bluuebunny/crossref_metadata_2025 huggingface dataset:
A case series of partial Horner's syndrome due to internal carotid artery dissection: More common than previously thought
Authors: Wallace I , Lockington D , McCarron MO
Published: March 2011

We report a series of patients, who presented to a district general hospital with painful partial Horner's Syndrome due to internal carotid artery dissection. None of the patients had a cerebral ischaemic complication and all were treated with aspirin. Internal carotid artery dissection is an important cause of headache and isolated partial Horner's Syndrome. We highlight that internal carotid artery dissection may present with subtle symptoms and signs and suggest that emergency, acute and general physicians need to have a low index of suspicion for this condition. We suggest that internal carotid artery dissection may be a more common event than previously thought due to improved imaging techniques. We describe ongoing efforts to answer the question whether anti-coagulation or anti-platelet therapy is the most appropriate treatment.
Timely Troponins Avoid Admissions: Clinical Assessment of Undifferentiated Chest Pain
Authors: Baker K , Harrison C
Published: March 2011

Background

Undifferentiated chest pain is a common presentation to acute medicine units. Targeted appropriately timed troponin analysis may reduce unnecessary admissions and relieve bed shortages. We investigated how reliably cardiac chest pain was identified clinically, whether patients had appropriately timed cardiac enzyme analysis, and implications upon rates of admission.

Method

A prospective data collection was completed on 100 consecutive patients admitted with undifferentiated chest pain to an acute receiving unit over 41 days. We excluded patients with acute coronary syndrome or myocardial infarction already confirmed or excluded. Troponin results were retrospectively documented.

Results

Of 100 patients admitted, 67 were thought to have cardiac type chest pain as their only or significant differential diagnosis, and 10 were subsequently confirmed as ACS or MI. Not all patients with cardiac type chest pain were assessed in accordance with SIGN guidelines. 38 patients were admitted overnight solely to await the result of troponin analysis, with a total of 411.5 hours spent waiting at an estimated cost of over £7400.

Conclusion

This study supports the extension of hours of troponin analysis or instant point of care (bedside) cardiac enzyme testing as a cost effective measure, warranting further examination in terms of laboratory service provision.
Titanium Intramedullary Nailing for Treatment of Simple Bone Cysts of the Long Bones in Children
Authors: Pogorelić Z , Furlan D , Biočić M , Meštrović J , Jurić I , Todorić D
Published: March 2011

Background

Simple or unicameral bone cysts are common benign fluid-filled lesions usually located in the long bones of children before skeletal maturity. Pathological fracture is common, and is often the presenting feature.

Aim

The objective of the present study was to evaluate the results of titanium intramedullary nailing for the treatment of unicameral bone cysts with or without a pathological fracture.

Methods

During the period 2001 to 2007, flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in 18 children. Four of these patients presented with a pathological fracture. The cyst was located in the humerus in 14 patients, in the femur in three, and in the tibia in one. The diagnosis was based on typical radiographs and computed tomography. The mean age of the patients at the time of surgery was 9.4 years, and the mean duration of follow-up was 53 months. Radiographic evaluation was performed, and the cyst was classified as completely healed, healed with residual radiolucency, recurred, or having no response.

Results

Mean hospital stay was 24 hours. At one to four weeks postoperatively, all patients were pain free and had full range of motion of adjacent joints. Radiographic signs of cyst healing were present at three months in all patients, and all cysts healed ompletely. All of the cysts responded to treatment, with no cyst recurrence. No major complications were observed.

Conclusion

Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to normal activities
The Changing Face of Hepatitis B in Greater Glasgow: epidemiological trends 1993–2007
Authors: Barclay ST , Cameron S , Mills PR , Priest M , Ross F , Fox R , Goulding C , Forrest EH , Morris AJ , Neilson M , Stanley AJ
Published: March 2011

Background and Aims

Whilst hepatitis B (HBV) is historically uncommon in Scotland, anecdotal experience suggests an increasing prevalence of chronic infection. We sought to establish whether the incidence of chronic HBV is increasing in Greater Glasgow, and whether patients are assessed in secondary care.

Methods

The regional virus centre database identified HBV surface antigen (HBsAg) positive samples. For adult patients tested in Glasgow between 1993–2007 the first positive test was identified and classified as acute or chronic infection serologically. Clinic referral and attendance data was then obtained.

Results

1,672 patients tested HBsAg positive; 1051 with chronic infection, 421 acute and 200 indeterminate. New diagnoses of HBV remained stable over time, however falling numbers of acute cases were mirrored by a rise in chronic cases from 40 to 119 per annum between 2000 and 2007. Of 193 patients diagnosed in 2006 and 2007, 51% were not seen in secondary care due to non referral (43%) or non attendance (8%).

