bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro induction of hexaploid plants from triploid hybrids of Pennisetum purpureum and Pennisetum glaucum
Authors: Campos J. M. S. , Davide L. C. , Salgado C. C. , Santos F. C. , Costa P. N. , Silva P. S. , Alves C. C. S. , Viccini L. F. , Pereira A. V.
Published: January 2009

This study describes an efficient in vitro method using colchicine‐treated triploid seedlings of Napiergrass and Pearl millet hybrids to produce hexaploid hybrids and their subsequent identification with flow cytometry. It also describes chromosome count and stomatal morphology and their use to ploidy analysis. Four‐hundred and eighty triploid seeds, representing 12 different hybrids were sterilized and transferred to MS media to induce chromosome doubling. Surviving plants were analysed by flow cytometry. From six triploid (control) and hexaploid plants, the stomata sizes and frequency were analysed. Chromosome count was performed only in the plants identified as hexaploid. Seventeen plants were identified as hexaploid by flow cytometry analysis. Further confirmation of the hexaploid condition was performed with stomatal morphology (stomatal frequency reduction and stomatal length increase) and chromosome count (2n = 6x = 42). Chromosome doubling has numerous applications in Pennisetum breeding. It can be used to restore the fertility of interspecific hybrids and to improve seed size.
QTL mapping and marker‐assisted selection for Fusarium head blight resistance in wheat: a review
Authors: Buerstmayr H. , Ban T. , Anderson J. A.
Published: January 2009

During the past decade, numerous studies have been published on molecular mapping of Fusarium head blight (FHB) resistance in wheat. We summarize the relevant findings from 52 quantitative trait loci (QTL) mapping studies, nine research articles on marker‐assisted selection and seven on marker‐assisted germplasm evaluation. QTL for FHB resistance were found on all wheat chromosomes except chromosome 7D. Some QTL were found in several independent mapping studies indicating that such QTL are stable and therefore useful in breeding programmes. We summarize and update current knowledge on the genetics of FHB resistance in wheat resulting from QTL mapping investigations and review and suggest FHB breeding strategies based on the available information and DNA markers.
Clinically diagnosed glomus vagale tumour treated with external beam radiotherapy: A review of the published reports
Authors: Evans JM , Collins M
Published: January 2009

The aim of the study was to present a case of clinically diagnosed glomus vagale in a 42‐year‐old Aboriginal woman treated with external beam radiotherapy and to carry out a review of the published work. The details of presentation, diagnosis, treatment and follow up of the patient are discussed. A review of the published work was carry out using MEDLINE database with respect to aetiology, clinical presentation, diagnosis, treatment and expected outcomes. Glomus vagale tumours are a subtype of paragangliomas of the head and neck derived from extra‐adrenal paraganglia of the autonomic nervous system. They are typically slow‐growing, benign masses that are often asymptomatic and rarely show signs of hypersecretion. Treatment options include embolization, surgical excision, radiotherapy or surveillance. Radiotherapy is often used for extensive lesions where surgery is considered prohibitively morbid. Following treatment relapse rates are low with the most patients achieving long‐term control. Our patient presented with an extensive lesion compressing the wall of the carotid artery and invading the jugular fossa to involve the clivus. Surgery was offered; however, the patient opted for external beam radiotherapy. A dose of 45 Gy in 25 fractions was delivered with 6‐MV photons employing a CT‐planned, wedge pair technique. Glomus vagale tumours are rare and should be managed in a multidisciplinary head and neck clinic with both surgical and radiation oncology opinions offered. The toxicities and outcomes of both methods should be discussed.
Benign cardiac tumours: Cardiac CT and MRI imaging appearances
Authors: Salanitri J , Lisle D , Rigsby C , Slaughter R , Edelman R
Published: January 2009

Primary benign cardiac tumours are rarely found in clinical practice and are generally evaluated with echocardiography. However, with the increasing usage of helical multislice CT, the initial detection and evaluation of these masses may be made by the radiologist during routine daily practice for other indications. The echocardiographic, CT and cardiac MRI appearances of various benign cardiac tumours and masses are described and illustrated in this review.
Differential diagnosis of T2 hyperintense spinal cord lesions: Part A
Authors: Bou‐Haidar P , Peduto AJ , Karunaratne N
Published: January 2009

