Metastable CrMnNi steels processed by laser powder bed fusion: experimental assessment of elementary mechanisms contributing to microstructure, properties and residual stress.

The complex thermal history imposed by the laser-based powder bed fusion of metals (PBF-LB/M) process is known to promote the evolution of unique microstructures. In the present study, metastable CrMnNi steels with different nickel contents and, thus, different phase stabilities are manufactured by PBF-LB/M. Results clearly reveal that an adequate choice of materials will allow to tailor mechanical properties as well as residual stress states in the as-built material to eventually redundantize any thermal post-treatment. The chemical differences lead to different phase constitutions in as-built conditions and, thus, affect microstructure evolution and elementary deformation mechanisms upon deformation, i.e., twinning and martensitic transformation. Such alloys designed for additive manufacturing (AM) highlight the possibility to tackle well-known challenges in AM such as limited damage tolerance, porosity and detrimental residual stress states without conducting any post treatments, e.g., stress relieve and hot isostatic pressing. From the perspective of robust design of AM components, indeed it seems to be a very effective approach to adapt the material to the process characteristics of AM.

Standardized suturing can prevent slackening or bursting suture lines in midline abdominal incisions and defects.

PURPOSE: Incisional hernias often follow open abdominal surgery. A small-stitch-small-bite suture might close the incision durably. We analyzed specific details of this closure technique and assessed their influence on the closure stability. METHODS: The effects of cyclic loads, simulating coughs were investigated on a bench test. We prepared porcine bellies in the median line and bovine flanks parallel to the muscle fibers with 15 cm long incisions. Then we punched round or rhomboid defects with a diameter of 5-10 cm into the center of the incision. Monomax® 2-0 and Maxon® 1 and 2-0 were used as suture materials. We tested the durability of the closure with pressure impacts of 210 mmHg repeated 425 times. Throughout the experiments, we modified the suturing technique, the surgeon, the tissue tension, the defect size and shape and the suture diameter. RESULTS: Standardizing the suture technique improved the durability of the closure significantly. Any other variations showed minor influences after standardization. All incisions with round defects up to 7.5 cm width withstood 425 impacts using standardized suturing. Unstandardized sutures failed in all cases. When closing an incision with a 10 cm wide defect, the tissues ruptured frequently next to the suture line. We defined criteria to standardize this suturing technique. For the first time, we developed a suture factor related to the durability of a sutured tissue closure. We integrated the suture factor into the concept of biomechanically durable repairs. CONCLUSIONS: Suturing the abdominal wall with a standardized suturing technique improves its durability significantly.

Biomechanics applied to incisional hernia repair - Considering the critical and the gained resistance towards impacts related to pressure.

BACKGROUND: Incisional hernia repair is burdened with recurrence, pain and disability. The repair is usually carried out with a textile mesh fixed between the layers of the abdominal wall. METHODS: We developed a bench test with low cyclic loading. The test uses dynamic intermittent strain resembling coughs. We applied preoperative computed tomography of the abdomen at rest and during Valsalva's maneuver to the individual patient to analyze tissue elasticity. FINDINGS: The mesh, its placements and overlap, the type and distribution of fixation elements, the elasticity of the tissue of the individual and the closure of the abdominal defect-all aspects influence the reconstruction necessary. Each influence can be attributed to a relative numerical quantity which can be summed up into a characterizing value. The elasticity of the tissues within the abdominal wall of the individual patient can be assessed with low-dose computed tomography of the abdomen with Valsalva's maneuver. We established a procedure to integrate the results into a surgical concept. We demonstrate potential computer algorithms using non-rigid b-spline registration and artificial intelligence to further improve the evaluation process. INTERPRETATION: The bench test yields relative values for the characterization of hernia, mesh and fixation. It can be applied to patient care using established procedures. The clinical application in the first ninety-six patients shows no recurrences and reduced pain levels after one year. The concept has been spread to other surgical groups with the same results in another fifty patients. Future efforts will make the abdominal wall reconstruction more predictable.

