[Fear of childbirth among nulliparous women: Relations with pain during delivery, post-traumatic stress symptoms, and postpartum depressive symptoms]. / La peur de l'accouchement chez des nullipares: lien avec la douleur lors de l'accouchement, les symptômes de stress post-traumatique et les symptômes dépressifs post-partum.

OBJECTIVE: Fear of childbirth is common in women who are pregnant with their first child and is associated with important consequences such as abortions and miscarriages. Twenty percent of nulliparous women seem to exhibit a mild or moderate fear, while 6% present an excessive and irrational fear known as tocophobia. Tocophobia is suggested to be associated with many negative consequences such as postpartum depression (PPD) and Post-traumatic stress (PTS). However, there is little empirical evidence to support these relationships. Recently, Fairbrother and Woody (2007) did not observe a link between the fear of childbirth and symptoms of PPD and PTS in nulliparous women. Some results, near the significance level, could be explained by a lack of statistical power. The present study focused on the link between the fear of childbirth and the process of delivery, the perception of pain, PPD and PTS. More specifically, it aimed to test three hypotheses: (i) fear of childbirth will be linked to the process of delivery, especially regarding the perception of pain, the use of anaesthesia and the use of Caesarean section; (ii) a high level of fear of childbirth will be associated with more negative postpartum consequences (namely PPD/PTS symptoms); (iii) the process of delivery and pain will also be related to post-delivery symptoms. Mediation effects were tested. METHOD: Data from a longitudinal study were used to meet the hypotheses. A total of 176 nulliparous pregnant women responded to questionnaires at two time measurements (during pregnancy and at 5weeks postpartum). RESULTS: Fear of childbirth is related to the perception of pain at birth among women delivering vaginally, in the absence of anaesthesia. It is also linked to symptoms of PPD and PTS, regardless of whether or not anaesthesia was used. Fear of childbirth also appears to be strongly associated to symptoms of PTS in women who have experienced an unplanned caesarean section. Thus, symptoms of postpartum PTS could play a mediating role in the link between fear of childbirth and PPD. CONCLUSIONS: These results support the relevance of taking into account the fear of childbirth and perception of pain in connection with symptoms of PTS and PPD in nulliparous women. The unplanned caesarean section (including emergency caesarean) also appears to be important in the study of the relationship between fear and symptoms of PTS. Fear of childbirth could render the experience of childbearing more negative and predispose to PTS and PPD. Enabling psychological vulnerabilities could also be an interesting avenue for understanding these links. Limitations are discussed.

The systemic control of circadian gene expression.

The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.

New immediate release formulation for deterring abuse of methadone.

CONTEXT: Drug abusers are known to take a dosage form containing an opioid analgesic and crush, shear, grind, chew, or dissolve it in water or in alcohol, in order to extract the opioid component. OBJECTIVE: Develop an anti abuse immediate release formulation using methadone as model drug. MATERIALS AND METHODS: Tablets combining methadone and alkalizing agents were manufactured. A methadone assay was used to determine extraction efficiency from tablets in aqueous and alcohol solvents. In vitro dissolution testing was used to determine drug release in different media. RESULTS AND DISCUSSIONS: Meglumine-based formulations prevented extraction of 70 to 100% of methadone from tablets. Addition of this alkalizing agent caused methadone to precipitate out of a solution along with other ingredients and be retained on standard filters. Meglumine-containing and control tablets showed similar dissolution profiles in acidic media, suggesting adequate solubilisation of the drug early in the gastrointestinal tract. Finally, stability upon storage of the formulations for 6 months at 25°C/60%RH and 40°C/75%RH was confirmed. CONCLUSION: Incorporation of an alkalizing agent into methadone tablets significantly reduced the preparation of a methadone solution for intravenous administration and abuse, while allowing the formulation to release methadone in gastric media and provide desired pharmacological effect.

Secular trends of hip fractures in Québec, Canada.

