Markers of vitamin D metabolism and premenstrual symptoms in healthy women with regular cycles.

STUDY QUESTION: Are insufficient 25-hydroxyvitamin D (25(OH)D) concentrations, and other markers of vitamin D metabolism, associated with premenstrual symptoms in healthy women with regular menstrual cycles? SUMMARY ANSWER: 25(OH)D insufficiency was associated with specific physical premenstrual symptoms, while no associations were observed with psychological symptoms or with other markers of vitamin D metabolism. WHAT IS KNOWN ALREADY: Prior studies evaluating vitamin D and premenstrual symptoms have yielded mixed results, and it is unknown whether 25(OH)D insufficiency and other markers of vitamin D metabolism are associated with premenstrual symptoms. STUDY DESIGN, SIZE, DURATION: We used two cohorts of women with regular menstrual cycles; 1191 women aged 18-40 years in EAGeR (cross-sectional analysis of a prospective cohort within a randomized trial) and 76 women aged 18-44 years in BioCycle (prospective cohort). In EAGeR, premenstrual symptoms over the previous year were assessed at baseline, whereas in BioCycle, symptoms were assessed prospectively at multiple points over two menstrual cycles with symptoms queried over the previous week. In both cohorts, symptomatology was assessed via questionnaire regarding presence and severity of 14 physical and psychological symptoms the week before and after menses. Both studies measured 25(OH)D in serum. We also evaluated the association of additional markers of vitamin D metabolism and calcium homeostasis, including intact parathyroid hormone (iPTH), calcium (Ca), fibroblast growth factor 23 (FGF23), and 1,25 dihydroxyvitamin D (1,25(OH)2D) with premenstrual symptoms in the BioCycle cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: One cohort of women actively seeking pregnancy (Effects of Aspirin in Gestation and Reproduction (EAGeR)) and one cohort not seeking pregnancy (BioCycle) were evaluated. Log-binomial regression was used to estimate risk ratios (RR) and 95% CIs for associations between insufficient 25(OH)D (<30 ng/ml) and individual premenstrual symptoms, adjusting for age, BMI, race, smoking, income, physical activity, and season of blood draw. MAIN RESULTS AND THE ROLE OF CHANCE: 25(OH)D insufficiency was associated with increased risk of breast fullness/tenderness (EAGeR RR 1.27, 95% CI 1.03, 1.55; BioCycle RR 1.37, 95% CI 0.56, 3.32) and generalized aches and pains (EAGeR RR 1.33, 95% CI 1.01, 1.78; BioCycle 1.36, 95% CI 0.41, 4.45), though results were imprecise in the BioCycle study. No associations were observed between insufficient 25(OH)D and psychological symptoms in either cohort. In BioCycle, iPTH, Ca, FGF23, and 1,25(OH) 2D were not associated with any premenstrual symptoms. LIMITATIONS, REASONS FOR CAUTION: Results from the EAGeR study were limited by the study design, which assessed both 25(OH)D at baseline and individual premenstrual symptoms over the past year at the baseline. As such, reverse causality is a potential concern. Though premenstrual symptoms were assessed prospectively in the BioCycle cohort, the power was limited due to small sample size. However, results were fairly consistent across both studies. WIDER IMPLICATIONS OF THE FINDINGS: Serum 25(OH)D may be associated with risk and severity of specific physical premenstrual symptoms. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract nos. HHSN267200603423, HHSN267200603424, and HHSN267200603426). JG.R. and D.L.K. have been funded by the NIH Medical Research Scholars Program, a public-private partnership jointly supported by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

Teaching humanitarian surgery: Filling the gap between NGO needs and subspecialized surgery through a novel inter-university certificate.

