bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of microtubules and tea1p in establishment and maintenance of fission yeast cell polarity
Authors: Sawin Kenneth E. , Snaith Hilary A.
Published: January 2004

Microtubules and the protein tea1p have important roles in regulating cell polarity in the fission yeast Schizosaccharomyces pombe. Here, using combinations of drugs, environmental perturbations and genetic mutants, we demonstrate that once a cell polarity axis is established, microtubules have at best a minor role in maintaining the cortical actin cytoskeleton and the rate and direction of cell growth. In addition, we find that after perturbations that disrupt cell polarity and the cortical actin cytoskeleton, microtubules are not required for re-establishment of polarity per se. However, after such perturbations, the distribution of cytoplasmic microtubules plays an important role in dictating the position of sites of polarity re-establishment. Furthermore, this influence of microtubule distribution on site selection during polarity re-establishment requires the presence of tea1p, suggesting that tea1p is crucial for coupling microtubule distribution to the regulation of cell polarity. Our results suggest a model in which, at the cellular level, two distinct and separable mechanisms contribute to how tea1p regulates site selection during polarity re-establishment. First, tea1p remaining at cell tips after cortical depolarization can serve as a cortical landmark for microtubule-independent site selection; second, tea1p newly targeted to the cell cortex by association with microtubules can promote the formation of polarity axes de novo.
Dense-core granules: a specific hallmark of the neuronal/neurosecretory cell phenotype
Authors: Malosio Maria Luisa , Giordano Tiziana , Laslop Andrea , Meldolesi Jacopo
Published: January 2004

Expression of dense-core granules, a typical exocytic organelle, is widely believed to be controlled by coordinate gene expression mechanisms specific to neurones and neurosecretory cells. Recent studies in PC12 cells, however, have suggested the number of granules/cells depends on the levels of only one of their cargo proteins, chromogranin A, regulating the metabolism of the other proteins, and thus the composition of the organelles, by an on/off switch mechanism. In addition, transfection of chromogranin A was reported to induce appearance of dense-core granules in the non-neurosecretory fibroblasts of the CV-1 line. Here the role of chromogranin A has been reinvestigated using not the heterogeneous PC12 line but several clones isolated therefrom. In these clones, investigated as such or after transfection with chromogranin A antisense sequences, the ratio between chromogranin A and its secretory protein mate, chromogranin B, was not constant but highly and apparently randomly variable. Variability of the chromogranin A/chromogranin B ratio was seen by confocal immunofluorescence also among the cells of single clones and subclones and among the granules of single cells. Moreover, stable and transient transfections of chromogranin A in a PC12 clone characterised by a low number of dense-core granules (one fifth of the reference clone) failed to modify significantly the number of the organelles, despite the several-fold increase of the granin. Finally, in three types of non-neurosecretory cells (CV-1, adenocarcinoma TS/A and a clone of PC12 incompetent for secretion) the transfected chromogranin A accumulated mostly in the Golgi/transGolgi area and was released rapidly from resting cells (constitutive secretion) as revealed by both immunofluorescence during cycloheximide treatment and pulse-chase experiments. Only a minor fraction was sorted to discrete organelles that were not dense-core granules, but primarily lysosomes because they contained no chromogranin B, and were largely positive for the late endosomal-lysosomal markers, lamp1 and lamp3. Dense-core granules are therefore true hallmarks of neurones and neurosecretory cells. Their number/cell appears independent of chromogranin A and their composition does not appear to be constant; in particular, they exhibit considerable, and so far unexplained variability in the chromogranin A/chromogranin B ratio.
The giant mudskipperPeriophthalmodon schlosserifacilitates active NH4+ excretion by increasing acid excretion and decreasing NH3 permeability in the skin
Authors: Ip Yuen K. , Randall David J. , Kok Timothy K. T. , Barzaghi Cristiana , Wright Patricia A. , Ballantyne James S. , Wilson Jonathan M. , Chew Shit F.
Published: January 2004