UNLABELLED: This study examined the secular trends of hip fracture incidence among individuals 50 years and older in Québec between 1993 and 2004. Age-standardized rates decreased at both the provincial and regional levels. The largest relative decrease was observed among younger females, and rates declined more slowly in the elderly. INTRODUCTION: The population of the province of Québec is among the oldest in North America. Before the trend rupture reported in the late 1990s in several countries, hip fracture (HF) incidence rates did not show a secular trend (between 1981 and 1992). This study examined the secular trends of HF incidence at the provincial level and in two of the most important urban areas of the province, Montréal and Québec City, between 1993 and 2004. METHODS: All hospitalisations of individuals 50 years and older living in the province of Québec between 1993 and 2004 with a main diagnosis of HF were included. Standardized rates of HF incidence were calculated for females and males, 50-74 years and 75 years and older. RESULTS: The Québec City area showed a strong decreasing trend in HF rates for younger females, but the other groups did not show an obvious trend. Although our models did not support the existence of significant differences in trends between both areas, the rates of HF of younger males and, to a lesser extent, of older women in the Montréal area were significantly higher than in the Québec City area. CONCLUSIONS: Differences observed in hip fracture rates as well as in secular trends between age groups and gender emphasise the need for decision makers to rely on results based on age-specific and sex-specific analyses.

Environmental characteristics associated with campylobacteriosis: accounting for the effect of age and season.

Campylobacteriosis is a leading cause of acute bacterial gastroenteritis. An ecological study was undertaken to explore the association between environmental characteristics and incidence of campylobacteriosis in relation to four age groups and two seasonal periods. A multi-level Poisson regression model was used for modelling at the municipal level. High ruminant density was positively associated with incidence of campylobacteriosis, with a reduced effect as people become older. High poultry density and presence of a large poultry slaughterhouse were also associated with higher incidence, but only for people aged 16-34 years. The effect of ruminant density, poultry density, and slaughterhouses were constant across seasonal periods. Other associations were detected with population density and average daily precipitation. Close contacts with farm animals are probably involved in the associations observed. The specificity of age and season on this important disease must be considered in further studies and in the design of preventive measures.

[French adaptation and validation of a scale measuring the fear of childbirth]. / Évaluation de la peur de l'accouchement. Validation et adaptation française d'une échelle mesurant la peur de l'accouchement.

OBJECTIVES: The fear of childbirth, a central aspect of tokophobia, recently started to capture the attention of the scientific community as a potential determinant of obstetric and post-natal complications. However, studies on this subject are still few and this can be partly explained by the lack of validated instruments, especially in French. This paper presents the results from two studies designed to develop and evaluate the psychometric properties of a French version of the Traumatic Event Scale (TES), adapted to assess fear of childbirth (Söderquist et al., 2004 [21]). METHOD: The first study presents details regarding the development of this scale and checks the quality of the resulting items as well as their internal consistency, convergent validity and factorial validity. This study relied on a sample of 65 mothers with at least one child under the age of 36 months. In the second study, the psychometric properties of the instrument developed in Study 1 were tested more systematically on a sample of 204 women who were at the time experiencing their first pregnancy. RESULTS AND CONCLUSION: The results from the first study show adequate psychometric properties, strong correlations with measurements assessing worry, and support a five factor model. Results from this second study replicated the results from the first one on the basis of confirmatory factor analyses. Findings presented in these studies confirm that this instrument presents very good psychometric properties as a measurement of the fear of childbirth in pregnant women.

Mortality and morbidity peaks modeling: An extreme value theory approach.

