In vitro biomechanical properties of porcine perineal tissues to better understand human perineal tears during delivery.

INTRODUCTION: Data concerning the mechanical properties of the perineum during delivery are very limited. In vivo experiments raise ethical issues. The aim of the study was to describe some of the biomechanical properties of each perineal tissue layer collected from sows in order to better understand perineal tears during childbirth. MATERIAL AND METHODS: Samples of each perineal tissue layer were obtained from the skin, the vagina, the external anal sphincter (EAS), the internal anal sphincter (IAS), and the anal mucosa of fresh dead sows. They were tested in quasi-static uniaxial tension using the testing machine Mach-1®. Tests were performed at a displacement velocity of 0.1 mm·s-1. Stress-strain curves of each perineal tissue layer before the first damage for each sow were obtained and modeled using a hyperelastic Yeoh model described by three coefficients: C1, C2, and C3. Pearson correlation coefficients were calculated to measure the correlation between the C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture for each perineal tissue layer. Pearson correlation was computed between C1 and the number of microfailures before complete rupture for each tissue. RESULTS: Ten samples of each perineal tissue layer were analyzed. Mean values of C1 and corresponding standard deviations were 46 ± 15, 165 ± 60, 27 ± 10, 19 ± 13, 145 ± 28 kPa for the perineal skin, the vagina, the EAS, the IAS, and the anal mucosa, respectively. According to this same sample order, the first microfailure in the population of 10 sows appeared at an average of 54%, 27%, 70%, 131%, and 22% of strain. A correlation was found between C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture (r = 0.7, p = 0.02) or the number of microfailures before complete rupture only for the vagina (r = 0.7, p = 0.02). CONCLUSIONS: In this population of fresh dead sow's perineum, the vagina and the anal mucosa were the stiffest tissues. The IAS and EAS were more extensible and less stiff. A significantly positive correlation was found between C1 and the duration between the first microfailure and the complete rupture of the vagina, and the duration between the first microfailure and the complete rupture of the vagina.

Aberrant activation of five embryonic stem cell-specific genes robustly predicts a high risk of relapse in breast cancers.

BACKGROUND: In breast cancer, as in all cancers, genetic and epigenetic deregulations can result in out-of-context expressions of a set of normally silent tissue-specific genes. The activation of some of these genes in various cancers empowers tumours cells with new properties and drives enhanced proliferation and metastatic activity, leading to a poor survival prognosis. RESULTS: In this work, we undertook an unprecedented systematic and unbiased analysis of out-of-context activations of a specific set of tissue-specific genes from testis, placenta and embryonic stem cells, not expressed in normal breast tissue as a source of novel prognostic biomarkers. To this end, we combined a strict machine learning framework of transcriptomic data analysis, and successfully created a new robust tool, validated in several independent datasets, which is able to identify patients with a high risk of relapse. This unbiased approach allowed us to identify a panel of five biomarkers, DNMT3B, EXO1, MCM10, CENPF and CENPE, that are robustly and significantly associated with disease-free survival prognosis in breast cancer. Based on these findings, we created a new Gene Expression Classifier (GEC) that stratifies patients. Additionally, thanks to the identified GEC, we were able to paint the specific molecular portraits of the particularly aggressive tumours, which show characteristics of male germ cells, with a particular metabolic gene signature, associated with an enrichment in pro-metastatic and pro-proliferation gene expression. CONCLUSIONS: The GEC classifier is able to reliably identify patients with a high risk of relapse at early stages of the disease. We especially recommend to use the GEC tool for patients with the luminal-A molecular subtype of breast cancer, generally considered of a favourable disease-free survival prognosis, to detect the fraction of patients undergoing a high risk of relapse.

Access to innovation through clinical trials and the national early access program for patients with lung cancer in France: focus on atezolizumab and durvalumab.