Background: Access to surgical care is a global health burden. A broad spectrum of surgical competences is required in the humanitarian context whereas current occidental surgical training is oriented towards subspecialties. We proposed to design a course addressing the specificities of surgery in the humanitarian setting and austere environment.Method: The novelty of the course lies in the implication of academic medical doctors alongside with surgeons working for humanitarian non-governmental organizations (NGO). The medical component of the National Defense participated regarding particular topics of war surgery. The course is aimed at trained surgeons and senior residents interested in participating to humanitarian missions.Results: The program includes theoretical teaching on surgical knowledge and skills applied to the austere context. The course also covers non-medical aspects of humanitarian action such as international humanitarian law, logistics, disaster management and psychological support. It comprises a large-scale mass casualty exercise and a practical skills lab on surgical techniques, ultrasonography and resuscitation. Attendance to the four teaching modules, ATLS certification and succeeding final examinations provide an interuniversity certificate.30 participants originating from 11 different countries joined the course. Various surgical backgrounds, training levels as well as humanitarian experience were represented.Feedback from the participants was solicited after each teaching module and remarks were applied to the following session. Overall participant evaluations of the first course session are presented.Conclusion: Teaching humanitarian surgery joining academic and field actors seems to allow filling the gap between high-income country surgical practice and the needs of the humanitarian context.

[Social support after traumatism]. / Soziale Unterstützung nach Traumatisierung.

The classical concept of social support has recently become of relevance again, particularly in the context of traumatized patient groups, which include refugees and migrants. This article summarizes the evidence from social support research, e. g. different types of positive effects as well as context, gender and cultural aspects. These aspects are highlighted by means of studies stemming from applied healthcare research and thus describe a wide range of health effects, e.g. increased well-being and reduced depressive symptoms, improved functional abilities, better immune status and longevity. Two new trauma-specific differentiations of the social support concept are introduced: societal acknowledgement as a trauma survivor and disclosure of traumatic experiences. Against this background several implications for working with refugees arise: promotion of self-efficacy and posttraumatic maturation as well as the treatment of mental disorders show considerable benefits from focusing on social support. Finally, possibilities emerging from digital communication media are discussed, which are particularly relevant in this context.

Assessing particle kinematics via template matching algorithms.

Template matching algorithms represent a viable tool to locate particles in optical images. A crucial factor of the performance of these methods is the choice of the similarity measure. Recently, it was shown in [Gao and Helgeson, Opt. Express 22 (2014)] that the correlation coefficient (CC) leads to good results. Here, we introduce the mutual information (MI) as a nonlinear similarity measure and compare the performance of the MI and the CC for different noise scenarios. It turns out that the mutual information leads to superior results in the case of signal dependent noise. We propose a novel approach to estimate the velocity of particles which is applicable in imaging scenarios where the particles appear elongated due to their movement. By designing a bank of anisotropic templates supposed to fit the elongation of the particles we are able to reliably estimate their velocity and direction of motion out of a single image.

Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis.

STUDY QUESTION: What is the contemporary prevalence of infertility in world populations and how do they differ by methodological and study characteristics? SUMMARY ANSWER: Pooled estimates of lifetime and period prevalence of 12-month infertility were 17.5% and 12.6%, respectively, but this varied by study population and methodological approach. WHAT IS KNOWN ALREADY: Infertility affects millions of individuals worldwide. Accurate measures of its magnitude are needed to effectively address and manage the condition. There are distinct challenges and variation in how infertility is defined and measured, limiting comparability of estimates across studies. Further research is needed to understand whether and how differences in methodological approaches and study characteristics account for heterogeneity in estimates. STUDY DESIGN SIZE DURATION: We conducted a systematic review and meta-analysis. Six electronic databases, websites of relevant organizations, and conference proceedings were systematically searched. Searches were limited to those published between 1 January 1990 and 11 March 2021, with no language restrictions. PARTICIPANTS/MATERIALS SETTING METHODS: Descriptive and random-effects meta-analysis models were used to examine range of estimates and generate estimates of pooled lifetime and period prevalence of 12-month infertility, respectively, among representative populations. Meta-regression using restricted maximum likelihood was applied to account for definitional and study characteristics and to obtain adjusted estimates. Risk of bias was assessed with a validated tool. MAIN RESULTS AND THE ROLE OF CHANCE: The search yielded 12 241 unique records of which 133 studies met the criteria for the systematic review. There were 65 and 69 studies that provided data for lifetime and period prevalence of 12-month infertility, respectively. Five methodological approaches were identified: prospective time-to-pregnancy (TTP) design, current duration design, retrospective TTP design, self-reported infertility measure and constructed infertility measure. Ranges for lifetime (3.3-39.7%) and period estimates (1.6-34.0%) were similar and wide even after accounting for methodological and study characteristics. Pooled estimates of lifetime and period prevalence were 17.5% (95% CI: 15.0, 20.3, n = 37 studies, I 2 = 99.5%) and 12.6% (95% CI: 10.7, 14.6, n = 43 studies, I 2 = 99.8%), respectively, with some variation in magnitude by region and methodological approach, but with most CIs overlapping. LIMITATIONS REASONS FOR CAUTION: Pooled estimates generated from meta-analysis were derived from 12-month infertility prevalence estimates that were heterogeneous across different domains, even after adjusting for definitional and study characteristics. The number of studies was small for certain strata from which pooled estimates were derived (e.g. there were only two studies for lifetime prevalence in Africa). WIDER IMPLICATIONS OF THE FINDINGS: While findings show a high prevalence of infertility globally and regionally, it also reveals variation in measures to ascertain and compare infertility prevalence. More systematic and comprehensive collection of data using a consistent definition is needed to improve infertility prevalence estimates at global, regional and country-levels. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the World Health Organization. The authors have no conflicts of interest. REGISTRATION NUMBER: PROSPERO CRD42020211704.

