bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of potential predictor variables on gastric evacuation in Atlantic cod Gadus morhua feeding on fish prey: parameterization of a generic model
Authors: Andersen N. G.
Published: January 2012

The parameter values of a generic model of gastric evacuation were estimated from evacuation data on Atlantic cod Gadus morhua fed meals of four fish prey: herring Clupea harengus, sprat Sprattus sprattus, lesser sandeel Ammodytes tobianus and dab Limanda limanda. The effects on evacuation of photoperiod and pre‐experimental treatment of prey were also tested. Freshly killed A. tobianus were evacuated from the stomach of G. morhua at a rate similar to the value estimated from conspecifics kept deep‐frozen and subsequently thawed prior to the evacuation experiment. The evacuation rate in G. morhua exposed to continuous light did not differ from the rate obtained from fish maintained under a 12L:12D photoperiod. The evacuation rates estimated from the latter fish in the dark and light periods, respectively, were likewise similar. These results indicate that the resistance of prey to the digestive processes is not altered significantly by the pre‐experimental treatment of prey and that there is no diurnal variation per se in the rate of evacuation for G. morhua. Therefore, it is believed that the present parameterization of the evacuation model should prove especially useful for studying the role of G. morhua as a top predator in natural systems.
Does alcohol consumption really affect asymmetry perception? A three‐armed placebo‐controlled experimental study
Authors: Halsey Lewis G. , Huber Joerg W. , Hardwick Jennifer C.
Published: January 2012

Aims  A possible explanation for increased levels of attractiveness of faces when under the influence of alcohol is the reduced ability to perceive bilateral asymmetry. This study tested the degree of preference by alcohol‐dosed and non‐alcohol‐dosed participants for symmetrical faces and their ability to detect facial symmetry, while controlling for other explanations.

Design  Volunteers were recruited to a random allocation experiment with three conditions: alcoholic drink (alcohol dosed), non‐alcoholic drink (placebo) and diluted orange cordial (control). Data on concentration, personality and demographics were collected. Dependent variables were symmetry preference and detection.

Setting  Laboratory, University of Roehampton.

Participants  A total of 101 participants, mainly students (41 alcohol‐dosed, 40 placebo, 20 control).

Measurements  Participants provided verbal responses to images of faces which were presented on a computer screen for 5 seconds each; the first task required a preference judgement and the second task consisted of a forced‐choice response of whether or not a face was symmetrical. Levels of concentration, weight and level of alcohol dose were measured, and demographics plus additional psychological and health information were collected using a computer‐based questionnaire.

Findings  In contrast to a previous investigation, there was no difference in symmetry preference between conditions (P = 0.846). In agreement with previous findings, participants who had not drunk alcohol were better at detecting whether a face was symmetrical or asymmetrical (P = 0.043). Measures of concentration did not differ between conditions (P = 0.214–0.438). Gender did not affect ability to detect symmetry in placebo or alcohol‐dosed participants (P = 0.984, 0.499); however, alcohol‐dosed females were shown to demonstrate greater symmetry preference than alcohol‐dosed males (P = 0.004).

Conclusions  People who are alcohol‐dosed are subtly less able to perceive vertical, bilateral asymmetry in faces, with gender being a possible moderating factor.
The clinical impact of single inhaler therapy in asthma
Authors: Czarnecka K. , Chapman K. R.
Published: January 2012

Background

Low‐dose budesonide/formoterol combination used in the SMART fashion with symptom‐reactive supplemental dosing has been reported to reduce asthma exacerbations as compared to the use of budesonide alone or to lower doses of budesonide/formoterol without supplemental dosing.

Objective

We undertook to review the non‐exacerbation outcomes of SMART therapy and to assess the patient education implications of this treatment strategy.

Materials & Methods

Systematic review.

Results

Patients treated with this strategy appear to be under‐treated in that the majority fail to achieve guideline‐defined control standards. The SMART strategy has not been tested against equivalent or higher doses of budesonide/formoterol given in symptom‐prevention fashion. Existing educational strategies that focus on recognition of poor disease control may not be applicable with SMART therapy and the use of action plans has not been clarified with this symptom‐reactive strategy. There is some evidence from that the current clinical use of SMART therapy may be contaminated frequently by the concurrent prescription of short‐acting bronchodilators. There is no information on long‐term outcomes with a symptom‐reactive ICS/LABA strategy but the use of the strategy for one year has been associated with rising sputum and airway biopsy eosinophil counts.

Conclusion

Despite fewer severe exacerbations with SMART therapy as compared to ICS monotherapy or lower dose ICS/LABA therapy, the strategy produces poor day‐to‐day control of symptoms and is associated with increasing inflammation.