Machine learning in infection management using routine electronic health records: tools, techniques, and reporting of future technologies.

BACKGROUND: Machine learning (ML) is increasingly being used in many areas of health care. Its use in infection management is catching up as identified in a recent review in this journal. We present here a complementary review to this work. OBJECTIVES: To support clinicians and researchers in navigating through the methodological aspects of ML approaches in the field of infection management. SOURCES: A Medline search was performed with the keywords artificial intelligence, machine learning, infection∗, and infectious disease∗ for the years 2014-2019. Studies using routinely available electronic hospital record data from an inpatient setting with a focus on bacterial and fungal infections were included. CONTENT: Fifty-two studies were included and divided into six groups based on their focus. These studies covered detection/prediction of sepsis (n = 19), hospital-acquired infections (n = 11), surgical site infections and other postoperative infections (n = 11), microbiological test results (n = 4), infections in general (n = 2), musculoskeletal infections (n = 2), and other topics (urinary tract infections, deep fungal infections, antimicrobial prescriptions; n = 1 each). In total, 35 different ML techniques were used. Logistic regression was applied in 18 studies followed by random forest, support vector machines, and artificial neural networks in 18, 12, and seven studies, respectively. Overall, the studies were very heterogeneous in their approach and their reporting. Detailed information on data handling and software code was often missing. Validation on new datasets and/or in other institutions was rarely done. Clinical studies on the impact of ML in infection management were lacking. IMPLICATIONS: Promising approaches for ML use in infectious diseases were identified. But building trust in these new technologies will require improved reporting. Explainability and interpretability of the models used were rarely addressed and should be further explored. Independent model validation and clinical studies evaluating the added value of ML approaches are needed.

Biomechanical comparison of polylactide-based versus titanium miniplates in mandible reconstruction in vitro.

OBJECTIVES: Evaluation of the mechanical integrity and reliability of polylactide-based miniplates for osseous free flap fixation at the mandible in an experimental study setup of a mandible reconstruction model. MATERIAL AND METHODS: 1.0mm titanium miniplates (group TI) (MatrixMandible, DePuy Synthes, Umkirch, Germany) and 1.5mm polylactide miniplates (group PL) (Inion CPS, Inion Oy, Tampere, Finland) were used to fix a polyurethane (PU) fibula segment to a PU mandible reconstruction model using monocortical non-locking screws. Mastication was simulated via unilateral cyclic dynamic loading at 1Hz with increasing loads (+ 0.15N/cycle, Bionix, MTS, USA). A 3D optical tracking system (Aramis, GOM, Braunschweig, Germany) was used to determine interosteotomy movements (IOM). RESULTS: IOM were higher in the polylactide group (distal: P=0.001, mesial: P=0.001). Differences in mean stiffness (titanium: 478±68N/mm; polylactide: 425±38N/mm, P=0.240) and mean force at a vertical displacement of 1.0mm (titanium: 201.6±87.1N; polylactide: 141.3±29.9N, P=0.159) were not significant. CONCLUSIONS: The results of this study suggest that polylactide-based miniplates provide reduced mechanical integrity and higher interosteotomy movements in comparison to titanium miniplates in vitro. Indications for clinical use of polylactide-based miniplates in mandible reconstruction have to be placed critically. Future studies will focus on clinical complications of polylactide-based plates in risk patients.

Promoting abnormal grain growth in Fe-based shape memory alloys through compositional adjustments.

Iron-based shape memory alloys are promising candidates for large-scale structural applications due to their cost efficiency and the possibility of using conventional processing routes from the steel industry. However, recently developed alloy systems like Fe-Mn-Al-Ni suffer from low recoverability if the grains do not completely cover the sample cross-section. To overcome this issue, here we show that small amounts of titanium added to Fe-Mn-Al-Ni significantly enhance abnormal grain growth due to a considerable refinement of the subgrain sizes, whereas small amounts of chromium lead to a strong inhibition of abnormal grain growth. By tailoring and promoting abnormal grain growth it is possible to obtain very large single crystalline bars. We expect that the findings of the present study regarding the elementary mechanisms of abnormal grain growth and the role of chemical composition can be applied to tailor other alloy systems with similar microstructural features.

