Characterization of Md5-BAC-REV-LTR virus as Marek's disease vaccine in commercial meat-type chickens: protection and immunosuppression.

Md5-BAC-REV-LTR is a recombinant Marek's disease virus (MDV), with an insertion of the long terminal repeat (LTR) of reticuloendotheliosis virus (REV) into the genome of the highly virulent MDV strain rMd5. It has been shown that Md5-BAC-REV-LTR does not induce tumours and confers high protection against challenge with MDV in 15 × 7 chickens. The objective of the present study was to evaluate the protection and safety (in terms of oncogenicity and immunosuppression) of Md5-BAC-REV-LTR in commercial meat-type chickens bearing maternal antibodies against MDV. Our results show that sub-cutaneous administration of Md5-BAC-REV-LTR at 1 day of age conferred high protection (protection index PI = 84.2) against an early challenge (1 day) by contact exposure to shedder birds infected with the vv+ MDV 648A strain. In such stringent challenge conditions, Md5-BAC-REV-LTR was more protective than a commercial CVI988 (PI = 12.4) and similar to the experimental vaccine Md5-BACΔmeq (PI = 92.4). Furthermore, Md5-BAC-REV-LTR did not induce either tumours or immunosuppression in this study. Immunosuppression was evaluated by the relative lymphoid organ weights and also by the ability of the vaccine to induce late-MDV-induced immunosuppression associated with reactivation of the virus. This study shows that Md5-BAC-REV-LTR has the potential to be used as a MD vaccine and is highly protective against early challenge with vv+ MDV.RESEARCH HIGHLIGHTSMd5-BAC-REV-LTR is highly protective against early challenge with vv+ MDV in commercial meat-type chickens.Md5-BAC-REV-LTR does not cause early immunosuppression.Md5-BAC-REV-LTR does not cause late immunosuppression.Unlike other serotype 1 vaccines, Md5-BAC-REV-LTR is not detected in feather pulp at 7 days post vaccination.

The practice of polypharmacy involving herbal and prescription medicines in the treatment of diabetes mellitus, hypertension and gastrointestinal disorders in Jamaica

The interference in the metabolism of a drug by another drug, food or other foreign chemical is commonly observed and often leads to clinically significant adverse drug reactions. In Jamaica, there is an extensive use of natural products as medicines, although there is little information on whether natural medicines are used along with prescription medicines, which might increase the likelihood of drug adversities. This current pilot survey was initiated to gain information on the prevalence of such polypharmacy practices. Two concurrent surveys were carried out in Kingston (an urban parish) and Clarendon (a rural parish) in 743 patients above age 14 years with diabetes mellitus, hypertension and gastrointestinal disorders of persons who visited health centres and pharmacies. Patrons visiting these places at various times of the day were informed of the nature of the questionnaire and willing participants with the above disease conditions and who were on prescription medicines were included in the survey. The results indicated that 80 of the respondents reported combining natural products in their treatment along with prescription medicines, with only 13 of those patients informing their physicians of such practices. Such polypharmacy practices were independent of the type of disease among both males and females and was statistically most prevalent (p < 0.001) in the 47-57-year age group. There was a significant association (p < 0.001) between such treatment practices and place of residence with 92 of the rural community engaging in polypharmacy but 70 of the urban did likewise. Therefore, being aware of the prevalence of multiple therapy practices would be especially useful when designing a pharmaco-vigilance system

The practice of polypharmacy involving herbal and prescription medicines in the treatment of diabetes mellitus, hypertension and gastrointestinal disorders in Jamaica.

The interference in the metabolism of a drug by another drug, food or other foreign chemical is commonly observed and often leads to clinically significant adverse drug reactions. In Jamaica, there is an extensive use of natural products as medicines, although there is little information on whether natural medicines are used along with prescription medicines, which might increase the likelihood of drug adversities. This current pilot survey was initiated to gain information on the prevalence of such polypharmacy practices. Two concurrent surveys were carried out in Kingston (an urban parish) and Clarendon (a rural parish) in 743 patients above age 14 years with diabetes mellitus, hypertension and gastrointestinal disorders of persons who visited health centres and pharmacies. Patrons visiting these places at various times of the day were informed of the nature of the questionnaire and willing participants with the above disease conditions and who were on prescription medicines were included in the survey. The results indicated that 80% of the respondents reported combining natural products in their treatment along with prescription medicines, with only 13% of those patients informing their physicians of such practices. Such polypharmacy practices were independent of the type of disease among both males and females and was statistically most prevalent (p < 0.001) in the 47-57-year age group. There was a significant association (p < 0.001) between such treatment practices and place of residence with 92% of the rural community engaging in polypharmacy but 70% of the urban did likewise. Therefore, being aware of the prevalence of multiple therapy practices would be especially useful when designing a pharmaco-vigilance system.

