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PubMed1991

Subtyping panic disorder by major depression and avoidance behaviour and the response to active treatment.

In order to establish the clinical validity of currently used ways of subtyping panic disorder the predictive power of associated current avoidance behaviour and (secondary) major depression for the response to active treatment (alprazolam, imipramine) was tested. The analysis was based on the data from the Cross-National-Collaborative-Panic-Study. Limited support for validity evidenced by predicting drug response was found for grading panic disorder by the severity of avoidance behaviour; patients with panic attacks and agoraphobia are more responsive to imipramine (compared with alprazolam) when using the reduction of the total number of panic attacks (or of spontaneous panic attacks) as the outcome criterion; patients without any avoidance behaviour did better with alprazolam (compared with imipramine).

Adult↗

PubMed1991

Avoidance behaviour: a predictor of the efficacy of pharmacotherapy in panic disorder?

The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study (n = 1134 patients); in this double blind randomized trial alprazolam, imipramine and placebo were compared during an 8-week treatment period. Patients with extensive avoidance behaviour (agoraphobia) had the most profit from the active drugs. Counter expectancy these specific drug effects were most pronounced in avoidance behaviour. Active drugs (in particular imipramine) were especially more effective than placebo if the patients presented with associated avoidance behaviour. The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder.

Adult↗

PubMed1990

Depression and panic anxiety: the effect of depressive co-morbidity on response to drug treatment of patients with panic disorder and agoraphobia.

Numerous studies have established that there is increased co-morbidity of depressive symptoms among patients with panic disorder with and without agoraphobia, but questions remain as to whether the symptom pattern and clinical course are similar to that of primary depressions. The Cross-National Collaborative Panic Study was initiated to study the effects of alprazolam, a triazolobenzodiazepine, in the treatment of panic disorder. In the first phase, which included more than 500 subjects, alprazolam was compared against placebo. In the second phase, alprazolam was compared with imipramine and placebo in a double-blind, randomized, controlled trial. Results of both the first and second phases will be reviewed as they bear on the issue of drug treatment of secondary depression accompanying panic disorder. The presence of depressive symptoms does not adversely influence anti-panic and anti-phobic response to medication. Equivalent drug-placebo differences occur on multiple measures of anxiety--including the number and intensity of panic attacks, phobias, anticipatory anxiety, and overall anxiety.

Agoraphobia↗

PubMed1992

Cutoff assignment strategies for enhancing randomized clinical trials.

The randomized clinical trial (RCT) is the preferred method for assessing the efficacy of treatments. Recent ethical and logistical criticisms suggest that new variations of the traditional RCT are needed. Some of these criticisms may be addressed with new hybrid designs that combine random assignment with assignment by one or more cutoff values on a baseline variable (e.g., severity of illness). In a simple version of such a "cutoff-based" RTC, persons scoring below a cutoff score on a baseline measure (i.e., the least severely ill) are automatically assigned to the control-treated group, those scoring above a second, higher cutoff (i.e., the most ill) are automatically assigned to the test-treated group, and those scoring in the interval between the cutoff scores (i.e., the moderately ill) are randomly assigned to either group. Depending on the baseline score, the patient is assigned to treatment either randomly or by the need-based, clinically related baseline score. Six cutoff-based design variations are studied via simulations and compared with the traditional RCT and the single-cutoff (i.e., regression-discontinuity) design. All variations yield unbiased estimates of the treatment effect but estimates differ in efficiency, with the RCT being most efficient and the single-cutoff design being least efficient. Secondary analyses of data from the Cross-National Collaborative Study of the Effects of Alprazolam (Xanax) on panic are conducted for each variation by selectivity discarding cases from the original dataset to stimulate cutoff-based assignment. The results confirm the simulations and illustrate how cutoff-based designs might look with real data.

Alprazolam↗

PubMed1990

Sleep studies and neurochemical correlates in panic disorder and agoraphobia.

Although panic disorder is classified by the DSM III among the anxiety disorders, there is evidence from epidemiological and neurochemical studies that links panic to the affective disorders. In addition several of the effective pharmacological treatments suggest, as in the depressive disorders, serotonergic involvement. As part of the evaluation of patients who would take part in the Cross National Collaborative Panic study, polysomnography, the dexamethasone suppression test and platelet imipramine binding and 5HT-uptake were scheduled. 44 patients who met DSM III criteria on the SCID interview schedule for Panic Disorder consented to enter the study. After being medication free for two weeks, these patients had three consecutive all night polysomnograms, followed by a dexamethasone suppression test and platelet study of imipramine binding and 5HT-uptake. In our studies we were unable to find for the panic group as a whole a correlation with reported parameters of sleep architecture in endogenous depression. Similarly the imipramine binding differentiated the panickers from the depressed group. Only the 5HT-uptake was similar in both groups. We also found a subgroup of panickers who resembled depressives in terms of the imipramine binding, 5HT-uptake platelet studies and REM latency. In the analysis of the imipramine and 5HT-uptake over the treatment period, we noted changes which suggest a role for serotonin, certainly in a subgroup of panickers and possibly for the group of panic disorder as a whole.