Conclusion

Chronic HBV trebled in Glasgow between 2000 and 2007. Most patients were not assessed in secondary care. Improved levels of clinic referral and attendance are required to ensure best care for HBV patients in Glasgow.
Fallopian serous papillary cystadenofıbroma: a persistent adnexial mass
Authors: Kahyaoglu Serkan , Kahyaoglu Inci , Sengul Ilker , Sengul Demet , Parlak Omer
Published: March 2011

We present a fallopian tube serous papillary cystadenofibroma detected during surgery for a persistent adnexial mass, examine the immunohistochemical profile, and discuss the origin of this rare neoplasm. A 33 year old Turkish woman presented with mild pelvic pain with duration of two years. Current ultrasonographic examination revealed a 95x 68 milimeters dimensioned thin walled paraovarian cyst without solid components. On pathological examination serous papillary cystadenofibroma of tuba uterina. Cystadenofibromas of the fallopian tube are mostly asymptomatic and diagnosed incidentally. Despite their benign nature, surgical excision is the choice of therapy because of the possible malign transformation and emergent situations like cyst torsion or rupture.
Malaria in rural Lanarkshire
Authors: Murie Jill , Urquhart Lorraine
Published: March 2011

Introduction

Malaria is preventable, yet infection still occurs in UK travellers to tropical destinations. Effective health education, chemoprophylaxis and early identification of malaria are essential in primary care.

Case presentation

A 20 year old man presented with a fever associated with extreme lethargy and general myalgia during the H1N1 ‘pandemic’ in 2009. He was one of party of four people returning from The Gambia. Malaria was diagnosed and, following admission, Plasmodium falciparum parasites were identified. He was treated with intravenous quinine and doxycycline and made a full recovery. Two other members of the wedding party had flu like symptoms, but did not have malaria. One was diabetic.

Conclusion

Malaria must be considered in the differential diagnosis of fever in all people returning from the tropics. Primary care teams need to be aware of and encourage prevention strategies for people traveling to malarious areas. Diabetic patients may require dosage adjustments to prevent hypoglycaemia associated with anti-malarials.
Significant deficiencies in the overnight use of a Standardised Early Warning Scoring system in a teaching hospital
Authors: Gordon Claire F , Beckett Daniel J
Published: March 2011

National Institute for Health and Clinical Excellence guidelines recommend the use of ‘Track and Trigger’ systems to identify early clinical deterioration. The Standardised Early Warning Score (SEWS) is used in the Royal Infirmary of Edinburgh. Previous work, suggested that the frequency and accuracy of SEWS documentation varied throughout the hospital. A prospective study was performed over a 14-night period looking at SEWS documentation in patients causing clinical concern requiring medical review, or triggering a SEWS of 4 (the ‘trigger’ score). SEWS charts were examined the following morning. In the ward arc, SEWS documentation was correct in only 21% of cases. The most frequent errors were one or more observations omitted (64%), SEWS total not calculated (55%) or incorrectly calculated (21%). Up to five errors per chart were noted. The observations most frequently omitted were respiratory rate, temperature and neurological status. In contrast, SEWS documentation was correct in 68% of patients in the combined assessment unit (CAU). This study demonstrates significant deficiencies in the overnight use of SEWS, particularly on the ward arc. This is particularly concerning as this study was limited only to patients already causing clinical concern, and highlights that basic observations are often incomplete, and the SEWS chart poorly understood and acted upon. SEWS recording and documentation was significantly better in CAU ( P < 0.001, FET), where there is a dedicated, ongoing SEWS education programme for nursing and medical staff. We recommend this is rolled out across the hospital. Alternative methods of improving the use of SEWS are considered.
Do orthopaedic surgeons practice what they preach?
Authors: Gupta Sanjay , Muller Scott D
Published: March 2011

Good medical practice predicates a contemporary knowledge of the literature. The British edition of the Journal of Bone and Joint Surgery (JBJS [ Br]) is considered one of the leading orthopaedic journals. While seeking guidance on proposed changes to departmental policy, discussion with some high-profile units raised concerns regarding the implementation of their published clinical recommendations. We intended to contact the publishing departments, to establish their routine practice with respect to the topic on which they have written. We reviewed all articles published in JBJS ( Br) between January 2005 and December 2006. Target papers were those that recommended a change in practice. The originating department was contacted by telephone and communication sought from an individual not directly involved in the publication, but on whom the change in practice would impact. Seventy-nine papers; representing the work of 87 separate hospitals from 22 different countries, were identified. We found that published articles were being followed in 56% of cases, 42% were not. Our study demonstrates that a large proportion of institutions making clinical recommendations are not practising them. Have we exposed a fundamental flaw in the publication of clinical research? In conclusion, we do practice what we preach… sometimes.
Small can be beautiful: 10 years managing colorectal cancer in a rural general hospital
Authors: Grant A J , Sedgwick D M
Published: March 2011

