Coupling of LMS with a fs-laser ablation ion source: elemental and isotope composition measurements

Mass spectrometric analysis of elemental and isotopic compositions of several NIST standards is performed by a miniature laser ablation/ionisation reflectron-type time-of-flight mass spectrometer (LMS) using a fs-laser ablation ion source (775 nm, 190 fs, 1 kHz). The results of the mass spectrometric studies indicate that in a defined range of laser irradiance (fluence) and for a certain number of accumulations of single laser shot spectra, the measurements of isotope abundances can be conducted with a measurement accuracy at the per mill level and at the per cent level for isotope concentrations higher and lower than 100 ppm, respectively. Also the elemental analysis can be performed with a good accuracy. The LMS instrument combined with a fs-laser ablation ion source exhibits similar detection efficiency for both metallic and non-metallic elements. Relative sensitivity coefficients were determined and found to be close to one, which is of considerable importance for the development of standard-less instruments. Negligible thermal effects, sample damage and excellent characteristics of the fs-laser beam are thought to be the main reason for substantial improvement of the instrumental performance compared to other laser ablation mass spectrometers.

Performance evaluation of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations in planetary space research

Key performance features of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations of the chemical composition of planetary surfaces are presented. This mass spectrometer is well suited for elemental and isotopic analysis of raw solid materials with high sensitivity and high spatial resolution. In this study, ultraviolet laser radiation with irradiances suitable for ablation (< 1 GW/cm2) is used to achieve stable ion formation and low sample consumption. In comparison to our previous laser ablation studies at infrared wavelengths, several improvements to the experimental setup have been made, which allow accurate control over the experimental conditions and good reproducibility of measurements. Current performance evaluations indicate significant improvements to several instrumental figures of merit. Calibration of the mass scale is performed within a mass accuracy (Δm/m) in the range of 100 ppm, and a typical mass resolution (m/Δm) ~600 is achieved at the lead mass peaks. At lower laser irradiances, the mass resolution is better, about (m/Δm) ~900 for lead, and limited by the laser pulse duration of 3 ns. The effective dynamic range of the instrument was enhanced from about 6 decades determined in previous study up to more than 8 decades at present. Current studies show high sensitivity in detection of both metallic and non-metallic elements. Their abundance down to tens of ppb can be measured together with their isotopic patterns. Due to strict control of the experimental parameters, e.g. laser characteristics, ion-optical parameters and sample position, by computer control, measurements can be performed with high reproducibility. Copyright © 2012 John Wiley & Sons, Ltd.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for intermediate- and high-risk pulmonary embolism

AIMS No standardized local thrombolysis regimen exists for the treatment of pulmonary embolism (PE). We retrospectively investigated efficacy and safety of fixed low-dose ultrasound-assisted catheter-directed thrombolysis (USAT) for intermediate- and high-risk PE. METHODS AND RESULTS Fifty-two patients (65 ± 14 years) of whom 14 had high-risk PE (troponin positive in all) and 38 intermediate-risk PE (troponin positive in 91%) were treated with intravenous unfractionated heparin and USAT using 10 mg of recombinant tissue plasminogen activator per device over the course of 15 h. Bilateral USAT was performed in 83% of patients. During 3-month follow-up, two [3.8%; 95% confidence interval (CI) 0.5-13%] patients died (one from cardiogenic shock and one from recurrent PE). Major non-fatal bleeding occurred in two (3.8%; 95% CI, 0.5-13%) patients: one intrathoracic bleeding after cardiopulmonary resuscitation requiring transfusion, one intrapulmonary bleeding requiring lobectomy. Mean pulmonary artery pressure decreased from 37 ± 9 mmHg at baseline to 25 ± 8 mmHg at 15 h (P < 0.001) and cardiac index increased from 2.0 ± 0.7 to 2.7 ± 0.9 L/min/m(2) (P < 0.001). Echocardiographic right-to-left ventricular end-diastolic dimension ratio decreased from 1.42 ± 0.21 at baseline to 1.06 ± 0.23 at 24 h (n = 21; P < 0.001). The greatest haemodynamic benefit from USAT was found in patients with high-risk PE and in those with symptom duration < 14 days. CONCLUSION A standardized catheter intervention approach using fixed low-dose USAT for the treatment of intermediate- and high-risk PE was associated with rapid improvement in haemodynamic parameters and low rates of bleeding complications and mortality.