Adult↗

PubMed2026

Watershed-scale risk assessment of cadmium contamination in Chinese cropland soils: Dual pathways of irrigation input and flood-driven transport.

Irrigation and flood events serve as critical pathways for the transport of cadmium (Cd) from industrial sources into cropland soils at the watershed scale, constituting a major driver of widespread Cd contamination in China's cropland soil. This study evaluated the risk of Cd contamination in cropland soils across China's nine major river basins at the watershed scale, focusing on the contributions of irrigation and flood events, and conducted a sensitivity analysis of key risk factors. The assessment was conducted within a framework that considered factors including hazard, exposure, and vulnerability. The results revealed that numerous watersheds in southeastern China are exposed to dual pressures of Cd contamination risks in cropland soils, driven by both irrigation practices and flood events. Watersheds categorized as High-High, High-Moderate, or Moderate-High risk, reflecting combined Cd contamination risks from irrigation and flood, are vital to China's grain production, contributing 67.1 % of the national cropland area and 66.4 % of the grain yield. The study suggests localized strategies for managing cropland soils Cd contamination risks from irrigation and flood at the watershed scale in China, alongside strengthened cross-regional collaboration in southeastern China.

Cadmium↗

PubMed2026

An introductory practical guide to secondary data analysis in pediatric urology.

INTRODUCTION: Secondary data analysis (SDA) has become an increasingly important approach in pediatric urology, enabling the study of long-term outcomes, care variation, and disparities in populations with chronic or congenital urologic conditions. With the growing availability of large datasets, a structured approach to designing and conducting SDA studies is increasingly relevant. OBJECTIVES: To provide an introductory, practical guide to SDA in pediatric urology by (1) summarizing commonly used data sources with representative studies, (2) outlining a stepwise approach to designing and executing SDA studies, and (3) highlighting key methodological considerations, limitations, and opportunities for future work. STUDY DESIGN: Narrative review of existing literature and commonly used datasets relevant to pediatric urology, including administrative claims, hospital encounter databases, clinical registries, electronic health record networks, and population-based surveys. RESULTS: Data sources differ in scope, clinical granularity, longitudinal follow-up, and representativeness, and each is suited to specific research questions. We present a practical workflow for SDA, including dataset selection, cohort definition, and analytic planning. Linkage across datasets can provide a more comprehensive view of care patterns and outcomes, although feasibility is influenced by legal, technical, and data-quality constraints. DISCUSSION: SDA enables population-level analyses and the study of rare conditions that are challenging to evaluate through single-center or prospective designs. However, careful cohort definition, feasibility assessment, and awareness of data limitations are essential to ensure validity and interpretability. CONCLUSION: SDA provides a scalable, cost-efficient framework for generating meaningful evidence in pediatric urology. Continued efforts to harmonize data elements, improve linkage infrastructure, and support cross-institution collaboration will enhance the quality and impact of future research. This article provides a practical framework and examples to support the design and execution of SDA studies.

Humans↗

PubMed2026

CYClones: a highly powered, fully genotyped, eight-parent yeast mapping population.

The budding yeast Saccharomyces cerevisiae is a remarkably adaptable organism that thrives in diverse environments. Global sequencing of natural isolates has revealed extensive genetic diversity within the species. Here, we describe the construction and characterization of CYClones (Collaborative Yeast Cross clones), a library of 11,392 segregants generated from a multiparent funnel cross of eight genetically diverse parental strains. To enable the genetic dissection of complex traits, we imputed whole-genome sequences for all segregants and show that CYClones captures a substantial fraction of the global genetic diversity of S. cerevisiae. Haplotype representation is well maintained, with each parental haplotype present at >5% frequency across >95% of the genome. Simulations demonstrate that CYClones has ≥95% power to detect variants with heritability as low as 0.36%, with mapping resolution often finer than the length of a single gene. In summary, CYClones is a powerful community resource for dissecting the genetic architecture of complex and quantitative traits, uncovering context-dependent mutational effects, and identifying causal variants underlying phenotypic diversity.

Saccharomyces cerevisiae↗

PubMed1991

Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study.

As part of the cross-national collaborative panic study, a double-blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM-III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention-to-treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow-up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long-term drug treatment or combinations of drug treatment and psychotherapy should be evaluated.