Periophthalmodon schlosseri is an amphibious and obligatory air-breathing teleost, which is extremely tolerant to environmental ammonia. It actively excretes NH4+ in ammonia loading conditions. For such a mechanism to operate efficaciously the fish must be able to prevent back flux of NH3. P. schlosseri could lower the pH of 50 volumes (w/v) of 50% seawater in an artificial burrow from pH 8.2 to pH 7.4 in 1 day, and established an ambient ammonia concentration of 10 mmol l-1 in 8 days. It could alter the rate of titratable acid efflux in response to ambient pH. The rate of net acid efflux (H+ excretion)in P. schlosseri was pH-dependent, increasing in the order pH 6.0<7.0<8.0<8.5. Net acid flux in neutral or alkaline pH conditions was partially inhibited by bafilomycin, indicating the possible involvement of a V-type H+-ATPase. P. schlosseri could also increase the rate of H+ excretion in response to the presence of ammonia in a neutral (pH 7.0) external medium. Increased H+ excretion in P. schlosseri occurred in the head region where active excretion of NH4+ took place. This would result in high concentrations of H+ in the boundary water layer and prevent the dissociation of NH4+, thus preventing a back flux of NH3 through the branchial epithelia. P. schlosseriprobably developed such an `environmental ammonia detoxification' capability because of its unique behavior of burrow building in the mudflats and living therein in a limited volume of water. In addition, the skin of P. schlosseri had low permeability to NH3. Using an Ussing-type apparatus with 10 mmol l-1 NH4Cl and a 1 unit pH gradient (pH 8.0 to 7.0), the skin supported only a very small flux of NH3 (0.0095 μmol cm-2 min-1). Cholesterol content (4.5 μmol g-1) in the skin was high, which suggests low membrane fluidity. Phosphatidylcholine, which has a stabilizing effect on membranes, constituted almost 50% of the skin phospholipids, with phosphatidyleserine and phsophatidylethanolamine contributing only 13% and 15%, respectively. More importantly, P. schlosseri increased the cholesterol level (to 5.5 μmol g-1) and altered the fatty acid composition (increased total saturated fatty acid content) in its skin lipid after exposure to ammonia (30 mmol l-1 at pH 7.0) for 6 days. These changes might lead to an even lower permeability to NH3 in the skin, and reduced back diffusion of the actively excreted NH4+ as NH3 or the net influx of exogenous NH3, under such conditions.
Temperature regulation in burying beetles (Nicrophorusspp.:Coleoptera: Silphidae): effects of body size, morphology and environmental temperature
Authors: Merrick Melissa J. , Smith Rosemary J.
Published: January 2004

This study compares the thermoregulatory ability of three species of burying beetle (Coleoptera: Silphidae: Nicrophorus hybridus, Nicrophorus guttula and Nicrophorus investigator) that vary significantly in body size. It also explores possible mechanisms for temperature regulation in burying beetles, including physiological and behavioral thermoregulatory strategies, and the influence of environmental temperatures on body temperature and activity times. We measured beetle thoracic and abdominal temperatures before and after short (<5 s) flights, and thoracic temperature during sustained, tethered flights and following flight in the field. We calculated two measures of thermoregulatory ability: the slope of post-flight thoracic temperature against ambient air temperature and the slope of post-flight thoracic temperature against operative flight temperature. Thoracic temperatures following flight were significantly higher than abdominal temperatures, and the largest species, N. hybridus, was determined to be the better thermoregulator, with regression slopes closer to zero (0.315–0.370) than N. guttula (0.636–0.771) or N. investigator (0.575–0.610). We also examined the roles that insulation, wing loading, physiological heat transfer, basking and perceived environmental temperature play on temperature regulation and activity times in Nicrophorus. This study shows that body size, morphological features,such as wing loading and insulation, and perceived environmental temperatures affect thermoregulation and activity times in burying beetles.
Calcium responses of chicken trigeminal ganglion neurons to methyl anthranilate and capsaicin
Authors: Kirifides Michael L. , Kurnellas Michael P. , Clark Larry , Bryant Bruce P.
Published: January 2004

Using digital fluorescence imaging, we determined the effects of methyl anthranilate (MA), an avian irritant, and capsaicin (CAP), a mammalian irritant, on intracellular calcium ([Ca2+]i) in chicken trigeminal neurons. Concentration–response functions indicated that the threshold for inducing increases in [Ca2+]i was higher for CAP (30 μmol l–1) than for MA (10 μmol l–1). The maximum magnitudes of [Ca2+]iin response to MA and CAP were compared after normalization to 40 mmol l–1 KCl. At equal concentrations (300 μmol l–1), trigeminal neurons responded with a greater change in[Ca2+]i to MA (78% of KCl) than to CAP (43% of KCl). Furthermore, at 300 μmol l–1, 48% of neurons responded to MA whereas only 16% responded to CAP. The increases in[Ca2+]i induced by both MA and CAP were dependent upon extracellular calcium. While the calcium responses to MA were also dependent on extracellular sodium, responses to CAP were not. There were separate but overlapping populations of neurons sensitive to MA and CAP. Taken together,the higher threshold concentration of CAP, the higher response magnitude to MA than CAP and the greater number of neurons sensitive to MA than CAP provide a rationale for the observed behavioral differences of birds to these two compounds. Finally, the findings that the calcium responses to MA and CAP have different ion dependencies and that there are separate populations sensitive to these compounds suggest different transduction mechanisms mediating chicken trigeminal responses to MA and CAP.
Why is it worth flying at dusk for aquatic insects? Polarotactic water detection is easiest at low solar elevations
Authors: Bernáth Balázs , Gál József , Horváth Gábor
Published: January 2004