Increasing hernia size requires higher GRIP values for a biomechanically stable ventral hernia repair.

BACKGROUND: Increasing hernia sizes lead to higher recurrence rates after ventral hernia repair. A better grip might reduce the failure rates. MATERIAL AND METHODS: A biomechanical model delivering dynamic intermittent strain (DIS) was used to assess grip values at various hernia orifices. The model consists of a water-filled aluminium cylinder covered with tissues derived from pig bellies which are punched with a central defect varying in diameter. DIS was applied mimicking coughs lasting for up to 2 s with peak pressures between 180 and 220 mmHg and a plateau phase of 0.1 s. Ventral hernia repair was simulated with hernia meshes in the sublay position secured by tacks, glue or sutures as needed to achieve certain grip values. Grip was calculated taking into account the mesh: defect area ratio and the fixation strength. Data were assessed using non-parametric statistics. RESULTS: Using a mesh classified as highly stable upon DIS testing (DIS class A) a reduced overlap without fixation led to early slippage (p < 0.001). With the application of 16 fixation points, transmural sutures were better than tacks with Securestrap® being better than Absorbatack® (p < 0.001). Plotting the likelihood of a durable repair as a function of the calculated grip higher grip values were needed with increasing hernia diameter to achieve biomechanical stability. This is important for clinical work since the calculated grip values both from a registry and from published data tend to drop as hernia sizes increase indicating biomechanical instability. CONCLUSION: The experimental work reported here demonstrates for the first time that higher grip values should be reached when repairing larger ventral hernias.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

OBJECTIVES: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. METHODS: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. RESULTS: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. CONCLUSIONS: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Time-dependent functional role of the contralesional motor cortex after stroke.

After stroke, movements of the paretic hand rely on altered motor network dynamics typically including additional activation of the contralesional primary motor cortex (M1). The functional implications of contralesional M1 recruitment to date remain a matter of debate. We here assessed the role of contralesional M1 in 12 patients recovering from a first-ever stroke using online transcranial magnetic stimulation (TMS): Short bursts of TMS were administered over contralesional M1 or a control site (occipital vertex) while patients performed different motor tasks with their stroke-affected hand. In the early subacute phase (1-2 weeks post-stroke), we observed significant improvements in maximum finger tapping frequency when interfering with contralesional M1, while maximum grip strength and speeded movement initiation remained unaffected. After > 3 months of motor recovery, disruption of contralesional M1 activity did not interfere with performance in any of the three tasks, similar to what we observed in healthy controls. In patients with mild to moderate motor deficits, contralesional M1 has a task- and time-specific negative influence on motor performance of the stroke-affected hand. Our results help to explain previous contradicting findings on the role of contralesional M1 in recovery of function.

Bridging with reduced overlap: fixation and peritoneal grip can prevent slippage of DIS class A meshes.

PURPOSE: Ventral hernia repair can be performed safely using meshes which are primarily stable upon dynamic intermittent straining (DIS) at recommended overlap. In specific clinical situations, e.g., at bony edges, bridging of the hernial orifice with reduced overlap might be necessary. To gain insight into the durability of various applications, two different meshes with the best tissue grip known so far were assessed. METHODS: The model uses dynamic intermittent strain and comprises the repetition of submaximal impacts delivered via a hydraulically driven plastic containment. Pig tissue simulates a ventral hernia with a standardized 5 cm defect. Commercially available meshes classified as primarily stable at recommended overlap were used to bridge this defect at recommended and reduced overlap. RESULTS: Using Parietex Progrip®, the peritoneum adds sufficient stability at least to a 2.5 cm overlap. Using Dynamesh Cicat®, four gluing spots with Glubran® are sufficient to stabilize a 3.75 cm overlap. A 2.5 cm overlap is stabilized with eight bonding spots Glubran® and 8 bonding spots combined with four sutures stabilize a 1.25 cm overlap. Here again, an intact peritoneum stabilizes the reconstruction significantly. CONCLUSIONS: Based on a pig tissue model, a total of 23 different conditions were tested. A DIS class A mesh can be easily stabilized bridging a 5 cm hernial orifice with reduced overlap. Caution must be exerted to extend these results to other DIS classes and larger hernial orifices. Further DIS investigations can improve the durability of hernia repair.