Clinical Relevance

The symptom‐reactive strategy described as SMART therapy is associated with poor symptom control of asthma.
Severe asthma: from characteristics to phenotypes to endotypes
Authors: Wenzel S.
Published: January 2012

Asthma, and severe asthma, in particular, is increasingly recognized as a heterogeneous disease. While traditional views of asthma have centered around a childhood onset disease with an allergic component, several large scale network studies are now confirming that severe asthma can present in multiple different ways, only 30–50% of which meet traditional childhood onset allergic criteria. To understand the different groups better, initial studies have attempted to define phenotypes of severe asthma. A phenotype is defined as the integration of different characteristics that are the product of the interaction of the patient's genes with the environment. Both clinical and statistical approaches have identified at least 3–5 phenotypes of severe asthma. However, these phenotypes, in isolation, do not identify the immunopathology that makes these clinical phenotypes distinct or identifies a target population for a specific approach to therapy. As biological characteristics are identified, phenotypes should continue to evolve towards asthma endotypes. The identification of these endotypes, either by matching biology, genetics and therapeutic responses to therapy with clinically or statistically defined phenotypes or through unbiased genetic and genomic approaches, remains limited. Moving forward, this integration of genetics, biology and clinical characteristics should substantially enhance our ability to effectively treat complex heterogeneous diseases, such as severe asthma.
Increased serum activin‐A differentiates alcoholic from cirrhosis of other aetiologies
Authors: Voumvouraki Argyro , Notas George , Koulentaki Mairi , Georgiadou Maria , Klironomos Stefanos , Kouroumalis Elias
Published: January 2012

Eur J Clin Invest 2012

Background  Activin‐A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin‐A in chronic liver diseases. To identify the origin of activin‐A, levels in the hepatic vein were also estimated.

Materials and methods  Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I–II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis.

Results  Activin‐A levels were significantly increased (P < 0·001) in serum of patients with AC (median 673 pg/mL, range 449–3279), compared with either controls (149 pg/mL, 91–193) or patients with viral cirrhosis (189 pg/mL, 81–480), CHC (142 pg/mL, 65–559) PBC stage I–II (100 pg/mL, 59–597) and PBC stage IV (104 pg/mL, 81–579). Only patients with AC‐associated HCC had significantly increased levels of activin‐A (2403 pg/mL, 1561–7220 pg/mL). Activin‐A serum levels could accurately discriminate AC from cirrhosis of other aetiologies and noncirrhotic alcoholic fatty liver with fibrosis.

Conclusions  Increased serum levels of activin‐A only in patients with alcohol‐related cirrhosis or HCC suggest a possible role of this molecule in the pathophysiology of AC. Further research is warranted to elucidate its role during the profibrotic process and its possible clinical applications.
Novel pathway directed by σE to cause cell lysis in Escherichia coli
Authors: Murata Masayuki , Noor Rashed , Nagamitsu Hiroshi , Tanaka Shuhei , Yamada Mamoru
Published: January 2012

A large number of Escherichia coli cells become viable but nonculturable at early stationary phase, most of which are directed to lysis in cells with an enhanced active σE level. In this study, we examined the effect of small noncoding RNAs, MicA and RybB, as σE regulon as well as regulators of outer membrane protein (Omp) genes, on the lysis process. micA‐ and rybB‐disrupted mutations almost completely suppressed the cell lysis. Increased expression of micA and rybB or disrupted mutation of ompA, ompC and ompW led to a significant level of cell lysis. The suppression by Mg2+ was found to maintain the integrity of the Omp‐repressed outer membrane. Taken together, the results suggest that the cell lysis proceeds in the cascade of σE → expression of micA and rybB → reduction in Omp proteins → disintegration of the outer membrane.
Contrasting introduction scenarios among continents in the worldwide invasion of the banana fungal pathogen Mycosphaerella fijiensis
Authors: ROBERT S. , RAVIGNE V. , ZAPATER M‐F. , ABADIE C. , CARLIER J.
Published: January 2012

Reconstructing and characterizing introduction routes is a key step towards understanding the ecological and evolutionary factors underlying successful invasions and disease emergence. Here, we aimed to decipher scenarios of introduction and stochastic demographic events associated with the global spread of an emerging disease of bananas caused by the destructive fungal pathogen Mycosphaerella fijiensis. We analysed the worldwide population structure of this fungus using 21 microsatellites and 8 sequence‐based markers on 735 individuals from 37 countries. Our analyses designated South‐East Asia as the source of the global invasion and supported the location of the centre of origin of M. fijiensis within this area. We confirmed the occurrence of bottlenecks upon introduction into other continents followed by widespread founder events within continents. Furthermore, this study suggested contrasting introduction scenarios of the pathogen between the African and American continents. While potential signatures of admixture resulting from multiple introductions were detected in America, all the African samples examined seem to descend from a single successful founder event. In combination with historical information, our study reveals an original and unprecedented global scenario of invasion for this recently emerging disease caused by a wind‐dispersed pathogen.
Small regulatory RNAs control the multi‐cellular adhesive lifestyle of Escherichia coli
Authors: Jørgensen Mikkel Girke , Nielsen Jesper S. , Boysen Anders , Franch Thomas , Møller‐Jensen Jakob , Valentin‐Hansen Poul
Published: January 2012