Using 180° field-of-view imaging polarimetry, we measured the reflection-polarization patterns of two artificial surfaces (water-dummies) in the red, green and blue spectral ranges under clear and partly cloudy skies at different solar elevations. The dummies consisted of a horizontal glass pane with a matt black or matt light grey cloth underneath, imitating a dark or bright water body, respectively. Assuming that polarotactic water insects interpret a surface as representing water if the degree of linear polarization of reflected light is higher than a threshold and the deviation of the direction of polarization from the horizontal is lower than a threshold, we calculated the proportion, P, of the artificial surfaces detected polarotactically as water. We found that at sunrise and sunset P is maximal for both water-dummies and their reflection-polarizational characteristics are most similar. From this, we conclude that polarotactic water detection is easiest at low solar elevations, because the risk that a polarotactic insect will be unable to recognize the surface of a dark or bright water body is minimal. This partly explains why many aquatic insect species usually fly en masse at dusk. The daily change in the reflection-polarization pattern of water surfaces is an important visual ecological factor that may contribute to the preference of the twilight period for habitat searching by polarotactic water insects. Air temperature at sunrise is generally low, so dusk is the optimal period for polarotactic aquatic insects to seek new habitats.
Nitrogen metabolism in the African lungfish (Protopterus dolloi)aestivating in a mucus cocoon on land
Authors: Chew Shit F. , Chan Noelle K. Y. , Loong Ai M. , Hiong Kum C. , Tam Wai L. , Ip Yuen K.
Published: January 2004

This study aimed to elucidate the strategies adopted by the African slender lungfish, Protopterus dolloi, to ameliorate the toxicity of ammonia during short (6 days) or long (40 days) periods of aestivation in a layer of dried mucus in open air in the laboratory. Despite decreases in rates of ammonia and urea excretion, the ammonia content in the muscle, liver, brain and gut of P. dolloi remained unchanged after 6 days of aestivation compared with the control fasted for 6 days. For specimens aestivated for 40 days, the ammonia contents in the muscle, liver and gut were significantly lower than those of the control fasted for 40 days, which suggests a decrease in the rate of ammonia production. In addition, there were significant increases in contents of alanine, aspartate and glutamate in the muscle, which suggests decreases in their catabolism. During the first 6 days and the last 34 days of aestivation, the rate of ammonia production was reduced to 26% and 28%, respectively, of the control rate (6.83 μmol day–1g–1 on day 0). During the first 6 days and the next 34 days of aestivation, the averaged urea synthesis rate was 2.39-fold and 3.8-fold,respectively, greater than the value of 0.25 μmol day–1g–1 for the day 0 control kept in water. No induction of activities of the ornithine-urea cycle (OUC) enzymes was observed in specimens aestivated for 6 days, because the suppression of ammonia production led to a light demand on the OUC capacity. For specimens aestivated for 40 days, the activities of carbamoyl phosphate synthetase, ornithine transcarbamylase and argininosuccinate synthetase + lyase were significantly greater than those of the control fasted for 40 days. This is in agreement with the observation that the rate of urea synthesis in the last 34 days was greater than that in the first 6 days of aestivation. P. dolloi aestivated in a thin layer of dried mucus in open air with high O2 tension throughout the 40 days of aestivation, which could be the reason why it was able to sustain a high rate of urea synthesis despite this being an energy-intensive process. Our results indicate that a reduction in ammonia production and decreases in hepatic arginine and cranial tryptophan contents are important facets of aestivation in P. dolloi.
The fracture properties and mechanical design of human fingernails
Authors: Farren L. , Shayler S. , Ennos A. R.
Published: January 2004

Fingernails are a characteristic feature of primates, and are composed of three layers of the fibrous composite keratin. This study examined the structure and fracture properties of human fingernails to determine how they resist bending forces while preventing fractures running longitudinally into the nail bed. Nail clippings were first torn manually to examine the preferred crack direction. Next, scissor cutting tests were carried out to compare the fracture toughness of central and outer areas in both the transverse and longitudinal direction. The fracture toughness of each of the three isolated layers was also measured in this way to determine their relative contributions to the toughness. Finally, the structure was examined by carrying out scanning electron microscopy of free fracture surfaces and polarized light microscopy of nail sections.

