A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy.

Impact of follow-up consultations for ICU survivors on post-ICU syndrome: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of routine follow-up consultations versus standard of care for intensive care unit (ICU) survivors. METHODS: Systematic literature review from five databases (Cochrane CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL), reference lists, citation tracking, and ongoing/unpublished trials. Randomized controlled trials investigating post-ICU consultations in adults with outcomes such as quality of life (QOL), anxiety, depression, posttraumatic stress disorder (PTSD), physical ability, cognitive function, and return to work were included. Two reviewers extracted data and assessed quality independently. The mean differences, risk ratios, and 95 % confidence intervals were calculated depending on outcome measures. RESULTS: From 1544 citations, five trials were included (855 patients). The overall risk of bias was low in two trials, unclear in two trials, and high in one trial. The overall quality of evidence was low. The trials assessed follow-up interventions defined as consultations informing survivors about their ICU stay. One trial found no effect on QOL. Pooling data from two trials (n = 374) showed a protective effect on risk of new onset PTSD at 3-6 months after ICU (risk ratio 0.49, 95 % CI 0.26-0.95). There was no effect on other outcomes. CONCLUSIONS: The evidence indicates that follow-up consultations might reduce symptoms of PTSD at 3-6 months after ICU discharge in ICU survivors, but without affecting QOL and other outcomes investigated. This review highlights that planning of future RCTs should aim to standardize interventions and outcome measures to allow for comparisons across studies.

In vivo assessment of breast muscle, abdominal fat and total fat volume in meat-type chickens by magnetic resonance imaging.

Measurements were performed on commercial broiler chickens by magnetic resonance imaging (MRI) tomography. A total of 72 chickens were scanned at the age of 6, 7, 8, 10, 16 and 20 weeks. MRI scans based on spin echo sequence were taken in the three orthogonal planes. The volume of the pectoral muscles increased from 259 cm3 to 1035 cm3 in males and from 250 cm3 to 875 cm3 in females between 6 and 20 weeks of age. Abdominal fat volume increased from 18.9 cm3 to 153.2 cm3 in males and from 19.3 cm3 to 267.0 cm3 in females between 7 and 20 weeks of age. Total body fat volume increased from 129 cm3 to 557 cm3 in males and from 171 cm3 to 1321 cm3 in females between 6 and 20 weeks of age. The correlation coefficients between the total volume of fat pixels and the amount of abdominal fat determined in the coronal plane by MRI were 0.85 and 0.95 in the male and female sex, respectively. Changes found in the pectoral muscles (mm. pectorales) as well as in total and abdominal fat volume were in close agreement with dissection data obtained at the slaughterhouse and with laboratory data based on the measurement of total body chemical composition in both sexes. This MRI method can be a good complement to computed tomography (CT) scanning in the transversal plane.

Telepresence interface with applications to microsurgery and surgical simulation.

To address the needs for performing microsurgical procedures, the SRI telepresence surgery workstation has been combined with a pair of micromanipulator arms. The prototype microsurgery system has been tested with ex-vivo tasks similar to those required for surgical procedures, such as cutting, grasping, suturing, and knot tying. Initial animal testing has been done on a rat model in which end-to-end anastomosis of the femoral artery (approximately 1 millimeter in diameter) was completed with ten rats, and 100% patency was obtained. To address the needs of surgical training, SRI has begun to develop a system that uses a 6-DOF telepresence workstation. A computer-generated stereo image is reflected in a mirror and appears to be superimposed on the surgeon's hands, creating an immersive and realistic environment. Tools held in the surgeon's hands are connected to left- and right-hand manipulators that both continuously measure tool position/orientation and apply force/torque to the tools. Furthermore, the visual image and tool locations are registered, so that the user perceives that he or she is looking at and moving the simulated tools in the visual image.

Ultrasound tissue characterization of breast biopsy specimens: expanded study.