Small regulatory RNA molecules have recently been recognized as important regulatory elements of developmental processes in both eukaryotes and bacteria. We here describe a striking example in Escherichia coli that can switch between a single‐cell motile lifestyle and a multi‐cellular, sessile and adhesive state that enables biofilm formation on surfaces. For this, the bacterium needs to reprogramme its gene expression, and in many E. coli and Salmonella strains the lifestyle shift relies on control cascades that inhibit flagellar expression and activate the synthesis of curli, extracellular adhesive fibres important for co‐aggregation of cells and adhesion to biotic and abiotic surfaces. By combining bioinformatics, genetic and biochemical analysis we identified three small RNAs that act by an antisense mechanism to downregulate translation of CsgD, the master regulator of curli synthesis. Our demonstration that basal expression of each of the three RNA species is sufficient to downregulate CsgD synthesis and prevent curli formation indicates that all play a prominent role in the curli regulatory network. Our findings provide the first clue as to how the Rcs signalling pathway negatively regulates curli synthesis and increase the number of small regulatory RNAs that act directly on the csgD mRNA to five.
Implications of nasopharynx‐associated lymphoid tissue (NALT) in the development of allergic responses in an allergic rhinitis mouse model
Authors: Kim D.‐Y. , Fukuyama S. , Nagatake T. , Takamura K. , Kong I. G. , Yokota Y. , Lee C. H. , Kiyono H.
Published: January 2012

Background

Nasopharynx‐associated lymphoid tissue (NALT) serves as an important inductive site for mucosal immunity in the upper respiratory tract. Despite its importance in the mucosal immune system, little is known regarding the role of NALT in airway allergic immune responses. We aimed to elucidate the role of NALT in the induction of upper airway allergic responses in a mouse model.

Methods

Inhibitor of DNA binding/differentiation 2 (Id2)−/− and Id2+/− mice was exposed to the ovalbumin (OVA)‐induced allergic rhinitis model, because the former resulted in the NALT deficiency. The allergic parameters, such as allergic symptoms, serum OVA‐specific immunoglobulin E (IgE) levels, eosinophil infiltration, and cytokine profiles in the nasal mucosa, were compared between Id2−/− and Id2+/− groups.

Results

NALT‐null, Id2−/− mice displayed significantly lower allergic responses compared with Id2+/− mice, as demonstrated by lower levels of allergic symptoms, serum OVA‐specific IgE, eosinophilic infiltration, and local Th2 cytokine transcriptions. To determine which of two factors, that is, the absence of NALT or the alteration of immunocompetent cell populations caused by the Id2 deficiency, has a larger effect on the attenuated allergic immune responses in Id2−/− mice, lethally irradiated Id2−/− mice were engrafted with C57BL/6 wild‐type bone marrow cells and showed still significantly lower allergic immune responses compared with equally treated Id2+/− mice. In addition, IgE class switch recombination‐associated molecules, such as ε immunoglobulin heavy‐chain germline gene transcript, ε mRNA, and activation‐induced cytidine deaminase mRNA, were detected in NALT from OVA‐sensitized wild‐type mice.

Conclusion

These results show the critical role of NALT for the induction of allergic responses in the upper airway at least in part by means of class switching to IgE in situ.
Intranasal fentanyl in the treatment of acute pain – a systematic review
Authors: HANSEN M. S. , MATHIESEN O. , TRAUTNER S. , DAHL J. B.
Published: January 2012

Due to its non‐invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non‐invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out‐of‐hospital treatment and the paediatric population. The objective of this systematic review was to evaluate the current evidence of IN fentanyl in the treatment of acute pain. Reports of randomized controlled trials (RCTs) of IN fentanyl in treatment of pain were systematically sought using the PubMed database, Embase, Google scholar, Cochrane database, and Cumulative Index to Nursing and Allied Health Literature. Reports were considered for inclusion if they were double‐blinded randomized controlled trials (RCTs) of IN fentanyl in the treatment of acute pain. Thirty‐two RCTs were identified, and 16 were included in the final analysis. No significant analgesic differences between IN fentanyl and intravenous (IV) fentanyl were demonstrated in treatment of acute and post‐operative pain. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. In the paediatric population, results demonstrated some analgesic effect of IN fentanyl following myringotomy, no analgesic effect following voiding cystourethrography, and finally, no significant analgesic difference after long bone fractures, in burns patients, and in post‐operative pain relief when compared to IV morphine, oral morphine, or IV fentanyl, respectively. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. However, the significant deficiencies in trials investigating acute and post‐operative pain, and the paediatric population makes firm recommendations impossible.
Venous flow dynamics during spinal block in normotensive and hypertensive elderly patients: a duplex ultrasonographic study
Authors: KIL H. K. , SUK E. H. , LEE M. H. , BANG E. C. , HONG J‐Y.
Published: January 2012

Background

Spinal block induces hyperkinetic change in lower extremity blood flow. We compared the venous flow dynamic responses to spinal block in normotensive and hypertensive elderly patients.