When nails were torn, cracks were always diverted transversely, parallel to the free edge of the nail. Cutting tests showed that this occurred because the energy to cut nails transversely, at approximately 3 kJ m–2,was about half that needed (approx. 6 kJ m–2) to cut them longitudinally. This anisotropy was imparted by the thick intermediate layer,which comprises long, narrow cells that are oriented transversely; the energy needed to cut this layer transversely was only a quarter of that needed to cut it longitudinally. In contrast the tile-like cells in the thinner dorsal and ventral layers showed isotropic behaviour. They probably act to increase the nail's bending strength, and as they wrap around the edge of the nail, they also help prevent cracks from forming. These results cast light on the mechanical behaviour and care of fingernails.
A hierarchical analysis of the scaling of force and power production by dragonfly flight motors
Authors: Schilder Rudolf J. , Marden James H.
Published: January 2004

Maximum isometric force output by single muscles has long been known to be proportional to muscle mass0.67, i.e to muscle cross-sectional area. However, locomotion often requires a different muscle contraction regime than that used under isometric conditions. Moreover, lever mechanisms generally affect the force outputs of muscle–limb linkages, which is one reason why the scaling of net force output by intact musculoskeletal systems can differ from mass0.67. Indeed, several studies have demonstrated that force output by intact musculoskeletal systems and non-biological systems is proportional to motor mass1.0. Here we trace the mechanisms that cause dragonflies to achieve a change from muscle mass0.67 scaling of maximum force output by single flight muscles to mass1.0 scaling of dynamic force output by the intact dragonfly flight motor. In eight species of dragonflies, tetanic force output by the basalar muscle during isometric contraction scaled as muscle mass0.67. Mean force output by the basalar muscle under dynamic conditions (workloops) that simulated in vivo maximum musculoskeletal performance was proportional to muscle mass0.83, a significant increase in the scaling exponent over that of maximum isometric force output. The dynamic performance of the basalar muscle and the anatomy of its lever, consisting of the second moment of area of the forewing (d2) and the distance between the muscle apodeme and the wing fulcrum (d1), were used to analyze net force output by the integrated muscle-lever system(Find). The scaling of d2 conformed closely to the expected value from geometic similarity (proportional to muscle mass0.31), whereas d1 scaled as muscle mass0.54, a significant increase over the expected value from geometric similarity. Find scaled as muscle mass1.036, and this scaling exponent was not significantly different from unity or from the scaling exponent relating maximum load-lifting by flying dragonflies to their thorax mass. Thus, the combined effect of a change in the scaling of force output by the muscle during dynamic contraction compared to that during isometric contraction and the departure from geometric similarity of one of the two lever arm lengths provides an explanation for how mass1.0 scaling of force output by the intact musculoskeletal system is accomplished. We also show that maximum muscle mass-specific net work and power output available scale as mass0.43 and mass0.24, respectively.
Drosophila CG8422encodes a functional diuretic hormone receptor
Authors: Johnson Erik C. , Bohn Laura M. , Taghert Paul H.
Published: January 2004

Diuretic hormone 44 (DH) is a bioactive neuropeptide that mediates osmotic balance in a wide variety of insects through increases in cAMP. It is structurally similar to mammalian corticotrophin releasing factor (CRF)peptides. In the moth Manduca and the cricket Acheta,functional studies have shown that its cognate receptor (DH-R) is related to the mammalian CRF receptor. The Drosophila genome contains two genes(CG8422 and CG12370) orthologous to Manduca and Acheta DH-Rs. Here, we present multiple lines of evidence to support the hypothesis that the orphan CG8422 G-protein-coupled receptor is a functional DH-R. When expressed in mammalian cells, CG8422 conferred selective sensitivity to DH, as indicated by translocation of aβ-arrestin-2-GFP reporter from the cytoplasm to the cell membrane. Consistent with its in vivo activities in other insects, DH activation of CG8422 elicited increases in a cAMP reporter system(CRE-luciferase), with an EC50 of 1.7 nmol l-1. CG8422 activation by DH also led to increases in intracellular calcium but at substantially higher doses (EC50 ∼300 nmol l-1). By microarray analysis, the CG8422 transcript was detectable in Drosophila head mRNA of different genotypes and under different environmental conditions. The identification of a Drosophila receptor for the DH neuropeptide provides a basis for genetic analysis of this critical factor's roles in maintaining physiological homeostasis.
A three-dimensional kinematic analysis of tongue flicking inPython molurus
Authors: de Groot Jurriaan H. , van der Sluijs Inke , Snelderwaard Peter Ch. , van Leeuwen Johan L.
Published: January 2004