Assessing the GRIP of Ventral Hernia Repair: How to Securely Fasten DIS Classified Meshes.

Recurrences are frequently observed after ventral hernia repair. Based on clinical data, the mesh-defect area ratio (MDAR) can lead to lower recurrence rates. Using dynamic intermittent strain (DIS) in a pig tissue model, MDAR can be modified to give a measure called grip to better assess the mechanical stability of ventral hernia repair. The focus of this experimental study is to assess the different aspects of mesh overlap (OL) and fixation only in bridging repair of ventral hernias. DIS mimics coughing actions in an ex vivo model with the repetition of submaximal impacts delivered via a hydraulically driven plastic containment. Tissue derived from pig bellies simulates a ventral hernia with varying defect sizes. MDAR is calculated from the hernia orifice and the mesh OL. Commercially available meshes were strengthened with glue, tacks, and sutures to bridge the defects. The reconstructions are strained with up to 425 dynamic impacts. The grip of each repair is assessed using MDAR modified by the strength of the fixation. The DIS classification is based on bridging of a 5 cm ventral hernia orifice with an OL of 5 cm in a sublay position. The classification discriminates meshes properties upon DIS strain. MDAR is calculated to be 9 under these conditions. Decreasing the OL or increasing the hernia orifice reduces MDAR to numbers below 9. MDAR is modified to reach GRIP. Closure of the peritoneum adds about 4 to the grip given by MDAR. The multiplying factor of a transmural suture or one tack of Securestrap® or Protack® is 0.5 times the number of tacks applied. The multiplier given by a bonding spot of Glubran® is similar to that of an Absorbatack® being 0.33. Plotting the likelihood of a bridging repair to survive more than 400 DIS impacts versus the grip estimated from the factors given above, the grip to be passed for a durable repair is 10 for Parietex Progrip®, and Dynamesh Cicat® and 25 for Dynamesh IPOM®. Clinical data previously published can be reculculated to assess MDAR and permit an estimation of the grip of the reconstruction. In these recalculations, a correlation between MDAR and long-term recurrence rates is found. A dimensionless number called grip can be calculated. The grip can be modified by fixation in a reproducible way. A higher grip can improve the durability of ventral hernia repair. We believe that a higher grip leads to lower recurrence rates in the clinical setting.

Growth in stratospheric chlorine from short-lived chemicals not controlled by the Montreal Protocol.

We have developed a chemical mechanism describing the tropospheric degradation of chlorine containing very short-lived substances (VSLS). The scheme was included in a global atmospheric model and used to quantify the stratospheric injection of chlorine from anthropogenic VSLS ( ClyVSLS) between 2005 and 2013. By constraining the model with surface measurements of chloroform (CHCl3), dichloromethane (CH2Cl2), tetrachloroethene (C2Cl4), trichloroethene (C2HCl3), and 1,2-dichloroethane (CH2ClCH2Cl), we infer a 2013 ClyVSLS mixing ratio of 123 parts per trillion (ppt). Stratospheric injection of source gases dominates this supply, accounting for ∼83% of the total. The remainder comes from VSLS-derived organic products, phosgene (COCl2, 7%) and formyl chloride (CHClO, 2%), and also hydrogen chloride (HCl, 8%). Stratospheric ClyVSLS increased by ∼52% between 2005 and 2013, with a mean growth rate of 3.7 ppt Cl/yr. This increase is due to recent and ongoing growth in anthropogenic CH2Cl2-the most abundant chlorinated VSLS not controlled by the Montreal Protocol.