Methods

Following spinal block using 10 mg 0.5% (w/v) bupivacaine, we measured changes in blood pressure, heart rate, and venous flow dynamics of the popliteal vein by duplex ultrasonography in 20 normotensive (NBP group) and 18 hypertensive (HIBP group) patients.

Results

Spinal block caused significant decreases in blood pressure in both groups; similar rates of hypotension were observed. At baseline, peak velocity, time‐averaged maximum velocity, and time‐averaged mean velocity were higher in the HIBP than in the NBP group. During spinal block, peak velocity increased in both groups, and the between‐group differences were no longer significant. At baseline, volume flow in the two groups was similar and increased by 141.5% in the NBP and 131.7% in the HIBP group during spinal block.

Conclusions

Blood pressure and flow dynamics in the popliteal vein showed similar changes during spinal anaesthesia in elderly patients taking antihypertensive medication and normotensive patients, despite differences in baseline values.
Central venous oxygen saturation is a good indicator of altered oxygen balance in isovolemic anemia
Authors: KOCSI S. , DEMETER G. , FOGAS J. , ÉRCES D. , KASZAKI J. , MOLNÁR Z.
Published: January 2012

Background

Red blood cell transfusion is done primarily as a means to improve oxygen delivery (DO2). Current transfusion guidelines are based solely on hemoglobin levels, regardless of actual DO2 need. As central venous oxygen saturation (ScvO2) may reflect imbalances in DO2 and consumption (VO2) the aim of this study was to investigate the value of ScvO2 as an indicator of oxygen balance in isovolemic anemia.

Methods

After splenectomy, anesthetized Vietnamese mini pigs (n = 13, weight range: 18–30 kg) underwent controlled bleeding in five stages (T0–T5). During each stage approximately 10% of the estimated starting total blood volume was removed and immediately replaced with an equal volume of colloid. Hemodynamic measurements and blood gas analysis were then performed.

Results

Each stage of bleeding resulted in a significant fall in hemoglobin, T0: 125 (113–134) to T5: 49 (43–55) g/l [T0: 7.7 (6.9–8.2) to T5: 3.0 (2.6–3.4) mmol/l]. The O2‐extraction (VO2/DO2) increased significantly only from T3: 35 (21–40) %, P < 0.05. The change of ScvO2 showed a similar pattern and dropped below the physiological threshold of 70% at T4: 68 (61–76) %. At this point, hemoglobin was below the recommended transfusion trigger value, 59 (53–67) g/l [3.6 (3.3–4.1) mmol/l]. There was a strong significant association between ScvO2 (< 70%) and VO2/DO2 (> 30%): r = −0.71, r2 = 0.50, P < 0.001.

Conclusion

The results of this study show that ScvO2 reflects changes of VO2/DO2 in isovolemic anemia better than Hb alone, therefore it may be used as an additional indicator of blood transfusion in clinical practice.
Xenon is not superior to isoflurane on cardiovascular function during experimental acute pulmonary hypertension
Authors: ROEHL A. B. , STEENDIJK P. , ROSSAINT R. , BLEILEVENS C. , GOETZENICH A. , HEIN M.
Published: January 2012

Background

Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle.

Methods

Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A2 analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL‐6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme‐linked immunosorbance assays and reverse‐transcription polymerase chain reaction.

Results

After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL‐6 was determined in the right ventricle.

Conclusions

These results do not support the idea that xenon is more beneficial than isoflurane in right ventricular failure during pulmonary hypertension. Isoflurane did not compromise systolic ventricular function during acute PHT it only led to vasodilation in contrast to xenon.
Anatomical Architecture of the Brachial Plexus in the Common Hippopotamus (Hippopotamus amphibius) with Special Reference to the Derivation and Course of its Unique Branches
Authors: Yoshitomi S. , Kawashima T. , Murakami K. , Takayanagi M. , Inoue Y. , Aoyagi R. , Sato F.
Published: January 2012

The anatomy of the brachial plexus in the common hippopotamus (Hippopotamus amphibius), which has not been previously reported, was first examined bilaterally in a newborn hippopotamus. Our observations clarified the following: (1) the brachial plexus comprises the fifth cervical (C5) to first thoracic (T1) nerves. These formed two trunks, C5–C6 and C7–T1; in addition, the axillary artery passed in between C6 and C7, (2) unique branches to the brachialis muscle and those of the lateral cutaneous antebrachii nerves ramified from the median nerve, (3) nerve fibre analysis revealed that these unique nerve branches from the median nerve were closely related and structurally similar to the musculocutaneous (MC) nerve; however, they had changed course from the MC to the median nerve, and (4) this unique branching pattern is likely to be a common morphological feature of the brachial plexus in amphibians, reptiles and certain mammals.
Medical students' beliefs and attitudes towards schizophrenia before and after undergraduate psychiatric training in Greece
Authors: Economou Marina , Peppou Lily E. , Louki Eleni , Stefanis Costas N.
Published: January 2012

Aims:  The aim of the present study was to explore medical students' beliefs and attitudes towards people with schizophrenia (PwS) prior to receiving any training in psychiatry and to assess the impact of the psychiatric placement on changing them.

