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Introduction: Recurrence of splenic volvulus after splenopexy in children is rare. A consensus on the optimal surgical strategy in splenic volvulus is lacking. Case Presentation: An 11-year-old female presented left upper quadrant abdominal pain for 24 hours following a short-lived appearance of an epigastric bulge. A CT-scan demonstrated findings consistent with splenic volvulus, without distal arterial flow. She underwent an exploratory laparoscopy, splenic detorsion, and splenopexy to the abdominal wall using two non-resorbable, knotless, unidirectional barbed sutures. The patient was discharged on day 2 after the procedure. A 6-month follow-up ultrasound showed a normally perfused spleen. Then months after the operation she presented with the same abdominal symptoms. A CT scan confirmed the recurrence of the splenic volvulus. She underwent a second laparoscopy, splenic detorsion, and splenopexy with a tailor-made mesh bag anchored to the abdominal wall. She recovered well from that operation. At 10 months of follow up she has had no recurrent of symptoms and the spleen is well vascularized by ultrasound. Conclusion: Simple splenopexy using direct sutures to abdominal wall may not be sufficient to create adequate adhesions and prevent recurrence. The use of a mesh may have a higher success rate.

À partir d’une série d’entretiens et d’un corpus de documents, l’article analyse la manière dont les professionnels qui produisent et promeuvent des souvenirs numériques mobilisent des discours éthiques pour défendre leurs produits à travers deux exemples : d’une part, celui de la construction des algorithmes qui sélectionnent les souvenirs et, d’autre part, celui de l’incitation au partage des souvenirs. Ces deux exemples permettent de mettre en évidence les ressorts matériels des positionnements éthiques adoptés par les professionnels des souvenirs numériques, qui fonctionnent comme des arguments de justification a posteriori. L’article se conclut en inscrivant ce travail symbolique de requalification de contraintes matérielles en positions éthiques dans les stratégies d’« ethics-washing » (Green, 2021) des industries de la tech.

Abstract Background The aims of the “médecin traitant” or referring physician (RP) reform, introduced in France in 2004, were to improve the organisation and quality of care and to allow for greater equity, particularly in terms of prevention. The objective of our study was to evaluate the effect of having a declared RP on the uptake of screening for breast and cervical cancers, and to explore the mechanisms involved. Methods We used an existing dataset of 1,072,289 women, which combines data from the Health Insurance information systems, with census data. We built multivariable logistic regression models to study the effect of having a RP on the uptake of mammography and pap smear, adjusted for age, socio-economic level, health status and healthcare provision. We secondarily added to this model the variable “having consulted a General Practitioner (GP) within the year”. Finally, we evaluated the interaction between the effect of having a referring physician and the area of residence (metropolitan/urban/rural). Results Patients who had a declared RP had a significantly higher uptake of mammography and pap smear than those who did not. The strength of the association was particularly important in very urban areas. The effect of having visited a GP seemed to explain a part of the correlation between having a RP and uptake of screening. Conclusions Lower rates of gynaecological screening among women without an RP compared to those with an RP may partly reflect a specific behaviour pattern in women less adherent to the health care system. However, this result also shows the importance of the RP, who assumes the key role of relaying public health information in a more personalised and adapted way.

Assez méconnues dans leur diversité, les procédures d’initiative populaire sont de plus en plus présentes dans les constitutions des États. Permettant aux citoyens d’être plus directement impliqués dans le processus normatif et dans le contrôle de l’activité de leurs représentants, de telles procédures tentent de répondre à la défiance citoyenne et de donner plus de légitimité à la manière dont fonctionnent les démocraties. Dans les travaux de recherche, elles sont généralement appréhendées à travers l’étude d’un système juridique en particulier ou d’un type de mécanisme. Ainsi, les procédures de référendum d’initiative populaire, appelées « initiatives populaires directes », ont tendance à mobiliser les commentaires de la doctrine et des médias en raison de leur visibilité et de la radicalité de certains sujets adoptés. Les initiatives populaires indirectes, ou d’agenda, sont beaucoup moins étudiées et pourtant sont souvent présentes à l’échelle nationale et même supranationale, à l’instar de l’Initiative citoyenne européenne. Les initiatives suspensives ou abrogatives sont également prévues dans certains États mais, à l’exception de l’Italie et de la Suisse, font l’objet de peu de commentaires. Les procédures révocatoires, permettant notamment d’éprouver les choix effectués par les élus ou leur probité au cours d’un mandat, font l’objet d’études qui restent souvent cantonnées aux États-Unis. L’intérêt de cette contribution est de proposer une typologie des différentes formes d’initiatives populaires pour témoigner de la richesse des mécanismes consacrés en droit constitutionnel. Même si beaucoup de ces initiatives échouent à atteindre leur objectif premier, elles peuvent contribuer à sensibiliser les élus aux effets de leurs choix et comportements et attirer l’attention de l’ensemble de la communauté politique sur certains sujets.