There has been much recent debate on the relationship between surgical volume and outcomes. The aim of this study was to assess the ability of a rural general hospital to provide care for patients with colorectal cancer in a small-volume practice. A retrospective review of patients treated in a rural general hospital, between January 1993 and December 2002, was undertaken. Patient demographics, disease characteristics, treatments and complications were all recorded. Ninety-eight patients had a final diagnosis of colorectal cancer. There was an equal male: female ratio and an average age of 69 years (40–88 years). Eighty-five percent underwent treatment with curative intent. The postoperative complication rate was low (2% wound infections, 2.3% anastomotic leak rate) and Dukes-specific five-year survival was satisfactory (A > 80%, B and C > 60%). In conclusion, this study adds weight to the argument that even with low-volume workload, satisfactory results can still be obtained.
Survey of general practitioners’ attitudes to prescribing statins in different patient groups: a web-based survey
Authors: Macklin J , Morrison G
Published: March 2011

Low rates of statin prescribing have been noted in several major studies of patients with schizophrenia and the aim of this study was to investigate clinicians’ attitudes to prescribing statins to different patient groups. The general practitioners (GPs) in Dumfries and Calloway were randomized into two groups. They received an email invitation to a web-based survey. The survey asked for treatment recommendation for three patient vignettes, each with a 10-year cardiovascular risk of 20%. In one group descriptions of the patient included type 1 diabetes, epilepsy and unemployed and in the other group these were replaced by type 2 diabetes, schizophrenia and retired. The questionnaires had no other differences. After three email invites, 53 questionnaires were completed (40% of a potential 133 participants). Statin therapy was recommended by 88% and 85% of respondents for patients with type 1 and type 2 diabetes, respectively; by 37% of respondents for patients with schizophrenia and 31% for patients with epilepsy; by 33% of respondents for retired patients and 23% of respondents for patients who are unemployed. This study demonstrates under-prescribing of statins. This was not worse for patients with schizophrenia as compared with patients with epilepsy. This suggests that the low rates of treatment of metabolic risk factors in patients with schizophrenia are not the result of clinician bias when compared with patients with epilepsy. Clinician bias, however, may reduce the chances of an unemployed patient receiving statin treatment.
Hibernoma in a 16-year-old boy
Authors: Whitaker J K H , Motiwale S
Published: March 2011

A hibernoma is a rare benign tumour of brown adipose tissue. We report a hibernoma overlying the scapula of a 16-year-old boy.
Simultaneous presentation of type 1 diabetes and Graves’ disease
Authors: Ahmad F A , Mukhopadhyay B
Published: March 2011

The association between type 1 diabetes mellitus and autoimmune thyroid disease is well documented in the literature. Both can coexist although one endocrinopathy usually precedes the other. The simultaneous new onset of both diseases is rarely seen. Hyperthyroidism can precipitate and complicate the management of diabetic ketoacidosis by masking its classical clinical features. Persistent tachycardia after correction of acidosis and dehydration, may be the only suggestion of another coexisting illness such as thyrotoxicosis. We describe the case of a previously healthy woman who developed new onset type 1 diabetes mellitus and Craves’ disease, and presented with diabetic ketoacidosis.
Lamb pays lip service: two cases of ecthyma contagiosum (orf)
Authors: Wet Carl de , Murie Jill
Published: March 2011

Ecthyma contagiosum (orf) is caused by a parapox virus, which results in ulcerative stomatitis of mainly sheep and goats. The disease may be transmitted to humans through direct contact. Complications are rare in healthy individuals, who rarely report the disease. Two married, recreational sheep farmers, were bitten on their index fingers by an affected lamb. While the husband made an uneventful recovery after oral flucloxacillin, his wife was admitted to hospital with necrosis of her finger, cellulitis and lymphangitis requiring intravenous clindamycin. She subsequently developed a generalized maculopapular rash, which was initially thought to be an adverse drug reaction, but, on hindsight, may have been erythema multiforme associated with orf. Orf is a common zoonosis, rarely reported in general practice. The disease is usually self-limiting and resolves in 6–8 weeks, but complications may occur. The diagnosis should be considered in at-risk occupational and religious groups.
Precipitating factors and patient outcomes in acute kidney injury treated with renal replacement therapy
Authors: Mcmillan Merlin , Mactier Robert
Published: March 2011

Acute kidney injury (AKI) is not uncommon in acute hospital admissions. AKI treated with renal replacement therapy (RRT) has a wide spectrum of causes and the mortality rate at 90 days, approaches 50%. This study was performed to analyse the identifiable causes and outcomes of all cases of AKI treated with RRT in the Glasgow Royal Infirmary (GRI) renal wards during 2007. This study identified 65 cases of AKI treated with RRT from the GRI renal unit electronic patient record (EPR). Causes of AKI, modality of RRT and patient outcomes were retrieved from the EPR and discharge letters. The main outcome measures were the mortality rate and the percentage of patients still receiving RRT at 90 days. More than one precipitating factor was identified in half of the cases of dialysis-dependent AKI. Sepsis, hypovolaemia and nephrotoxic drugs were the main contributory factors and were observed in 52%, 40% and 23% of the cases, respectively. The mortality rate was 29% at 90 days. This study shows that the aetiology of AKI is often multifactorial and the 90-day mortality rate of AKI treated with RRT is still high.
Practice Prize Winner—Dynamic Marketing Budget Allocation Across Countries, Products, and Marketing Activities
Authors: Fischer Marc , Albers Sönke , Wagner Nils , Frie Monika
Published: March 2011

Previous research on marketing budget decisions has shown that profit improvement from better allocation across products or regions is much higher than from improving the overall budget. However, despite its high managerial relevance, contributions by marketing scholars are rare.