Hyperintense spinal cord signal on T2‐weighted images is seen in a wide‐ranging variety of spinal cord processes including; simple MR artefacts, congenital anomalies and most disease categories. Characterization of the abnormal areas of T2 signal as well as their appearance on other MR imaging sequences, when combined with clinical context and laboratory investigations, will often allow a unique diagnosis, or at least aid in narrowing the differential diagnosis. A wide range of instructive cases is discussed here with review of the published reports focusing on pertinent MR features to aid in diagnosis.
Evaluation of thickness and appearance of anterior talofibular and calcaneofibular ligaments in normal versus abnormal ankles with MRI
Authors: Dimmick S , Kennedy D , Daunt N
Published: January 2009

Injuries to the lateral ligaments of the ankle are common in medical practice. The most commonly injured ligaments are the anterior talofibular (ATFL) and calcaneofibular (CFL) ligaments. When undertaking MRI evaluation of ankle injuries it is important to understand the normal dimensions, appearance and variations of these ligaments. Twenty‐eight consecutive patients referred for MRI of the ankle underwent bilateral scanning. The thickness of normal and abnormal ATFL and CFL was determined. The mean thickness of the ATFL was 2.19 ± 0.6 mm and the CFL measured 2.13 ± 0.5 mm. One normal ankle had an extremely thin ATFL (0.8 mm) with an otherwise normal appearance, whereas two ankles had an ATFL with a high attachment, both of which were deemed to be normal variants. Nineteen per cent of normal CFLs were noted to consist of a lateral hypointense band with a medial isointense medial band. Two variations of normal ATFL, one normal variant CFL and a measurement of the normal thickness of the ATFL and CFL have been presented in this paper. These variations have not been described previously by other authors. It is envisaged that these findings will assist in the MRI assessment of the lateral ankle ligaments.
18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience
Authors: McCarthy M , Yuan JB , Campbell A , Lenzo NP , Butler‐Henderson K
Published: January 2009

18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.
Percutaneous antegrade ureteric stent removal using a rigid alligator forceps
Authors: Given MF , Geoghegan T , Lyon SM , McGrath F , Lee MJ
Published: January 2009

To evaluate the safety and efficacy of percutaneous antegrade ureteric stent removal using a rigid alligator forceps. Twenty patients were included in our study. Indications for ureteric stent insertion included stone disease (n = 7), malignancy (n = 8) and transplant anastomotic strictures (n = 5). Stent retrieval was carried out for proximal stent placement/migration in seven patients and encrustation in the remaining 13. Twenty‐two stents were successfully retrieved in 20 patients. There was one technical failure (5%). There were no major complications. We had four minor complications, which included nephrostomy site pain (n = 2), periprocedural sepsis (n = 1) and a small urinoma (n = 1). All patients settled with conservative management. Percutaneous radiologically guided antegrade ureteric stent removal with an alligator forceps is safe and effective, particularly when initial surgical removal has failed.
Survey of the learning activities of Australasian radiation oncology specialist trainees
Authors: Holt T , Bydder S , Bloomfield L
Published: January 2009

Trainee radiation oncologists must master a substantial body of skills and knowledge to become competent specialists. The resources available to support this are limited. We surveyed the 90 registrars enrolled in the Royal Australian and New Zealand College of Surgeons (RANZCR) radiation oncology training programme to obtain a range of information about their learning activities (with a significant focus on part 1 teaching). Responses were received from 59 registrars (66% of those eligible). Trainees reported spending a median 2.5 h per week (range 0–10 h) in formal teaching activities. With regard to part 1 exam preparation, 83% reported having had physics teaching – the median quality was 5/7; 88% had radiobiology teaching – the median quality was 4/7; 52% had anatomy teaching – the median quality was 3/7. Registrars training within the RANZCR radiation oncologists training programme perceive their own clinical learning environment as generally good; however’ 50% of respondents felt that more teaching was needed for part 1 subjects. This compared with only 19% of respondents who felt that more teaching was required for part 2 exam preparation. Innovative solutions, such as centralized web‐based teaching, may help to address weaknesses in part 1 teaching. With increasing demands on radiation oncologists and trainees it will be important to monitor learning environments.
Hyperosmolar coma due to exclusive glucose accumulation: Recognition and computations
Authors: BARTOLI ETTORE , SAINAGHI PIER PAOLO , BERGAMASCO LUCA , CASTELLO LUIGI
Published: January 2009

Aim:  To avoid electrolyte derangements during correction of hyperosmolar coma (HC), PNaPREDICTED at the end of correction is presently estimated from plasma glucose (PG, mM/L). When the rise in plasma osmolality (Posm) is entirely due to glucose addition (GA, mM) to the extracellular volume (ECV), this PNa prediction can be improved by correctly estimating GA and any associated water loss (ΔV), while excluding any concomitant Na loss (ΔNa).