Complex plasmas in external fields: the role of non-hamiltonian interactions.

Dedicated experiments with strongly coupled complex plasmas in external electric fields were carried out under microgravity conditions using the PK-4 dc discharge setup. The focus was put on the comparative analysis of the formation of stringlike anisotropic structures due to reciprocal (hamiltonian) and nonreciprocal (non-hamiltonian) interactions between microparticles (induced by ac and dc fields, respectively). The experiments complemented by numerical simulations demonstrate that the responses of complex plasmas in these two regimes are drastically different. It is suggested that the observed difference is a manifestation of intrinsic thermodynamic openness of driven strongly coupled systems.

Long-term evolution of the three-dimensional structure of string-fluid complex plasmas in the PK-4 experiment.

Microparticle suspensions in a polarity-switched discharge plasma of the Plasmakristall-4 facility on board the International Space Station exhibit string-like order. As pointed out in [Phys. Rev. Research 2, 033314 (2020)2643-156410.1103/PhysRevResearch.2.033314], the string-order is subject to evolution on the timescale of minutes at constant gas pressure and constant parameters of polarity switching. We perform a detailed analysis of this evolution using the pair correlations and length spectrum of the string-like clusters (SLCs). Average exponential decay rate of the SLC length spectrum is used as a measure of string order. The analysis shows that the improvement of the string-like order is accompanied by the decrease of the thickness of the microparticle suspension, microparticle number density, and total amount of microparticles in the field of view. This suggests that the observed long-term evolution of the string-like order is caused by the redistribution of the microparticles, which significantly modifies the plasma conditions.

Ion thrusters for electric propulsion: Scientific issues developing a niche technology into a game changer.

The transition from old space to new space along with increasing commercialization has a major impact on space flight, in general, and on electric propulsion (EP) by ion thrusters, in particular. Ion thrusters are nowadays used as primary propulsion systems in space. This article describes how these changes related to new space affect various aspects that are important for the development of EP systems. Starting with a historical overview of the development of space flight and of the technology of EP systems, a number of important missions with EP and the underlying technologies are presented. The focus of our discussion is the technology of the radio frequency ion thruster as a prominent member of the gridded ion engine family. Based on this discussion, we give an overview of important research topics such as the search for alternative propellants, the development of reliable neutralizer concepts based on novel insert materials, as well as promising neutralizer-free propulsion concepts. In addition, aspects of thruster modeling and requirements for test facilities are discussed. Furthermore, we address aspects of space electronics with regard to the development of highly efficient electronic components as well as aspects of electromagnetic compatibility and radiation hardness. This article concludes with a presentation of the interaction of EP systems with the spacecraft.

beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2.