In this paper, we introduce an innovative and feasible solution to the dynamic marketing budget allocation problem for multiproduct, multicountry firms. Specifically, our decision support model allows determining near-optimal marketing budgets at the country–product–marketing–activity level in an Excel-supported environment each year. The model accounts for marketing dynamics and a product's growth potential as well as for trade-offs with respect to marketing effectiveness and profit contribution. The model has been successfully implemented at Bayer, one the world's largest pharmaceutical and chemical firms. The profit improvement potential is more than 50% and worth nearly €500 million in incremental discounted cash flows.
Evaluation of a Real-Time PCR Assay for the Detection of the Klebsiella pneumoniae Carbapenemase Genes in Microbiological Samples in Comparison With the Modified Hodge Test
Authors: Raghunathan Aditya , Samuel Linoj , Tibbetts Robert J.
Published: March 2011

Transfer of the blaKPC genes encoding the Klebsiella pneumoniae carbapenemase (KPC) are increasingly responsible for emerging carbapenem resistance. The modified Hodge test (MHT) is recommended for the detection of KPC. We compared MHT with a real-time polymerase chain reaction (PCR) assay targeting common subtypes of blaKPC, using previously described forward and reverse primer sequences. The PCR product was detected using SYBR Green (Applied Biosystems, Foster City, CA) and confirmed by melt curve analysis. PCR was positive in 96% (52/54) of isolates that were MHT+, 90% (28/31) of MHT– isolates were PCR–, and the results were strongly correlated (P = .0001; Fisher exact test). The PCR assay is a sensitive, specific, and rapid test for detecting blaKPC genes. It could help optimize patient care by reducing the time taken to institute appropriate antimicrobial therapy and so help improve patient outcomes.
Usefulness of Multiparametric Flow Cytometry in Detecting Composite Lymphoma
Authors: Demurtas Anna , Aliberti Sabrina , Bonello Lisa , Di Celle Paola Francia , Cavaliere Cristina , Barreca Antonella , Novero Domenico , Stacchini Alessandra
Published: March 2011

Composite lymphoma (CL) is a rare occurrence of 2 or more morphologically and immunophenotypically distinct lymphoma clones in a single anatomic site. A retrospective analysis of 1,722 solid tissue samples clinically suggestive of lymphoma was carried out in our institute during a 12-year period to evaluate the efficacy of flow cytometry (FC) in identifying CL. We report 17 CL cases. A strong correlation between morphologic findings and FC was observed in 13 cases (76%). In the 4 cases diagnosed as non-Hodgkin lymphoma plus Hodgkin lymphoma, although FC did not detect Reed-Sternberg cells, it accurately identified the neoplastic B- or T-cell component. In 3 cases, FC indicated the need to evaluate an additional neoplastic component that was not morphologically evident. Our data demonstrate that FC immunophenotyping of tissues may enhance the performance of the diagnostic morphologic evaluation of CL. To the best of our knowledge, this is the first report in the literature of a wide series of CL studied also by FC.
Laser-trapping assembling dynamics of molecules and proteins at surface and interface
Authors: Masuhara Hiroshi , Sugiyama Teruki , Rungsimanon Thitiporn , Yuyama Ken-ichi , Miura Atsushi , Tu Jing-Ru
Published: March 2011

Laser trapping of molecules and proteins in solution at room temperature is made possible by irradiating 1064-nm continuous-wave (CW) laser with power around 1 W. Although conventional small molecules are not trapped at the focal point, molecules that can form clusters upon assembling and proteins whose size is close to 10 nm are gathered, giving unique assembly structure. Glycine in H2O shows crystallization, urea in D2O gives a millimeter-sized giant droplet, and cobalt oxide-filled ferritin protein confirms assembly followed by precipitation. Solute concentration, solvent, and laser power are important factors for determining trapping and assembling phenomena, and the laser focal position is very critical. These unique behaviors are realized by setting the irradiation at the air/solution surface, inside the solution, and at the glass/solution interface. Laser trapping-induced crystallization, liquid/liquid phase separation, and precipitation are compared with the previous results and considered. After summarizing the results, we describe our future perspective and plans.
Toward targeted photodynamic therapy
Authors: Phillips David
Published: March 2011