Methods:  Indicating with 0 the normal conditions, with 1 the HC, establishes an exclusive GA accumulation. We derived the equations for computing GA, ΔV and PNaPREDICTED. Computer simulations of HC were performed by adding the known GA while subtracting the known ΔV and ΔNa in different combinations, obtaining exact values of PNa1 and . Applying our formulas, we recognized and discarded all cases with concomitant ΔNa, and we computed GA, ΔV and PNaPREDICTED from PNa1 and , as if they had been measured in patients. We extended these same calculation algorithms to 68 patients with HC.

Results:  In computer simulations, true and calculated GA, ΔV and PNaPREDICTED were identical, such that regression and correlation coefficients were 1 (P < 0.0001). Out of the 68 patients recruited, 13 fulfilled the boundary conditions of an exclusive GA addition. The true values, obtained by balance studies performed on these patients, were not different from and significantly correlated with the calculated data (R2 = 0.99, P < 0.001).

Conclusion:  Our new model system for HC and the new formulas improve to near exactness the accuracy in estimating PNaPREDICTED, helping the physician to avoid unwanted electrolyte derangements during treatment.
Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive‐choice behaviour and salience learning in rats
Authors: Pothuizen Helen H. J. , Jongen‐Rêlo Ana L. , Feldon Joram , Yee Benjamin K.
Published: January 2009

The nucleus accumbens can be subdivided into at least two anatomically distinct subregions: a dorsolateral ‘core’ and a ventromedial ‘shell’, and this distinction may extend to a functional dissociation. Here, we contrasted the effects of selective excitotoxic core and medial shell lesions on impulsive‐choice behaviour using a delayed reward choice paradigm and a differential reward for low rates of responding (DRL) test, against a form of salience learning known as latent inhibition (LI). Core lesions led to enhanced impulsive choices as evidenced by a more pronounced shift from choosing a continuously reinforced lever to a partially reinforced lever, when a delay between lever press and reward delivery was imposed selectively on the former. The core lesions also impaired performance on a DRL task that required withholding the response for a fixed period of time in order to earn a reward. Medial shell lesions had no effect on these two tasks, but abolished the LI effect, as revealed by the failure of stimulus pre‐exposure to retard subsequent conditioning to that stimulus in an active avoidance procedure in the lesioned animals. As expected, selective core lesions spared LI. The double dissociations demonstrated here support a functional segregation between nucleus accumbens core and shell, and add weight to the hypothesis that the core, but not the shell, subregion of the nucleus accumbens is preferentially involved in the control of choice behaviour under delayed reinforcement conditions and in the inhibitory control of goal‐directed behaviour.
Electrical coupling induces bistability of rhythms in networks of inhibitory spiking neurons
Authors: Bem Tiaza , Le Feuvre Yves , Rinzel John , Meyrand Pierre
Published: January 2009

Information processing in higher brain structures is thought to rely on the synchronization of spiking neurons. Increasing evidence indicates that, within these structures, inhibitory neurons are linked by both chemical and electrical synapses. However, how synchronized states may emerge from such circuits is not fully understood. Using snail neurons interconnected through a dynamic‐clamp system, we show that networks of spiking neurons linked by both reciprocal inhibition and electrical coupling can express two coexisting coordination patterns of different rhythms. One of these patterns consists of antiphase firing of the network partners whereas, in the other, neurons fire synchronously. Switching between patterns may be evoked immediately by transient stimuli, demonstrating bistability of the network. Thus electrical coupling can provide a potent way for instantaneous reconfiguration of activity patterns in inhibitory spiking networks without alteration of intrinsic network properties by modulatory processes.
Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine
Authors: Tindell Amy J. , Berridge Kent C. , Zhang Jun , Peciña Susana , Aldridge J. Wayne
Published: January 2009

Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new ‘Profile Analysis’, we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive‐sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue‐triggered relapse in human addicts.
Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model
Authors: Dowd Eilís , Monville Christelle , Torres Eduardo M. , Wong Liang‐Fong , Azzouz Mimoun , Mazarakis Nicholas D. , Dunnett Stephen B.
Published: January 2009

Although viral vector‐mediated delivery of glial cell‐line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.
GABAergic synaptic transmission modulates swimming in the ascidian larva
Authors: Brown E. R. , Nishino A. , Bone Q. , Meinertzhagen I. A. , Okamura Y.
Published: January 2009

