bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the accuracy of the spectral photocurrent method for the determination of minority carrier diffusion length
Authors: Wee D. , Parish G. , Nener B.
Published: April 2012

The non-scanning, junction-based photocurrent method is one of many techniques that have been devised to determine the minority carrier diffusion length in semiconductor materials. The accuracy of this method is the subject of this paper and the investigation focuses on the theoretical equation that relates the diffusion length to the measured photocurrent produced by a Schottky barrier diode. Specifically, the investigation concentrates on a commonly used assumption in the derivation of this equation, which is that carriers arriving at the edge of the depletion region are swept away from the depletion edge toward the surface barrier at a velocity that is much greater than the diffusion velocity. The subsequent analysis and the results presented in this paper are based on experiments using p-type GaN. The results obtained from numerical simulations show that both velocities have comparable magnitude and the assumption in question is technically incorrect, especially when the diffusion length is very short, as is common for p-type GaN. However, further analysis also shows that in practice this does not adversely affect the accuracy of the diffusion values calculated. In fact, when the diffusion length is very short, the common equation results in calculated diffusion length values that are more accurate compared to those derived from the more detailed equation. This is an indirect consequence of the choice of the effective depletion width and hence, the relative proportion of the drift and diffusion currents.
In-situ electron holography of surface potential response to gate voltage application in a sub-30-nm gate-length metal-oxide-semiconductor field-effect transistor
Authors: Ikarashi Nobuyuki , Takeda Hiroshi , Yako Koichi , Hane Masami
Published: April 2012

The response of the electrostatic potential distribution within a metal-oxide-semiconductor field-effect transistor (MOSFET) to an external electric field was revealed using electron holography cross-sectional in-situ observation while applying the gate voltage to a transistor scaled down to a 25-nm gate length. Charging effects due to electron irradiation were taken into account by using complementary numerical device simulation. Direct observation of the channel potential and its response to the gate voltage can be used to determine the gate electrode effective work-function for scaled MOSFETs.
Peripherality and Integration: Industrial Growth and Decline in the Greek Regions
Authors: Petrakos George , Fotopoulos Georgios , Kallioras Dimitris
Published: April 2012

Peripheral European economies are often characterized by unfavorable structural regularities and geographical coordinates, making the process of economic integration an experience possibly associated with welfare losses at the regional level. Such types of arguments are at variance with the neoclassical understanding of the operation of the spatial economy, making the study of a weak industrial base in the EU periphery an interesting assignment with implications for theory and policy. We develop an empirical model accounting for industrial (manufacturing) growth and decline in the Greek regions in the period following EU membership (1981–2005). Given that Greek regions are characterized as lagging behind and structurally weak for the entire period under consideration, understanding the factors behind their industrial experience may have a value added for many regions with similar characteristics, especially in the new and potential EU member states.
Subsistence Farming, Incomes, and Agricultural Livelihoods in the New Member States of the European Union
Authors: Davidova Sophia , Fredriksson Lena , Gorton Matthew , Mishev Plamen , Petrovici Dan
Published: April 2012

Drawing on primary survey data and the literature on sustainable livelihoods, we analyse agricultural households in five new member states of the EU which possess a large subsistence and semisubsistence farming sector. The study indicates that the contribution of subsistence farming to household incomes is significant. The profiling of agricultural households, using cluster analysis, reveals four main types which differ significantly in terms of engagement in nonmarketed production. The poorest households form the largest cluster. They possess low natural, physical, and social capital, operating small-scale and undercapitalised farms with little nonagricultural income. The main EU Common Agricultural Policy instruments are not well suited to respond to the specific needs of these poor subsistence farmers.
A Coronal Jet Ejection from a Sunspot Light Bridge
Authors: Liu S.
Published: April 2012

Chromospheric brightening and Hα surges are evident and common phenomena along sunspot light bridges. In this paper, a coronal jet ejection from a sunspot light bridge is presented. Using data from the Solar Dynamics Observatory and Hinode satellites, it is confirmed that the jet has its root near the light bridge. This suggests that the jet may be a result of reconnection between the main sunspot and the light bridge. Due to the processing of jet ejecta, the intensity and width of the light bridge show changes to some extent. This also suggests that the jet is related to the interaction between light bridge and umbra, possibly owing to magnetic reconnection or heated plasma trapped in the light bridge escaping and moving along field lines.
Statewide Validation of Hospital-Reported Central Line–Associated Bloodstream Infections: Oregon, 2009
Authors: Oh John Y. , Cunningham Margaret C. , Beldavs Zintars G. , Tujo Jennifer , Moore Stephen W. , Thomas Ann R. , Cieslak Paul R.
Published: April 2012

Background.

Mandatory reporting of healthcare-associated infections is common, but underreporting by hospitals limits meaningful interpretation.

Objective.

To validate mandatory intensive care unit (ICU) central line–associated bloodstream infection (CLABSI) reporting by Oregon hospitals.

Design.

Blinded comparison of ICU CLABSI determination by hospitals and health department–based external reviewers with group adjudication.

Setting.

Forty-four Oregon hospitals required by state law to report ICU CLABSIs.

Participants.

Seventy-six patients with ICU CLABSIs and a systematic sample of 741 other patients with ICU-related bacteremia episodes.

Methods.

External reviewers examined medical records and determined CLABSI status. All cases with CLABSI determinations discordant from hospital reporting were adjudicated through formal discussion with hospital staff, a process novel to validation of CLABSI reporting.

Results.