Adolescent↗

PubMed1992

International reliability of a diagnostic intake procedure for panic disorder.

Test-retest diagnostic reliability interviews using the Upjohn version of the Structured Clinical Interview for DSM-III (SCID) were conducted with 72 patients at 13 international sites of the Cross-National Collaborative Panic Study. Agreement on the diagnosis of panic disorder was very good. For the subtypes (uncomplicated, with limited phobic avoidance, and agoraphobia), agreement was fair to good.

Adolescent↗

PubMed2025

Multi-omics technologies: Novel tools and methods for assessing nerve injury and regeneration.

Recently, with the rapid advancement of multi-omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, new tools and approaches have been introduced for studying nerve injury and regeneration. This review highlights the application and progress of multi-omics in uncovering the mechanisms of nerve injury, guiding the development of regenerative strategies, and promoting clinical translation. By integrating multi-omics datasets, researchers can comprehensively track dynamic molecular changes following nerve injury, including abnormal gene expression, disrupted protein signaling, altered metabolic programs, and shifts in the immune microenvironment. Single-cell multi-omics technologies resolve cellular heterogeneity, revealing the distinct functions of neurons, glial cells, and immune cell subpopulations during the injury response. Spatially resolved transcriptomics maintain the spatial context of lesion and regeneration sites, enabling precise localization for targeted interventions. Multi-omics technologies not only identify key molecular players involved in nerve regeneration but also create opportunities for personalized medicine. Nonetheless, integrating multi-omics data poses technical challenges, including high dimensionality, batch effects, and algorithmic constraints, while ethical concerns related to stem cell therapy and gene editing require stringent oversight. To transition from structural reconstruction to functional remodeling, future research should emphasize artificial intelligence-driven data integration, organ-on-a-chip modeling, and cross-disciplinary collaboration to overcome existing technical barriers and accelerate the clinical application of neuroregenerative therapies.

artificial intelligence↗

PubMed1992

Pretreatment anxiety level as differential predictor in outpatients with panic disorder.

The pretreatment anxiety level is supposed to be a very important unspecific treatment factor. Main purpose of this study is to test whether the patients' pretreatment anxiety level is a general or a specific predictor of treatment response and whether mildly, moderately, and severely anxious patients can be differentially characterized by other diagnostic and clinical variables. 103 patients (37 males, 66 females; mean +/- sd age 35.6 +/- 9.5 years), a subsample of the Second Phase of the Cross-National Collaborative Panic Study, were included in the present study. A high positive correlation of initial anxiousness with the number of panic attacks at the end of treatment was found, moreover high positive correlations with most other baseline assessments. Initially severely anxious patients are the severest ill patients with the least treatment response, and that in all treatment groups. The pretreatment anxiety level predicts the number of panic attacks as well as the degree of avoidance behavior in both drug groups, whereas it predicts anticipatory anxiety intensity in the placebo group.

Adult↗

PubMed1991

The Health of the Public Program at the University of Washington: a new role for academic medical centers.

The University of Washington Health of the Public Program has convened a consortium composed of the region's academic medical center, the two largest managed care plans in Washington, and representatives of the state's major private and public purchasers of health care. The consortium's purpose is to test the feasibility of collaboratively collecting cross-system data, assessing variations in practice, and implementing site-specific interventions to improve the management of common illnesses and encourage preventive care. Changes under way in the ambulatory training environment and in the undergraduate curriculum as a result of the consortium's initial efforts are described. In today's climate of cost consciousness and concerns about quality, academic medical centers can play an important role in helping to improve community-wide outcomes of care.

Academic Medical Centers↗

PubMed1992

A psychodynamic approach to the master treatment plan.

Formulating master treatment plans for the hospital treatment of psychiatric patients is especially challenging to psychodynamically oriented clinicians unaccustomed to reducing complex intrapsychic and interpersonal phenomena to specific observable behaviors. In collaboration with a wide cross section of hospital staff members, the authors developed a conceptual framework for treatment plans compatible with psychodynamic thinking. They describe the treatment evaluation research from which the format of the treatment plan evolved, as well as the guide they developed to facilitate its implementation .

Activities of Daily Living↗

PubMed1989

Specificity of antigens on UV radiation-induced antigenic tumor cell variants measured in vitro and in vivo.