Tissue classification by examining sets of ultrasound parameters is an elusive goal. We report analysis of measurements of ultrasound speed, attenuation and backscatter in the range 3 to 8 MHz in breast tissues at 37 C. Statistical discriminant analysis and neural net analysis were employed. Data were acquired from 24 biopsy and 7 mastectomy specimens. Best separation of the classes normal, benign, and malignant occurred in the 18 cases where two tissue classes were present in the same specimen and parameters were corrected for within-patient mean; then 85-90% of cases in test sets were correctly classified. Most errors comprised misclassified benign cases. The neural net was comparable to discriminant analysis and slightly superior in separating normal and malignant classes.

Advanced telepresence surgery system development.

SRI International is currently developing a prototype remote telepresence surgery system, for the Advanced Research Projects Agency (ARPA), that will bring life-saving surgical care to wounded soldiers in the zone of combat. Remote surgery also has potentially important applications in civilian medicine. In addition, telepresence will find wide medical use in local surgery, in endoscopic, laparoscopic, and microsurgery applications. Key elements of the telepresence technology now being developed for ARPA, including the telepresence surgeon's workstation (TSW) and associated servo control systems, will have direct application to these areas of minimally invasive surgery. The TSW technology will also find use in surgical training, where it will provide an immersive visual and haptic interface for interaction with computer-based anatomical models. In this paper, we discuss our ongoing development of the MEDFAST telesurgery system, focusing on the TSW man-machine interface and its associated servo control electronics.

Restriction endonuclease analysis of herpesviruses isolated from two peninsular bighorn sheep (Ovis canadensis cremnobates).

In 1989, herpesviruses were isolated from nasal swabs taken from two peninsular bighorn sheep (Ovis canadensis cremnobates) in the Anza-Borrego Desert State Park, San Diego County, California (USA). Using restriction endonuclease analysis (REA) with Pst1 enzyme, each isolate was found to be similar to the Cooper strain of infectious bovine rhinotracheitis virus (IBRV). The REA patterns of the two herpesviruses from bighorn sheep were typical of either field strains or vaccine strains of IBRV commonly associated with cattle in the USA.

Three-dimensional ultrasonic reflection and attenuation imaging.

A three-dimensional, volumetric, data acquisition and reconstruction system for ultrasonic imaging is described. The method entails storing the digitized waveforms from each element of a multielement annular array, with bidirectional mechanical scanning. The system was implemented through digitization of the RF signals from each of the rings of an annular-array transducer, storage of the signals in computer memory, and offline image reconstruction. Initial reflection and reflex transmission images acquired with this system are presented. The results of different image reconstruction algorithms are demonstrated.

Reflex transmission imaging improves ultrasonic visualization and characterization of calculi for lithotripsy applications.

A new ultrasound technique combining reflex transmission imaging (RTI) and integrated reflection C-scan (IRCS) imaging is being developed to enhance visualization of calculi for lithotripsy applications. Reflex transmission imaging/integrated reflection C-scan ultrasound produces orthographic images (similar to flat-field x-ray films) that improve the delineation of stone from soft tissue. Integrated reflection C-scan imaging is based on reflectivity while RTI is based on transmissivity of structures (stones) in the focal plane. Quantitative measurements of reflectance (IRCS) and attenuation (RTI) show potential for stone characterization and assessment of the degree of fragmentation. In vitro and in vivo images are presented.

Apparatus for ultrasound tissue characterization of excised specimens.

Apparatus is described for measurement of sound speed and ultrasound attenuation coefficients by the substitution technique in the frequency range 3 to 8 MHz. Phase-cancellation artifacts leading to overestimation of attenuation coefficients are avoided by use of an acoustoelectric transducer. Specimens confined by polystyrene windows can be interrogated by focused ultrasound beams at selected locations spaced on a grid of 3 x 3 mm voxels. Pulse time of flight is measured with an accuracy of 30 ns, yielding sound speeds accurate to +/- 6.7 m/s, for samples 10 mm thick. Uncertainties in measured insertion losses range from 0.1 dB in low-loss (10 dB) specimens to 0.5 dB in high-loss (25 dB) specimens.

Ultrasound tissue characterization of breast biopsy specimens.