PURPOSE: Tumor genomic profiling and PD-L1 testing mean lung cancer management can be tackled through a personalized approach. Targeted therapies and immunotherapy are necessary to improve survival and preserve the patients' quality of life. Early access to innovation before marketing authorization (MA) is possible in France through clinical trials and an early-access program called a Temporary Authorization for Use (ATU), which is a unique regulatory system in Europe. This study aims to assess the impact of early access to innovation through clinical trials and ATUs in thoracic oncology. METHODS: Data from clinical trials between 2018 and 2021 and ATUs between 2005 and 2019 were collected internally and assessed for drugs in thoracic oncology, with specific focus on 2 ATUs, respectively, atezolizumab and durvalumab. RESULTS: From 2018 to 2021, the National Agency for the Safety of Medicines and Health Products authorized 145 clinical trials in lung cancer. Between 2005 and 2019, 19 drugs obtained an EU MA or an MA extension for a therapeutic indication in lung cancer. During this period, 11 of these drugs were granted an ATU, corresponding to 6851 patients treated. Of this total number of patients, data were collected for 33.1% and 71.2%, who received durvalumab and atezolizumab, respectively. Real-life efficacy data were consistent with the clinical trial data. CONCLUSION: Over the past 15 years, clinical trials and the French early access program have allowed considerable early access to therapeutic innovation in real life for patients, especially in thoracic oncology.

Discrepancies between dihydropyrimidine dehydrogenase phenotyping and genotyping: What are the explanatory factors?

AIM: Dihydropyrimidine dehydrogenase (DPD) deficiency can be detected by phenotyping (measurement of plasma uracil [U], with U ≥ 16 µg/L defining a partial deficiency) and/or by genotyping (screening for the four most frequent DPYD variants). We aimed to determine the proportion of discrepancies between phenotypic and genotypic approaches and to identify possible explanatory factors. METHODS: Data from patients who underwent both phenotyping and genotyping were retrospectively collected. Complementary genetic analyses (genotyping of the variant c.557A>G and DPYD sequencing) were performed for patients with U ≥ 16 µg/L without any common variants. The characteristics of patients classified according to the congruence of the phenotyping and genotyping approaches were compared (Kruskal-Wallis test), and determinants of U levels were studied in the whole cohort (linear model). RESULTS: Among the 712 included patients, phenotyping and genotyping were discordant for 12.5%, with 63 (8.8%) having U ≥ 16 µg/L in the absence of a common variant. Complementary genetic investigations marginally reduced the percentage of discrepancies to 12.1%: Among the nine additional identified variants, only the c.557A>G variant, carried by three patients, had been previously reported to be associated with DPD deficiency. Liver dysfunction could explain certain discordances, as ASAT, ALP, GGT and bilirubin levels were significantly elevated, with more frequent liver metastases in patients with U ≥ 16 µg/L and the absence of a DPYD variant. The impact of cytolysis was confirmed, as ASAT levels were independently associated with increased U (p < 0.001). CONCLUSION: The frequent discordances between DPD phenotyping and genotyping approaches highlight the need to perform these two approaches to screen for all DPD deficiencies.

[Early access to innovative drugs, ethical impacts]. / Accès précoce aux médicaments innovants, impacts éthiques.

EARLY ACCESS TO INNOVATIVE DRUGS, ETHICAL IMPACTS In France, the average time between marketing authorisation and patient access to drugs is 530 days, this period takes into account the period of price negotiation and reimbursement specific to countries that provide medical coverage to the entire population. Regarding innovation, since 1994, the introduction of the ATU system has made it possible to reduce this delay. The new system set up in July 2021 includes the ANSM and HAS with the objective of linking the access decision and the reimbursement decision of the innovation. Nevertheless, therapeutic innovation can give rise to ethical problems: the performance of repeated biopsies in a patient with limited survival, a non-existent benefit in terms of quality of life or survival of certain innovations, the interest of opinion leaders and industrials which is not always that of the patient, opposition in the analysis of a benefit depending on whether one is a methodologist, a physician, a public decision- maker or a patient, and lastly, a price which is not related to the efficacy of the health products but rather to the acceptability or the sustainability of our health care system.