Recently, a requirement for beta-arrestin-mediated endocytosis in the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by several G protein-coupled receptors (GPCRs) has been proposed. However, the importance of this requirement for function of ERK1/2 is unknown. We report that agonists of Galphaq-coupled proteinase-activated receptor 2 (PAR2) stimulate formation of a multiprotein signaling complex, as detected by gel filtration, immunoprecipitation and immunofluorescence. The complex, which contains internalized receptor, beta-arrestin, raf-1, and activated ERK, is required for ERK1/2 activation. However, ERK1/2 activity is retained in the cytosol and neither translocates to the nucleus nor causes proliferation. In contrast, a mutant PAR2 (PAR2deltaST363/6A), which is unable to interact with beta-arrestin and, thus, does not desensitize or internalize, activates ERK1/2 by a distinct pathway, and fails to promote both complex formation and cytosolic retention of the activated ERK1/2. Whereas wild-type PAR2 activates ERK1/2 by a PKC-dependent and probably a ras-independent pathway, PAR2(deltaST363/6A) appears to activate ERK1/2 by a ras-dependent pathway, resulting in increased cell proliferation. Thus, formation of a signaling complex comprising PAR2, beta-arrestin, raf-1, and activated ERK1/2 might ensure appropriate subcellular localization of PAR2-mediated ERK activity, and thereby determine the mitogenic potential of receptor agonists.

fcc-bcc phase transition in plasma crystals using time-resolved measurements.

Three-dimensional plasma crystals are often described as Yukawa systems for which a phase transition between the crystal structures fcc and bcc has been predicted. However, experimental investigations of this transition are missing. We use a fast scanning video camera to record the crystallization process of 70 000 microparticles and investigate the existence of the fcc-bcc phase transition at neutral gas pressures of 30, 40, and 50 Pa. To analyze the crystal, robust phase diagrams with the help of a machine learning algorithm are calculated. This work shows that the phase transition can be investigated experimentally and makes a comparison with numerical results of Yukawa systems. The phase transition is analyzed in dependence on the screening parameter and structural order. We suggest that the transition is an effect of gravitational compression of the plasma crystal. Experimental investigations of the fcc-bcc phase transition will provide an opportunity to estimate the coupling strength Γ by comparison with numerical results of Yukawa systems.

The suturing concept for laparoscopic mesh fixation in ventral and incisional hernia repair: Mid-term analysis of 400 cases.

BACKGROUND: The authors describe a minimally invasive treatment of moderate to large incisional and ventral hernia defects using Parietex composite mesh. METHODS: All defects are closed laparoscopically or through a minilaparotomy using sutures, and the composite mesh is fixed intraperitonally using transabdominal fixation with nonabsorbable sutures to avoid the use of staple or tack fixation, which has been associated with various complications, including major loop adhesion and mesh migration. The midterm results for 400 patients are presented in terms of efficacy and safety. RESULTS: During a mean follow-up period of 28 months for 80% of the patients, the median operating time was 74 min and the median hospital stay was 3 days. There were eight seromas (2%), all on large defects. Transient pain was experienced by 10 patients (2.5%), and resolved over time with analgesic treatment. There was one early case of sepsis (0.25%), attributable to secondary breakdown of the bowel wall in a case of recurrent incisional hernia, which led to removal of the mesh. Residual chronic parietal pain was reported for 10 patients (2.5%), 2 of whom were released after excision of neuroma; 3 trocar-site herniations (0.75%); and lipoma formation on the site of the hernia sac in 6 cases (1.5%). CONCLUSION: Laparoscopic ventral hernia treatment using Parietex composite mesh is an effective and safe procedure. Morbidity and recurrence rates are low, and the 2-year outcomes are promising, with no prosthesis migration or complication related to intraperitoneal positioning of the mesh.

Machine-learning approach for local classification of crystalline structures in multiphase systems.