Hospitalizations and deaths belong to the most studied health variables in public health. Those variables are usually analyzed through mean events and trends, based on the whole dataset. However, this approach is not appropriate to comprehend health outcome peaks which are unusual events that strongly impact the health care network (e.g. overflow in hospital emergency rooms). Peaks can also be of interest in etiological research, for instance when analyzing relationships with extreme exposures (meteorological conditions, air pollution, social stress, etc.). Therefore, this paper aims at modeling health variables exclusively through the peaks, which is rarely done except over short periods. Establishing a rigorous and general methodology to identify peaks is another goal of this study. To this end, the extreme value theory appears adequate with statistical tools for selecting and modeling peaks. Selection and analysis for deaths and hospitalizations peaks using extreme value theory have not been applied in public health yet. Therefore, this study also has an exploratory goal. A declustering procedure is applied to the raw data in order to meet extreme value theory requirements. The application is done on hospitalization and death peaks for cardiovascular diseases, in the Montreal and Quebec metropolitan communities (Canada) for the period 1981-2011. The peak return levels are obtained from the modeling and can be useful in hospital management or planning future capacity needs for health care facilities, for example. This paper focuses on one class of diseases in two cities, but the methodology can be applied to any other health peaks series anywhere, as it is data driven.

Transcription of the mouse secretory protease inhibitor p12 gene is activated by the developmentally regulated positive transcription factor Sp1.

We have previously shown that a trans-acting protein produced in some tissue culture cells positively control the transcriptional activity directed by the mouse p12 promoter. This nuclear protein exerts its positive activity by interacting with a regulatory sequence designated p12.A and located between the TATA and CCAAT box elements on the p12 gene promoter. Using DNase I and dimethyl sulfate methylation interference footprinting techniques coupled with gel retardation assays, we found evidence that the protein which binds to the p12.A element is the well-known transcription factor Sp1. Mutational analysis in transient transfection assays confirmed the positive activity exerted by this protein in every cell line tested. In agreement with this observation, we detected a p12.A-Sp1 binding activity in nuclear extracts prepared from all cell lines used. However, a similar binding activity could not be detected in a number of nuclear extracts prepared from normal mouse tissues. In this report, we provide the evidence that the lack of Sp1-binding activity results from the degradation of Sp1 in the kidney, liver, and pancreas of the mouse.

Two distinct protein isoforms are encoded by ntk, a csk-related tyrosine protein kinase gene.

Recently, we and others have cloned cDNAs encoding a second member of the Csk family of inhibitory tyrosine protein kinases, which we have termed Ntk. Intriguingly, the mouse ntk cDNA sequences published by two independent groups differed by the presence or absence of a 136 nucleotide-insert near their 5' ends. In this report, we demonstrate that this 136 nucleotide-sequence likely corresponds to a complete exon in the ntk gene (termed exon 2), and that the two types of cDNAs/transcripts are produced by alternative splicing. Using ribonuclease protection assays, it was also established that brain and lymphoid organs, as well as most hemopoietic cells, predominantly expressed ntk transcripts lacking exon 2. In contrast, selected hemopoietic cell lines, such as the immature myeloid cell lines 32D cl3(G) and WEHI-3B, exclusively possessed exon 2-bearing RNAs. Interestingly, exon 2 introduced a novel in-frame upstream AUG in the ntk transcript, which is in the appropriate context for translation initiation. Evidence was obtained that this AUG is utilized in vivo, and that it extends the amino-terminal sequence of Ntk by 40 amino acids. Indeed, while exon 2-deficient ntk RNAs were translated into a 52 kilodalton (kDa) polypeptide (p52ntk), those bearing exon 2 produced a 56 kDa protein (p56ntk). Furthermore, p56ntk, but not p52ntk, was recognized by an antiserum directed against the novel amino-terminal sequence encoded by exon 2. Additional biochemical characterizations showed that p52ntk and p56ntk were localized to the cytoplasm, and that they partially accumulated in the detergent-insoluble cellular fraction. This last finding suggested that the Ntk proteins can associate with the cytoskeleton. Finally, through linkage analysis of two multilocus crosses, the ntk gene was mapped to Chromosome 10 in the mouse. Taken together, these data showed that ntk, a csk-related tyrosine protein kinase gene, encodes two protein isoforms expressed in distinct cell types. Moreover, they raised the possibility that Ntk may be involved in the regulation of Src-like enzymes in detergent-insoluble cellular compartments.