Methods:  A questionnaire addressing beliefs, attitudes and desired social distance from PwS was distributed to all final year medical students before the beginning of their 4‐week undergraduate psychiatric placement and upon its completion.

Results:  Students did not endorse stereotypes commonly attached to PwS, such as being dangerous, lazy or of lower intelligence, but they held the view that PwS are unpredictable and suffer from split personality. Furthermore, the baseline level of desired social distance was found to increase as the intimacy of the interaction increased, and the only variable associated with it was personal experience of serious mental illness. Moreover, the placement was found to have either no influence at all or in a negative direction. Upon its completion more students were found to believe that PwS cannot recover, have no insight into their condition, cannot make reasonable decisions, cannot work in regular jobs and are dangerous to the public. No difference was recorded in social distance scores.

Conclusions:  A close and critical examination of the various elements of the undergraduate placement in psychiatry is needed in order to develop an evidence‐based, fully rounded education with an anti‐stigma orientation.
Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non‐deficit schizophrenia
Authors: Kitis Omer , Ozalay Ozgun , Zengin E. Burcak , Haznedaroglu Damla , Eker M. Cagdas , Yalvac Dilek , Oguz Kaya , Coburn Kerry , Gonul Ali Saffet
Published: January 2012

Aims:  Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non‐deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non‐deficit schizophrenia.

Methods:  Twenty‐nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non‐deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion‐based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software – Diffusion tool box software.

Results:  The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non‐deficit patients and the controls. There were no differences between non‐deficit schizophrenia patients and controls.

Conclusion:  These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.
Inhibition of sympathetic neuroeffector transmission in human corpus cavernosum
Authors: Gur Serap , Kadowitz Philip J. , Sikka Suresh C. , Bivalacqua Trinity J. , Hellstrom Wayne J. G.
Published: January 2012

Study Type – Aetiology (case control)

Level of Evidence 2b

What's known on the subject? and What does the study add?

In the present study the mechanisms regulating EFS‐evoked neurogenic contraction in the human corpus cavernosum (HCC) were investigated. Overall, our data adds to current knowledge that the NO‐independent heme dependent activation of sGC and the RhoA/Rho‐kinase signaling pathways play an important role in the regulation of neurogenic contractile activity in HCC tissue.

OBJECTIVE

To investigate the mechanisms of adrenergically mediated smooth muscle contraction in the human corpus cavernosum (HCC) using an organ bath approach.

METHODS

Human corpus cavernosum specimens were obtained from patients (aged 59–72 years) with erectile dysfunction (ED), undergoing penile prosthesis implantation surgery.

Isolated HCC strips (1 × 1 × 6 mm) were suspended in tissue bath chambers for isometric tension recording.

The effects of various drugs on neurogenic contractions evoked by electrical field stimulation (EFS) were investigated. The drugs included nitric oxide (NO) donors, phosphodiesterase 5 (PDE5) inhibitor, Rho kinase (ROCK) inhibitor, NO‐independent stimulator, L‐type Ca2+ channel blocker and α‐receptor antagonist.

RESULTS

Pre‐incubation with the NO donor sodium nitroprusside (SNP; 104 M) significantly reduced the initial peak increase in tension evoked by EFS (by 71%, P < 0.05). The PDE5 inhibitor sildenafil (10−4 M) reduced the increase in tension by 69%, while a combination of sildenafil and ROCK inhibitor, fasudil, inhibited tension by 81%.

The EFS‐induced contractile response at 80 Hz was decreased by 65% with fasudil and by 70% with isradipine (P < 0.001), while a combination of these drugs decreased the response by 88%. An NO‐independent stimulator soluble guanylate cyclase (sGC), BAY 41‐8543, significantly reduced the response (by 82%, P < 0.001) Phentolamine, an α‐receptor antagonist, nearly eliminated the contractile response (98%, P < 0.001).

CONCLUSIONS

These data suggest that neurogenic contractions are mediated by an increase in Ca(2+) influx via L‐type voltage‐gated Ca(2+) channels and that an increase in Ca(2+) sensitivity is mediated by the ROCK pathway and the PDE5 enzyme system as well as by the inhibitory NO/sGC/cGMP pathway.

The neurogenic contractile response in HCC is mediated by several intracellular pathways, including adrenergic receptors, Ca(2+) entry, Ca(2+) sensitization and activation of the PDE5 enzyme. The Rho‐kinase (ROCK) inhibitor fasudil, L‐type Ca(2+) channel antagonist isradipine, and PDE5 inhibitor sildenafil, as well as a NO‐independent stimulator of sGC, had similar inhibitory effects, suggesting parallel mechanisms in the HCC.
Low testosterone level predicts prostate cancer in re‐biopsy in patients with high grade prostatic intraepithelial neoplasia
Authors: García‐Cruz Eduard , Piqueras Marta , Ribal Maria José , Huguet Jorge , Serapiao Rodrigo , Peri Lluis , Izquierdo Laura , Alcaraz Antonio
Published: January 2012

Study Type – Prognosis (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

High grade prostatic intraepithelial neoplasia (HGPIN) is a risk factor for prostate cancer (PCa), but only multifocality is an indication for early rebiopsy. Other risk factors for PCa development from HGPIN remain unknown. PCa is related to testosterone. Testosterone has been proven to be linked to PCa detection and poor prognosis PCa.

