Position paper: improving governance for effective veterinary services in developing countries--a priority for donor funding.

Livestock contributes significantly to the world economy. However, animal diseases and food safety are still major constraints on livestock-sector productivity, economic growth, the reduction of poverty and food security. Efficient and effective governance of Veterinary Services throughout the world is a fundamental requirement for addressing the global animal health and related public health threats. Recent work by the World Organisation for Animal Health (OIE) through the application of the Tool for the Evaluation of Performance of Veterinary Services (PVS Tool) and related Gap Analysis (both of which form part of the PVS Pathway) has indicated that a significant proportion of the national Veterinary Services worldwide do not meet the essential requirements for good governance. This shortcoming poses a significant risk for many developing countries and their trading partners when considered in the context of the growing trade in animal-source foods, and the burgeoning global livestock population. Well-managed, transparent and credible Veterinary Services, in both the public and private sector, are essential for mitigating animal disease risks and ensuring sustainable incomes for vulnerable producers. They are also vital for limiting the public health risks posed by zoonotic diseases. This paper is intended to highlight the impact of governance on the delivery of veterinary services in a development context and the benefits generated by improving veterinary governance. It recognises 'global public good' elements embedded in the good governance of Veterinary Services, and it could also provide an operational development investment roadmap that builds on the OIE PVS Pathway, and innovative financing options based on government commitments supported by donor programmes.

Modeling action potential generation during single and dual electrode stimulation of CA3 axons in hippocampal slice.

Despite widespread use of electrical stimulation of hippocampal brain slices, the precise sites of action potential initiation and propagation are unknown. To better understand these sites, we modeled axon recruitment by coupling stimulation-induced electric potential fields to biophysical models of CA3 axon arbors in mouse hippocampal brain slices. Geometrically realistic CA3 axon arbors were generated from prior anatomic observations. For single electrode stimulation, 95% of initiation sites were no further than 135microm away and propagation sites were no further than 875microm. Using dual electrode stimulation, additional axon arbor pieces were recruited, an effect that increased with distance between stimulating electrodes.

Submyelin potassium accumulation may functionally block subsets of local axons during deep brain stimulation: a modeling study.

Deep brain stimulation has been used for over a decade to relieve the symptoms of Parkinson's disease, although its mechanism of action remains poorly understood. To better understand the direct effects of DBS on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K(+) accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K(+) accumulation in the submyelin space. The functional block occurs for a range of model parameters: high stimulation frequencies (>130 Hz); high extracellular K(+) concentrations (>3 x 10(-3) M); low maximum Na(+)/K(+) ATPase current densities (<0.026 A m(-2)); low diffusion coefficients for K(+) diffusion out of the submyelin space (<2.4 x 10(-9) m(2) s(-1)); small periaxonal space widths of the myelin attachment sections (<2.7 x 10(-9) m) and perinodal/internodal sections (<8.4 x 10(-9) m). These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency.

Synchrony: a neural correlate of somatosensory attention.

We investigated whether synchrony between neuronal spike trains is affected by the animal's attentional state. Cross-correlation functions between pairs of spike trains in the second somatosensory cortex (SII) of three macaque monkeys trained to switch attention between a visual task and a tactile task were computed. We previously showed that the majority of recorded neuron pairs (66%) in SII cortex fire synchronously while the animals performed either task and that in a subset of neuron pairs (17%), the degree of synchrony was affected by the animal's attentional state. Of the neuron pairs that showed changes in synchrony with attention, about 80% showed increased synchrony when the animal attended to the tactile stimulus. Here, we show that peak correlation typically occurred at a delay <25 ms; most commonly the delay was close to zero. Half-widths of the correlation peaks were distributed between a few milliseconds and hundreds of milliseconds, with the majority lying <100 ms and the mode of the distribution around 20-30 ms. Maximal change in synchrony occurred mainly during the periods when the stimulus was present, and synchrony usually increased when attention was on the tactile stimulus. If periods of elevated firing rates around the motor response times were removed from the analysis, the percentage of pairs that changed the degree of synchrony with attention more than doubled (from 35 to 72%). The observed effects did not depend on details of the statistical criteria or of the time window used in the analysis.

Variability and coding efficiency of noisy neural spike encoders.