The forked snake tongue is a muscular organ without hard skeletal support. A functional interpretation of the variable arrangement of the intrinsic muscles along the tongue requires a quantitative analysis of the motion performance during tongue protrusion and flicking. Therefore, high-speed fluoroscopy and high-speed stereo photogrammetry were used to analyse the three-dimensional shape changes of the tongue in Python molurus bivittatus (Boidae). The posterior protruding part of the tongue elongated up to 130% while the flicking anterior portion elongated maximally 60%. The differences in tongue strains relate to the absence or presence,respectively, of longitudinal muscle fibres in the peripheral tongue. Maximum overall protrusion velocity (4.3 m s–1) occurred initially when the tongue tip left the mouth. Maximum tongue length of ∼0.01 body length (20 mm) was reached during the first tongue flick. These observations are discussed within the scope of the biomechanical constraints of hydrostatic tongue protrusion: a negative forward pressure gradient, longitudinal tongue compliance and axial tongue stiffness. The three-dimensional deformation varied along the tongue with a mean curvature of 0.06 mm–1and a maximum value of 0.5 mm–1. At the basis of the anterior forked portion of the tongue tips, extreme curvatures up to 2.0 mm–1 were observed. These quantitative results support previously proposed inferences about a hydrostatic elongation mechanism and may serve to evaluate future dynamic models of tongue flicking.
In situcardiac performance of Pacific bluefin tuna hearts in response to acute temperature change
Authors: Blank Jason M. , Morrissette Jeffery M. , Landeira-Fernandez Ana M. , Blackwell Susanna B. , Williams Thomas D. , Block Barbara A.
Published: January 2004

This study reports the cardiovascular physiology of the Pacific bluefin tuna (Thunnus orientalis) in an in situ heart preparation. The performance of the Pacific bluefin tuna heart was examined at temperatures from 30°C down to 2°C. Heart rates ranged from 156 beats min–1 at 30°C to 13 beats min–1 at 2°C. Maximal stroke volumes were 1.1 ml kg–1 at 25°C and 1.3 ml kg–1 at 2°C. Maximal cardiac outputs were 18.1 ml kg–1 min–1 at 2°C and 106 ml kg–1 min–1 at 25°C. These data indicate that cardiovascular function in the Pacific bluefin tuna exhibits a strong temperature dependence, but cardiac function is retained at temperatures colder than those tolerated by tropical tunas. The Pacific bluefin tuna's cardiac performance in the cold may be a key adaptation supporting the broad thermal niche of the bluefin tuna group in the wild. In situ data from Pacific bluefin are compared to in situ measurements of cardiac performance in yellowfin tuna and preliminary results from albacore tuna.
Swimming of larval zebrafish: ontogeny of body waves and implications for locomotory development
Authors: Müller Ulrike K. , van Leeuwen Johan L.
Published: January 2004

Fish larvae, like most adult fish, undulate their bodies to propel themselves. A detailed kinematic study of the larval body wave is a prerequisite to formulate a set of functional requirements that the locomotor system must fulfil to generate the observed swimming kinematics. Lateral displacement and curvature profiles were obtained for zebrafish (Danio rerio) larvae at 2–21 days post-fertilisation for three swimming behaviours (cyclic swimming, slow starts and fast startle responses) using high-speed video. During cyclic swimming, fish larvae maintain tail beat frequencies of up to 100 Hz. The corresponding longitudinal strains, estimated from the peak curvatures of the midline, reach up to 0.19 in superficial tissue. The strain rate can reach 120 s–1. The wave of curvature travels along the body at a near-constant rate. Posterior to the stiff head, body-lengthspecific curvature is high and rises gently along the entire trunk to a maximum value of 6. Burst-and-coast swimming generates similar peak curvatures to cyclic swimming, but curvature rises more steeply from head to tail. Fish larvae exhibit phase shifts of 57–63°between the wave of lateral displacement and the wave of curvature, resulting in a 1:1.2 ratio of body wave length to curvature wave length. During C-starts, muscle strain can reach 0.19 and superficial longitudinal strain rates approach 30 s–1. Fish larvae do not initiate their escape response with a standing wave of curvature, although their C-starts approach a standing wave as the larvae grow older. The performance demands derived from swimming kinematics suggest that larval axial muscles have very short contraction cycles (10 ms), experience considerable strains (up to 0.2)and strain rates (up to 30 s–1 in white muscle fibres) yet are able to power swimming for several seconds.
`Futile cycle' enzymes in the flight muscles of North American bumblebees
Authors: Staples James F. , Koen Erin L. , Laverty Terence M.
Published: January 2004

In the flight muscles of European bumblebees, high activities of fructose-1,6-bisphosphatase (FbPase) relative to phosphofructokinase (PFK)have suggested a thermogenic `futile cycle' important for regional endothermy. We find generally low activities of FbPase (0.7-19.7 units g-1thorax) in North American Bombus species, with the exception of Bombus rufocinctus, where activity (43.1 units g-1 thorax)is comparable with that of European congeners. These data, taken with estimates of maximal rates of heat production by cycling, do not support a significant thermogenic role for the PFK/FbPase cycle. In agreement with earlier studies, both PFK and FbPase activities were found to scale allometrically with body size (allometric exponents -0.18 and -1.33,respectively). The cycle may serve to supplement thermogenesis or amplify glycolytic flux in rest-to-flight transitions, especially in smaller bees.
Sodium and potassium currents of larval zebrafish muscle fibres
Authors: Buckingham Steven D. , Ali Declan W.
Published: January 2004