ACCÈS PRÉCOCE AUX MÉDICAMENTS INNOVANTS, IMPACTS ÉTHIQUES. En France, la durée moyenne entre l'autorisation de mise sur le marché (AMM) et l'accès des patients aux médicaments remboursables est de 530 jours ; ce délai tient compte de la période de négociation du prix et de remboursement propre aux pays qui assurent une couverture médicale de l'ensemble de la population. Depuis 1994, la mise en place des autorisations temporaires d'utilisation (ATU) a permis de diminuer ce délai pour les thérapeutiques innovantes. Le nouveau dispositif d'accès précoce, mis en place en juillet 2021, intègre l'ANSM et la HAS dans l'objectif de lier décision d'accès et décision de remboursement. Néanmoins, l'innovation thérapeutique peut susciter des problèmes éthiques : réalisation de biopsies itératives chez un patient avec une survie limitée ; bénéfice inexistant en matière de qualité de vie ou de survie de certaines innovations ; intérêt des leaders d'opinion et des industriels qui n'est pas toujours le même que celui du patient ; opposition dans l'analyse d'un bénéfice selon que l'on est méthodologiste, médecin, décideur public ou patient ; prix non relié à l'efficacité des produits de santé mais plutôt à l'acceptabilité ou la soutenabilité de notre système de prise en charge.

Evolution of breast cancer incidence in young women in a French registry from 1990 to 2018: Towards a change in screening strategy?

BACKGROUND: The worldwide incidence of invasive breast cancer in women is increasing according to several studies. This increase in incidence seems to be higher in young women (< 40 years). However, the reasons for this trend are poorly understood. This article aims to provide the most recent estimates of this trend and assess whether there is indeed an increase in the incidence of breast cancer among young women to strengthen prevention campaigns. METHODS: We collected data from the Isere cancer registry in France of all invasive breast cancers from January 1990 to December 2018. The standardized incidence rate was calculated for four age groups (< 40 years, 40-49 years, 50-74 years, ≥ 75 years) for this period. The 10-year relative survival was evaluated for each age group age for two periods (1990-1999 and 2000-2008). From 2011 to 2013, we analyzed the incidence and 5-year relative survival by tumor subtype (triple negative, luminal, HER2 amplified) for each age group. RESULTS: A total of 23,703 cases were selected, including 1343 young women (< 40 years). The incidence of invasive breast cancer increased annually by 0,8% (95% CI 0,7; 1) in all age groups combined from 1990 to 2018. The highest incidence increase is found among young women, by 2,1% annually (95% CI 1,3; 2,8). Regarding tumor subtypes from 2011 to 2018, the incidence of triple negatives increases higher in young women (+ 1,4% by year, 95% CI - 8,2; 11) and those over 75 years (+ 4% by year, 95% CI - 5,1; 13,2), but the results are not statistically significant. 10-year relative survival in young women increased from 74,6% (95% CI 69,6; 78,9) to 78,3%(95% CI 73,7; 82,1) between 1990-1999 and 2000-2008, respectively. Five-year relative survival is better in young women among triple negative and HER2 amplified. CONCLUSION: Our study confirms the current trend of increasing the incidence of breast cancer in young women, associated with improved survival very likely attributable to earlier diagnosis due to increased awareness, and improvements in treatment. A better individualized risk-based screening strategy is needed for these patients. Additional studies will be needed to more accurately assess the risk of developing breast cancer and improve diagnostic performance.

An agent-based model of vibration-induced intimal hyperplasia.

Acute exposure to hand-arm transmitted vibrations (HAVs) may decrease the wall shear stress (WSS) exerted by the blood flow on the arterial endothelium. In the case of chronic exposure to HAVs, these WSS changes can lead to arterial growth and remodeling potentially induced by an intimal hyperplasia phenomenon. Accordingly, we implemented an agent-based model (ABM) that captures the hemodynamics-driven and mechanoregulated cellular mechanisms involved in vibration-induced intimal hyperplasia. Our ABM was combined with flow loop experiments that investigated the WSS-modulated secretion of the platelet-derived growth factor BB (PDGF-BB) by the endothelial cells. The ABM rules parameters were then identified and calibrated using our experimental findings and literature data. The model was able to replicate the basal state (no vibration) as well as predict a 30% stenosis resulting from a chronic drop of WSS values mimicking exposure to vibration during a timeframe of 10 years. The study of the influence of different WSS-modulated phenomena on the model showed that the magnitude of stenosis largely depends on the migratory effects of PDGF-BB and the mitogenic effects of Transforming Growth Factor [Formula: see text] on the Smooth Muscle Cells. The results also proved that the fall in circumferential stress due to arterial layer thickening to a great extent accounts for the degradation of the Extracellular Matrix in the media.