Encoding synaptic inputs as a train of action potentials is a fundamental function of nerve cells. Although spike trains recorded in vivo have been shown to be highly variable, it is unclear whether variability in spike timing represents faithful encoding of temporally varying synaptic inputs or noise inherent in the spike encoding mechanism. It has been reported that spike timing variability is more pronounced for constant, unvarying inputs than for inputs with rich temporal structure. This could have significant implications for the nature of neural coding, particularly if precise timing of spikes and temporal synchrony between neurons is used to represent information in the nervous system. To study the potential functional role of spike timing variability, we estimate the fraction of spike timing variability which conveys information about the input for two types of noisy spike encoders--an integrate and fire model with randomly chosen thresholds and a model of a patch of neuronal membrane containing stochastic Na(+) and K(+) channels obeying Hodgkin-Huxley kinetics. The quality of signal encoding is assessed by reconstructing the input stimuli from the output spike trains using optimal linear mean square estimation. A comparison of the estimation performance of noisy neuronal models of spike generation enables us to assess the impact of neuronal noise on the efficacy of neural coding. The results for both models suggest that spike timing variability reduces the ability of spike trains to encode rapid time-varying stimuli. Moreover, contrary to expectations based on earlier studies, we find that the noisy spike encoding models encode slowly varying stimuli more effectively than rapidly varying ones.

Subthreshold voltage noise due to channel fluctuations in active neuronal membranes.

Voltage-gated ion channels in neuronal membranes fluctuate randomly between different conformational states due to thermal agitation. Fluctuations between conducting and nonconducting states give rise to noisy membrane currents and subthreshold voltage fluctuations and may contribute to variability in spike timing. Here we study subthreshold voltage fluctuations due to active voltage-gated Na+ and K+ channels as predicted by two commonly used kinetic schemes: the Mainen et al. (1995) (MJHS) kinetic scheme, which has been used to model dendritic channels in cortical neurons, and the classical Hodgkin-Huxley (1952) (HH) kinetic scheme for the squid giant axon. We compute the magnitudes, amplitude distributions, and power spectral densities of the voltage noise in isopotential membrane patches predicted by these kinetic schemes. For both schemes, noise magnitudes increase rapidly with depolarization from rest. Noise is larger for smaller patch areas but is smaller for increased model temperatures. We contrast the results from Monte Carlo simulations of the stochastic nonlinear kinetic schemes with analytical, closed-form expressions derived using passive and quasi-active linear approximations to the kinetic schemes. For all subthreshold voltage ranges, the quasi-active linearized approximation is accurate within 8% and may thus be used in large-scale simulations of realistic neuronal geometries.

Rate limitations of unitary event analysis.

Unitary event analysis is a new method for detecting episodes of synchronized neural activity (Riehle, Grün, Diesmann, & Aertsen, 1997). It detects time intervals that contain coincident firing at higher rates than would be expected if the neurons fired as independent inhomogeneous Poisson processes; all coincidences in such intervals are called unitary events (UEs). Changes in the frequency of UEs that are correlated with behavioral states may indicate synchronization of neural firing that mediates or represents the behavioral state. We show that UE analysis is subject to severe limitations due to the underlying discrete statistics of the number of coincident events. These limitations are particularly stringent for low (0-10 spikes/s) firing rates. Under these conditions, the frequency of UEs is a random variable with a large variation relative to its mean. The relative variation decreases with increasing firing rate, and we compute the lowest firing rate, at which the 95% confidence interval around the mean frequency of UEs excludes zero. This random variation in UE frequency makes interpretation of changes in UEs problematic for neurons with low firing rates. As a typical example, when analyzing 150 trials of an experiment using an averaging window 100 ms wide and a 5 ms coincidence window, firing rates should be greater than 7 spikes per second.

Differences in the capacity of several biochemical bone markers to assess high bone turnover in early menopause and response to alendronate therapy.