The sensitizers in common use for photodynamic therapy (PDT) are summarized, and approaches to the improvement of these outlined. Selectivity in the targeting of sensitizers to tumor cells and tissue is highly desirable, as is water solubility and prevention of aggregation. Some new free sensitizers are described, based upon thepyropheophorbide a(PPa) structure, and their photophysical properties, distribution in cells via confocal fluorescence microscopy, and cell kill properties described. A novel approach to targeting is to covalently attach such sensitizers to monoclonal antibody fragments, and recent work on the attachment ofpyropheophorbide ato such monoclonal antibody fragments is reviewed, with a demonstration of the increased efficiency of cell kill, and the treatment of a solid human tumor in a mouse model described. Finally, an alternative method of achieving selectivity based upon two-photon excitation (TPE) using porphyrin dimer sensitizers is reviewed, and the use of these to kill tumor cells is compared with the use of a commercially available PDT sensitizer (Visudyne). TPE of a porphyrin dimer sensitizer is shown to be capable of sealing blood vessels in a mouse model.
Tuning plasmon transitions and their applications in organic photochemistry
Authors: Scaiano Juan C. , Netto-Ferreira José C. , Alarcon Emilio , Billone Paul , Alejo Carlos J. Bueno , Crites Charles-Oneil L. , Decan Matthew , Fasciani Chiara , González-Béjar María , Hallett-Tapley Geniece , Grenier Michel , McGilvray Katherine L. , Pacioni Natalia L. , Pardoe Andrea , René-Boisneuf Laetitia , Schwartz-Narbonne Rachel , Silvero M. Jazmín , Stamplecoskie Kevin G. , Wee Tse-Luen
Published: March 2011

The ketone-photoinduced formation of Au, Ag, and Cu nanoparticles from their corresponding ions in solution has been carried out using benzoin photoinitiators. Ketones are good photosensitizers for nanoparticle synthesis not because of the energy they can absorb or deliver, but rather because of the reducing free radicals they can generate. Efficient photochemical nanoparticle generation thus requires a careful selection of substrates and experimental conditions such that free radical generation occurs with high quantum efficiency, where metal ion precursors do not inhibit radical formation. A key consideration to achieve nanoparticle synthesis with short exposure times is to minimize excited-state quenching by metal ions. Applications of nanostructures in catalysis require control of the nanoparticle characteristics, such as dimension, morphology, and surface properties. Part of this article describes the strategies to modify photochemically prepared particles. Finally, we illustrate some of the nanoparticle applications that interest us, with some emphasis on plasmon-mediated processes.
ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells
Authors: Genvigir Fabiana D.V. , Rodrigues Alice C. , Cerda Alvaro , Hirata Mario H. , Curi Rui , Hirata Rosario D.C.
Published: March 2011

Background: Enterocytes play a crucial role in high-density lipoprotein (HDL) biogenesis. Statins and ezetimibe are potent lowering-cholesterol drugs, which can also influence HDL plasma concentrations. We hypothesized that these drugs could modulate the expression of intestinal ABCA1and ABCG1, two genes involved in HDL metabolism.

Methods: Caco-2 cells were used as a model of the human intestinal cells and were treated with statins (0.01–1 μmol/L) and/or ezetimibe (0.5–5.0 μmol/L) for 12 h or 24 h. Gene expression was examined using real-time PCR.

Results:
ABCA1 level was more abundant than ABCG1 in Caco-2 cells. ABCA1 was downregulated after 12-h and 24-h treatment with atorvastatin (0.1 and 1.0 μmol/L) or simvastatin (0.01, 0.1 and 1 μmol/L) (p<0.05). In statin-treated cells, ABCG1 levels remained unaltered. Ezetimibe alone did not induce change of ABCA1 or ABCG1 mRNA levels (p>0.05) but 24-h ezetimibe (2.5 or 5.0 μmol/L) plus simvastatin (1 μmol/L) treatment decreased the transcription of ABCA1 and ABCG1 (p<0.05).

Conclusions: Our findings reveal that, at the concentrations studied, statins isolated or combined with ezetimibe, but not ezetimibe alone, downregulate ABCA1 mRNA expression in Caco-2 cells. Moreover, simvastatin combined with ezetimibe treatment also decrease the ABCG1 levels in these cells.
A comparison of simple allometric and maturation models for the prediction of morphine clearance in pediatrics
Authors: Mahmood Iftekhar
Published: March 2011

Background:The objective of this study is to predict morphine clearance in children (preterm neonates to 10-month-old infants) by maturation models that include age and weight and to compare the predictive performance of morphine maturation models with simple allometric models.

Methods: Age, weight, and morphine clearance data were obtained from the literature. A maturation model (n=60) for morphine was developed using data from preterm and term neonates to 5-year-old children. The allometric models were developed using the same data as the maturation model. The predictive performance of the models was tested in 88 children of different age groups.