Survival, cost and added therapeutic benefit of drugs granted early access through the French temporary authorization for use program in solid tumors from 2009 to 2019.

Decisions on market authorization (MA) and reimbursement have different durations across countries because of health technology assessment (HTA) procedures and negotiations between manufacturers and national authorities. To overcome this delay, France has implemented a Temporary Authorization for Use (ATU) program that allows early access to drugs before MA, in order to treat patients with unmet medical needs. The objectives of our study were to establish the added therapeutic benefit (ATB) of ATUs for solid tumors and to investigate the correlations between three tools evaluating ATB and survival outcomes and drug costs. Data on ATUs granted from January 2009 to December 2019 to treat solid tumors were analyzed. An assessment of their ATB was conducted using the American Society of Clinical Oncology-Value Framework (ASCO-VF), the European Society for Medical Oncology-Magnitude Clinical Benefit Scale (ESMO-MCBS) and the French HTA criterion, clinical added value (CAV). The latter score determines reimbursement and national market access. Thirty-five drugs in 39 indications were granted ATUs. All of them obtained MA and derived a clinical benefit to be reimbursed by the Social Security. Twenty-eight (71.8%) had CAV compared to preexisting therapies. 24/38 (63.2%) had a 4-5 ESMO-MCBS score and 19/33 (57.6%) had an ASCO-VF score over 45. No correlations were found between cost, PFS, OS, CAV and ASCO-VF score, while high ESMO-MCBS scores were correlated to OS. In conclusion, many patients were treated with innovations before MA thanks to ATU, although there are discrepancies between ATB scales, hence the importance of international collaboration in the evaluation of innovative therapies.

Prenatal quantification of human foetal lung and liver elasticities between 24 and 39 weeks of gestation using 2D shear wave elastography.

OBJECTIVES: To quantify and model normal foetal lung and liver elasticities between 24 and 39 weeks of gestation (WG) using two-dimensional shear wave elastography (2D-SWE). To assess the impact of the distance between the probe and the target organ on the estimation of elasticity values. METHODS: Measurements of normal foetal lungs and liver elasticity were prospectively repeated monthly between 24 and 39 WG in 72 foetuses using 2D-SWE. Elasticity was quantified in the proximal lung and in the region inside the hepatic portal sinus. The distance between the probe and the target organ was recorded. Trajectories representing foetal lung and liver maturation from at least 3 measurements over time were modelled. RESULTS: The average elasticity for the lung and liver was significantly different from 24 WG to 36 WG (p < 0.01). Liver elasticity increased during gestation (3.86 kPa at 24 WG versus 4.45 kPa at 39 WG). From 24 WG to 32 WG, lung elasticity gradually increased (4.12kPa at 24 WG, 4.91kPa at 28 WG, 5.03kPa at 32 WG, p < 0.002). After 32 WG, lung elasticity decreased to 4.54kPa at 36 WG and 3.94kPa at 39 WG. The dispersion of the average elasticity values was greater for the lung than for the liver (p < 0.0001). Variation in the elasticity values was less important for the liver than for the lung. The values were considered valid and repeatable except for a probe-lung distance above 8cm. CONCLUSION: Foetal lung and liver elasticities evolve differently through gestation. This could reflect the tissue maturation of both organs during gestation. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03834805 KEY POINTS: • Prenatal quantification of foetal lung elasticity using 2D shear wave elastography could be a new prenatal parameter for exploring foetal lung maturity. • Liver elasticity increased progressively from 24 weeks of gestation (WG) to 39 WG, while lung elasticity increased first between 24 and 32 WG and then decreased after 32 WG. • The values of elasticity are considered valid and repeatable except for a probe-lung distance above 8cm.

In vivo skin anisotropy dataset from annular suction test.