The mechanical power output of the flight muscles of blue-breasted quail (Coturnix chinensis) during take-off.

Blue-breasted quail (Coturnix chinensis) were filmed during take-off flights. By tracking the position of the centre of mass of the bird in three dimensions, we were able to calculate the power required to increase the potential and kinetic energy. In addition, high-speed video recordings of the position of the wings over the course of the wing stroke, and morphological measurements, allowed us to calculate the aerodynamic and inertial power requirements. The total power output required from the pectoralis muscle was, on average, 390 W kg(-1), which was similar to the highest measurements made on bundles of muscle fibres in vitro (433 W kg(-1)), although for one individual a power output of 530 W kg(-1) was calculated. The majority of the power was required to increase the potential energy of the body. The power output of these muscles is the highest yet found for any muscle in repetitive contractions. We also calculated the power requirements during take-off flights in four other species in the family Phasianidae. Power output was found to be independent of body mass in this family. However, the precise scaling of burst power output within this group must await a better assessment of whether similar levels of performance were measured across the group. We extended our analysis to one species of hawk, several species of hummingbird and two species of bee. Remarkably, we concluded that, over a broad range of body size (0.0002-5 kg) and contractile frequency (5-186 Hz), the myofibrillar power output of flight muscles during short maximal bursts is very high (360-460 W kg(-1)) and shows very little scaling with body mass. The approximate constancy of power output means that the work output varies inversely with wingbeat frequency and reaches values of approximately 30-60 J kg(-1) in the largest species.

The novel aerodynamics of insect flight: applications to micro-air vehicles.

The wing motion in free flight has been described for insects ranging from 1 to 100 mm in wingspan. To support the body weight, the wings typically produce 2-3 times more lift than can be accounted for by conventional aerodynamics. Some insects use the fling mechanism: the wings are clapped together and then flung open before the start of the downstroke, creating a lift-enhancing vortex around each wing. Most insects, however, rely on a leading-edge vortex (LEV) created by dynamic stall during flapping; a strong spanwise flow is also generated by the pressure gradients on the flapping wing, causing the LEV to spiral out to the wingtip. Technical applications of the fling are limited by the mechanical damage that accompanies repeated clapping of the wings, but the spiral LEV can be used to augment the lift production of propellers, rotors and micro-air vehicles (MAVs). Design characteristics of insect-based flying machines are presented, along with estimates of the mass supported, the mechanical power requirement and maximum flight speeds over a wide range of sizes and frequencies. To support a given mass, larger machines need less power, but smaller ones operating at higher frequencies will reach faster speeds.

A computational fluid dynamic study of hawkmoth hovering

A computational fluid dynamic (CFD) modelling approach is used to study the unsteady aerodynamics of the flapping wing of a hovering hawkmoth. We use the geometry of a Manduca sexta-based robotic wing to define the shape of a three-dimensional 'virtual' wing model and 'hover' this wing, mimicking accurately the three-dimensional movements of the wing of a hovering hawkmoth. Our CFD analysis has established an overall understanding of the viscous and unsteady flow around the flapping wing and of the time course of instantaneous force production, which reveals that hovering flight is dominated by the unsteady aerodynamics of both the instantaneous dynamics and also the past history of the wing.

A coherent leading-edge vortex with axial flow was detected during translational motions of both the up- and downstrokes. The attached leading-edge vortex causes a negative pressure region and, hence, is responsible for enhancing lift production. The axial flow, which is derived from the spanwise pressure gradient, stabilises the vortex and gives it a characteristic spiral conical shape.