A dosimetric study of radionuclide therapy for bone marrow ablation

In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 ($\sp{166}$Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of $\sp{166}$Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of $\sp{166}$Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of $\sp{166}$Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head.^ A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six $\sp{166}$Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with radiation dose estimates for the bone marrow calculated from the standard and regional technique. The results showed the regional technique values correlated more closely to several clinical response parameters. (Abstract shortened by UMI.) ^

In Vitro Testing of a Temporary Catheter-Based Aortic "Parachute" Valve

Recently developed technologies allow aortic valve implantation off-pump in a beating heart. In this procedure, the native, stenotic aortic valve is not removed, but simply crushed by a pressure balloon mounted on a percutaneous catheter. Removal of the native aortic cusps before valve replacement may reduce the incidence of annular or cuspal calcium embolization and late perivalvular leaks and increase implantable valve size. However, a temporary valve system in the ascending aorta may be necessary to maintain hemodynamic stability by reducing acute aortic regurgitation and left ventricular volume overload. This study evaluates the hemodynamic effects of a wire-mounted, monoleaflet, temporary valve apparatus in a mechanical cardiovascular simulator. Aortic flow, systemic pressure and left ventricular pressure were continuously monitored. An intraluminal camera obtained real-time proximal and distal images of the valve in operation. Insertion of the parachute valve in the simulator increased diastolic pressure from 7 to 38 mm Hg. Cardiac output increased from 2.08 to 4.66 L/min and regurgitant volume decreased from 65 to 23 mL. In conclusion, placement of a temporary valve in the ascending aorta may help maintain hemodynamic stability and improve off-pump aortic valve replacement.

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

BACKGROUND In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01166997.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis.

Patients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the post-thrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute ilio-femoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0-6%) and 6 minor bleedings (7%; 95%CI, 3-14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74-94%) and 96% (95% CI, 88-99%), respectively. At three months, 88% (95% CI, 78-94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81-99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with ilio-femoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.

Microsurgical and laser ablation analysis of leaf positioning and dorsoventral patterning in tomato

Leaves are arranged according to regular patterns, a phenomenon referred to as phyllotaxis. Important determinants of phyllotaxis are the divergence angle between successive leaves, and the size of the leaves relative to the shoot axis. Young leaf primordia are thought to provide positional information to the meristem, thereby influencing the positioning of new primordia and hence the divergence angle. On the contrary, the meristem signals to the primordia to establish their dorsoventral polarity, which is a prerequisite for the formation of a leaf blade. These concepts originate from classical microsurgical studies carried out between the 1920s and the 1970s. Even though these techniques have been abandoned in favor of genetic analysis, the resulting insights remain a cornerstone of plant developmental biology. Here, we employ new microsurgical techniques to reassess and extend the classical studies on phyllotaxis and leaf polarity. Previous experiments have indicated that the isolation of an incipient primordium by a tangential incision caused a change of divergence angle between the two subsequent primordia, indicating that pre-existing primordia influence further phyllotaxis. Here.. we repeat these experiments and compare them with the results of laser ablation of incipient primordia. Furthermore. we explore to what extent the different pre-existing primordia influence the size and position of new organs. and hence phyllotaxis. We propose that the two youngest primordia (P-1 and P-2) are sufficient for the approximate positioning of the incipient primordium (I-1), and therefore for the perpetuation of the generative spiral, whereas the direct contact neighbours of I-1 (P-2 and P-3) control its delimitation and hence its exact size and position. Finally. we report L I specific cell ablation experiments suggesting that the meristem L-1 layer is essential for the dorsoventral patterning of leaf primordia.