Results: The maturation and allometric models predicted morphine clearance in children with the same degree of accuracy or error. Out of 88 subjects, the prediction error of 50% or less was observed in slightly >60% of the subjects. Almost 40% of the subjects showed a prediction error >50%, 20% of which showed an error ≥100%. Although both the maturation and allometric models provided a good prediction of morphine clearance in many children, they were less accurate for many others.

Conclusions: High intersubject variability in morphine clearance probably led to less than adequate performance of the models. However, there could be many drugs for which intersubject variability in clearance might not be as high as morphine clearance and in those situations these models could perform reasonably well.
Allegory, blending, and censorship in modern literature
Authors: Hamilton Craig
Published: March 2011

I argue that politically subversive texts written in allegorical form attain their significance because they are conceptual blends. Political allegories allow writers to criticise regimes indirectly since writers can count on readers to mentally contruct appropriate blends. Readers are naturally driven to find new values that fit an allegory's fixed roles, often yielding new meaning for texts in different contexts. Unfortunately, politically subversive allegories may be censored when censors run the same blends. The three main texts discussed here – Bulgakov's Heart of a Dog, Orwell's Animal Farm, and Miller's The Crucible – are often interpreted as political allegories. I turn to conceptual blending theory to show in some detail how those readings arise. When it comes to allegory and censorship, I suggest that conceptual blending theory can offer us new insights into these timeless topics.
Against pan-narrator theories
Authors: Köppe Tilmann , Stühring Jan
Published: March 2011

Most narratologists today maintain that all fictional narratives have a fictional narrator that is to be distinguished from its author. Call this a “pan-narrator theory” (PN). In this essay, we argue that there are good reasons against this position, while important arguments that seem to speak in favor of it can be shown to be ultimately untenable. We start by offering a brief sketch of a theory of fiction that serves as the basis of our considerations and then defend the view that there is no need, theoretical or pragmatic, to postulate a fictional narrator for every fictional narrative.
Allosteric modulation of ATP-gated P2X receptor channels
Authors: Coddou Claudio , Stojilkovic Stanko S. , Huidobro-Toro J. Pablo
Published: March 2011

Seven mammalian purinergic receptor subunits, denoted P2X1–P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites.
Pten KnockdownIn VivoIncreases Excitatory Drive onto Dentate Granule Cells
Authors: Luikart Bryan W. , Schnell Eric , Washburn Eric K. , Bensen AeSoon L. , Tovar Kenneth R. , Westbrook Gary L.
Published: March 2011

Some cases of autism spectrum disorder have mutations in the lipid phosphatase, phosphatase and tensin homolog on chromosome 10 (Pten). Tissue specific deletion of Pten in the hippocampus and cortex of mice causes anatomical and behavioral abnormalities similar to human autism. However, the impact of reductions in Pten on synaptic and circuit function remains unexplored. We usedin vivostereotaxic injections of lentivirus expressing a short hairpin RNA to knock down Pten in mouse neonatal and young adult dentate granule cells. We then assessed the morphology and synaptic physiology between 2 weeks and 4 months later. Confocal imaging of the hippocampus revealed a marked increase in granule cell size and an increase in dendritic spine density. The onset of morphological changes occurred earlier in neonatal mice than in young adults. We used whole-cell recordings from granule cells in acute slices to assess synaptic function after Pten knockdown. Consistent with the increase in dendritic spines, the frequency of excitatory miniature and spontaneous postsynaptic currents increased. However, there was little or no effect on IPSCs. Thus, Pten knockdown results in an imbalance between excitatory and inhibitory synaptic activity. Because reductions in Pten affected mature granule cells as well as developing granule cells, we suggest that the disruption of circuit function by Pten hypofunction may be ongoing well beyond early development.
Complement Receptor 2Is Expressed in Neural Progenitor Cells and Regulates Adult Hippocampal Neurogenesis
Authors: Moriyama Maiko , Fukuhara Takeshi , Britschgi Markus , He Yingbo , Narasimhan Ramya , Villeda Saul , Molina Hector , Huber Brigitte T. , Holers Mike , Wyss-Coray Tony
Published: March 2011

Injury and inflammation are potent regulators of adult neurogenesis. As the complement system forms a key immune pathway that may also exert critical functions in neural development and neurodegeneration, we asked whether complement receptors regulate neurogenesis. We discovered that complement receptor 2 (CR2), classically known as a coreceptor of the B-lymphocyte antigen receptor, is expressed in adult neural progenitor cells (NPCs) of the dentate gyrus. Two of its ligands, C3d and interferon-α (IFN-α), inhibited proliferation of wild-type NPCs but not NPCs derived from mice lackingCr2(Cr2−/−), indicating functionalCr2expression. Young and oldCr2−/−mice exhibited prominent increases in basal neurogenesis compared with wild-type littermates, whereas intracerebral injection of C3d resulted in fewer proliferating neuroblasts in wild-type than inCr2−/−mice. We conclude thatCr2regulates hippocampal neurogenesis and propose that increased C3d and IFN-α production associated with brain injury or viral infections may inhibit neurogenesis.
Pleasure-Related Analgesia Activates Opioid-Insensitive Circuits
Authors: Kut Elvan , Candia Victor , von Overbeck Jan , Pok Judit , Fink Daniel , Folkers Gerd
Published: March 2011