The leading-edge vortex created during previous translational motion remains attached during the rotational motions of pronation and supination. This vortex, however, is substantially deformed due to coupling between the translational and rotational motions, develops into a complex structure, and is eventually shed before the subsequent translational motion.

Estimation of the forces during one complete flapping cycle shows that lift is produced mainly during the downstroke and the latter half of the upstroke, with little force generated during pronation and supination. The stroke plane angle that satisfies the horizontal force balance of hovering is 23.6 degrees , which shows excellent agreement with observed angles of approximately 20-25 degrees . The time-averaged vertical force is 40 % greater than that needed to support the weight of the hawkmoth.

Measuring the angle of attack of beating insect wings: robust three-dimensional reconstruction from two-dimensional images

A robust technique for determining the angle of attack of insect wings from film of free flight has to date proved elusive. This report describes the development of two new methods ­ the Strips and Planes techniques ­ which were designed to overcome some of the limitations experienced in previous studies. The accuracy and robustness of these novel methods were tested extensively using simulated hawkmoth wing outlines generated for a realistic range of wing positions and torsion. The results were compared with those from two existing methods ­ the Symmetry and Landmarks procedures. The performance of the latter technique will be strongly species-dependent; it could not be successfully applied to hawkmoth flight because of practical difficulties in obtaining suitable landmarks. The Planes method was the least successful of the remaining techniques, especially during those phases of the wingbeat when the orientations of the two wings relative to the camera viewpoint were similar. The Symmetry and Strips methods were tested further to investigate the effects on their performance of introducing additional camber or wing motion asymmetry. The results showed clearly that the Strips method should be the technique of choice wherever the axis of wing torsion is close to the longitudinal axis of the wing. The procedure involves the experimenter matching a model wing divided into chordwise strips to the true wing outline digitized from high-speed film. The use of strips rather than the points digitized in previous studies meant that the analysis required only one wing outline to be digitized. Symmetry of motion between the left and right wings is not assumed. The implications of requiring human input to the Strips method, as opposed to the strictly numerical algorithms of the alternative techniques, are discussed. It is argued that the added flexibility that this provides in dealing with images which have typically been recorded in suboptimal conditions outweighs the introduction of an element of subjectivity. Additional observations arising from the use of the Strips analysis with high-speed video sequences of hawkmoth flight are given.

Power output from a flight muscle of the bumblebee Bombus terrestris. I. Some features of the dorso-ventral flight muscle

1. Isometric contractions from the asynchronous dorso-ventral flight muscle of the bumblebee Bombus terrestris were slow and rather weak. The twitch duration (onset to 50 % relaxation) was approximately 300 ms at 30 °C and 170 ms at 40 °C. The maximum tetanic tension was approximately 40 kN m-2; the ratio of twitch force to tetanic force was approximately 0.2. 2. The unstimulated muscle was quite resistant to stretch, with a low-frequency stiffness of 730 kN m-2 at muscle lengths close to that of the muscle in vivo. The length­tension curve for active tetanic tension (that is the increase in tension above the passive level during stimulation) was very narrow, with a half-width equal to only 17 % of the optimal length. 3. The muscle strain during tethered flight was approximately 2 % peak-to-peak, occasionally reaching 3 %. Strain amplitude increased with wing stroke frequency. The thoracic vibration frequency of escape buzzing, during which the wings are not extended but are folded over the abdomen, was approximately twice that of tethered flight but the muscle strain was similar to that of flight.

The mechanics of flight in the hawkmoth Manduca sexta. I. Kinematics of hovering and forward flight.

High-speed videography was used to record sequences of individual hawkmoths in free flight over a range of speeds from hovering to 5 ms-1. At each speed, three successive wingbeats were subjected to a detailed analysis of the body and wingtip kinematics and of the associated time course of wing rotation. Results are presented for one male and two female moths. The clearest kinematic trends accompanying increases in forward speed were an increase in stroke plane angle and a decrease in body angle. The latter may have resulted from a slight dorsal shift in the area swept by the wings as the supination position became less ventral with increasing speed. These trends were most pronounced between hovering and 3 ms-1, and the changes were gradual; there was no distinct gait change of the kind observed in some vertebrate fliers. The wing rotated as two functional sections: the hindwing and the portion of the forewing with which it is in contact, and the distal half of the forewing. The latter displayed greater fluctuation in the angle of rotation, especially at the lower speeds. As forward speed increased, the discrepancy between the rotation angles of the two halfstrokes, and of the two wing sections, became smaller. The downstroke wing torsion was set early in the halfstroke and then held constant during the translational phase.