Machine learning is one of the most popular fields in computer science and has a vast number of applications. In this work we will propose a method that will use a neural network to locally identify crystal structures in a mixed phase Yukawa system consisting of fcc, hcp, and bcc clusters and disordered particles similar to plasma crystals. We compare our approach to already used methods and show that the quality of identification increases significantly. The technique works very well for highly disturbed lattices and shows a flexible and robust way to classify crystalline structures that can be used by only providing particle positions. This leads to insights into highly disturbed crystalline structures.

Left paraduodenal hernia: a case report.

Congenital internal hernias often remain unrecognized since they are infrequent and produce nonspecific abdominal symptoms. Abdominal imaging during a symptomatic episode leads to the diagnosis. Surgical treatment is essential regarding the risks of incarceration. We report a case of left paraduodenal hernia misdiagnosed for over thirty years despite extensive imaging and surgical exploration.

Investigation and improvement of three-dimensional plasma crystal analysis.

In this work, existing methods for plasma crystal analysis are investigated using artificial and simulated calibration data, which reproduce a multiphase system consisting of fcc, hcp, and bcc crystal data. Disturbances of the artificial data including Gaussian noise, stretching, and randomly missing particles are used to investigate the methods thoroughly. A popular method, called bond order parameter, has been repeatedly criticized as a structure analysis tool and will be improved with the help of a recent development. The method is called the bcc-sensitive Minkowski structure metric. It enhances robustness and consistency, while remaining compatible with previous bond-order-based results. Also, a promising method rooted in the molecular dynamics community is tested, yielding detailed insight of bond-order-specific drawbacks. With this investigation, the state of three-dimensional plasma crystal analysis will be significantly improved.

Plasmakristall-4: New complex (dusty) plasma laboratory on board the International Space Station.

New complex-plasma facility, Plasmakristall-4 (PK-4), has been recently commissioned on board the International Space Station. In complex plasmas, the subsystem of µm-sized microparticles immersed in low-pressure weakly ionized gas-discharge plasmas becomes strongly coupled due to the high (103-104 e) electric charge on the microparticle surface. The microparticle subsystem of complex plasmas is available for the observation at the kinetic level, which makes complex plasmas appropriate for particle-resolved modeling of classical condensed matter phenomena. The main purpose of PK-4 is the investigation of flowing complex plasmas. To generate plasma, PK-4 makes use of a classical dc discharge in a glass tube, whose polarity can be switched with the frequency of the order of 100 Hz. This frequency is high enough not to be felt by the relatively heavy microparticles. The duty cycle of the polarity switching can be also varied allowing to vary the drift velocity of the microparticles and (when necessary) to trap them. The facility is equipped with two videocameras and illumination laser for the microparticle imaging, kaleidoscopic plasma glow observation system and minispectrometer for plasma diagnostics and various microparticle manipulation devices (e.g., powerful manipulation laser). Scientific experiments are programmed in the form of scripts written with the help of specially developed C scripting language libraries. PK-4 is mainly operated from the ground (control center CADMOS in Toulouse, France) with the support of the space station crew. Data recorded during the experiments are later on delivered to the ground on the removable hard disk drives and distributed to participating scientists for the detailed analysis.

Particle charge in the bulk of gas discharges.

An experimental determination of particle charge in a bulk dc discharge plasma covering a wide range of neutral gas pressures, was recently reported [S. Ratynskaia, Phys. Rev. Lett. 93, 085001 (2004)]. The charges obtained were several times smaller than the predictions of collisionless orbital motion limited theory. This discrepancy was attributed to the effect of ion-neutral collisions. In the present paper a more detailed description of this experiment is provided and additional experimental results obtained with particles of different sizes are reported. The measurements are compared with molecular dynamics simulations of particle charging for conditions similar to those of the experiment, with other available experimental data on particle charge in the bulk of gas discharges, and with a simple analytical model accounting for ion-neutral collisions. All the considered evidence indicates that ion-neutral collisions represent a very important factor, which significantly affects (reduces) the particle charge under typical discharge conditions.

Imaging of non-traumatic abdominal emergencies in adults.