Recent findings suggest that pain and pleasure share common neurochemical circuits, and studies in animals and humans show that opioid-mediated descending pathways can inhibit or facilitate pain. We explored the role of endogenous opioid neurotransmission in pleasure-related analgesia. μ-Opioidergic activity was blocked with 0.2 mg/kg naloxone to assess its effects on hedonic responses to pleasant emotional pictures (International Affective Picture System) and its modulating effects on heat pain tolerance. Naloxone did not alter subjective and autonomous reactions to pleasure induction or overall mood of participants. In addition, pleasure-related increases in pain tolerance persisted after reversal of endogenous μ-opioidergic neurotransmission. Subjective pain intensity and unpleasantness ratings increased after naloxone administration. These findings suggest that, in addition to opioid-sensitive circuits, mainly opioid-insensitive pain-modulating circuits are activated during pleasure-related analgesia.
Born with an Ear for Dialects? Structural Plasticity in the Expert Phonetician Brain
Authors: Golestani Narly , Price Cathy J. , Scott Sophie K.
Published: March 2011

Are experts born with particular predispositions, or are they made through experience? We examined brain structure in expert phoneticians, individuals who are highly trained to analyze and transcribe speech. We found a positive correlation between the size of left pars opercularis and years of phonetic transcription training experience, illustrating how learning may affect brain structure. Phoneticians were also more likely to have multiple or split left transverse gyri in the auditory cortex than nonexpert controls, and the amount of phonetic transcription training did not predict auditory cortex morphology. The transverse gyri are thought to be establishedin utero; our results thus suggest that this gross morphological difference may have existed before the onset of phonetic training, and that its presence confers an advantage of sufficient magnitude to affect career choices. These results suggest complementary influences of domain-specific predispositions and experience-dependent brain malleability, influences that likely interact in determining not only how experience shapes the human brain but also why some individuals become engaged by certain fields of expertise.
Corticospinal Motor Neurons and Related Subcerebral Projection Neurons Undergo Early and Specific Neurodegeneration in hSOD1G93ATransgenic ALS Mice
Authors: Özdinler P. Hande , Benn Susanna , Yamamoto Ted H. , Güzel Mine , Brown Robert H. , Macklis Jeffrey D.
Published: March 2011

Amyotrophic lateral sclerosis (ALS) is characterized by predominant vulnerability and central degeneration of both corticospinal/corticobulbar motor neurons (CSMN; “upper motor neurons”) in cerebral cortex, and spinal/bulbar motor neurons (SMN; “lower motor neurons”) in spinal cord and brainstem. Increasing evidence indicates broader cerebral cortex pathology in cognitive, sensory, and association systems in select cases. It remains unclear whether widely accepted transgenic ALS models, in particular hSOD1G93Amice, undergo degeneration of CSMN and molecularly/developmentally closely related populations of nonmotor projection neurons [e.g., other subcerebral projection neurons (SCPN)], and whether potential CSMN/SCPN degeneration is specific and early. This relative lack of knowledge regarding upper motor neuron pathology in these ALS model mice has hindered both molecular-pathophysiologic understanding of ALS and their use toward potential CSMN therapeutic approaches. Here, using a combination of anatomic, cellular, transgenic labeling, and newly available neuronal subtype-specific molecular analyses, we identify that CSMN and related nonmotor SCPN specifically and progressively degenerate in hSOD1G93Amice. Degeneration starts quite early and presymptomatically, by postnatal day 30. Other neocortical layers, cortical interneurons, and other projection neuron populations, even within layer V, are not similarly affected. Nonneuronal pathology in neocortex (activated astroglia and microglia) is consistent with findings in human ALS cortex and in affected mouse and human spinal cord. These results indicate previously unknown neuron type-specific vulnerability of CSMN/sensory and association SCPN, and identify that characteristic dual CSMN and SMN degeneration is conserved in hSOD1G93Amice. These results provide a foundation for detailed investigation of CSMN/SCPN vulnerability and toward potential CSMN therapeutics in ALS.
Surprise Signals in Anterior Cingulate Cortex: Neuronal Encoding of Unsigned Reward Prediction Errors Driving Adjustment in Behavior
Authors: Hayden Benjamin Y. , Heilbronner Sarah R. , Pearson John M. , Platt Michael L.
Published: March 2011

