) and by pulse contour analysis using an arterial line and the Vigileo monitor (Edwards Lifesciences) during both normothermia (>36 °C) and hypothermia. Continuous CO from both monitors was compared (Bland–Altman) and concordance of changes measured in consecutive 8-min intervals was measured. Results Mean cardiac output was 3.9 ± 1.2 l/min during hypothermia and 6.1 ± 2.6 l/min during normothermia ( p < 0.001). During hypothermia (normothermia), bias was 0.23 (0.77) l/min, precision (1 SD) was 0.6 (0.72) l/min, and the limits of agreement were −1.06 to 1.51 (−0.64 to 2.18) l/min, corresponding to a percentage error of ±34% (±24%). Concordance of directional CO changes >10% was 53.9% in hypothermia and 51.4% in normothermia. Conclusion Induced hypothermia was not associated with increased bias or limits of agreement for the comparison of Vigileo and continuous thermodilution, but percentage error was high during normothermia and increased further during hypothermia. Less than 50% of clinically relevant CO changes during hypothermia were concordant.

Simulation of evolution implemented in the mutualistic symbioses towards enhancing their ecological efficiency, functional integrity and genotypic specificity

We created the mathematical model for the evolution of the Efficiency of Mutualistic Symbioses (EMS) which was estimated as the microsymbiont impacts on the host’s reproductive potential. Using the example of rhizobia–legume interaction, the relationships were studied between EMS and Functional Integrity of Symbiosis (FIS) which is represented as a measure for concordance of changes in the partners’ genotypic frequencies under the environmental fluctuations represented by the minor deviations of the systemic model parameters. The FIS indices correlate positively with EMS values suggesting an enhancement of FIS via the natural selection operating in the partners’ populations in favor of high EMS. Due to this selection, nodular habitats may be closed for colonization by the non-beneficial bacterial strains and the Genotypic Specificity of Mutualism (GSM) in partners’ interactions is enhanced: the selective advantage of host-specific vs non-host-specific mutualists is increasing. The novelty of our model is to suggest a selective background for macroevolutionary events reorganizing the structure and functions of symbiotic systems and to present its evolution as a result of shifting the equilibrium between different types of mutualists under the impacts of the symbiosis-stipulated modes of natural selection.

Involvement of N-cholinergic synapses in regulating RNA metabolism in sympathetic neurons and satellite gliocytes

RNA contents in the cytoplasm of neurons and satellite gliocytes in the cranial cervical ganglion of rabbits were determined by photographic cytophotometry during pharmacological blockade of N-cholinergic (N-Ch) synapses with the N-cholinolytic dimecoline (s.c. doses of 10, 30, and 50 mg/kg) and during the gradual decrease and elimination of blockade (1-11 h after dosage). Partial blockade and blockade of intermediate intensity induced concordant variations in RNA contents in the two cell types. This concordance in changes was impaired in conditions of complete blockade. Analysis of these results suggests that N-Ch synaptic processes in the sympathetic ganglion directly modulate quantitative changes in RNA levels in the neuron cytoplasm and represent a factor synchronizing the metabolism of neuronal and glial RNA.

Relationship Between the Hamilton Depression Rating Scale and the Montgomery-Åsberg Depression Rating Scale in Depressed Elderly: A Meta-analysis

To determine whether the sensitivity of the Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) to treatment effects are comparable in geriatric antidepressant randomized controlled trials by developing and validating an equation that links between the two instruments. Literature search for this meta-analysis was based on three sources: MEDLINE, a recent related meta-analysis, and experts in geriatric antidepressant trials. The search resulted in 11 relevant geriatric antidepressant trial studies that administered both instruments for symptom ratings. The authors used baseline ratings as a model-building sample and postrandomization ratings as a validation sample. HDRS scores were prorated into HDRS17, a 17-item HDRS, for analysis. The development and validation was based on a total number of 1,874 subjects. The correlations were high between baseline mean HDRS17 and MADRS ratings (r = 0.80; Fisher's z = 1.09, N = 25, p <0.0001) and between postrandomization ratings (r = 0.88, Fisher's z = 1.39, N = 65, p <0.0001). The following equation was derived: HDRS17 = -1.58 + 0.86 x MADRS. The difference between observed and estimated HDRS17 in a validation sample consisting of postrandomization follow-up means did not depend on magnitudes of HDRS17. Although generalizability of findings into a broader population could be limited, and the authors could not assess concordance of changes of particular item constructs between HDRS and MADRS ratings, both ratings are comparable in assessing changes in overall depressive symptom severity in response to antidepressants in depressed elderly at aggregated group mean levels.

Discordant changes in plasma ACTH and β-lipotropin/β-endorphin levels in Clshing's disease patients with depression

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and β-lipotropin/β-endorphin (β-LPH/β-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean[±SD] depressed ood score=0.17±0.4; modified Hamilton Depression scale score=7.6±4.5) and five as severly and five as severely depressed (mean depressed mood score=2.4±0.5; modified Hamilton Depession scale score=15±5.6) ( p<0.05). ACTH and β-LPH/β-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and β-LPH/β-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed=90.0±16.7; severely depressed=34.6±8.7 ( p<0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0mmg dexamethasone administration. These initial findings, taken together with data in related areas, suggest that greater diversity in regulation and consecretion of ACTH and β-LPH/β-E may occur than is currently suspected. Such diversity may play a role in the relationship between HPA axis dysregulation and mood disorders.

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Assessment of fluorescein angiograms.

Quantitation of the earliest changes in abnormal retinal morphology using fluorescein angiography is potentially superior to retinal photography. However, the critical importance of flawless technique, limitations in the size of the field available for detailed study, and observer variability constitute major disadvantages. A protocol describing standards of photography and of injection was developed. Methodology for counting microaneurysms (Ma) was developed at a central laboratory and applied in suitable photographs obtained at 0 (baseline), 4, and 8 mo in 68 patients. Counts of "definite" or "possible" Ma were made on films projected under standard conditions by two observers known to achieve consistently reproducible results. Semiquantitative assessment of diffusibility of fluorescein reflecting capillary leakage was performed in 61 patients. Leakage was graded according to three degrees of severity permitting study of observer variation, concordance of change in pairs of eyes, and treatment effects. The average number of Ma at baseline was slightly higher in the continuous subcutaneous insulin infusion (CSII) group than in the conventional insulin treatment (CIT) group, but the difference was not statistically significant at the 0.05 level. At both 4 and 8 mo, definite Ma were more prevalent in the CSII group, and the difference was statistically significant at the 0.05 level using both parametric and nonparametric tests. In 27 CSII and 23 CIT patients having complete sets of 0, 4, and 8-mo photographs, Ma counts increased during the 0-4-mo interval. During the 4-8 mo interval, a further increase occurred in the CSII group but contrasted with a decrement observed in the CIT group, which showed no net change from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)