Non-traumatic abdominal pathology is one of the most common reasons for consultation in emergency care services. Abdominal pain is the presenting symptom for many diseases, which often requires urgent care. Clinical history and physical examination are rarely sufficient to establish a definite diagnosis and imaging is usually necessary. The choice of imaging modality is oriented by the clinical context and guided by the institutional capabilities, safety and cost-effectiveness of the available tests. Plain radiographs have little or no place in the evaluation of the acute abdomen. Magnetic resonance imaging (MRI) still has limited availability in many hospitals, thus narrowing the imaging choice to ultrasound (US) and computerized tomography (CT). No scientific evidence exists to allow the imposition of one single strategy. At the present time, the clinician may choose either routine US evaluation complemented by CT in case the US is inconclusive or first-line CT (except for the evaluation of right lower quadrant [RLQ] pain, right upper quadrant [RUQ] pain and in pregnant women where ultrasound is the first-line study).

Prediction of toxicity but not of clinical course by determining carboplatin exposure in patients with epithelial ovarian cancer treated with a combination of carboplatin and cisplatin.

We present the data from 105 patients with primary epithelial ovarian cancer, who received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as one treatment arm of a prospective randomized trial. Values for first-course carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade 3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square p<0.0001). No single case of ototoxicity was found in the low AUC group but in 12% of patients in the high AUC group (chi-square p=0.003). Determination of carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first cycle of combined treatment with carboplatin and cisplatin.

Effect of the dilution rate on the mode of oscillation in continuous cultures of Saccharomyces cerevisiae.

The growth properties of the asymmetric budding yeast Saccharomyces cerevisiae were analysed during spontaneous oscillations in continuous cultures at varying dilution rates D. The length of the oscillation period changed between 1.4 and 14 h in response to the decrease of dilution rate from 0.15 to 0.05 h-1. The distribution of parent and daughter cells in the population was determined microscopically after staining the bud scars and DNA. Most of the data obtained fits a theoretical population balance model assuming two-classes of subpopulations and integer ratios between the generation times of both classes. Some data has to be described by an extended population model assuming there is one parent and two daughter cell classes. How changes of dilution rate may cause an accidental switch of the mode of oscillation is demonstrated. Glucose consumption and metabolite production were measured off-line by enzymatic methods and gas exchange was monitored on-line. All these data of one period point to internal and external signals responsible for the synchronisation of the cell cycle.

The influence of obesity on the disease-free survival in primary breast cancer.

Hyper-estrogenism is more common in obese than in non-obese women. Consequently obesity has been shown to increase the risk of hormone department tumors. Some investigators have claimed that obesity at the time of primary treatment may be an independent prognostic factor for breast cancer, but this issue is still controversial. Therefore, we conducted a retrospective analysis to assess the influence of obesity at the time of primary treatment on disease-free survival (DFS). Obesity was defined as an excess of more than 25% of ideal weight according to Broca's index ([Height (cm) -100])-10%). The Cox-model was used for multivariate analysis. Mean follow-up was 61 (range 6-126) months. 295 (62.3%) patients were classified as of normal weight and 178 (37.6%) as obese. Mean excess of ideal weight was 8.9 kilograms (kg) in premenopausal and 13.9 kg in postmenopausal patients (non-parametric t-test p < 0.00001). Patients with tumor size < 20mm, 20-50mm and > 50mm had a means excess of the real weight of 10.6kg, 12.5kg and 16.1kg, respectively (non-parametric t-test p < 0.0001). Percentual excess of real weight compared to ideal weight was 22.4 [+/-21.2] kg in patients without recurrence and 21.5 [+/-21.9] in patients with recurrent disease (nonparametric t-test p = 0.7256). Univariate analysis revealed no significant association between obesity and the DFS. Multivariate analysis identified axillary lymph node involvement as the only statistically significant prognostic factor for disease-free survival (RR 1.55; 95%-confidence interval 1.02-2.36; p:0.0368). Because of the high correlations and node-status, tumor size and histological grading, the other factors failed to be prognostically relevant in this analysis. Obesity was not found to influence DFS of patients with primary breast cancer and is therefore unlikely to constitute an independent prognostic factor. It may, however, contribute to delayed diagnosis, since a significant proportion of obese patients were diagnosed with local advanced disease.