This study shows that low free and bioavailable testosterone levels are associated with an increased risk of PCa in a rebiopsy after HGPIN diagnosis. Men with low testosterone levels and HGPIN could therefore be considered a high‐risk cohort for developing PCa.

OBJECTIVE

To determine the relevance of the hormonal profile of patients with high grade prostatic intraepithelial neoplasia (HGPIN) and its relationship to prostate cancer (PCa) in rebiopsy.

PATIENTS AND METHODS

We prospectively analysed 82 consecutive patients with a diagnosis of HGPIN without PCa in a prostate biopsy between September 2007 and December 2009.

Of these 82 patients, 45 underwent rebiopsy and their hormonal profile was determined (testosterone and sex hormone‐binding globulin [SHBG]) as part of our clinical protocol.

Patient age, PSA level, prostate volume, PSA density, testosterone, free testosterone, bioavailable testosterone and SHBG were recorded prospectively.

A comparative study between those patients with a positive rebiopsy and those with a negative rebiopsy was performed.

RESULTS

We found that free testosterone (P= 0.04), bioavailable testosterone (P= 0.04) and SHBG (P= 0.02) were significantly associated with a positive rebiopsy.

Other variables such as age (P= 0.745), PSA level (P= 0.630), prostate volume (P= 0.690), PSA density (P= 0.950), testosterone (P= 0.981) and prostatic intraepithelial neoplasia multifocality (P= 0.777) were not associated with the presence of adenocarcinoma in the rebiopsy.

CONCLUSIONS

Patients with adenocarcinoma of the prostate after a diagnosis of HGPIN have higher SHBG levels and lower calculated free testosterone levels than patients with a negative rebiopsy.

Testosterone levels might be a useful indication for rebiopsy after HGPIN diagnosis.
Increased accumulation and stability of rotavirus VP6 protein in tobacco chloroplasts following changes to the 5′ untranslated region and the 5′ end of the coding region
Authors: Inka Borchers A.‐M. , Gonzalez‐Rabade Nuria , Gray John C.
Published: January 2012

Rotavirus is the main cause of gastroenteritis in children worldwide, and the World Health Organisation has recommended that a rotavirus vaccine should be included in all infant immunization programmes. VP6 is the most immunogenic rotavirus subunit and is a potential target for an oral subunit vaccine. VP6 accumulated at up to 3% of total soluble protein in the young leaves of transplastomic tobacco plants, but the protein was unstable and was lost as the leaves aged. The aim of this study was to alter the 5′‐untranslated region (5′‐UTR) and the 5′ end of the coding region of VP6 cDNA in an attempt to increase the expression and stability of VP6 protein in tobacco chloroplasts. The inclusion of the 5′‐UTR from gene 10 of bacteriophage T7 (T7g10) and the addition of 15 nucleotides, encoding five additional amino acid residues, at the 5′ end of the coding region increased the expression to >15% of total leaf protein and stabilized the protein in ageing leaves. Plants containing VP6 expression constructs with the rbcL 5′‐UTR and with the native VP6 5′ end of the coding region produced VP6 protein at only 1.9% of total leaf protein. Both the T7g10 5′‐UTR and the additional 15 nucleotides increased transcript accumulation and translational efficiency compared with VP6 constructs containing the rbcL 5′‐UTR. The VP6 protein produced from all gene constructs appeared to be susceptible to proteolytic processing at its N‐terminal region. However, in all transplastomic lines, VP6 proteins assembled into the trimeric form found in the rotavirus capsid.
Engineering of benzylglucosinolate in tobacco provides proof‐of‐concept for dead‐end trap crops genetically modified to attract Plutella xylostella (diamondback moth)
Authors: Møldrup Morten E. , Geu‐Flores Fernando , de Vos Martin , Olsen Carl E. , Sun Joel , Jander Georg , Halkier Barbara A.
Published: January 2012

Glucosinolates are biologically active natural products characteristic of crucifers, including oilseed rape, cabbage vegetables and the model plant Arabidopsis thaliana. Crucifer‐specialist insect herbivores, like the economically important pest Plutella xylostella (diamondback moth), frequently use glucosinolates as oviposition stimuli. This suggests that the transfer of a glucosinolate biosynthetic pathway to a non‐crucifer would stimulate oviposition on an otherwise non‐attractive plant. Here, we demonstrate that stable genetic transfer of the six‐step benzylglucosinolate pathway from A. thaliana to Nicotiana tabacum (tobacco) results in the production of benzylglucosinolate without causing morphological alterations. Benzylglucosinolate‐producing tobacco plants were more attractive for oviposition by female P. xylostella moths than wild‐type tobacco plants. As newly hatched P. xylostella larvae were unable to survive on tobacco, these results represent a proof‐of‐concept strategy for rendering non‐host plants attractive for oviposition by specialist herbivores with the long‐term goal of generating efficient dead‐end trap crops for agriculturally important pests.
PRICE FLOORS AND QUALITY CHOICE
Authors: Bilotkach Volodymyr
Published: January 2012