To characterize the anisotropic and viscoelastic behaviors of the skin, we conducted an experimental campaign of in-vivo suction tests using the CutiScan®CS100 device from Courage and Khazaka electronics. In this data paper, we present the raw acquired data of the tests and their respective treated data. The tests were performed 30 times on the anterior forearm of a 28-year-old Caucasian male at different pressure set-points, ranging from 100 to 500 mbar with an increment of 20 mbar, at ambient temperature in a windowless room. The primary dataset consists of videos recorded by a probe camera associated with the CutiScan® device during the tests. After data treatment with DIC (Digital Image Correlation) technique and based on a homemade Python program, we have obtained secondary data tables and 2D displacement for all mapped grid nodes.

Patterns of Sequelae in Women with a History of Localized Breast Cancer: Results from the French VICAN Survey.

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey "vie après cancer" VICAN (January-June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue (p = 0.03) and an increase in cognitive sequelae was reported (p = 0.03). Two latent classes were identified-functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.

Comparative study on anticancer drug access times between FDA, EMA and the French temporary authorisation for use program over 13 years.

INTRODUCTION: The cancer incidence continues to rise worldwide. Medical innovation has a major impact on patient survival, but within drug development, it can take more than 10 years to obtain marketing authorisation (MA). The time required for access to therapeutic innovation remains critical, so France has developed a specific expanded access program named ATU, which allows the administration of drugs before the European Medicines Agency (EMA) approval. The purpose of this study is to put in perspective the average time to access antineoplastic drugs worldwide, taking into account ATU, US Food and Drug Administration (FDA) and EMA approvals. METHODS: The ATU system allows the use of a medicine before its MA, under exceptional conditions. All antineoplastic drugs in oncology that have benefited from the ATU system are analysed in terms of tumour site, biomarkers and number of patients who have access to the drug. RESULTS: Between 1st January 2007 and 31st December 2019, 36 of 64 drugs (56.2%) that received MA in oncology were assigned an ATU, to the benefit of 16,927 patients. Thanks to the ATU, 25 of 36 drugs (69.4%) were made available early, on average 203 d (95% CI, 76-330) before FDA approval and on average 428 d (95% CI, 272-583) before EMA approval. Only three of 36 drugs were approved by the EMA before the FDA, and the average time lapse between European MA and FDA approval for these 36 drugs was 216 d (95% CI, 140-293). CONCLUSION: This article demonstrates that the ATU system allows patients to benefit from therapeutic innovations before MA in Europe and USA, with full coverage by the healthcare system.

Factors associated with survival of patients with solid Cancer alive after intensive care unit discharge between 2005 and 2013.

BACKGROUND: At intensive care unit (ICU) admission, the issue about prognosis of critically ill cancer patients is of clinical interest, especially after ICU discharge. Our objective was to assess the factors associated with 3- and 6-month survival of ICU cancer survivors. METHODS: Based on the French OutcomeRea™ database, we included solid cancer patients discharged alive, between December 2005 and November 2013, from the medical ICU of the university hospital in Grenoble, France. Patient characteristics and outcome at 3 and 6 months following ICU discharge were extracted from available database. RESULTS: Of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from ICU. The main primary cancer sites were digestive (31%) and thoracic (26%). The 3- and 6-month mortality rates were 33 and 41%, respectively. Factors independently associated with 6-month mortality included ECOG performance status (ECOG-PS) of 3-4 (OR,3.74; 95%CI: 1.67-8.37), metastatic disease (OR,2.56; 95%CI: 1.34-4.90), admission for cancer progression (OR,2.31; 95%CI: 1.14-4.68), SAPS II of 45 to 58 (OR,4.19; 95%CI: 1.76-9.97), and treatment limitation decision at ICU admission (OR,4.00; 95%CI: 1.64-9.77). Interestingly, previous cancer chemotherapy prior to ICU admission was independently associated with lower 3-month mortality (OR, 0.38; 95%CI: 0.19-0.75). Among patients with an ECOG-PS 0-1 at admission, 70% (n = 66) and 61% (n = 57) displayed an ECOG-PS 0-2 at 3- and 6-months, respectively. At 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care. CONCLUSIONS: Factors associated with 6-month mortality are almost the same as those known to be associated with ICU mortality. We highlight that most patients recovered an ECOG-PS of 0-2 at 3 and 6 months, in particular those with a good ECOG-PS at ICU admission and could benefit from an anticancer treatment following ICU discharge.

Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer.

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.

Multimodal investigation of a keloid scar by combining mechanical tests in vivo with diverse imaging techniques.