The steady-state and kinetic properties of Na+ and K+currents of inner (white) and outer (red) muscles of zebrafish larvae 4–6 days post-fertilization (d.p.f.) are described. In inner muscle, the outward currents were half-activated at –1.0 mV and half-inactivated at–30.4 mV, and completely inactivated within 100 ms of depolarization. The inward currents of inner fibres were half-activated at –7.3 mV and half-inactivated at –74.5 mV and completely inactivated within 5 ms of depolarization. Inner muscle fibres were found to support action potentials,while no action potentials could be evoked in outer muscles. In inner muscle fibres, all tested levels of depolarizing current above a threshold value evoked only one action potential. However, spiking at frequencies of up to 200 cycles s–1 was evoked by the injection of depolarizing pulses separated by short hyperpolarizing currents. We suggest that the properties of the inward sodium and outward potassium currents permit high frequency firing in response to a pulsatile depolarizing input of the kind expected in fast swimming, whilst safeguarding against tetany during a strong depolarization.
Female reply strategies in a duetting Australian bushcricket,Caediciasp. (Phaneropterinae: Tettigoniidae: Orthoptera)
Authors: Bailey Winston J. , Hammond Thomas J.
Published: January 2004

Duetting is common between the sexes of phaneropterine bushcrickets(Phaneropterinae: Tettigoniidae: Orthoptera). In this paper we describe the complex duet of an undescribed Australian species within the genus Caedicia. The male's call consists of three parts, of which the final part contains information of the species' identity and most reliably elicits the female's response. The timing of her reply usually occurs within a period of about 1 s after the male has completed his signal but may also start during the male's call. Females reply with brief clicks ranging from 1 to >10,adjusting this reply number to changes in male call duration and intensity. By using computer-synthesised calls, we discovered that the female times her reply both from cues within the male call, when she starts the reply before its conclusion, and from the end of the call, in the case where the reply follows the male call. As the number of clicks in the reply increases so the interval between clicks decreases; the female fits her entire reply within a critical time window following the male's call. The male call intensity had a marginal effect on female reply strategy. We suggest a model based on levels of female motivation, by which females may set the number of clicks in reply as well as the reply latency.
Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus)
Authors: de Margerie E. , Robin J.-P. , Verrier D. , Cubo J. , Groscolas R. , Castanet J.
Published: January 2004

Microstructure–function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones(humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3–5 weeks after hatching) and identified the associated bone tissue types (`laminar', `longitudinal', `reticular' or`radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 μm day–1 (mean 55 μm day–1). There was a highly significant relationship between bone tissue type and growth rate (P<10–6). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered(P<10–5) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.
The changing world of work
Authors: Nolan Peter
Published: January 2004

Focusing on paid employment rather than work in its multiple forms, this paper highlights key developments in the UK labour market, presents new findings from two nationally representative sample surveys, and advances some conclusions about the contradictory effects of change and continuity in paid work in the early years of the twenty-first century. Reference is made to international developments to place the UK in a broader context.
International rescue? The dynamics and policy implications of the international recruitmen of nurses to the UK
Authors: Buchan James
Published: January 2004

This paper focuses on one global aspect of the current health sector workforce policy agenda - the international recruitment and migration of health workers. It does so primarily by using a case study of the recruitment of nurses to the UK, as a means of exploring the policy challenges and associated research questions. The paper highlights the limitations in comparing national data on the nursing workforce, illustrating the extent to which currently collated national data can present a misleading picture of staff:population ratios in different countries. It then reports on the significant growth in the numbers of nurses entering the UK from other countries, using registration data. In 2001/02, more than 16 000 nurses entered the UK nursing register from non-UK sources. In this year, for the first time, the number exceeded the number of home-trained nurses. An analysis of postcode data highlights that these non-UK nurses have a younger age profile than home-based registered nurses and are more likely to report a postcode in London and south-east England. The paper also examines the push and pull factors that contribute to the international mobility of health workers. The paper concludes by examining the policy implications of this growing reliance on international recruitment, including the effect of the ethical guidelines on international recruitment introduced by the Department of Health in England.
Educating the future workforce: Building the evidence about interprofessional learning
Authors: Humphris Debra , Hean Sarah
Published: January 2004

This paper addresses the theme of interprofessional education for health and social care professionals as it affects the development of the workforce. The drivers for change in the UK, typified by the Bristol Royal Infirmary and Victoria Climbié inquiries and the response to these in the form of Department of Health policy, are discussed. The need for rapid development of the evidence base around this subject is evident from literature reviews of the impact of interprofessional education. Directions for future research and investment in this area are proposed, including the need for a stronger theoretical base and for longitudinal studies over extended periods of time in order to examine short, medium and long-term outcomes in relation to health care practice.
Changing the skill-mix of the health care workforce
Authors: Sibbald Bonnie , Shen Jie , Mcbride Anne
Published: January 2004

Objective

Changing workforce skill-mix is one strategy for improving the effectiveness and efficiency of health care. Our aim was to summarise available research into the success or failure of skill-mix change in achieving planned outcomes.