Multicentric evaluation of the MDR phenotype in leukemia. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

The wide discrepancies in the frequency of 'positive' samples for multidrug resistance (MDR) phenotype within the same type of tumor observed in the literature justified the need for the definition of consensus recommendations. To define standard techniques of MDR phenotype measurement, we ran a large multicentric evaluation of the different methods available. Thirty-six French centers participated in the study, and 742 samples of 2-10 x 10(6) viable cells were sent by overnight express mail between December 1993 and February 1996. The same batches of MRK16, 4E3 and UIC2 were used. Nineteen samples of leukemia (12 AML, 1 ALL, 6 lymphoproliferative syndromes) and six leukemic cell lines with different levels of MDR expression were tested. Five meetings reached agreement concerning the guidelines for each technique, except immunocytochemistry. The 19 fresh samples were tested by each center using one to four techniques among cytofluorometry, immunocytochemistry, functional tests and RT-PCR. Five samples were diagnosed as 'negative' according to local criteria, with few discordant results (0 to 16% of 'positive' results). For all the 14 remaining samples, large discrepancies were observed from center to center, and from one technique to another. No correlations could be found between techniques. Flow cytometric analysis of cells already exposed to MRK16 or control IgG2A, fixed in paraformaldehyde and sent to centers did not reduce the discrepancies between centers in two of the four samples with moderate expression, emphasizing the role of histogram interpretation. The use of alternative monoclonal antibodies (4E3 and UIC2) did not reduce the discrepancies observed. In a second step, the K562 parental cell line, a low resistant subline (K562/HHT100, x7 resistance index to DNR) and a high resistant subline (K562/HHT300, x125 resistance index to DNR) were sent blindly three times, with an increasing level of recommendations for flow cytometry. Dramatic improvements were observed in cytometric results when the result was expressed as the ratio of arithmetic mean of fluorescence of antibody (10 microg of MRK16)/arithmetic mean of fluorescence of control (10 microg IgG2A): the proportion of expected results increased from 61 to 100% for K562, and from 37 to 85% for K562/HHT100. For uptake and drug efflux measurements, the use of 1 h uptake of 0.1 microM of rhodamine, followed by 1 h efflux +/-10 microM of verapamil, permitted an increased reproducibility of the technique from 71 to 100% for K562 and K562/HHT100. Whatever the technique used, concordant results were obtained for K562/HHT300. The immunocytochemistry, using several antibodies (MRK16, JSB1 and C219) gave many non-interpretable results (44%), due to a frequent high background and discordant results between antibodies in the same centers, and discordant conclusions between centers. The group does not recommend this technique for circulating tumoral cells.

Induction of DAP12 phosphorylation, calcium mobilization, and cytokine secretion by Ly49H.

The ability of several Ly49 family members to inhibit natural killer (NK) cell functions through recruitment of SHP-1 phosphatase has been reported. In contrast, the mechanisms underlying the activating signal generated by Ly49D are poorly understood. A homodimeric phosphoprotein (pp16) that physically and functionally associates with Ly49D has been described. In this study, a rabbit anti-mouse pp16 antiserum was generated and used to demonstrate that pp16 corresponds to the recently described DAP12 molecule. In addition, we show that a second Ly49 family member that lacks an immunoreceptor tyrosine-based inhibitory motif and contains a charged residue in the transmembrane domain, Ly49H, also associates with DAP12. Furthermore, we show that engagement of the Ly49H/DAP12 complex results in phosphorylation of DAP12, intracellular calcium mobilization, and tumor necrosis factor secretion in transfected cells. These results thus provide evidence that Ly49H is an activating receptor that associates with DAP12, previously described as a pp16 component of the Ly49D receptor complex.

The murine NK2.1 antigen: a 130 kD glycoprotein dimer expressed by a natural killer cell subset of the spleen, thymus and lymph nodes.