In attentional models of learning, associations between actions and subsequent rewards are stronger when outcomes are surprising, regardless of their valence. Despite the behavioral evidence that surprising outcomes drive learning, neural correlates of unsigned reward prediction errors remain elusive. Here we show that in a probabilistic choice task, trial-to-trial variations in preference track outcome surprisingness. Concordant with this behavioral pattern, responses of neurons in macaque (Macaca mulatta) dorsal anterior cingulate cortex (dACC) to both large and small rewards were enhanced when the outcome was surprising. Moreover, when, on some trials, probabilities were hidden, neuronal responses to rewards were reduced, consistent with the idea that the absence of clear expectations diminishes surprise. These patterns are inconsistent with the idea that dACC neurons track signed errors in reward prediction, as dopamine neurons do. Our results also indicate that dACC neurons do not signal conflict. In the context of other studies of dACC function, these results suggest a link between reward-related modulations in dACC activity and attention and motor control processes involved in behavioral adjustment. More speculatively, these data point to a harmonious integration between reward and learning accounts of ACC function on one hand, and attention and cognitive control accounts on the other.
Astrocytes Control Glutamate Receptor Levels at Developing Synapses through SPARC–β-Integrin Interactions
Authors: Jones Emma V. , Bernardinelli Yann , Tse Yiu Chung , Chierzi Sabrina , Wong Tak Pan , Murai Keith K.
Published: March 2011

Neurons recruit numerous mechanisms to facilitate the development of synaptic connections. However, little is known about activity-dependent mechanisms that control the timing and fidelity of this process. Here we describe a novel pathway used by neurons to regulate glutamate receptors at maturing central synapses. This pathway relies on communication between neurons and astrocytes and the ability of astrocytes to release the factor SPARC (secreted protein, acidic and rich in cysteine). SPARC expression is dynamically regulated and plays a critical role in determining the level of synaptic AMPARs. SPARC ablation in mice increases excitatory synapse function, causes an abnormal accumulation of surface AMPARs at synapses, and impairs synaptic plasticity during development. We further demonstrate that SPARC inhibits the properties of neuronal β3-integrin complexes, which are intimately coupled to AMPAR stabilization at synapses. Thus neuron–glial signals control glutamate receptor levels at developing synapses to enable activity-driven modifications of synaptic strength.
Diffusion-Weighted Imaging Tractography-Based Parcellation of the Human Parietal Cortex and Comparison with Human and Macaque Resting-State Functional Connectivity
Authors: Mars Rogier B. , Jbabdi Saad , Sallet Jérôme , O'Reilly Jill X. , Croxson Paula L. , Olivier Etienne , Noonan MaryAnn P. , Bergmann Caroline , Mitchell Anna S. , Baxter Mark G. , Behrens Timothy E. J. , Johansen-Berg Heidi , Tomassini Valentina , Miller Karla L. , Rushworth Matthew F. S.
Published: March 2011

Despite the prominence of parietal activity in human neuroimaging investigations of sensorimotor and cognitive processes, there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species, but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI)-based tractography, and functional interactions were assessed by correlations in activity measured with functional MRI at rest. Resting-state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment, and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into 10 component clusters. The resting-state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex.
Stargazin (TARP γ-2) Is Required for Compartment-Specific AMPA Receptor Trafficking and Synaptic Plasticity in Cerebellar Stellate Cells
Authors: Jackson Alexander C. , Nicoll Roger A.
Published: March 2011

In the cerebellar cortex, parallel fiber-to-stellate cell (PF-SC) synapses exhibit a form of synaptic plasticity manifested as a switch in the subunit composition of synaptic AMPA receptors (AMPARs) from calcium-permeable, GluA2-lacking to calcium-impermeable, GluA2-containing receptors. Here, we examine the role of stargazin (γ-2), canonical member of the transmembrane AMPAR regulatory protein (TARP) family, in the regulation of GluA2-lacking AMPARs and synaptic plasticity in SCs from epileptic and ataxicstargazermutant mice. We found that AMPAR-mediated synaptic transmission is severely diminished instargazerSCs, and that the rectification index (RI) of AMPAR current is reduced. Activity-dependent plasticity in the rectification of synaptic AMPARs is also impaired instargazerSCs. Despite the dramatic loss in synaptic AMPARs, extrasynaptic AMPARs are preserved. We then examined the role of stargazin in regulating the rectification of extrasynaptic AMPARs in nucleated patches and found, in contrast to previous reports, that wild-type extrasynaptic AMPARs have moderate RI values (average RI = 0.38), while those instargazerSCs are low (average RI = 0.24). The GluA2-lacking AMPAR blocker, philanthotoxin-433 (PhTx-433), was used as an alternative measure of GluA2 content in wild-type andstargazerSCs. Despite the difference in RI, PhTx-433 sensitivity of both synaptic and extrasynaptic AMPARs remains unchanged, suggesting that the dramatic changes in RI and the impairment in synaptic plasticity observed in thestargazermouse are not the result of a specific impairment in GluA2 trafficking. Together, these data suggest that stargazin regulates compartment-specific AMPAR trafficking, as well as activity-dependent plasticity in synaptic AMPAR rectification at cerebellar PF-SC synapses.