Methods

A systematic search for existing reviews of research into skill-mix was conducted. Databases searched included: MEDLINE, CINAHL, PsychINFO, Cochrane Library, HMIC, Centre for Reviews and Dissemination, and Department of Health Research Findings Register. Search terms included keywords defining the type of publication, clinical area, type of health personnel and the focus of the article (role change, skill-mix, etc.). English language publications from 1990 onwards were included. Two reviewers independently identified relevant publications, graded the quality of reviews and extracted findings. In addition, the wider literature was scanned to identify which factors were associated with the success or failure of skill-mix change.

Results

A total of 9064 publications were identified, of which 24 met our inclusion criteria. There was a dearth of research, particularly for role changes involving workers other than doctors or nurses. Cost-effectiveness was generally not evaluated, nor was the wider impact of change on health care systems. The wider literature suggested that factors promoting success include: introducing ‘treatments’ of proven efficacy; appropriate staff education and training; removal of unhelpful boundary demarcations between staff or service sectors; appropriate pay and reward systems; and good strategic planning and human resource management. Unintended consequences sometimes occurred in respect of: staff morale and workload; coordination of care; continuity of care; and cost.

Conclusions

In order to make informed choices, health care planners need good research evidence about the likely consequences of skill-mix change. The findings from existing research need to be made more accessible while the dearth of evidence makes new research necessary.
Diversity and consistency: The challenge of maintaining quality in a multidisciplinary workforce
Authors: Cooper Richard , Stoflet Sandra
Published: January 2004

Non-physician clinicians have become prominent providers of patient services within the practice of medicine. They include nurse practitioners and clinical nurse specialists, physician assistants, the alternative and complementary disciplines (chiropractic, naturopathy and acupuncture), mental health providers (psychologists, clinical social workers, counsellors and therapists) and specialty disciplines (optometrists, podiatrists, nurse anaesthetists and nurse–midwives). Although these various disciplines have differing histories and philosophic frameworks, which create distinctive approaches to patient care, they have shared a struggle to obtain recognition and autonomy through state licensure, to expand their state-granted practice prerogatives and to achieve broader reimbursement from third-party payers and managed care. Most entered into a growth spurt beginning in the early 1990s. All now provide care that not only overlaps that of physicians but that complements and supplements that care. The central question is, how does their care contribute to quality? The evidence thus far shows that non-physician clinicians throughout the range of disciplines can produce high-quality outcomes under particular circumstances. However, the strongest body of evidence is derived from care that is at the least complex end of the clinical spectrum or that is provided under the umbrella of physicians. Unfortunately, few studies have critically examined the outcomes of non-physician clinicians at the leading edge of their practice prerogatives and under conditions that are free of physician oversight. Thus, while the principle that they can deliver high quality care within the practice of medicine is unequivocally true, more research is needed to test this principle under conditions of greater clinical complexity and autonomy, and, pending the results of such research, caution must be exercised in applying this principle too broadly.
Regulating the health care workforce: Next steps for research
Authors: Davies Celia
Published: January 2004

This article explores the recent ferment surrounding professional self-regulation in medicine and other health professions. It reviews the academic literature and sets out an agenda for research. The first section considers definitions, acknowledging the particularly complex regulatory maze in UK health care at present, in which professional self-regulation is only one part. The second section reviews academic writing, currently dispersed among the disciplines. ‘The logic of light touch regulation’, a feature of the 19th century establishment of the General Medical Council, can perhaps shed light on present debates. Alongside the intense political spotlight on regulation in the wake of the Bristol case, consumer-led research and consumer pressure to rethink the principles of regulation has emerged. This is examined in the third section. Finally, themes for research are advanced. First, there is a need to explore the changing relationship between the state and professions and implications, not only for the professions but for health care more broadly. Second, calls for a new professionalism need to be given clearer content. Third, the moves towards more lay involvement in regulatory bodies need study. Fourth, questions of human rights and professional registers must be explored. Fundamental questions of what professional self-regulation can hope to achieve and where it fits in relation to government ambitions as a whole, remain unresolved. Alongside the work programme of the new overarching regulator, there may well be scope for a new style of public enquiry covering the whole territory of regulation.
Health care workforce research: Identifying the agenda
Authors: Black Nick , Rafferty Anne Marie , West Elizabeth , Gough Pippa
Published: January 2004

Research can contribute to resolving some of the workforce challenges that all heath care systems face. In an attempt to identify the research agenda, key stakeholders in the UK were brought together and background papers were presented by academics with expertise in seven related but distinct areas: global issues; professional boundaries; education; regulation; workplaces; professional-patient interaction; and organisation and management. The research questions identified in each area are described along with some methodological challenges. It is hoped that this will encourage research in this crucial area of health services by facilitating a coherent approach to the diverse needs identified.
Role of Corticosteroids in Septic Shock
Authors: Burry Lisa D , Wax Randy S
Published: January 2004

OBJECTIVE

To highlight the role of relative adrenal insufficiency in the outcome of critically ill patients with sepsis and systematically review the literature regarding the use of corticosteroids for management of severe sepsis/septic shock.