Abstract Background To promote improved coordination between general practice and hospital, the French clinical trial CREDO (“Concertation de REtour à DOmicile”) is testing an innovative experimental consultation for patients with metastatic cancer who are returning home. This consultation involves the patient, the patient’s referring GP (GPref) and a GP with specific skills in oncology (GPonc) in a specialized care center. The objective of our study is to explore the satisfaction of GPsref about this consultation, in the phase of interaction between GPonc and GPref. Methods This observational, cross-sectional, multicenter study explored the satisfaction of GPsref who had participated in this type of consultation, via a telephone survey. Results One Hundred GPsref responded to the questionnaire between April and September 2019 (overall response rate: 55%). 84.5% were satisfied with the consultation, and the majority were satisfied with its methods. Half of the GPsref learned new information during the consultation, three-quarters noted an impact on their practice, and 94.4% thought that this type of coordination between the GPref and the oncology specialist could improve general practice - hospital coordination. Conclusions For GPs, the CREDO consultation seems to be practical and effective in improving the coordination between general medicine and hospital. GPs would benefit from such coordination for all patients with cancer, several times during follow-up and at each occurrence of a medically significant event.

Background: Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies. Methods: We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment. Results: Of 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT.In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 [0.97; 1.74], but taxanes was significantly associated with worse PFS (HZR = 1.48 [1.14; 1.93]).In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 [0.79; 1.44] and HZR = 0.81 [0.58; 1.13], respectively), while for PFS, taxanes was inferior (HZR = 1.33 [1.06–1.67]) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 [0.46; 0.87]).For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab. Conclusions: With the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.

Physical and societal risks across the natural, managed, and built environments are becoming increasingly complex, multi-faceted, and compounding. Such risks stem from socio-economic and environmental stresses that co-evolve and force tipping points and instabilities. Robust decision-making necessitates extensive analyses and model assessments for insights toward solutions. However, these exercises are consumptive in terms of computational and investigative resources. In practical terms, such exercises cannot be performed extensively—but selectively in terms of priority and scale. Therefore, an efficient analysis platform is needed through which the variety of multi-systems/sector observational and simulated data can be readily incorporated, combined, diagnosed, visualized, and in doing so, identifies “hotspots” of salient compounding threats. In view of this, we have constructed a “triage-based” visualization and data-sharing platform—the System for the Triage of Risks from Environmental and Socio-Economic Stressors (STRESS)—that brings together data across socio-environmental systems, economics, demographics, health, biodiversity, and infrastructure. Through the STRESS website, users can display risk indices that result from weighted combinations of risk metrics they can select. Currently, these risk metrics include land-, water-, and energy systems, biodiversity, as well as demographics, environmental equity, and transportation networks. We highlight the utility of the STRESS platform through several demonstrative analyses over the United States from the national to county level. The STRESS is an open-science tool and available to the community-at-large. We will continue to develop it with an open, accessible, and interactive approach, including academics, researchers, industry, and the general public.

The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.

This paper investigates brain–behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

Introduction The combination of a CDK4/6 inhibitor with an aromatase inhibitor (AI) has recently become the gold standard for AI-sensitive first line treatment of oestrogen receptor-positive (ER+) HER2-negative (HER2−) advanced breast cancer. However, most patients receiving this combination will ultimately progress and require further therapies.Several studies have demonstrated that the onset of a ESR1 gene mutation lead to AIs resistance in the advanced setting. ESR1 mutations can be detected in circulating tumour DNA (ctDNA) using a digital PCR assay. Our study aims to prove the clinical efficacy of periodic monitoring for emerging or rise of ESR1 mutations in ctDNA to trigger an early change from AI plus palbociclib to fulvestrant plus palbociclib treatment while assessing global safety.Methods PADA-1 is a randomised, open-label, multicentric, phase III trial conducted in patients receiving AI and palbociclib as first line therapy for metastatic ER +HER2- breast cancer. 1000 patients will be included and treated with palbociclib in combination with an AI. Patients will be screened for circulating blood ESR1 mutation detection at regular intervals. Patients for whom a rising circulating ESR1 mutation is detected without tumour progression (up to N=200) will be randomised (1:1) between (1) Arm A: no modification of therapy; and (2) Arm B: palbociclib in combination with fulvestrant, a selective ER down-regulator. At tumour progression, an optional crossover will be offered to patients randomised in arm A. The coprimary endpoints are (1) Grade ≥3 haematological toxicities and their associations with baseline characteristics and (2) progression-free survival in randomised patients.Ethics and dissemination The study has been approved by the French medicines agency (ANSM) and by an ethics committee (ref 01/17_1 CPP Ouest-IV Nantes) in January 2017. The trial results will be published in academic conference presentations and international peer-reviewed journals.Trial registration numbers EudraCT: 2016-004360-18; NCT03079011.

Abstract Background Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. Methods Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the ‘Seintinelles’ connected network (collaborative research platform). Discussion This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. Trial registration This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028–45. Recruitment Status: Recruiting. Protocol version Version n° 4.2 dated from Feb 19, 2021. Trial sponsor Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

Abstract With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.