To examine the role of the amino acid GABA in the locomotion of basal chordates, we investigated the pharmacology of swimming and the morphology of GABA‐immunopositive neurones in tadpole larvae of the ascidians Ciona intestinalis and Ciona savignyi. We verified that electrical recording from the tail reflects alternating muscle activity during swimming by correlating electrical signals with tail beats using high‐speed video recording. GABA reversibly reduced swimming periods to single tail twitches, while picrotoxin increased the frequency and duration of electrical activity associated with spontaneous swimming periods. Immunocytochemistry for GABA revealed extensive labelling throughout the larval central nervous system. Two strongly labelled regions on either side of the sensory vesicle were connected by an arc of labelled fibres, from which fibre tracts extended caudally into the visceral ganglion. Fibre tracts extended ventrally from a third, more medial region in the posterior sensory vesicle. Two rows of immunoreactive cell bodies in the visceral ganglion extended neurites into the nerve cord, where varicosities were seen. Thus, presumed GABAergic neurones form a network that could release GABA during swimming that is involved in modulating the time course and frequency of periods of spontaneous swimming. GABAergic and motor neurones in the visceral ganglion could interact at the level of their cell bodies and/or through the presumed GABAergic fibres that enter the nerve cord. The larval swimming network appears to possess some of the properties of spinal networks in vertebrates, while at the same time possibly showing a type of peripheral innervation resembling that in some protostomes.
Chronic nicotine exposure during adolescence differentially influences calcium‐binding proteins in rat anterior cingulate cortex
Authors: Liu Jen‐Jane , Mohila Carrie A. , Gong Yuna , Govindarajan Nalini , Onn Shao‐Pii
Published: January 2009

We have recently shown that chronic amphetamine exposure selectively up‐regulates parvalbumin (PV) calcium‐binding proteins in the anterior cingulate cortex (ACC). In this study, we evaluated the effects of chronic nicotine (NIC) exposure on PV, calbindin D28k (CB) and calretinin (CR) calcium‐binding protein immunostaining in ACC GABAergic interneurons. Chronic NIC exposure for 3 weeks in adolescent rats, either via drinking water (the oral group) or by twice daily subcutaneous injections (the injection group), resulted in the expression of high levels of CR proteins in the ACC but not in the parietal cortex. Larger increases in the density of CR‐immunoreactive (ir) neurons were noted in the NIC‐injected rats at 0‐day withdrawal (45% increase) compared with the oral group (26% increase). The larger increases in CR‐ir neuron density in the NIC‐injected rats were also reflected by prominent CR‐ir processes across cortical layers. The density of PV‐ir neurons was also increased (37%) at 0‐day withdrawal but only in the oral NIC group and no changes in CB‐ir neuron density were observed in either NIC group. Combined dual‐immunofluorescence and confocal microscopy revealed that somatodendritic α4 nicotinic acetylcholine receptors colocalized with cortical neurons stained positively for CR, PV or CB. These results suggest that CR‐ and/or PV‐ir‐containing GABA interneurons may be involved in channeling the effects of NIC in the ACC, which is closely associated with the ventral basal ganglia circuit that is linked to brain reward function.
Imaging LTP of presynaptic release of FM1‐43 from the rapidly recycling vesicle pool of Schaffer collateral–CA1 synapses in rat hippocampal slices
Authors: Stanton Patric K. , Winterer Jochen , Zhang Xiao‐lei , Müller Wolfgang
Published: January 2009

Recent studies using the styryl dye FM1‐43 and two‐photon microscopy to directly visualize transmitter release at CA3–CA1 excitatory synapses in the hippocampus have demonstrated that activity‐dependent long‐term potentiation (LTP) and long‐term depression are associated with alterations in vesicular release. It is not known whether particular vesicle pools preferentially express these alterations or what second messenger cascades are involved. To address these questions, we selectively loaded FM1‐43 into the rapidly recycling pool (RRP) of vesicles by use of a brief hypertonic shock to release and load the RRP. We demonstrate here that the induction of LTP can lead to a selective long‐lasting enhancement in presynaptic release from the RRP, while reserve pool kinetics remain unchanged. LTP of RRP release was N‐methyl‐d‐aspartate receptor‐dependent and also required production of the intercellular messenger NO and activation of receptor tyrosine kinase. Measurement of FM1‐43 stimulus‐evoked uptake rates following induction of LTP confirmed that LTP produces more rapid recycling of vesicles released by electrical stimulation, consistent with an enhanced release probability from the RRP.
Reconfiguration of multiple motor networks by short‐ and long‐term actions of an identified modulatory neuron
Authors: Faumont Serge , Combes Denis , Meyrand Pierre , Simmers John
Published: January 2009