We measured bone mineral density (BMD), four markers of bone formation [bone alkaline phosphatase (bAP), osteocalcin (Oc), N- and C-terminal propeptide of type I procollagen (PINP and PICP respectively)] and five markers of bone resorption [serum C-terminal telopeptide of type I collagen (CTx), urinary CTx, N-terminal cross-linked telopeptide (NTx), free and total deoxypyridinoline (fDpd and tDpd respectively)] in 28 healthy premenopausal women (45.7 +/- 3.0 years), 15 early (< 7 years) healthy menopausal women (53.8 +/- 3.1 years) and 20 osteoporotic women (65.3 +/- 8.2 years). Bone markers and BMD were also measured in the osteoporotic women 4.1 +/- 0.2 and 12.6 +/- 1.2 months after the beginning of alendronate therapy (Fosamax, 10 mg/day) respectively (BMD in 16/20). We calculated the intra-individual coefficient of variation (iCV) and the least significant change (LSC) for each bone marker from a subset of 9 healthy premenopausal women (32 +/- 5 years) who had a first and a second morning void urine collection (FMV and SMV respectively) and a blood sample on 4 nonconsecutive days (mean interval 14 +/- 3 days). None of the bone markers was correlated with BMD (except p = 0.043 between serum Oc and hip BMD). All markers, except fDpd, were increased significantly in early menopausal women when compared with the premenopausal group. Serum CTx presented the highest increase at menopause (+67.8%) and identified the highest rate (11/15) of early menopausal women with bone turnover above the premenopausal range. The iCVs for bone formation markers (7.2-14.4%) were lower than those for bone resorption markers (14.6-22.3%). The iCVs obtained on FMV and SMV were not different. The decrease after 4 months of alendronate was significant for each bone marker but variable from one marker to another. Serum CTx showed the largest decrease (70.8%) and identified the highest number of biologically responding patients (change > LSC; n = 17/20). A significant change in serum CTx after 4 months of alendronate was the best predictor of a significant gain in spine BMD (i.e., > or = 27 mg/cm2) after 1 year of therapy, allowing 15 of 16 patients (94%) to be classified correctly (one false-positive). Urinary NTx/Cr was the second best predictor. Despite a moderately high iCV (20.6%), serum CTx appeared the most effective of the markers tested and could be of interest for the detection of high bone turnover and the longitudinal monitoring of alendronate therapy in the individual patient. It must be stressed that serum PINP and urinary NTx and tDpd compared very similarly with serum CTx for monitoring alendronate therapy.

Attention modulates synchronized neuronal firing in primate somatosensory cortex.

A potentially powerful information processing strategy in the brain is to take advantage of the temporal structure of neuronal spike trains. An increase in synchrony within the neural representation of an object or location increases the efficacy of that neural representation at the next synaptic stage in the brain; thus, increasing synchrony is a candidate for the neural correlate of attentional selection. We investigated the synchronous firing of pairs of neurons in the secondary somatosensory cortex (SII) of three monkeys trained to switch attention between a visual task and a tactile discrimination task. We found that most neuron pairs in SII cortex fired synchronously and, furthermore, that the degree of synchrony was affected by the monkey's attentional state. In the monkey performing the most difficult task, 35% of neuron pairs that fired synchronously changed their degree of synchrony when the monkey switched attention between the tactile and visual tasks. Synchrony increased in 80% and decreased in 20% of neuron pairs affected by attention.

Optimal detection of flash intensity differences using rod photocurrent observations.

The rod photocurrent contains two noise components that may limit the detectability of flash intensity increments. The limits imposed by the low- and high-frequency noise components were assessed by computing the performance of an optimal detector of increments in flash intensity. The limits imposed by these noise components depend on the interval of observation of the photocurrent signal. When the entire photocurrent signal, lasting 3 or more seconds, is observed, the low-frequency component of the photocurrent noise (attributed to the quantal noise of the incoming light, as well as random isomerizations of enzymes within the phototransduction cascade) is the most significant limitation on detectability. When only the first 380 ms or less is observed, the high-frequency component of the noise (due to the thermal isomerizations of the cGMP-gated channel) presents a significant limit on the detectability of flashes.

Intra- and submembrane particle densities during CO2 stimulation of H+ secretion in turtle bladder.

The apical cell membranes of the H+ secreting, alpha-intercalated cells of turtle urinary bladder (TB) are characterized by studs (cytoplasmic domains of V-adenosinetriphosphatase) on thin-section transmission electron microscopy and by intramembrane particles (spherical units, SPUs) occurring as rod-shaped particles on freeze-fracture electron microscopy. To examine the relationship between studs and SPUs, morphometric studies were carried out on bladders maintained in 5% CO2 and in the absence of exogenous CO2. The stud density per square micrometer of apical membrane was 3,909 +/- 352 (+/-SE) in four TBs (29 alpha-cells) at 5% CO2 and 3,667 +/- 448 (+/-SE) in the paired halves of the same bladders without CO2 (25 alpha-cells). Corresponding densities of SPUs counted on apical membranes of the same bladders (n = 4) were 3,941 +/- 545 in 5% CO2 and 3,599 +/- 511 without CO2. The similarity of the densities of studs and SPUs under both conditions indicates that each SPU within the membrane is matched by one stud projecting into the cytoplasm. The one-for-one relationship between studs and SPUs was preserved over a wide range of transport rates. Addition of CO2 caused only inconsistent increments in the densities of studs and SPUs despite substantial increases in H+ transport rate. Slight variations in spacing of studs were consistent with patterns of distribution of SPUs on fracture surfaces.