RESUMO Objetivo: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. Métodos: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. Resultados: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. Conclusão: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Purpose: Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy. Methods: The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified. Results: Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively. Conclusion: The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.

We address the optimization problem of antenna placement on satellite-mounted interferometric synthetic-aperture instruments. In classic designs, the antennas on satellites are aligned regularly on the satellite’s frame. Inspired by methods proposed for the placement of antennas in astronomical interferometers, such as ALMA or SKA, we explore irregular layouts and show that they are a valid alternative in terms of spatial resolution and reconstruction error. We formalize mathematically the optimization problem of irregularly placed antennas and we show that this kind of arrays can still be calibrated with the same methods used for regular arrays. Finally, this strategy is evaluated in the context of soil moisture and ocean salinity (SMOS) follow-up concepts, such as SMOS-HR (high resolution), for which the new optimized irregular configurations are compared to the regular ones.

El "dret a decidir", que es concediria a part de la població d'un estat, no està recollit expressament en les constitucions. Quan s’hi acosten certs conceptes, com ara el dret a l’autodeterminació, la demanda del dret a decidir requereix cada vegada més un fonament separat per evitar els obstacles, tant internacionals com constitucionals, a la secessió unilateral. Tot i que els contorns d’aquest dret continuen sent ambigus, el seu estatus constitucional comença a concretar-se a través de la jurisprudència del Tribunal Constitucional espanyol en particular que, per rebutjar aquest dret en la seva versió extrema (secessió unilateral), en consagra tanmateix la seva existència en una sentència del 2014. Tot i que és lògic que els estats contestin aquest dret des d’un punt de vista estrictament constitucional, no és menys cert que aquesta demanda expressa un desig polític. La dimensió política del conflicte entre l’Estat i l’entitat que reivindica el dret a decidir marca, sens dubte, els límits de la comprensió estrictament constitucional d’aquest dret. No obstant això, el dret constitucional manté un paper d’importància primordial a l’hora de definir les garanties democràtiques que podrien envoltar l’exercici d’aquest dret.

Background Targeted Therapies (TT) are among the therapeutic innovations for cancer treatment in outpatient settings. TT-related Adverse Events (AEs) are a source of loss of opportunity for patients if their management is inappropriate. Objectives The objective of this study was to describe the AE frequency and severity as reported by patients with cancer who received TT in ambulatory settings. A second objective was to describe the role of the general practitioner (GP) in the management of AEs. Methods All patients who started TT at a French Regional Cancer Centre in 2017–2018 were eligible for this 12-month prospective study. A self-administered questionnaire was distributed at inclusion and returned after three months. In the questionnaire, patients listed all AEs that occurred during this period and rated their severity. Occurrence and severity were compared with the rating by a specialised nurse. Patients also indicated the health professional they contacted first for the reported AE. Results Among the 247 eligible patients, 15 were excluded and 144 responded to the questionnaire. Fourteen different TTs have been prescribed. Asthenia (92.4%) and anorexia (64.6%) were the most frequent AE. Patients’ AE severity rating was more severe than the nurse’s rating for all drugs (p

BACKGROUND: To date, few data are available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and the role of early-life childcare arrangements in transmission of the virus. In this study, we assessed the SARS-CoV-2 seroprevalence in children less than 6 years of age in the canton of Fribourg and identified risk factors associated with seropositivity. METHODS: The COVPED study is a population-based cross-sectional study in children less than 6 years of age living in the canton of Fribourg, Switzerland, who presented to a private paediatrician or the paediatric emergency department of the Fribourg Hospital during a 9-week period between 11 January and 14 March 2021. Immunoglobulin G antibodies against SARS-CoV-2 trimeric spike protein were measured in capillary blood samples using an in-house Luminex assay. A mean fluorescence intensity ratio of above 6 was considered as positive. Metadata was collected through electronic questionnaires. Logistic regression analysis was performed to assess the risk of seropositivity and associated factors. RESULTS: A total of 871 children, with a median age of 33 months (range 6 days to 5 years 11 months) were included; 412 (47%) were female. Overall, 180 (21%, 95% confidence interval [CI] 18–24%) children were seropositive. Age as continuous variable was not associated with seropositivity risk, apart from a higher rate in children less than 3 months of age. Univariable analysis showed that female sex was associated with a lower seropositivity risk (unadjusted odds ratio [OR] 0.69, 95% CI 0.49–0.96; p = 0.03). Day-care attendance was also associated with a lower seropositivity risk (OR 0.67, 95% CI 0.47–0.95; p = 0.03), whereas all other childcare arrangements were not associated with seropositivity. No association was found between the number of children and adults present in extra-familial care and seropositivity. Multivariable analysis identified the number of household members above the age of 12 years being positive for SARS-CoV-2 as the main risk factor for seropositivity in children (adjusted odds ratio [aOR] 7.80, 95% CI 4.65–13.07; p