The pyloric and gastric motor pattern‐generating networks in the stomatogastric ganglion of the lobster Homarus gammarus are reconfigured into a new functional circuit by burst discharge in an identified pair of modulatory projection interneurons, originally named the pyloric suppressor (PS) neurons because of their inhibitory effects on pyloric network activity. Here we elucidate the actions of the PS neurons on individual members of the neighbouring gastric circuit, as well as describing their ability to alter synaptic coupling between the two networks. PS neuron firing has two distinct effects on gastric network activity: an initial short‐lasting action mediated by transient inhibition of most gastric motoneurons, followed by a long‐lasting circuit activation associated with a prolonged PS‐evoked depolarization of the medial gastric (MG) motoneuron and the single network interneuron, Int1. These long‐lasting effects are voltage‐dependent, and experiments with hyperpolarizing current injection and photoablation suggest that excitation of both the MG neuron and Int1 is critical for PS‐elicited gastric network rhythmicity. In parallel, PS neuron discharge persistently (lasting several minutes) enhances the strength of an inhibitory synaptic influence of the MG neuron on the pyloric dilator (PD)–anterior burster (AB) pacemaker neurons, thereby facilitating operational fusion of the two networks. Therefore, a single modulatory neuron may influence disparate populations of neurons via a range of very different and highly target‐specific mechanisms: conventional transient synaptic drive and up‐ or down‐modulation of membrane properties and synaptic efficacy. Moreover, distinctly different time courses of these actions allow different circuit configurations to be specified sequentially by a given modulatory input.
Post‐conditioning with lipopolysaccharide reduces the inflammatory infiltrate to the injured brain and spinal cord: a potential neuroprotective treatment
Authors: Davis Andrew E. M. , Campbell Sandra J. , Wilainam Panop , Anthony Daniel C.
Published: January 2009

Systemic infection often accompanies or precedes acute brain injury, but it remains unclear how the systemic response contributes to outcome. To examine this problem we have microinjected recombinant interleukin‐1beta (IL‐1β), a cytokine associated with acute brain injury, into the rat brain parenchyma and either preceded or followed this challenge with the intravenous injection of lipopolysaccharide (LPS), which mimics systemic inflammatory response syndrome. The microinjection of IL‐1β alone into the brain parenchyma gives rise to leukocyte mobilization in the blood, and to the delayed recruitment of neutrophils and monocytes to the brain with no evidence of blood–brain barrier breakdown or overt neuronal cell death. Systemic LPS pre‐conditioning resulted in a dose‐dependent reduction both in the number of circulating leukocytes and in the number of leukocytes recruited to the brain parenchyma after 12 h. Surprisingly, LPS given two hours after injury was equally effective in reducing the recruitment of leukocytes to the brain, which is more relevant to the management of clinical disease. In a more clinically relevant model of spinal cord injury, intravenous LPS post‐conditioning also reduced the numbers of leukocytes mobilized in the blood and recruited to the spinal cord and thus limited the breakdown of the blood–spinal cord barrier. The effects appear to be specific to LPS, as they were not observed after intravenous IL‐1β pre‐conditioning. Our studies suggest that individual pro‐inflammatory conditioning strategies may protect the injured central nervous system from the damaging consequences of leukocyte recruitment and may provide scope for novel therapeutic intervention.
GABARAP is not essential for GABAA receptor targeting to the synapse
Authors: O'Sullivan Gregory A. , Kneussel Matthias , Elazar Zvulun , Betz Heinrich
Published: January 2009

GABAA receptors (GABAARs) containing the γ2 subunit are thought to require the interacting protein GABARAP (GABAAR associated protein) for trafficking to the neuronal plasma membrane. In order to assess whether GABARAP is required for GABAA receptor accumulation at synaptic sites, we analysed a GABARAP knockout mouse. GABARAP deficient mice are phenotypically normal and do not show up‐regulation of other GABARAP homologues. Also, the total number of GABAARs, as assessed by benzodiazepine binding, is unaffected by the loss of GABARAP. Immunocytochemistry of cortical sections showed no differences in the expression and punctate distribution of the γ2 subunit and the receptor anchoring protein gephyrin between GABARAP deficient and wild‐type mice. Thus, GABARAP is not essential for trafficking γ2 subunit containing GABAARs to the neuronal plasma membrane or targeting them to inhibitory synapses.
Adult neurogenesis in the central olfactory pathway in the absence of receptor neuron turnover in Libinia emarginata
Authors: Sullivan Jeremy M. , Beltz Barbara S.
Published: January 2009