In vitro exposure of nonimmunogenic murine tumor cells to UV radiation (UVR) generates highly antigenic variants that are immunologically rejected by normal, syngeneic mice. The purpose of this study was to determine whether these antigenic variants cross-react immunologically with the parental tumor and whether the UVR-associated antigen unique to UVR-induced tumors is also present on the variants. Antigenic (regressor) variants and nonimmunogenic (progressor) clones derived from UV-irradiated cultures of the C3H K1735 melanoma and SF19 spontaneous fibrosarcoma cell lines were used to address these questions. In an in vivo immunization and challenge assay, the antigenic variants did not induce cross-protection among themselves, but each induced immunity against the immunizing variant, the parent tumor cells, and nonimmunogenic clones derived from UV-irradiated parent cultures. Therefore, the variants can be used to induce in mice a protective immunity that prevents the growth of the parent tumor and nonimmunogenic clones, but not other antigenic variants. In contrast, immunization with cells of the parental tumor or the nonimmunogenic clones induced no protective immunity against challenge with any of the cell lines. Utilizing the K1735 melanoma-derived cell lines in vitro, T-helper (Th) cells isolated from tumor-immunized mice were tested for cross-reactivity by their ability to collaborate with trinitrophenyl-primed B-cells in the presence of trinitrophenyl-conjugated tumor cells. Also, the cross-reactivity of cytotoxic T-lymphocytes from tumor-immunized mice was assessed by a 4-h 51Cr-release assay. Antigenic variants induced cytotoxic T-lymphocytes and Th activity that was higher than that induced by the parent tumor and nonimmunogenic clones from the UVR-exposed parent tumor and cross-reacted with the parental tumor cells and nonimmunogenic clones, but not with other antigenic variants. Furthermore, upon transplantation, the UVR-induced antigenic variants grew in UV-irradiated and immunosuppressed mice, but not in untreated mice indicating that the variants expressed the determinant recognized by suppressor T-cells present in UV-irradiated mice. These results demonstrate that highly antigenic cells generated by the in vitro exposure of two different murine tumors to UV radiation express a determinant shared with the parental tumor cells and nonimmunogenic clones, a unique variant-specific determinant and the suppressor cell-defined determinant present on UVR-induced tumors. Based on these results, two models are proposed to explain the make-up of the antigenic determinants present on the UVR-induced antigenic variants.

Animals↗

PubMed2026

A One Health approach to Antimicrobial Resistance: Concepts, challenges, and advances in omics.

Antimicrobial resistance (AMR) is a global threat driven by the interplay between microbial evolution and human activity. Antimicrobial use in human and veterinary medicine, as well as in agriculture, accelerates the selection and dissemination of resistant bacteria and genes across interconnected human, animal, and environmental reservoirs. These dynamic exchanges render single-sector interventions ineffective. A One Health approach integrating human, animal, and environmental health is therefore essential to understand and mitigate the emergence and spread of AMR. This chapter focuses on bacterial antimicrobial resistance, addressing key concepts, major challenges, and emerging technologies within a One Health framework. Advances in next-generation sequencing and omics technologies have transformed our capacity to resolve AMR at unprecedented scale and resolution. These tools enable the tracking of resistance genes and high-risk clones across ecosystems, uncover transmission pathways, and identify key drivers of dissemination. Such insights support real-time epidemiological surveillance, outbreak detection, and targeted interventions. However, translating these advances into routine practice remains a major challenge, requiring harmonized methodologies, data integration, and cross-sector coordination. Addressing AMR demands sustained collaboration across disciplines and stakeholders, including clinicians, veterinarians, farmers, researchers, policymakers, industry, and the public. And framing AMR as a shared ecological and societal responsibility underscores the urgency of coordinated global action. We call for the urgent integration of One Health principles into surveillance, policy, and innovation to preserve antimicrobial effectiveness and safeguard future health.

Humans↗

PubMed1986

HLA-B POT: a new HLA-antigen within the B7-cross reactive group.

In this report, a new HLA-B locus antigen is described (tentatively called POT). The antigen has been identified with antisera against the antigens that belong to the B7-cross reacting group. In a collaborative study, based on exchange of cells and sera, it was confirmed by population and family studies that the antigen is distinct from B7, Bw42 or Bw73 and is associated with Bw6. In absorption experiments with EBV-transformed cell lines, the POT-antigens removes preferentially anti-B7, Bw42 and Bw73 activity and to a lesser extent antibodies reactive with the B40 CREG-antigens.

Cross Reactions↗

PubMed1978

Cooperative cross-linking between two sets of membrane receptors: a model for B and T lymphocyte collaboration in immune response.

A molecular mechanism for B and T lymphocyte collaboration is proposed. Two sets of polivalent receptors, each one on a cell type, would interact with different epitopes of the antigen, resulting in a cross-linking of the receptors as the initial step in B lymphocyte activation. The mechanism can explain many known featrues of humoral immune response and accords with experimental findings on the blast transformation of B lymphocytes.

Antibody Formation↗