DATA SOURCES

A computerized search of MEDLINE, EMBASE, and the Cochrane Database was undertaken from 1966 to March 2003 using the search terms intensive care unit, critical care, corticosteroids, glucocorticoids, adrenal insufficiency, sepsis, and septic shock. Bibliographies of all articles retrieved were searched for relevant articles not identified by the computerized search.

DATA EXTRACTION/SYNTHESIS

Six trials were identified after publication of the meta-analyses (1995), with a total of 505 patients. The results of these trials in septic shock suggest that low-dose corticosteroids can reduce vasopressor requirements and hasten reversal of shock. Some of these trials suggested a possible mortality benefit from therapy, and no trial demonstrated an increase in mortality or significant adverse effects. The benefit of this therapy may depend on the presence of relative adrenal insufficiency, as identified by the adrenocorticotropic hormone stimulation test.

CONCLUSIONS

Low-dose corticosteroids should be administered to patients with septic shock empirically, but should be discontinued if relative adrenal insufficiency is not confirmed.
Single-Dose Azithromycin for Respiratory Tract Infections
Authors: Law Constance , Amsden Guy W
Published: January 2004

OBJECTIVE

To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults.

DATA SOURCES

A MEDLINE search (1990–September 2003) was performed to identify all pertinent studies and review articles. When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences.

STUDY SELECTION AND DATA EXTRACTION

All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections.

DATA SYNTHESIS

Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens. This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence. Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children. Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM. Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time.

CONCLUSION

Available data regarding single-dose azithromycin are promising. Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.
Osteoporosis: Point-of-Care Testing
Authors: DeHart Renee M , Gonzalez English H
Published: January 2004

OBJECTIVE

To review the literature concerning the utility of point-of-care (POC) testing devices for the diagnosis and management of osteoporosis.

DATA SOURCES

Articles were identified from a MEDLINE search (1993–June 2003). Additional references were obtained from cross-referencing the bibliographies of selected articles.

STUDY SELECTION AND DATA EXTRACTION

After evaluation of clinical trials and select review articles, articles comparing peripheral dual-energy absorptiometry (pDXA) or quantitative ultrasound (QUS) with central DXA (cDXA) measurements were emphasized in this analysis.

DATA SYNTHESIS

Sensitivity for detecting osteoporosis by QUS or pDXA varies widely (range 35–75%). Using adjusted T-score cutoffs increases sensitivity to 85–95%, at the price of reducing device specificity to 23–49%. Many states require a radiology technician to perform pDXA tests.

CONCLUSIONS

POC testing with peripheral devices should only be considered in areas with limited access to cDXA or for women who initially refuse cDXA testing. T scores of −1.0 or less with POC testing typically require further evaluation via cDXA. Many states require pDXAs to be performed by certified radiology technologists, making QUS use more feasible for pharmacists. POC testing should not be used for assessing response to osteoporosis therapy.
Once-Daily Cefazolin and Probenecid for Skin and Soft Tissue Infections
Authors: Cox Victoria C , Zed Peter J
Published: January 2004

OBJECTIVE

To review the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections (SSTI).

DATA SOURCES

MEDLINE (1966–July 2003), EMBASE (1980–July 2003), and PubMed (1966–July 2003) databases for English language, human reports were searched. Search terms included cefazolin, probenecid, cellulitis, and soft tissue infections.

STUDY SELECTION AND DATA EXTRACTION

Studies that described pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in conjunction with probenecid for SSTI were included. All studies were evaluated independently by both authors. For pharmacokinetic studies, the effect of probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical trials, efficacy and safety endpoints were evaluated. For efficacy endpoints, definition of cure was used as defined by each trial.

DATA SYNTHESIS

In all 3 pharmacokinetic studies identified, the addition of probenecid to cefazolin therapy prolonged the half-life and increased serum concentrations of cefazolin. This process allowed serum concentrations to be above the minimal inhibitory concentrations (MIC) for the most likely skin pathogens ( Staphylococcus aureus, β-hemolytic streptococci) at the end of the dosing interval. In the first of 2 clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of 98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In the second clinical trial, clinical success was reported in 51 (86%) of 59 patients receiving the same doses of cefazolin and probenecid as above compared with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral placebo daily.

CONCLUSIONS

Limited pharmacokinetic and clinical data suggest that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective regimen in the treatment of SSTI.