Murine natural killer (NK) cells express a few antigens not found on other leukocyte subsets. The NK1.1 antigen, that is present in only a few mouse strains, has been extensively characterized whereas our knowledge of the NK2.1 antigen, which is more commonly expressed, remains, as yet, limited. Our laboratory has previously reported the production of a mAb (4LO3311) recognizing a murine NK cell-specific molecule with a similar strain distribution as the NK2.1 antigen formerly defined with an NZB anti-BALB/c antiserum. In this study, we demonstrate by sequential immunoprecipitation that 4LO3311 represents the first NK2.1 antigen-specific mAb. This reagent was used to immunoprecipitate the NK2.1 antigen from 125I-labeled lysates of fresh NK-enriched spleen cells. SDS-PAGE analyses revealed that the NK2.1 antigen is expressed at the cell surface as a N-glycosylated disulfide-linked protein dimer with approximately 65 kD subunits. The NK2.1 antigen is likely to be anchored in the plasma membrane by a peptide moiety since its expression on NK cells was not affected by treatment with phosphatidylinositol-specific phospholipase C. In addition to be present on a splenic NK cell subset, the NK2.1 antigen is shown to be expressed by a small number of CD4-CD8-thymocytes and by a subset of CD4-CD8-IgG- lymph node cells. Finally, it is shown here that unlike the NKR-P1, the rat homologue of the murine NK1.1 antigen, neither the NK2.1 nor the NK1.1 antigen is expressed by polymorphonuclear leukocytes.

A short protocol for micro-purification of nuclear proteins from whole animal tissue.

Although a number of small-scale procedures have been described for the preparation of crude nuclear extracts from established cell lines, none were provided for the preparation of similar extracts from small amounts of animal tissue. In addition, no small-scale procedures contain enrichment steps that render the detection of low-abundant DNA-binding proteins easier. Here we describe a simple, efficient procedure for the rapid preparation of high-quality nuclear extracts from either whole animal tissue or established cell lines. It is based on a rapid isolation of the nuclei followed by a KCl extraction and a further micro-enrichment of the DNA binding proteins on heparin Sepharose CL-6B. Extracts prepared in such a way are suitable for the analysis of specific DNA/protein interactions by the use of gel shift assays or by DNaseI and dimethylsulfate footprinting techniques. Most importantly, the entire process can be fulfilled at minimal cost within a day on as little as one gram of fresh tissue, which renders this procedure extremely attractive for the analysis of DNA binding proteins involved in the control of gene expression.

Polymerase chain reaction using arbitrary primer for the design and construction of a DNA probe specific for Porphyromonas gingivalis.

In this work, we used a novel approach for the design and construction of DNA probes which requires no knowledge of target DNA sequence. We demonstrated that species-specific genetic markers, identified as such among monomorphic, randomly amplified DNA segments generated by the polymerase chain reaction with arbitrary primer can be labelled to yield so-called "anonymous probes". We report here on the construction of such an anonymous probe, 1146 bp long, specific for the Gram-negative anaerobe Porphyromonas gingivalis, a suspected major etiologic agent of chronic periodontitis in adults.

Expression of ps2 and cathepsin-d in breast-cancer.

Cytosolic levels of pS2 and Cathepsin D (Cath D) were compared in 145 primary breast cancer patients using the immunoradiometric (IRMA) assays ELSA-pS2-degrees and ELSA-Cath. D-degrees of Cis biointernational. The mean values were 20.04 +/- 41.75 ng pS2/mg of cytosol protein (cp) and 49.94 +/- 33.71 pmol Cath D/mg cp. The pS2 level was significantly associated with Estrogen Receptor (ER), Progesterone Receptor (PgR) and Cath D levels. Significant associations were also found between Log (pS2) or Log (Cath. D) and differentiation grade (SBR), between Log (pS2) and ER (+,-) or PgR (+,-), between Log (Cath. D) and PgR (+,-). No correlations were noted between Log (pS2) or Log (Cath D) and menopausal status, tumor size (T) and lymph node involvement (N), between pS2 and age, between Cath D and age, ER and PgR, between Log (Cath D) and ER (+,-). Contrary to Cath D, pS2 was strongly linked to steroid receptors.