Life‐long neurogenesis is a characteristic feature of the olfactory pathways of a phylogenetically diverse array of animals. In both vertebrates and invertebrates, the life‐long addition of olfactory interneurons in the brain occurs in parallel with the continuous proliferation of olfactory receptor neurons in the olfactory organ. It has been proposed that these two processes are related functionally, with new olfactory interneurons being added to accommodate the new olfactory receptor neurons added in the periphery. While this has not been tested directly because the two processes are not readily separable, this question can be addressed in the olfactory pathway of the crab, Libinia emarginata. Unlike most decapod crustaceans, which moult and grow throughout life, L. emarginata has a terminal, maturational moult after which animals become anecdysic (stop moulting). Because the addition of new receptor neurons in crustaceans is associated with moulting, a comparison of neurogenesis in immature and mature L. emarginata provides an opportunity to examine the interdependence of central and peripheral neurogenesis in the olfactory pathway. This study demonstrates that the continuous addition of olfactory receptor neurons in L. emarginata ceases at the terminal moult but that proliferation and differentiation of olfactory interneurons in the brain continues in mature animals. Contrary to the general assumption, therefore, continuous neurogenesis in the central olfactory pathway of this species does not occur as part of a process involving the coregulation of central and peripheral neurogenesis. These findings suggest that peripheral neurogenesis is not a requirement for continuous neurogenesis in the central olfactory pathway.
Intrathecal minocycline attenuates peripheral inflammation‐induced hyperalgesia by inhibiting p38 MAPK in spinal microglia
Authors: Hua Xiao‐Ying , Svensson Camilla I. , Matsui Tomohiro , Fitzsimmons Bethany , Yaksh Tony L. , Webb Michael
Published: January 2009

Activation of p38 mitogen‐activated protein kinase (p38) in spinal microglia is implicated in spinal nociceptive processing. Minocycline, a tetracycline derivative, displays selective inhibition of microglial activation, a function that is distinct from its antibiotic activity. In the present study we examined antinociceptive effects of intrathecal (IT) administration of minocycline in experimental models of inflammation‐evoked hyperalgesia in addition to the effect of minocycline on stimulation‐induced activation of p38 in spinal microglia. Intrathecal minocycline produced a dose‐dependent reduction of formalin‐evoked second‐phase flinching behaviour in rats, and prevented thermal hyperalgesia induced by carrageenan injection into the paw. In contrast, systemic delivery (intraperitoneally) of minocycline inhibited the first but not the second phase of formalin‐induced flinching, and it had no effect on carrageenan‐induced hyperalgesia. Centrally mediated hyperalgesia induced by IT delivery of N‐methyl‐d‐aspartate was completely blocked by IT minocycline. An increase in phosphorylation (activation) of p38 (P‐p38) was observed in the dorsal spinal cord after carrageenan paw injection, assessed by both Western blotting and immunohistochemistry. The increased P‐p38 immunoreactivity was seen primarily in microglia but also in a small population of neurons. Minocycline, at the IT dose that blocked carrageenan‐induced hyperalgesia, also attenuated the increased P‐p38 in microglia. In addition, minocycline suppressed lipopolysaccharide‐evoked P‐p38 in cultured spinal microglial cells. Taken together, these findings show that minocycline given IT produces a potent and consistent antinociception in models of tissue injury and inflammation‐evoked pain, and they provide strong support for the idea that this effect is mediated by direct inhibition of spinal microglia and subsequent activation of p38 in these cells.
Protein kinase C immunoreactivity in the pigmented and albino rat retina
Authors: Baker Gary E. , Dovey Maria , Davda Priesh , Guibal Christophe , Jeffery Glen
Published: January 2009

The albino retina is abnormal. The central region is under‐developed and some cell populations are reduced or increased in number. Not least of these anomalies is the deficit in the rod population in hypopigmented rodents and carnivores. Given this abnormality we have examined the distribution of rod bipolar cells in albino rats to determine whether this subsequent stage in the rod pathway is similarly disrupted. A monoclonal antibody to protein kinase C was used to determine the distribution of rod bipolar cells in juvenile and adult pigmented and albino rats. Immunoreactive rod bipolar cells and their processes were counted in transverse sections passing through both the central and peripheral retina. The mean densities of immunoreactive cells were significantly reduced in albino retinas at both juvenile (postnatal day 15) and adult stages, in the former by 14% and the latter by 9%. This was evident across the entire central‐to‐peripheral extent of the retina. The reduced rod photoreceptor population found in albinos appears therefore to be consequential for the magnitude of their major target population, rod bipolar cells. The decrease in the rod bipolar population indicates a change in retinal cytoarchitecture and implies a disruption of functional organization of the albino retina, especially that underlying the scotopic channel. This, coupled with observations that some other retinal interneuronal populations may be disrupted, implies disordered retinal processing in albinos and emphasizes the likelihood that abnormal visual function in albinos may be as much a result of anomalous retinal circuitry as of the known photoreceptor deficit or chiasmatic misrouting.
Survey of pediatric continuing professional development undertaken by consultant anesthetists1
Authors: HANHAM TIMOTHY M. , MCDONALD PHILIP F.
Published: January 2009

Background:  Whilst not all anesthetists have a regular pediatric commitment there is a need for out of hours cover of pediatric anesthesia. We have attempted to determine who covers pediatric anesthetic services in the District General Hospital setting.