This paper studies effects of price floors in a simple model of vertical product differentiation. We find that even non‐binding price floor (i.e., minimum price set below the lowest Nash equilibrium price in the baseline model) can increase quality on the market, if the cost of quality is sufficiently low. Where a binding price floor does not increase the equilibrium quality, it makes consumers worse off. There is also a possibility of over‐investment into quality as a result of the binding minimum price.
Counting in Hieroglyphic Luwian1
Authors: Bauer Anna H.
Published: January 2012

This study investigates Hieroglyphic Luwian nominal number marking in connection with numerals in a detailed corpus analysis, bringing together philology and linguistic analysis. The result is that the numerals ‘two’, ‘three’ and ‘four’ mostly take plural nouns, while numerals from ‘five’ onwards never do so. This leaves the language with a two‐tier system of grammatical number marking, which has many typological parallels. With lower numerals, plural marking in the noun is triggered by the inflection of the numerals themselves, and data from other languages in the region show that the (non‐) application of plural marking may well be an areal feature.
Contraction ofESTin Latin
Authors: Pezzini Giuseppe
Published: January 2012

The paper analyses the contraction ofest(‐st). This phenomenon is generally known as ‘prodelision’ or ‘aphaeresis’ and is considered a metrical sandhi phenomenon, graphically expressed only in early Latin texts. After the introduction (1), the paper presents the first systematic collection of the evidence for this form (2), followed by a phonological discussion (3), and by the conclusions (4), which aim to show that this was a more complex and widespread phenomenon than is normally believed, and to introduce its significance for other general linguistic topics such as cliticisation, the semantics ofsum, and the position of the Latin verb in the clause.1
India’s Trilemma: Financial Liberalisation, Exchange Rates and Monetary Policy1
Authors: Hutchison Michael , Sengupta Rajeswari , Singh Nirvikar
Published: January 2012

A key challenge for macroeconomic policy in open economies is how to simultaneously manage exchange rates, interest rates and capital account openness – the trilemma. This study calculates a trilemma index for India and investigates its evolution over time. We find that financial integration has increased markedly after the mid‐2000s, with corresponding limitations on monetary independence (MI) and exchange rate stability (ES). In addition, we empirically confirm that a rise in one trilemma variable is traded off with a drop in the weighted sum of the other two, i.e. the trilemma configuration is binding in India. Finally, we consider the implications of changes in the trilemma index for macroeconomic outcomes. We find that greater MI systemically contributes to lower inflation, so the twin goals of ES and capital account openness may create policy dilemmas in particular economic environments. ES is associated with less inflation volatility, suggesting that there may be secondary benefits channelled through import and commodity prices. In these relationships, however, changes in international reserves are not statistically significant, suggesting that foreign exchange market intervention has not mitigated the trilemma trade‐off in India.
The averaged periodogram estimator for a power law in coherency
Authors: Sela Rebecca J. , Hurvich Clifford M.
Published: January 2012

We prove the consistency of the averaged periodogram estimator (APE) in two new cases. First, we prove that the APE is consistent for negative memory parameters, after suitable tapering. Second, we prove that the APE is consistent for a power law in the cross‐spectrum and therefore for a power law in the coherency, provided that sufficiently many frequencies are used in estimation. Simulation evidence suggests that the lower bound on the number of frequencies is a necessary condition for consistency. For a Taylor series approximation to the estimator of the power law in the cross‐spectrum, we consider the rate of convergence and obtain a central limit theorem under suitable regularity conditions.
THE MEANING OF MARKET EFFICIENCY
Authors: Jarrow Robert A. , Larsson Martin
Published: January 2012

Fama defined an efficient market as one in which prices always “fully reflect” available information. This paper formalizes this definition and provides various characterizations relating to equilibrium models, profitable trading strategies, and equivalent martingale measures. These various characterizations facilitate new insights and theorems relating to efficient markets. In particular, we overcome a well‐known limitation in tests for market efficiency, i.e., the need to assume a particular equilibrium asset pricing model, called the joint‐hypothesis or bad‐model problem. Indeed, we show that an efficient market is completely characterized by the absence of both arbitrage opportunities and dominated securities, an insight that provides tests for efficiency that are devoid of the bad‐model problem. Other theorems useful for both the testing of market efficiency and the pricing of derivatives are also provided.
Diaspora and identity in the Viking Age
Authors: ABRAMS LESLEY
Published: January 2012

This article investigates the implications of the recent application of the term ‘diaspora’ to the overseas settlements of the Viking Age and offers a speculative assessment, based on literary, historical, archaeological, sculptural and onomastic evidence, of how the concept might contribute to our understanding of the cultural dynamics of the period. This exploratory look at connectivity in the ‘viking world’ considers the respective roles of the Scandinavian homelands and overseas settlements in the interplay of cultural forces from the ninth to the eleventh century.
J. L. Austin and Literal Meaning
Authors: Hansen Nat
Published: January 2012