Drug resistance in oncology: from concepts to applications.

The complex problem of drug resistance is discussed with respect to host toxicity, to tumor characteristics (kinetic resistance, heterogeneity of cell subpopulations, hypoxia, mutation and gene amplification), and to the medication itself (pharmacokinetic and pharmacodynamic resistance: cell membrane, intracellular metabolism, intracellular target). After detailing each type of resistance, the possibilities of fighting against drug resistance are explored (dealing with host toxicity, tumor characteristics and drugs--intensifying therapy, multiple drug therapy, biochemical modulation, particular modalities of drug administration). Finally, perspectives of research and development of new drugs are summarized.

Components and recognition of facial expression in the communication of emotion by actors.

This article addresses the issue of the communication of emotion by actors. In Study 1, the facial behavior of 6 actors portraying emotions as felt or unfelt were analyzed with the Facial Action Coding System. Results indicated that the portrayals of felt emotions were closer to the expression of genuine emotion than the portrayals of unfelt emotions for 3 of the 6 emotions under investigation. Study 2 examined the decoding of actors' portrayals from facial behavior. Decoders were found to be very accurate in recognizing the emotional category but not in judging the encoding condition.

An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3.

A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients.

Hypothyroidism following combined treatment for hypopharyngeal and laryngeal carcinoma.

The development of hypothyroidism following combined treatment for pharyngeal and laryngeal cancer has received little attention in the literature. We prospectively studied 32 patients over 4 years to determine the incidence of such hypothyroidism and to examine the effect of hemithyroidectomy associated with a combined treatment modality. All patients were men with pharyngeal or laryngeal squamous cell carcinomas and no prior history of thyroid disease. Treatment consisted of radical surgery (30 of 32 patients), followed by postoperative radiotherapy (31 patients). The results of thyroid function tests (free triiodothyronine, free thyroxine, and thyroid-stimulating hormone [TSH]) were all normal preoperatively; tests were repeated every 3 months after treatment. Elevation of TSH values in two successive blood samples was required to make a diagnosis of hypothyroidism. Of 12 patients who underwent hemithyroidectomy as part of total pharyngolaryngectomy and postoperative radiotherapy, 7 became hypothyroid a mean of 6 months after treatment. Twenty patients had similar combined treatment but without thyroid resection. Hypothyroidism developed a mean of 10 months after treatment in only four patients in this group (p less than 0.05). We conclude that hypothyroidism frequently develops following combined treatment for pharyngeal and laryngeal cancer even when thyroid resection has not been performed. Patients should be evaluated postoperatively and carefully monitored by means of serial thyroid function tests.

Experimental manipulation of intolerance of uncertainty: a study of a theoretical model of worry.

Intolerance of uncertainty has been identified as an important variable related to worry and Generalized Anxiety Disorder (GAD) [Dugas, M. J., Gagnon, F., Ladouceur, R., & Freeston, M. H. (1998). Generalized anxiety disorder: a preliminary test of a conceptual model. Behaviour Research and Therapy, 36, 215-226; Ladouceur, R., Dugas, M. J., Freeston, M. H., Rhéaume, J., Blais, F., Boisvert, J.-M., Gagnon, F., & Thibodeau, N. (1999). Specificity of Generalized Anxiety Disorder symptoms and processes. Behavior Therapy, 30, 197-207]. The goal of the present study was to clarify the relationship between this cognitive process and worry by experimentally manipulating intolerance of uncertainty. A gambling procedure was used to increase intolerance of uncertainty in one group (N = 21) and to decrease intolerance of uncertainty in another group (N = 21). The results indicate that participants whose level of intolerance of uncertainty was increased showed a higher level of worry, compared to participants whose level of intolerance of uncertainty was decreased. These results provide some initial clarifications as to the causal nature of the link between intolerance of uncertainty and worry. These results are coherent with our theoretical model of worry and GAD (Dugas et al., 1998), which stipulates that intolerance of uncertainty plays a key role in the acquisition and maintenance of excessive worry.