Hair analysis for Delta9-tetrahydrocannabinolic acid A--new insights into the mechanism of drug incorporation of cannabinoids into hair

Differentiation between external contamination and incorporation of drugs or their metabolites from inside the body via blood, sweat or sebum is a general issue in hair analysis and of high concern when interpreting analytical results. In hair analysis for cannabinoids the most common target is Delta9-tetrahydrocannabinol (THC), sometimes cannabidiol (CBD) and cannabinol (CBN) are determined additionally. After repeated external contamination by cannabis smoke these analytes are known to be found in hair even after performing multiple washing steps. A widely accepted strategy to unequivocally prove active cannabis consumption is the analysis of hair extracts for the oxidative metabolite 11-nor-9-carboxy-THC (THC-COOH). Although the acidic nature of this metabolite suggests a lower rate of incorporation into the hair matrix compared to THC, it is not fully understood up to now why hair concentrations of THC-COOH are generally found to be much lower (mostly <10 pg/mg) than the corresponding THC concentrations. Delta9-Tetrahydrocannabinolic acid A (THCA A) is the preliminary end product of the THC biosynthesis in the cannabis plant. Unlike THC it is non-psychoactive and can be regarded as a 'precursor' of THC being largely decarboxylated when heated or smoked. The presented work shows for the first time that THCA A is not only detectable in blood and urine of cannabis consumers but also in THC positive hair samples. A pilot experiment performed within this study showed that after oral intake of THCA A on a regular basis no relevant incorporation into hair occurred. It can be concluded that THCA A in hair almost exclusively derives from external contamination e.g. by side stream smoke. Elevated temperatures during the analytical procedure, particularly under alkaline conditions, can lead to decarboxylation of THCA A and accordingly increase THC concentrations in hair. Additionally, it has to be kept in mind that in hair samples tested positive for THCA A at least a part of the 'non-artefact' THC probably derives from external contamination as well, because in condensate of cannabis smoke both THC and THCA A are present in relevant amounts. External contamination by side stream smoke could therefore explain the great differences in THC and THC-COOH hair concentrations commonly found in cannabis users.

High-throughput procedure for tick surveys of tick-borne encephalitis virus and its application in a national surveillance study in Switzerland

Tick-borne encephalitis (TBE), a viral infection of the central nervous system, is endemic in many Eurasian countries. In Switzerland, TBE risk areas have been characterized by geographic mapping of clinical cases. Since mass vaccination should significantly decrease the number of TBE cases, alternative methods for exposure risk assessment are required. We established a new PCR-based test for the detection of TBE virus (TBEV) in ticks. The protocol involves an automated, high-throughput nucleic acid extraction method (QIAsymphony SP system) and a one-step duplex real-time reverse transcription-PCR (RT-PCR) assay for the detection of European subtype TBEV, including an internal process control. High usability, reproducibility, and equivalent performance for virus concentrations down to 5 x 10(3) viral genome equivalents/microl favor the automated protocol compared to the modified guanidinium thiocyanate-phenol-chloroform extraction procedure. The real-time RT-PCR allows fast, sensitive (limit of detection, 10 RNA copies/microl), and specific (no false-positive test results for other TBEV subtypes, other flaviviruses, or other tick-transmitted pathogens) detection of European subtype TBEV. The new detection method was applied in a national surveillance study, in which 62,343 Ixodes ricinus ticks were screened for the presence of TBE virus. A total of 38 foci of endemicity could be identified, with a mean virus prevalence of 0.46%. The foci do not fully agree with those defined by disease mapping. Therefore, the proposed molecular test procedure constitutes a prerequisite for an appropriate TBE surveillance. Our data are a unique complement of human TBE disease case mapping in Switzerland.