Keloids are pathologic scars, defined as fibroproliferative diseases resulting from abnormal wound responses, which grow beyond the original wound margins. They develop on specific pro-keloid anatomic sites frequently characterized by high stress states. The initiation and growth mechanisms of keloid are not well-understood. This study relates multimodal investigation of a keloid by using mechanical tests in vivo and imaging techniques. A single case composed of a keloid, the healthy skin surrounding the keloid, and the contralateral healthy skin on the upper arms of a woman has been investigated in extension and suction by using non-invasive devices dedicated to in vivo skin measurement. The thickness and microstructure of these soft tissues have been observed by echography, tomography and confocal microscopy. Displacement fields have been obtained by using digital image correlation. Unlike healthy skin, keloid is not a well-defined multilayer structure: the frontier between epidermis and dermis disappears. The mechanical behavior of keloid is highly different from healthy skin one. The R-parameters have been deduced from suction curves. Physical parameters as tissue extensibility, initial and final tangent moduli have been identified from the stress-strain curves. The extensibility (respectively, initial rigidity) of keloid is highly lower (respectively, higher) than that of healthy skin. To compare the final rigidity of keloid versus healthy skin, further tests have to be performed with higher strain values.

Unraveling the Metastability of C n2+ ( n = 2-4) Clusters.

Pure carbon clusters have received considerable attention for a long time. However, fundamental questions, such as what the smallest stable carbon cluster dication is, remain unclear. We investigated the stability and fragmentation behavior of C n2+ ( n = 2-4) dications using state-of-the-art atom probe tomography. These small doubly charged carbon cluster ions were produced by laser-pulsed field evaporation from a tungsten carbide field emitter. Correlation analysis of the fragments detected in coincidence reveals that they only decay to C n-1+ + C+. During C22+ → C+ + C+, significant kinetic energy release (∼5.75-7.8 eV) is evidenced. Through advanced experimental data processing combined with ab initio calculations and simulations, we show that the field-evaporated diatomic 12C22+ dications are either in weakly bound 3Πu and 3Σg- states, quickly dissociating under the intense electric field, or in a deeply bound electronic 5Σu- state with lifetimes >180 ps.

Development and characterization of a human dermal equivalent with physiological mechanical properties.

BACKGROUND/AIMS: Different models of reconstructed skin are available, either to provide skin wound healing when this process is deficient, or to be used as an in vitro model. Nevertheless, few studies have focused on the mechanical properties of skin equivalent. Indeed, human skin is naturally under tension. Taking into account these features, the purpose of this work was to obtain a cellularized dermal equivalent (CDE), composed of collagen and dermal fibroblasts. METHODS: To counteract the natural retraction of CDE and to maintain it under tension, different biomaterials were tested. Selection criteria were biocompatibility, bioadhesion properties, ability to induce differentiation of fibroblasts into myofibroblasts and mechanical characterization, considering that of skin in vivo. These assays led to the selection of honeycomb of polyester. CDE constructed on this biomaterial was further characterized mechanically using tensile tests. RESULTS: The results showed that mechanical features of the obtained dermal equivalent, including myofibroblasts, were similar to skin in vivo. CONCLUSION: The original model of dermal equivalent presented herein may be a useful tool for clinical use and as an in vitro model for toxicological/pharmacological research.

The analysis of forces needed for the suturing of elliptical skin wounds.

There is a lack of information regarding the forces required for suturing human wounds. The knowledge of suturing forces serves as complementary information for setting up the limiting geometry when using tissue adhesives and it might also be used in robot-assisted surgery. The main purpose of this paper was to evaluate the forces required for suturing selected skin wounds. An elliptical wound was chosen for our study. In this study a numerical analysis and in vivo experiments were performed. Regarding the numerical models, the maximum forces occurred in the middle of the elliptical wound in all cases. In the case of highest pre-stress used in these analyses the maximal force varied from 0.5 N for the smallest wound (30 × 5 mm) to 1.5 N for the largest wound (30 × 15 mm). The maximum peak force for the wound with a size of 46 × 13 mm was 3.2 N. The minimum peak force for the wound with a size of 36 × 5 mm was 1.1 N.