The mechanics of flight in the hawkmoth Manduca sexta. II. Aerodynamic consequences of kinematic and morphological variation.

Mean lift coefficients have been calculated for hawkmoth flight at a range of speeds in order to investigate the aerodynamic significance of the kinematic variation which accompanies changes in forward velocity. The coefficients exceed the maximum steady-state value of 0.71 at all except the very fastest speeds, peaking at 2.0 or greater between 1 and 2 ms-1. Unsteady high-lift mechanisms are therefore most important during hovering and slow forward flight. In combination with the wingtip paths relative to the surrounding air, the calculated mean lift coefficients illustrate how the relative contributions of the two halfstrokes to the force balance change with increasing forward speed. Angle of incidence data for fast forward flight suggest that the sense of the circulation is not reversed between the down- and upstrokes, indicating a flight mode qualitatively different from that proposed for lower-speed flight in the hawkmoth and other insects. The mid-downstroke angle of incidence is constant at 30-40 degrees across the speed range. The relationship between power requirements and flight speed is explored; above 5 ms-1, further increases in forward velocity are likely to be constrained by available mechanical power, although problems with thrust generation and flight stability may also be involved. Hawkmoth wing and body morphology, and the differences between males and females, are evaluated in aerodynamic terms. Steady-state force measurements show that the hawkmoth body is amongst the most streamlined for any insect.

Validation of the doubly labelled water technique for bumblebees Bombus terrestris (L.)

The doubly labelled water (DLW) technique was validated for the bumblebee Bombus terrestris (L.) using respirometry (RESP) from tethered roundabout flights. We injected small volumes (1 µl) of a mixture containing low concentrations of deuterium and 18O and withdrew 1-2 µl of haemolymph to determine initial 18O concentration. The injected isotopes were equilibrated with the body water pool after 10 min, and high material turnover allowed the analysis of final blood isotope concentrations after 5-7 h. On average (n=16), values measured using the DLW technique exceeded values measured using RESP by 3.1±9.9 %, a difference that was not statistically significant at the 99 % confidence level. The absolute error was 7.4±7.1 % (mean ± s.d.). Isotope dilution spaces of both deuterium and 18O were almost identical with the body water pool. We corrected for isotope fractionation, using a slightly higher value than usual for one of the fractionation factors. The single most important variable to influence DLW results, which could not be measured with the desired accuracy, was the volume of the final body water pool N. An overestimate of final N possibly resulted in the DLW overestimate.

Unsteady aerodynamics of insect flight.

Over the past decade, the importance of unsteady aerodynamic mechanisms for flapping insect flight has become widely recognised. Even at the fastest flight speeds, the old quasi-steady aerodynamic interpretation seems inadequate to explain the extra lift produced by the wings. Recent experiments on rigid model wings have confirmed the effectiveness of several postulated high-lift mechanisms. Delayed stall can produce extra lift for several chords of travel during the translational phases of the wingbeat. Lift can also be enhanced by circulation created during pronation and supination by rotational mechanisms: the fling/peel, the near fling/peel and isolated rotation. These studies have revealed large leading-edge vortices which contribute to the circulation around the wing, augmenting the lift. The mechanisms show distinctive patterns of vortex shedding from leading and trailing edges. The results of flow visualization experiments on tethered insects are reviewed in an attempt to identify the high-lift mechanisms actually employed. The fling/peel mechanism is clearly used by some insects. The near fling/peel is the wing motion most commonly observed, but evidence for the production of high lift remains indirect. For many insects, lift on the upstroke probably results from delayed stall instead of the flex mechanism of isolated rotation. The large leading-edge vortices from experiments on rigid model wings are greatly reduced or missing around the real insect wings, often making the identification of aerodynamic mechanisms inconclusive. A substantial spanwise flow component has been detected over the aerodynamic upper wing surface, which should transport leading-edge vorticity towards the wingtip before it has much time to roll up. This spanwise transport, arising from centrifugal acceleration, is probably a general phenomenon for flapping insect flight. It should reduce and stabilise any leading-edge vortices that are present, which is essential for preventing stall and maintaining the circulation of high-lift mechanisms during translation.