Development of a dynamic model for ventral hernia mesh repair.

INTRODUCTION: The adequate way of mesh fixation in laparoscopic ventral hernia repair is still subject to debate. So far, simulation has only been carried out in a static way, thereby omitting dynamic effects of coughing or vomiting. We developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS: An aluminium cylinder was equipped with a pressure controlled, fluid-filled plastic bag, simulating the abdominal viscera. A computer-controlled system allowed the control of influx and efflux, thus creating pressure peaks of up to 200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany). The model was controlled for the friction coefficient of the tissue against the mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS: The model was able to create pressure peaks equivalent to physiologic coughs or vomiting. Physiologic elasticity was thereby maintained. We could show that the friction coefficient is crucial to achieve a physiologic situation. The meshes showed a tendency to dislocate with an increasing number of coughs (Fig. 4). Nevertheless, when applied in a plain manner, the meshes withstood more cough cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS: The dynamic movement of the abdominal wall, the friction between tissue and mesh and the way of mesh application are crucial factors that have to be controlled for in simulation of ventral abdominal hernia closure. We could demonstrate that patient specific factors such as the frequency of coughing as well as the application technique influence the long term stability of the mesh.

[Patient participation in medical decision making within an integrated health care system in Germany: results of a controlled cohort study]. / Patientenbeteiligung bei medizinischen Entscheidungen in der Integrierten Versorgung Gesundes Kinzigtal: Ergebnisse einer kontrollierten Kohortenstudie.

An integrated health care project called "Gesundes Kinzigtal" was conducted in a rural area in Germany. As part of the project, physicians were trained and other measures were taken to enhance patient involvement in medical decision making. As part of the external evaluation, various effects regarding patient involvement in medical decision making, patient involvement and information preference, decision confidence, patient satisfaction with ambulatory care and patient quality of life were examined. The data were gathered by means of a questionnaire on an annual basis between 2007 and 2009. Effects were compared between patients who were participating in the integrated care project and two control groups. Analyses are based on the data of 1,205 patients. Over time all outcomes decreased slightly, except for information preference and physical quality of life. No statistically significant intervention effects on patient involvement in medical decision making or any other outcome variable could be found. The intensity of the training was presumably too low to establish an enduring change in the physician-patient interaction.

Molecular hydrogen (H2) emissions from gasoline and diesel vehicles.

This study assesses individual-vehicle molecular hydrogen (H2) emissions in exhaust gas from current gasoline and diesel vehicles measured on a chassis dynamometer. Absolute H2 emissions were found to be highest for motorcycles and scooters (141+/-38.6 mg km(-1)), approximately 5 times higher than for gasoline-powered automobiles (26.5+/-12.1 mg km(-1)). All diesel-powered vehicles emitted marginal amounts of H2 ( approximately 0.1 mg km(-1)). For automobiles, the highest emission factors were observed for sub-cycles subject to a cold-start (mean of 53.1+/-17.0 mg km(-1)). High speeds also caused elevated H2 emission factors for sub-cycles reaching at least 150 km h(-1) (mean of 40.4+/-7.1 mg km(-1)). We show that H2/CO ratios (mol mol(-1)) from gasoline-powered vehicles are variable (sub-cycle means of 0.44-5.69) and are typically higher (mean for automobiles 1.02, for 2-wheelers 0.59) than previous atmospheric ratios characteristic of traffic-influenced measurements. The lowest mean individual sub-cycle ratios, which correspond to high absolute emissions of both H2 and CO, were observed during cold starts (for automobiles 0.48, for 2-wheelers 0.44) and at high vehicle speeds (for automobiles 0.73, for 2-wheelers 0.45). This finding illustrates the importance of these conditions to observed H2/CO ratios in ambient air. Overall, 2-wheelers displayed lower H2/CO ratios (0.48-0.69) than those from gasoline-powered automobiles (0.75-3.18). This observation, along with the lower H2/CO ratios observed through studies without catalytic converters, suggests that less developed (e.g. 2-wheelers) and older vehicle technologies are largely responsible for the atmospheric H2/CO ratios reported in past literature.