Methods:  A postal survey of 170 consultant anesthetists in nine District General Hospitals was conducted looking at who is responsible for pediatric anesthetics and emergencies out of hours as well as pediatric anesthetic experience, resuscitation training and continuing professional development (CPD).

Results:  There was a 62% response rate with 98% of the consultants with on call duties also covering pediatric anesthetic emergencies. Fifty percent of consultants who responded were within 4 years of a pediatric‐specific resuscitation course, of which 93% had found it useful. However, 40% had never completed a pediatric resuscitation course or it could be considered out of date. Sixty‐three percent of consultants had had some sort of pediatric anesthetic update in the last 4 years.

Conclusions:  General anesthetists are responsible for elective and emergency anesthetics as well as the care of critically ill children outside of specialist centers. This is despite a proportion of these consultants not having regular pediatric experience, not having completed a recent pediatric resuscitation course and without pediatric anesthetic CPD.
Anesthetic considerations for major burn injury in pediatric patients
Authors: FUZAYLOV GENNADIY , FIDKOWSKI CHRISTINA W.
Published: January 2009

Major burn injury remains a significant cause of morbidity and mortality in pediatric patients. With advances in burn care and with the development of experienced multi‐disciplinary teams at regionalized burn centers, many children are surviving severe burn injury. As members of the multi‐disciplinary care team, anesthesia providers are called upon to care for these critically ill children. These children provide several anesthetic challenges, such as difficult airways, difficult vascular access, fluid and electrolyte imbalances, altered temperature regulation, sepsis, cardiovascular instability, and increased requirements of muscle relaxants and opioids. The anesthesia provider must understand the physiologic derangements that occur with severe burn injury as well as the subsequent anesthetic implications.
Comparison of glomerular filtration rate estimates vs. 24‐h creatinine clearance in HIV‐positive patients
Authors: Ravasi G , Lauriola M , Tinelli C , Brandolini M , Uglietti A , Maserati R
Published: January 2009

Background

Guidelines for kidney function monitoring and antiretroviral drug dosing are available and respectively refer to glomerular filtration rate and creatinine clearance (CrCl).

Objective

The aim of the study was to compare kidney function estimates vs. measured 24‐h CrCl in HIV‐infected subjects.

Methods

A cross‐sectional design was used, with comparison of Cockcroft–Gault (CG), original and simplified modification of diet in renal disease (MDRD) equations vs. measured 24‐h CrCl. Subjects were HIV‐infected, 18–70 years old, without pre‐existing kidney disease.

Results

Results are presented as mean (±standard deviation), unless otherwise stated. The study population consisted of 90 patients, of whom 71% were male, with a mean age of 45 years (±6.5 years). At the time of evaluation, the mean body mass index was 23 (±3.3); mean serum creatinine was 0.91 mg/dL (±0.2 mg/dL); and mean blood urea nitrogen (BUN) was 34.7 mg/dL (±10.6 mg/dL). Differences between paired methods were all significant (P<0.00001), except between CG and simplified MDRD (P=0.21; Pearson r=0.81). In univariate analysis, male gender, CD4 nadir, hepatitis B virus coinfection, BUN and current CD4 cell count showed a significant positive correlation (P<0.2) with the difference between measured 24‐h CrCl and either CG or simplified MDRD estimates. In multivariate analysis, only BUN showed a significant positive correlation (P<0.05).

Conclusions

Estimates were lower than the measurements of 24‐h CrCl. Original MDRD estimates were lower than those with other equations. CG and simplified MDRD estimates showed a satisfactory correlation.
Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)‐coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations
Authors: Audsley J , Arrifin N , Yuen LKW , Ayres A , Crowe SM , Bartholomeusz A , Locarnini SA , Mijch A , Lewin SR , Sasadeusz J
Published: January 2009

Objectives

The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV‐coinfected individuals receiving tenofovir (TDF).