Evaluation of temporary restorations' microleakage by means of electrochemical impedance measurements.

The aim of this study was to quantify the changes in the watertightness of three temporary filling materials over 1 wk with a new electrochemical technique: the impedance a measurement technique. Forty sound extracted human maxillary teeth were selected and prepared for the measurements. They were divided into three groups in addition to positive and negative controls. The resistance, and therefore the watertightness, of the intact crown and the resistance after preparation of an endodontic access cavity were registered. After a randomization procedure, 12 teeth were obturated with Cavit G, 12 teeth with Fermit-N, and 12 teeth with Intermediate Restorative Material (IRM). The changes in the resistance were measured first just after obturation (time 0), then after days 1, 2, 3, 4, and 7. The results showed that the IRM group was significantly more watertight than the Fermit-N group (p < 0.05) and much more than the Cavit G group (p < 0.005).

Microleakage of Cavit, CavitW, CavitG and IRM by impedance spectroscopy.

The aim of this study was to quantify the sealing ability of four temporary filling materials over 9 days using a new electrochemical technique. Fifty-two extracted human maxillary bicuspids were selected and prepared for the measurements. They were divided into four groups of 12 teeth each, in addition to two positive and two negative controls. After preparation of the endodontic access cavity the sealing ability was registered. After a randomization procedure one group was obturated with IRM, another group with Cavit, a third group with CavitW and the last group with CavitG. The sealability was measured just after obturation (time 0) and after days 1, 2, 3, 4, 7 and 9. The results showed that the IRM group was significantly more watertight than the different Cavit formulations. Throughout the experiment no significant difference was noticed between the Cavit and CavitW groups (P > 0.05). The CavitG group was significantly less watertight throughout the measurements (P < 0.05).

Scales of urine acidification: apical membrane-associated particles in turtle bladder.

Since the time of Smith, studies of urinary acidification have shifted their focus to ever smaller scales and have revealed iterative patterns or organization. For this review we focus on the organization of intra- and submembrane particles at the scale of the apical cell membrane of the H+ secreting, alpha intercalated cells. Particles were examined quantitatively by thin section and freeze-fracture (FF) electron microscopy. Ongoing studies in turtle bladder indicate that the density of submembrane particles (studs) per micron 2 is approximately the same as that of spherical units (SPUs) forming linear (rod-shaped) arrays on FF. This one-to-one relationship is observed in the presence or absence of CO2 and suggests that CO2-induced changes in H+ secretion do not involve dissociation of the intramembrane (channel) and cytoplasmic (catalytic) parts of the H-ATPase. Structure-function studies based on density estimates of the particles, morphometry of the H+ secreting cell population, and measurement of H+ transport rate prior to fixation permit functional correlation across scales of study.

Sch-28080 inhibits bafilomycin-sensitive H+ secretion in turtle bladder independently of luminal [K+].

To explore the possible contribution of an H-K-adenosine-triphosphatase (H-K-ATPase) to H+ secretion (JH) in the isolated turtle bladder, we measured electrogenic JH (JeH) as short-circuit current and total JH (JTH) by pH stat titration in the presence of ouabain at different ambient K+ concentration ([K+]) and during luminal addition of a known gastric H-K-ATPase inhibitor, Schering (Sch)-28080. JH was not reduced by decreasing ambient [K+] to undetectable or very low levels (< 0.05 mM by atomic absorption) and luminal BaCl2 addition to further reduce local [K+] at the apical membrane. These K(+)-removal studies indicate that H+ transport is not coupled to countertransport of K+. JTH did not exceed JeH at any point: in K(+)-free solutions JTH was 0.73 +/- 0.05, and JeH was 0.95 +/- 0.08 mumol/h; in standard (3.5 mM) K+ solutions JTH was 0.72 +/- 0.05 and JeH 0.98 +/- 0.06 mumol/h; in high (118 mM) K+ solutions JTH was 0.65 +/- 0.07 and JeH 0.94 +/- 0.08 mumol/h. Sch-28080 caused a rapid inhibition of JH, with similar half-maximal inhibitory concentrations (IC50) in K(+)-free, standard [K+], and high [K+] solutions. Bafilomycin inhibited JeH and JTH with an IC50 of approximately 100 nM. The observed non-potassium-competitive inhibition of JH by Sch-28080 and the bafilomycin sensitivity distinguish the H-ATPase of the turtle bladder from the gastric H-K-ATPase. The rapidity of the inhibition by Sch-28080 suggests that it acts at an accessible luminal site of the ATPase.