Intra-abdominal vagal blocking (VBLOC therapy): clinical results with a new implantable medical device.

BACKGROUND: A new medical device uses high-frequency electrical algorithms to create intermittent vagal blocking (VBLOC therapy). The aim is to assess the effects of vagal blocking on excess weight loss (EWL), safety, dietary intake, and vagal function. METHODS: An open-label, 3-center study was conducted in obese subjects (body mass index [BMI] 35-50 kg/m(2)). Electrodes were implanted laparoscopically on both vagi near the esophagogastric junction to provide electrical block. Patients were followed for 6 months for body weight, safety, electrocardiogram, dietary intake, satiation, satiety, and plasma pancreatic polypeptide (PP) response to sham feeding. To specifically assess device effects alone, no diet or exercise programs were instituted. RESULTS: Thirty-one patients (mean BMI, 41.2 +/- 1.4 kg/m(2)) received the device. Mean EWL at 4 and 12 weeks and 6 months after implant was 7.5%, 11.6%, and 14.2%, respectively (all P < .001); 25% of patients lost >25% EWL at 6 months (maximum, 36.8%). There were no deaths or device-related serious adverse events (AEs). Calorie intake decreased by >30% at 4 and 12 weeks and 6 months (all P 25 pg/mL (P = .02). Three patients had serious AEs that required brief hospitalization, 1 each for lower respiratory tract, subcutaneous implant site seroma, and Clostridium difficile diarrhea. CONCLUSIONS: Intermittent, intra-abdominal vagal blocking is associated with significant EWL and a desirable safety profile.

MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling.

ES-cell-based cardiovascular repair requires an in-depth understanding of the molecular mechanisms underlying the differentiation of cardiovascular ES cells. A candidate cardiovascular-fate inducer is the bHLH transcription factor MesP1. As one of the earliest markers, it is expressed specifically in almost all cardiovascular precursors and is required for cardiac morphogenesis. Here we show that MesP1 is a key factor sufficient to induce the formation of ectopic heart tissue in vertebrates and increase cardiovasculogenesis by ES cells. Electrophysiological analysis showed all subtypes of cardiac ES-cell differentiation. MesP1 overexpression and knockdown experiments revealed a prominent function of MesP1 in a gene regulatory cascade, causing Dkk-1-mediated blockade of canonical Wnt-signalling. Independent evidence from ChIP and in vitro DNA-binding studies, expression analysis in wild-type and MesP knockout mice, and reporter assays confirm that Dkk-1 is a direct target of MesP1. Further analysis of the regulatory networks involving MesP1 will be required to preprogramme ES cells towards a cardiovascular fate for cell therapy and cardiovascular tissue engineering. This may also provide a tool to elicit cardiac transdifferentiation in native human adult stem cells.

Localization of source regions of selected hydrofluorocarbons combining data collected at two European mountain stations.

Ground-based in situ measurements of hydrofluorocarbons HFC-125, HFC-134a, and HFC-152a, which are regulated under the Kyoto Protocol, are carried out at four European sites within the SOGE (System of Observation of Halogenated Greenhouse Gases in Europe) program. Concentrations measured at the high mountain stations of Jungfraujoch (Switzerland) and Mte Cimone (Italy) together with back-trajectory statistical analysis are used in order to identify potential source regions on a European scale. Combining concentration data recorded at the two sites allows to reduce one of the problem which is inherent to the back-trajectory approach, i.e. the localisation of "ghost" sources in the wake of real sources. In this way, a more reliable picture of the location of European potential source regions is given.