MIAWARA-C, a new ground based water vapor radiometer for measurement campaigns

In this paper a new 22 GHz water vapor spectro-radiometer which has been specifically designed for profile measurement campaigns of the middle atmosphere is presented. The instrument is of a compact design and has a simple set up procedure. It can be operated as a standalone instrument as it maintains its own weather station and a calibration scheme that does not rely on other instruments or the use of liquid nitrogen. The optical system of MIAWARA-C combines a choked gaussian horn antenna with a parabolic mirror which reduces the size of the instrument in comparison with currently existing radiometers. For the data acquisition a correlation receiver is used together with a digital cross correlating spectrometer. The complete backend section, including the computer, is located in the same housing as the instrument. The receiver section is temperature stabilized to minimize gain fluctuations. Calibration of the instrument is achieved through a balancing scheme with the sky used as the cold load and the tropospheric properties are determined by performing regular tipping curves. Since MIAWARA-C is used in measurement campaigns it is important to be able to determine the elevation pointing in a simple manner as this is a crucial parameter in the calibration process. Here we present two different methods; scanning the sky and the Sun. Finally, we report on the first spectra and retrieved water vapor profiles acquired during the Lapbiat campaign at the Finnish Meteorological Institute Arctic Research Centre in Sodankylä, Finland. The performance of MIAWARA-C is validated here by comparison of the presented profiles against the equivalent profiles from the Microwave Limb Sounder on the EOS/Aura satellite.

Transcatheter aortic valve implantation or surgical aortic valve replacement as redo procedure after prior coronary artery bypass grafting

The perioperative risk for redo surgical aortic valve replacement (S-AVR) in patients with severe aortic stenosis and prior coronary artery bypass grafting (CABG) is increased. Transcatheter aortic valve implantation (TAVI) represents an alternative. We assessed the perioperative and mid-term clinical outcome of patients undergoing S-AVR or TAVI.

Postmortem ventilation: A new method for improved detection of pulmonary pathologies in forensic imaging

Postmortem imaging has gained prominence in the field of forensic pathology. Even with experience in this procedure, difficulties arise in evaluating pathologies of the postmortem lung. The effect of postmortem ventilation with applied pressures of 10, 20, 30 and 40mbar was evaluated in 10 corpses using simultaneous postmortem computed tomography (pmCT) scans. Ventilation was performed via a continuous positive airway pressure mask (n=5), an endotracheal tube (n=4) and a laryngeal mask (n=1) using a portable home care ventilator. The lung volumes were measured and evaluated by a segmentation technique based on reconstructed CT data. The resulting changes to the lungs were analyzed. Postmortem ventilation at 40mbar induced a significant (p<0.05) unfolding of the lungs, with a mean volume increase of 1.32l. Small pathologies of the lung such as scarring and pulmonary nodules as well as emphysema were revealed, while inner livores were reduced. Even though lower ventilation pressures resulted in a significant (p<0.05) volume increase, pathologies were best evaluated when a pressure of 40mbar was applied, due to the greater reduction of the inner livores. With the ventilation-induced expansion of the lungs, a decrease in the heart diameter and gaseous distension of the stomach was recognized. In conclusion, postmortem ventilation is a feasible method for improving evaluation of the lungs and detection of small lung pathologies. This is because of the volume increase in the air-filled portions of the lung and reduced appearance of inner livores.

The new insight into dynamic crossover in glass forming liquids from the apparent enthalpy analysis

One of the most intriguing phenomena in glass forming systems is the dynamic crossover (T(B)), occurring well above the glass temperature (T(g)). So far, it was estimated mainly from the linearized derivative analysis of the primary relaxation time τ(T) or viscosity η(T) experimental data, originally proposed by Stickel et al. [J. Chem. Phys. 104, 2043 (1996); J. Chem. Phys. 107, 1086 (1997)]. However, this formal procedure is based on the general validity of the Vogel-Fulcher-Tammann equation, which has been strongly questioned recently [T. Hecksher et al. Nature Phys. 4, 737 (2008); P. Lunkenheimer et al. Phys. Rev. E 81, 051504 (2010); J. C. Martinez-Garcia et al. J. Chem. Phys. 134, 024512 (2011)]. We present a qualitatively new way to identify the dynamic crossover based on the apparent enthalpy space (H(a)(') = dlnτ/d(1/T)) analysis via a new plot lnH(a)(') vs. 1∕T supported by the Savitzky-Golay filtering procedure for getting an insight into the noise-distorted high order derivatives. It is shown that depending on the ratio between the "virtual" fragility in the high temperature dynamic domain (m(high)) and the "real" fragility at T(g) (the low temperature dynamic domain, m = m(low)) glass formers can be splitted into two groups related to f < 1 and f > 1, (f = m(high)∕m(low)). The link of this phenomenon to the ratio between the apparent enthalpy and activation energy as well as the behavior of the configurational entropy is indicated.

Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer

The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure.

Lordoplasty: report on early results with a new technique for the treatment of vertebral compression fractures to restore the lordosis

Cement augmentation using PMMA cement is known as an efficient treatment for osteoporotic vertebral compression fractures with a rapid release of pain in most patients and prevention of an ongoing kyphotic deformity of the vertebrae treated. However, after a vertebroplasty there is no chance to restore vertebral height. Using the technique of kyphoplasty a certain restoration of vertebral body height can be achieved. But there is a limitation of recovery due to loss of correction when deflating the kyphoplastic ballon and before injecting the cement. In addition, the instruments used are quite expensive. Lordoplasty is another technique to restore kyphosis by indirect fracture reduction as it is used with an internal fixateur. The fractured and the adjacent vertebrae are instrumented with bone cannulas bipediculary and the adjacent vertebrae are augmentated with cement. After curing of the cement the fractured vertebra is reduced by applying a lordotic moment via the cannulas. While maintaining the pretension the fractured vertebra is reinforced. We performed a prospective trial of 26 patients with a lordoplastic procedure. There was a pain relief of about 87% and a significant decrease in VAS value from 7.3 to 1.9. Due to lordoplasty there was a significant and permanent correction in vertebral and segmental kyphotic angle about 15.2 degrees and 10.0 degrees , respectively and also a significant restoration in anterior and mid vertebral height. Lordoplasty is a minimal invasive technique to restore vertebral body height. An immediate relief of pain is achieved in most patients. The procedure is safe and cost effective.

New concept for CTO recanalization using controlled antegrade and retrograde subintimal tracking: the CART technique

OBJECTIVES: To demonstrate the safety and feasibility of a new concept for CTO recanalization using a controlled antegrade and retrograde subintimal tracking technique (CART technique). BACKGROUND: A successful percutaneous recanalization of chronic coronary occlusions results in improved survival, as well as enhanced left ventricular function, reduction in angina, and improved exercise tolerance. However, successful recanalization of CTOs is still not optimal, and needs further improvements. METHODS: Ten patients with a CTO underwent the CART procedure. This technique combines the simultaneous use of the antegrade and retrograde approaches. A subintimal dissection is created antegradely and retrogradely, which allows the operator to limit the extension of the subintimal dissection in the CTO portion. A retrograde approach means that the occlusion site is approached in a retrograde fashion through the best collateral channel from any other patent coronary artery. RESULTS: The occlusion site was located in the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to 84 months. Vessel recanalization was achieved in all patients. In all cases, the subintimal dissection was limited to the CTO region. No complications occurred in the collateral channel used for the retrograde approach. There were no in-hospital major adverse cardiac events. CONCLUSIONS: The CART technique is feasible, safe, and has a high success rate.