Methods

This retrospective cross‐sectional study identified 28 HIV/HBV‐coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on‐TDF), and 24 also had samples available prior to treatment (pre‐TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (±3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR‐positive samples was sequenced and compared with reference HBV data.

Results

Of the pre‐TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on‐TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3–23 months). Lamivudine (3TC)‐resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF‐resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.

Conclusions

Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC‐resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.
Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance
Authors: Judd A , Ferrand RA , Jungmann E , Foster C , Masters J , Rice B , Lyall H , Tookey PA , Prime K
Published: January 2009

Objective

The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged ≥13 years.

Methods

A retrospective review of HIV diagnoses reported to well‐established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted.

Results

Forty‐two young people with vertically acquired HIV diagnosed aged ≥13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub‐Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13–20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/μL (range, 0–689 cells/μL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis.

Conclusion

A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age ≥13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV‐infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.
How does loss to follow‐up influence cohort findings on HIV infection? A joint analysis of the French hospital database on HIV, Mortalité 2000 survey and death certificates*
Authors: Lanoy E , Lewden C , Lièvre L , Tattevin P , Boileau J , Aouba A , Chêne G , Costagliola D ,   Clinical Epidemiologic Group of the French Hospital Database on HIV (ANRS CO4 FHDH),   Groupe d'Etude Mortalité 2000
Published: January 2009

Objective
We aimed to retrieve the vital status of patients lost to follow‐up (LFU), with no further visits for at least 12 months, for the 34 835 patients in the Agence Nationale de Recherche sur le SIDA CO4 French Hospital Database on HIV (ANRS CO4 FHDH) seen in 1999 and to examine how loss to follow‐up might influence estimates of survival and the impact of delayed access to care (DAC) on survival.

Methods
The status of LFU patients was established by using the mid‐2006 update of the FHDH in which their status 12 months after loss to follow‐up was added when available and by matching with the Mortalité 2000‐Epidemiological Centre for Medical Causes of Death (CépiDc) database, which included HIV‐infected patients dying in 2000. We compared Kaplan–Meier and hazard ratio (HR) estimates before and after correction for the status of LFU patients.

Results
In the mid‐2006 updated FHDH, of the patients seen in 1999, 7.5% were LFU: of these, 2.1% later returned for follow‐up, with a median time without follow‐up in an FHDH centre of 3.5 years, and 5.4% had no further FHDH visits whatsoever, of whom 29.8% died according to Mortalité 2000‐CépiDc. After correction, the estimated 1‐year survival rates following enrolment in 1999 differed between the original and updated analyses (97.1 vs. 95.9%, respectively; P=0.017); the estimates of mortality HRs associated with DAC did not differ during the first 6 months, but did differ for the 6–18‐month period.

Conclusions
Among LFU patients, 28.1% returned to follow‐up after several years and at least 21.4% died, which led to a slight overestimation of both survival and the impact of DAC on survival.
OCCUPATIONAL SPECIFICITY OF HUMAN CAPITAL*
Authors: Kambourov Gueorgui , Manovskii Iourii
Published: January 2009

We find that returns to occupational tenure are substantial. Everything else being constant, 5 years of occupational tenure are associated with an increase in wages of 12%–20%. Moreover, when occupational experience is taken into account, tenure with an industry or employer has relatively little importance in accounting for the wage one receives. This finding is consistent with human capital being occupation specific.
FIRM FRAGMENTATION AND URBAN PATTERNS*
Authors: Rossi‐Hansberg Esteban , Sarte Pierre‐Daniel , Owens iii Raymond
Published: January 2009

We document several empirical regularities regarding the evolution of urban structure in the largest U.S. metropolitan areas over the period 1980–90. These regularities relate to changes in resident population, employment, occupations, as well as the number and size of establishments in different sections of the metropolitan area. We then propose a theory of urban structure that emphasizes the location and internal structure decisions of firms. In particular, firms can decide to locate their headquarters and operation plants in different regions of the city. Given that cities experienced positive population growth throughout the 1980s, we show that firm fragmentation produces the diverse set of facts documented in the article.
DECENTRALIZING EQUALITY OF OPPORTUNITY*
Authors: Calsamiglia Caterina
Published: January 2009

In a global justice problem, equality of opportunity is satisfied if individual well‐being is independent of exogenous irrelevant characteristics. Policymakers, however, address questions involving local justice problems. We interpret a collection of local justice problems as the decentralized global justice problem. We show that controlling for effort locally, which is not required by the global justice objective, is sufficient for decentralizing equality of opportunity. Moreover, under some conditions, equalizing rewards to effort is not only sufficient but necessary. This implies in particular that most affirmative action policies may not contribute to providing equality of opportunity.