Beyond the vertebrates: achieving maximum power during flight in insects and hummingbirds.

Hummingbirds and insects are clearly extreme aerobic athletes. Hovering hummingbirds and insects exhibit the highest mass-specific metabolic rates found in vertebrates and invertebrates, respectively. Both groups of fliers have high mitochondrial volume densities in their locomotor muscles, but these do not exceed 35-40% of the fiber volume, presumably from a need to conserve myofibrils for force generation. A possible adaptation to this constraint is the observed greater packing of the inner mitochondrial membranes than occurs in mammalian mitochondria. Both hummingbirds and insects show higher rates of oxygen consumption per unit volume of mitochondria than do mammals. Additionally, volume-specific mitochondrial oxygen consumption in insects increases as body size decreases, unlike the size-independent pattern in mammals. Aerodynamic analysis of power output during hovering flight strongly suggests that both insects and hummingbirds operate with considerable elastic storage of kinetic energy, thereby decreasing their inertial power requirements. Both groups appear to hover with muscle power output close to 100 W kg-1. Muscle efficiency in hummingbirds is near 10%; in insects, muscle efficiency varies with body size, but at similarly low values. Scaling of efficiency with body size has also been reported in terrestrial mammals, suggesting a possible common mechanism. Both groups of hovering fliers can markedly increase their metabolic power inputs and mechanical power outputs above those required for basic hovering flight. These elite aerial athletes offer considerable insight into the constraints and demands on animal design for maximal aerobic capacity. Additionally, the similarities shown between the different phyla suggest the existence of common mechanisms and limitations in metabolic and mechanical performance. Insects in particular offer a number of advantages in pursuing questions such as the cause of the allometric scaling of muscle efficiency; this scaling can be examined within families, genera, or species with the additional benefit that insect muscles also perform well in vitro.

Inferences concerning crossbridges from work on insect muscle.

This paper presents a number of separate results concerning crossbridge attachment: [1] X-ray diffraction from live bumble bee flight muscle shows a set of layer lines distinct from that of relaxed Lethocerus, in which the apparent myosin helix is shorter than that of the actin. [2] Rigor crossbridges of Lethocerus are not rotatable by stretch. [3] Rabbit and Lethocerus fibres in rigor relaxed by ATP at -35 degrees C show evidence of non-rigor crossbridge attachment.

The effect of lateral tilt on maternal and fetal hemodynamic variables.

We measured maternal blood pressure and heart rate, fetal heart rate, and umbilical artery velocity waveforms in 25 healthy women placed in the supine and in both right and left 5 degrees and 10 degrees lateral tilt positions. Although we found no significant difference among these variables in the various maternal positions, two of 25 women became hypotensive and symptomatic in the supine and 5 degrees tilt positions. Because we could not predict which women would become symptomatic, we recommend lateral tilt of all pregnant women during operative procedures beyond 20 weeks' gestation, including those in the lithotomy position for vaginal delivery.

Preclinical abortions and endometriosis.

A single human chorionic gonadotropin determination was performed in 786 infertile women during the late luteal phase to determine the frequencies of preclinical abortions and whether the frequency was increased in women with endometriosis. Thirty-seven pregnancies (4.7% of cycles) were identified, of which six were classified as preclinical abortions (0.8%). In women with endometriosis, the frequency of preclinical abortions was 0.9% and was not statistically different from other infertile subgroups. This study suggests that preclinical abortions are not cause of infertility in either an infertile population as a whole or in the subgroup of women with endometriosis.

Power and efficiency of insect flight muscle.

The efficiency and mechanical power output of insect flight muscle have been estimated from a study of hovering flight. The maximum power output, calculated from the muscle properties, is adequate for the aerodynamic power requirements. However, the power output is insufficient to oscillate the wing mass as well unless there is good elastic storage of the inertial energy, and this is consistent with reports of elastic components in the flight system. A comparison of the mechanical power output with the metabolic power input to the flight muscles suggests that the muscle efficiency is quite low: less than 10%.