A new system for computer-aided preoperative planning and intraoperative navigation during corrective jaw surgery

A new system for computer-aided corrective surgery of the jaws has been developed and introduced clinically. It combines three-dimensional (3-D) surgical planning with conventional dental occlusion planning. The developed software allows simulating the surgical correction on virtual 3-D models of the facial skeleton generated from computed tomography (CT) scans. Surgery planning and simulation include dynamic cephalometry, semi-automatic mirroring, interactive cutting of bone and segment repositioning. By coupling the software with a tracking system and with the help of a special registration procedure, we are able to acquire dental occlusion plans from plaster model mounts. Upon completion of the surgical plan, the setup is used to manufacture positioning splints for intraoperative guidance. The system provides further intraoperative assistance with the help of a display showing jaw positions and 3-D positioning guides updated in real time during the surgical procedure. The proposed approach offers the advantages of 3-D visualization and tracking technology without sacrificing long-proven cast-based techniques for dental occlusion evaluation. The system has been applied on one patient. Throughout this procedure, we have experienced improved assessment of pathology, increased precision, and augmented control.

Preliminary results following reinforcement of the pulmonary autograft to prevent dilatation after the Ross procedure

OBJECTIVE: The Ross operation remains a controversially discussed procedure, because concern exists regarding late dilatation of the neoaortic root and progressive regurgitation of the autograft valve. We present our early experience with an external reinforcement of the autograft, which is inserted into a prosthetic Dacron graft with an artificial aortic root configuration. This detail should help to prevent neoaortic root dilatation. PATIENTS AND METHODS: Between 2006 and 2007, 12 patients (mean age 16 +/- 38 years; range 15-38 years) underwent a Ross procedure by this technique. Indications were aortic regurgitation (n = 2), aortic stenosis (n = 5), and combined aortic stenosis and insufficiency (n = 5). A bicuspid aortic valve was present in 9 patients. Balloon valvuloplasty had been performed in 7 patients. Follow-up was performed by clinical and echocardiographic examinations. RESULTS: No early or late deaths occurred in this small series, and freedom from reoperation is 100%. Echocardiographic follow-up confirmed absence of aortic insufficiency in 11 patients after a mean of 11 months (range 2-30 months). In 1 patient, a small asymmetric regurgitation jet was already observed at discharge echocardiography. As expected, no neoaortic root dilatation was observed during follow-up. All patients are in New York Heart Association class I. CONCLUSIONS: The present technique is a simple and reproducible technical step that does not require significant additional time. Inclusion of the autograft within a root prosthesis may be especially indicated in situations known for late autograft dilatation, namely, bicuspid aortic valve, predominant aortic insufficiency, and ascending aortic enlargement.

Testing Wisconsin asphalt mixtures for the 2002 AASHTO mechanistic design procedure

There has been a continuous evolutionary process in asphalt pavement design. In the beginning it was crude and based on past experience. Through research, empirical methods were developed based on materials response to specific loading at the AASHO Road Test. Today, pavement design has progressed to a mechanistic-empirical method. This methodology takes into account the mechanical properties of the individual layers and uses empirical relationships to relate them to performance. The mechanical tests that are used as part of this methodology include dynamic modulus and flow number, which have been shown to correlate with field pavement performance. This thesis was based on a portion of a research project being conducted at Michigan Technological University (MTU) for the Wisconsin Department of Transportation (WisDOT). The global scope of this project dealt with the development of a library of values as they pertain to the mechanical properties of the asphalt pavement mixtures paved in Wisconsin. Additionally, a comparison with the current associated pavement design to that of the new AASHTO Design Guide was conducted. This thesis describes the development of the current pavement design methodology as well as the associated tests as part of a literature review. This report also details the materials that were sampled from field operations around the state of Wisconsin and their testing preparation and procedures. Testing was conducted on available round robin and three Wisconsin mixtures and the main results of the research were: The test history of the Superpave SPT (fatigue and permanent deformation dynamic modulus) does not affect the mean response for both dynamic modulus and flow number, but does increase the variability in the test results of the flow number. The method of specimen preparation, compacting to test geometry versus sawing/coring to test geometry, does not statistically appear to affect the intermediate and high temperature dynamic modulus and flow number test results. The 2002 AASHTO Design Guide simulations support the findings of the statistical analyses that the method of specimen preparation did not impact the performance of the HMA as a structural layer as predicted by the Design Guide software. The methodologies for determining the temperature-viscosity relationship as stipulated by Witczak are sensitive to the viscosity test temperatures employed. The increase in asphalt binder content by 0.3% was found to actually increase the dynamic modulus at the intermediate and high test temperature as well as flow number. This result was based the testing that was conducted and was contradictory to previous research and the hypothesis that was put forth for this thesis. This result should be used with caution and requires further review. Based on the limited results presented herein, the asphalt binder grade appears to have a greater impact on performance in the Superpave SPT than aggregate angularity. Dynamic modulus and flow number was shown to increase with traffic level (requiring an increase in aggregate angularity) and with a decrease in air voids and confirm the hypotheses regarding these two factors. Accumulated micro-strain at flow number as opposed to the use of flow number appeared to be a promising measure for comparing the quality of specimens within a specific mixture. At the current time the Design Guide and its associate software needs to be further improved prior to implementation by owner/agencies.