Microsurgical and laser ablation analysis of interactions between the zones and layers of the tomato shoot apical meristern

Plants exhibit life-long organogenic and histogenic activity in a specialised organ, the shoot apical meristem. Leaves and flowers are formed within the ring-shaped peripheral zone, which surrounds the central zone, the site of the stem cells. We have undertaken a series of high-precision laser ablation and microsurgical tissue removal experiments to test the functions of different parts of the tomato meristem, and to reveal their interactions. Ablation of the central zone led to ectopic expression of the WUSCHEL gene at the periphery, followed by the establishment of a new meristem centre. After the ablation of the central zone, organ formation continued without a lag. Thus, the central zone does not participate in organogenesis, except as the ultimate source of founder cells. Microsurgical removal of the external L-1 layer induced periclinal cell divisions and terminal differentiation in the subtending layers. In addition, no organs were initiated in areas devoid of L-1, demonstrating an important role of the L-1 in organogenesis. L-1 ablation had only local effects, an observation that is difficult to reconcile with phyllotaxis theories that invoke physical tension operating within the meristem as a whole. Finally, regeneration of L-1 cells was never observed after ablation. This shows that while the zones of the meristem show a remarkable capacity to regenerate after interference, elimination of the L-1 layer is irreparable and causes terminal differentiation.

Probing the Allende meteorite with a miniature laser-ablation mass analyser for space application

We measured the elemental composition on a sample of Allende meteorite with a miniature laser ablation mass spectrometer. This Laser Mass Spectrometer (LMS) has been designed and built at the University of Bern in the Department of Space Research and Planetary Sciences with the objective of using such an instrument on a space mission. Utilising the meteorite Allende as the test sample in this study, it is demonstrated that the instrument allows the in situ determination of the elemental composition and thus mineralogy and petrology of untreated rocky samples, particularly on planetary surfaces. In total, 138 measurements of elemental compositions have been carried out on an Allende sample. The mass spectrometric data are evaluated and correlated with an optical image. It is demonstrated that by illustrating the measured elements in the form of mineralogical maps, LMS can serve as an element imaging instrument with a very high spatial resolution of µm scale. The detailed analysis also includes a mineralogical evaluation and an investigation of the volatile element content of Allende. All findings are in good agreement with published data and underline the high sensitivity, accuracy and capability of LMS as a mass analyser for space exploration.

Laser ablation and induced nano-particle synthesis

Laser pulses are largely used for processing and analysis of materials and in particular for nano-particle synthesis. This paper addresses fundamentals of the generation of nano-materials following specific thermodynamic paths of the irradiated material. Computer simulations using the hydro code MULTI and the SESAME equation of state have been performed to follow the dynamics of a target initially heated by a short laser pulse over a distance comparable to the metal skin depth.

Pulmonary veins to left atrium cycle length gradient predicts procedural and clinical outcomes of persistent atrial fibrillation ablation.

BACKGROUND Rapid pulmonary vein (PV) activity has been shown to maintain paroxysmal atrial fibrillation (AF). We evaluated in persistent AF the cycle length (CL) gradient between PVs and the left atrium (LA) in an attempt to identify the subset of patients where PVs play an important role. METHODS AND RESULTS Ninety-seven consecutive patients undergoing first ablation for persistent AF were studied. For each PV, the CL of the fastest activation was assessed over 1 minute (PVfast) using Lasso recordings. The PV to LA CL gradient was quantified by the ratio of PVfast to LA appendage (LAA) AF CL. Stepwise ablation terminated AF in 73 patients (75%). In the AF termination group, the PVfast CL was much shorter than the LAA CL resulting in lower PVfast/LAA ratios compared with the nontermination group (71±10% versus 92±7%; P<0.001). Within the termination group, PVfast/LAA ratios were notably lower if AF terminated after PV isolation or limited adjunctive substrate ablation compared with patients who required moderate or extensive ablation (63±6% versus 75±8%; P<0.001). PVfast/LAA ratio <69% predicted AF termination after PV isolation or limited substrate ablation with 74% positive predictive value and 95% negative predictive value. After a mean follow-up of 29±17 months, freedom from arrhythmia recurrence off-antiarrhythmic drugs was achieved in most patients with PVfast/LAA ratios <69% as opposed to the remaining population (80% versus 43%; P<0.001). CONCLUSIONS The PV to LA CL gradient may identify the subset of patients in whom persistent AF is likely to terminate after PV isolation or limited substrate ablation and better long-term outcomes are achieved.