Alice Crary has recently developed a radical reading of J. L. Austin's philosophy of language. The central contention of Crary's reading is that Austin gives convincing reasons to reject the idea that sentences have context‐invariant literal meaning. While I am in sympathy with Crary about the continuing importance of Austin's work, and I think Crary's reading is deep and interesting, I do not think literal sentence meaning is one of Austin's targets, and the arguments that Crary attributes to Austin or finds Austinian in spirit do not provide convincing reasons to reject literal sentence meaning. In this paper, I challenge Crary's reading of Austin and defend the idea of literal sentence meaning.
An Evaluation of the Projected Returns to Investors on 10 PFI Projects Commissioned by the National Health Service
Authors: Hellowell Mark , Vecchi Veronica
Published: January 2012

Abstract:  Drawing on the financial models of 10 PFI projects commissioned by the UK National Health Service (NHS), this article identifies the returns that are projected to be earned by private investors and evaluates these through the application of corporate finance methods. The paper begins with a description of the PFI model in the NHS and identifies the risks to which private sector costs and revenues are subject. An analytical framework grounded in capital budgeting techniques is outlined, and used to measure and evaluate investor returns. Cost of capital benchmarks are used as comparators to (1) assess the Internal Rate of Return for each project, and (2) as discount rates to calculate Benefit‐Cost Ratios. On both criteria, returns to investors on this group of PFI projects are shown to be much higher than would be sufficient to remunerate investors for the risk they bear.
Association of HIV viral load and CD4 cell count with human papillomavirus detection and clearance in HIV‐infected women initiating highly active antiretroviral therapy
Authors: Kang M , Cu‐Uvin S
Published: January 2012

Objectives

The extent to which highly active antiretroviral therapy (HAART) affects human papillomavirus (HPV) acquisition and clearance in HIV‐infected women is not well understood. We sought to describe high‐risk HPV detection and clearance rates over time since HAART initiation, based on time‐varying HIV viral load (VL) and CD4 T‐cell count, using novel statistical methods.

Methods

We conducted a retrospective analysis of data from the completed AIDS Clinical Trials Group (ACTG) A5029 study using multi‐state Markov models. Two sets of high‐risk HPV types from 2003 and 2009 publications were considered.

Results

There was some evidence that VL > 400 HIV‐1 RNA copies/mL was marginally associated with a higher rate of HPV detection [P = 0.068; hazard ratio (HR) = 4.67], using the older set of high‐risk HPV types. Such an association was not identified using the latest set of HPV types (P = 0.343; HR = 2.64). CD4 count >350 cells/μL was significantly associated with more rapid HPV clearance with both sets of HPV types (P = 0.001, HR = 3.93; P = 0.018, HR = 2.65). There was no evidence that HPV affects VL or CD4 cell count in any of the analyses.

Conclusions

High‐risk HPV types vary among studies and can affect the results of analyses. Use of HAART to improve CD4 cell count may have an impact on the control of HPV infection. The decrease in VL may also have an effect, although to a lesser degree.
Managing the burden of Alzheimer's disease: a partnership between caregiver and physician
Authors: Kurz Alexander
Published: January 2012

Alzheimer's disease is a progressive, neurodegenerative disease that preferentially afflicts the elderly. Its clinical features include impairment of cognitive function and decline in activities of daily living, as well as emotional and personality changes. The effective management of Alzheimer's disease requires a partnership between physician and caregiver. Caregivers play a crucial role in the long‐term care of demented patients. The demonstration that home‐based care is a more economically viable solution than institutional care has led to the realization that community‐based care must be supported and preserved if society is to cope with the burgeoning number of patients with Alzheimer's disease. Physicians depend upon caregivers to impart information concerning a patient's cognitive, functional and behavioural symptoms, whether for diagnosis, to assess the efficacy of a particular treatment, or to ascertain the staging of the disease. Caregivers suffer an enormous physical, emotional, financial and psychological burden as a consequence of the demands of caring. They are frequently at risk of ill‐health and depression themselves, jeopardizing their ability to care. These problems can be alleviated through support, information, education, counselling, and various treatment programmes, which the physician can provide either directly to the caregivers, or can arrange for them. Where caregivers have a more realistic expectation of their caregiving role, and of the patient's capabilities, they are invariably better able to cope. They can be taught to manage effectively the troublesome behavioural symptoms of Alzheimer's disease, which are the most distressing features for the caregiver. The result of a strong and effective alliance between caregiver and physician is a carer who is more accepting and realistic about the caregiving role, and therefore better able to rise to the demands of caring. In turn, the physician is fully informed about the patient and in the best possible position to prescribe treatment, whether pharmacological or non‐pharmacological, for the patient and/or caregiver. The patient whose behavioural symptoms are better managed, thereby reducing anxiety and aggression, receives an optimal level of care, both from the Caregiver and physician.