Non-invasive measurement of steroids in fish-holding water: important considerations when applying the procedure to behaviour studies

Fish behaviourists are increasingly turning to non-invasive measurement of steroid hormones in holding water, as opposed to blood plasma. When some of us met at a workshop in Faro, Portugal, in September, 2007, we realised that there were still many issues concerning the application of this procedure that needed resolution, including: Why do we measure release rates rather than just concentrations of steroids in the water? How does one interpret steroid release rates when dealing with fish of different sizes? What are the merits of measuring conjugated as well as free steroids in water? In the ‘static’ sampling procedure, where fish are placed in a separate container for a short period of time, does this affect steroid release—and, if so, how can it be minimised? After exposing a fish to a behavioural stimulus, when is the optimal time to sample? What is the minimum amount of validation when applying the procedure to a new species? The purpose of this review is to attempt to answer these questions and, in doing so, to emphasize that application of the non-invasive procedure requires more planning and validation than conventional plasma sampling. However, we consider that the rewards justify the extra effort.

The Ross procedure in infants and young children

BACKGROUND: This study reviews our experience with the Ross procedure in infants and young children. METHODS: From September 1993 to September 2004, 52 children less than 15 years of age underwent a Ross procedure. The patients ranged in age from 4 days to 15 years old (median, 5 years). Fifteen patients (29%) were less than 2 years of age. The predominant indication for the Ross procedure was aortic stenosis. Sixteen patients underwent a Ross-Konno procedure for severe left ventricular outflow tract obstruction. Thirty-four patients had 48 previous interventions. Preoperatively, 6 patients showed severe left ventricular dysfunction, and 2 of the patients required ventilation and inotropic support. Concomitant procedures were performed in 8 patients. Three patients had a mitral valve replacement, 2 patients had a ventricular septal defect closure and an aortic arch reconstruction, 2 patients had aortic arch reconstructions, and 1 patient had resection of a coarctation and a ventricular septal defect closure. RESULTS: Patients were followed up for a median of 43 months (range, 1 to 130). Overall survival was 85% +/- 5% at 1 and 82% +/- 5% at 2, 5, and 10 years. Hospital mortality was 5 of 52 patients (9.6%). All deaths occurred in neonates or infants less than 2 months of age, who needed urgent surgery. Three patients died late of noncardiac causes. At last follow-up, all patients were classified in New York Heart Association functional class I or II. No patient had endocarditis of the autograft or the right ventricular outflow tract replacement. During the follow-up, no event of thrombembolism was observed. No patient required the insertion of a permanent pacemaker. Overall freedom from reoperation is 57% +/- 15% at 10 years. One patient required the replacement of the autograft at 6 months postoperatively. The development of mild aortic insufficiency was observed in 24 patients, and moderate aortic insufficiency in 1 patient during follow-up. Freedom from reoperation for the right ventricular outflow tract replacement is 60% +/- 15% at 10 years. CONCLUSIONS: The Ross procedure represents an attractive approach to aortic valve disease in young children. However, a high early mortality rate has to be considered when performing this procedure in neonates or infants who present in critical preoperative condition.