Results of measurements of ultrasound speed and absorption coefficients in the range 3 to 8 MHz in breast tissues at 37 C are reported and analyzed in attempts to identify a set of ultrasound parameters capable of discriminating normal, benign, and malignant tissues. We analyzed 118 tissue regions, comprising 47 normal, 55 benign, and 16 malignant by straight-line fitting of frequency dependence of attenuation. Data for ten additional regions, for a total of 128, became available and were added to the cohort when we subsequently fitted quadratic curves. Sound speed consistently emerged as the variable with greatest discriminating power, particularly for separating normal from benign and malignant tissue. Great difficulty was encountered in discriminating benign from malignant, even when the jackknife technique was used. More success was found with classification and regression trees (CART), although results were sensitive to assigned misclassification costs. Best results from straight-line fits were obtained when discriminating malignant from combined normal/benign data after randomly assigning 75 percent of the data to the learning set and 25 percent to the test set. Then, 23 out of 25 normal/benign and 4 out of 4 malignant cases in the test set were correctly classified. With quadratic fitting, best results were obtained in the three-class case--the false positive rate for malignancy was reduced to zero in the learning (0/31) and test (0/10) sets. Nevertheless, the false negative rate increased to 13 out of 31 (42 percent) in the learning set, while attaining zero (0/4) in the test set.

Adenosine deaminase and porcine meat quality. I. Effect of dipyridamole on plasma free fatty acids, glucose, lactate and c-AMP in pigs representing high and low red cell adenosine deaminase activity.

The effect of dipyridamole--an adenosine uptake inhibitor--on the plasma concentration of free fatty acids (FFA), glucose, lactate and cyclic adenosine monophosphate (cAMP) has been examined in 2 groups of Landrace pigs representing low (Ada 0) and high (Ada A) red cell adenosine deaminase (Ada) activity. Pigs fitted with a jugular vein catheter were given dipyridamole (0.16 mg/kg/min) over a period of 30 min. The infusions were performed 22 h after the last meal at a time where pigs were found to show steady increase and decline in rates of lipolysis and glycogenolysis, respectively. The results showed that lipid mobilization as identified by the plasma FFA concentration was markedly depressed. During the infusion of dipyridamole similar degree of inhibition was seen in Ada 0 and Ada A pigs, however, in the period following the infusion, a significantly stronger suppression persisted in the Ada 0 pigs. Both the blood glucose and lactate level rose distinctly as a result of the dipyridamole treatment. This stimulation of the glycolysis rate was significantly more expressed in Ada 0 pigs compared to that of the Ada A pigs. When theophylline, an antagonist of adenosine, was given together with dipyridamole, the rise in the lactate level was considerably diminished. Dipyridamole also produced a distinct rise in the plasma cAMP levels.

Adenosine deaminase and porcine meat quality. II. Effects of adenosine analogues on plasma free fatty acids, glucose and lactate in pigs representing high and low adenosine deaminase red cell activity.

The adenosine analogues 5'-(N-ethyl) carboxamidoadenosine (NECA) and N6-(phenylisopropyl) adenosine (R-PIA) were shown to differ in their effect on the plasma level of free fatty acids (FFA), glucose and lactate in pigs representing low (Ada 0) and high (Ada A) red cell adenosine deaminase activity. At the same dosage range (0.001-0.005 mg/kg) R-PIA produced a much stronger suppression of the FFA level than NECA, indicating that A1 adenosine receptors predominate in porcine adipose tissue. Pretreatment with 8-phenyltheophylline completely abolished the antilipolytic effect of both adenosine analogues. NECA in contrast to R-PIA elevated the blood glucose concentration, suggesting that A2 adenosine receptors are involved in the stimulation of glycogenolysis. This effect of NECA was not altered by a beta-adrenoceptor blockade providing evidence for a direct effect of adenosine on glycogenolysis. Whereas the changes in plasma FFA following NECA administration were of similar magnitude in Ada A and Ada 0 pigs, the changes in the blood glucose concentration were different in these two groups of pigs.