Total parenteral nutrition and plasma lipoproteins in the rat: evidence for accelerated clearance of apo-A-I-rich HDL.

The effect of total parenteral nutrition (TPN) containing fat on plasma lipoproteins and apo-A-I-rich HDL catabolism was studied in the rat. TPN rats were intravenously infused for 5 days with a nutritive mixture containing amino acids, lipids (Intralipid 20%) and glucose. In spite of similar plasma levels of total cholesterol in TPN and control orally fed rats, density gradient ultracentrifugation of plasma samples gave evidence of marked differences in the lipoprotein profiles. In the density range 1.010-1.040, were found elevated amounts of apo-B-100 and apo-B-48 containing lipoproteins, as well as an increase in free cholesterol and phospholipids, the latter indicating that the plasma of TPN rats contained abnormal lipoprotein-X-like particles. The level of apo-E-rich HDL (density: 1.040-1.063) was not markedly changed, whereas that of typical HDL (d > 1.063) was lowered, with less apo-A-I and apo-A-IV, and low amounts of cholesterol and phospholipids were found in the most dense HDL3 fractions (d > 1.090) containing the bulk of apo-A-I-rich particles. After intravenous infusion of homologous [14C]sucrose-labelled HDL3, the clearance of these particles was 2-fold faster in TPN than in control rats, with a tissue uptake increased in the liver (+40%) and decreased in the small and large intestines (-60%). Because the pool of apo-A-I-rich HDL was dramatically reduced after 5 days of artificial feeding, the absolute catabolic rate of these lipoproteins was similar in the two groups. These data suggest that, in TPN rats lacking of chylomicron coat components as a source for HDL material, the fall in plasma levels of apo-A-I-rich HDL resulted mainly from accelerated turnover of these particles, mediated by increased uptake by the liver. Conversely, mucosa atrophy was probably involved in the reduced uptake of apo-A-I-rich HDL by the gastrointestinal tract.

[Gardner's syndrome: report of a case]. / Het syndroom van Gardner.

Gardner's syndrome consists of multiple polyposis of the large intestine and soft and hard tissue tumors. The syndrome should be considered in case of supernumerary teeth, odontomas, osteoma and soft tissue tumors. These findings often precede colonic involvement. Careful attention should be directed towards the family history. The importance of this syndrome lies in the great tendency of the polyps to become malignant. Dentist and oral surgeon play an important role in the early detection of this syndrome and thus prevention of malignant degeneration of the intestinal polyps.

Characteristics of apical Cl-HCO3 exchanger of bicarbonate-secreting cells in turtle bladder.

The apical anion exchanger of the beta-carbonic anhydrase (CA) cells differs from the basolateral exchanger of the alpha-cells by reduced sensitivity to disulfonic stilbenes and lack of immunoreactivity with antibodies to erythrocyte band 3 protein. To characterize the exchanger, we examined the effects on electroneutral bicarbonate secretion (JHCO3n) of Cl- replacement by gluconate, Br-, SO4(2-), and NO3- and of inhibition by 1) acetazolamide (ACZ) with and without pretreatment with sodium azide (NaN3), 2) furosemide, and 3) alpha-cyano-4-hydroxycinnamate (CHC). The Cl-dependent JHCO3n was 0.90 +/- 0.09 mumol/h, similar to the ACZ-inhibitable rate of 0.83 +/- 0.08 mumol/h with an apparent Km for Cl near 3.4 mM. Maximal JHCO3n was comparable at luminal pH 6.8 and 4.5. JHCO3n was reduced to approximately 21% in Br-, 13% in SO4(2-), and 7% in NO3- solutions compared with the rates in chloride solutions. ACZ inhibition was not abolished by pretreatment with NaN3. JHCO3n was only slightly inhibited (14%) by furosemide and not inhibited by CHC. In conclusion, the apical exchanger is selective for chloride and relatively resistant to inhibitors. Its dependence on luminal chloride is such that its transport rate is closely regulated by mucosal chloride at concentrations below 20 mM.