Hospital representatives and external reviewers agreed on CLABSI status in 782 (96%) of 817 bacteremia episodes (k = 0.77 [95% confidence interval (CI), 0.70-0.84]). Among the 27 episodes identified as CLABSIs by external reviewers but not reported by hospitals, the final status was CLABSI in 16 (59%). The measured sensitivities of hospital ICU CLABSI reporting were 72% (95% CI, 62%-81%) with adjudicated CLABSI determination as the reference standard and 60% (95% CI, 51%-69%) with external review alone as the reference standard (P = .07). Validation increased the statewide ICU CLABSI rate from 1.21 (95% CI, 0.95-1.51) to 1.54 (95% CI, 1.25-1.88) CLABSIs/1,000 central line–days; ICU CLABSI rates increased by more than 1.00 CLABSI/1,000 central line–days in 6 (14%) hospitals.

Conclusions.

Validating hospital CLABSI reporting improves accuracy of hospital-based CLABSI surveillance. Discussing discordant findings improves the quality of validation.
Healthcare-Associated Bloodstream Infections Secondary to a Urinary Focus The Québec Provincial Surveillance Results
Authors: Fortin Elise , Rocher Isabelle , Frenette Charles , Tremblay Claude , Quach Caroline
Published: April 2012

Objective.

Urinary tract infections (UTIs) are an important source of secondary healthcare-associated bloodstream infections (BSIs), where a potential for prevention exists. This study describes the epidemiology of BSIs secondary to a urinary source (U-BSIs) in the province of Québec and predictors of mortality.

Design.

Dynamic cohort of 9,377,830 patient-days followed through a provincial voluntary surveillance program targeting all episodes of healthcare-associated BSIs occurring in acute care hospitals.

Setting.

Sixty-one hospitals in Québec, followed between April 1, 2007, and March 31, 2010.

Participants.

Patients admitted to participating hospitals for 48 hours or longer.

Methods.

Descriptive statistics were used to summarize characteristics of U-BSIs and microorganisms involved. Wilcoxon and X2 tests were used to compare U-BSI episodes with other BSIs. Negative binomial regression was used to identify hospital characteristics associated with higher rates. We explored determinants of mortality using logistic regression.

Results.

Of the 7,217 reported BSIs, 1,510 were U-BSIs (21%), with an annual rate of 1.4 U-BSIs per 10,000 patient-days. A urinary device was used in 71% of U-BSI episodes. Identified institutional risk factors were average length of stay, teaching status, and hospital size. Increasing hospital size was influential only in nonteaching hospitals. Age, nonhematogenous neoplasia, Staphylococcus aureus, and Foley catheters were associated with mortality at 30 days.

Conclusion.

U-BSI characteristics suggest that urinary catheters may remain in patients for ease of care or because practitioners forget to remove them. Ongoing surveillance will enable hospitals to monitor trends in U-BSIs and impacts of process surveillance that will be implemented shortly.
MageComet—web application for harmonizing existing large-scale experiment descriptions
Authors: Xue Vincent , Burdett Tony , Lukk Margus , Taylor Julie , Brazma Alvis , Parkinson Helen
Published: April 2012

Motivation: Meta-analysis of large gene expression datasets obtained from public repositories requires consistently annotated data. Curation of such experiments, however, is an expert activity which involves repetitive manipulation of text. Existing tools for automated curation are few, which bottleneck the analysis pipeline.

Results: We present MageComet, a web application for biologists and annotators that facilitates the re-annotation of gene expression experiments in MAGE-TAB format. It incorporates data mining, automatic annotation, use of ontologies and data validation to improve the consistency and quality of experimental meta-data from the ArrayExpress Repository.

Availability and implementation: Source and tutorials for MageComet are openly available at goo.gl/8LQPR under the GNU GPL v3 licenses. An implementation can be found at goo.gl/IdCuA

Contact:  parkinson@ebi.ac.uk or xue.vin@gmail.com
Bradycardia and Pacemakers
Authors: Williams Howell J. , Williams Timothy M. , Dawkins Sam , Stephenson Philip B. O.
Published: April 2012

Bradycardia has been defined historically as a heart rate below 60 beats/minute (bpm). However, many healthy individuals have a resting heart rate below this and some groups (such as endurance athletes) may have a resting heart rate of less than 30 bpm. For this reason, a strict lower limit is probably not useful and clinicians should use the presence of symptoms as a guide to whether bradycardia warrants further investigation. The key role of the GP is in differentiating patients with pathological bradycardia, who need further investigation or referral, from those with physiological bradycardia who do not.
Simulation of general relativistic shock wave interactions by a locally inertial Godunov method featuring dynamical time dilation
Authors: Vogler Zeke , Temple Blake
Published: April 2012

We introduce the
locally inertial Godunov method with dynamical time dilation
, and use it to give a definitive numerical simulation of a point of shock wave interaction in general relativity starting from a new initial dataset. Prior work of Groah and Temple justifies meeting the Einstein constraint equations for the initial data only at the weak level of Lipshitz continuity in the metric. The forward time simulations, presented here, resolve the secondary wave in the Smoller–Temple shock wave model for an explosion into a static, singular, isothermal sphere. The backward time solutions indicate black hole formation from a smooth solution via collapse associated with an incoming rarefaction wave. A new feature is that space–time is approximated as locally flat in each grid cell so that Riemann problems and the Godunov method can be implemented. Clocks are then dynamically dilated to simulate effects of space–time curvature. Such points of shock wave interaction are more singular than points on single shock surfaces because the coordinate systems that make space–time locally flat on single shock surfaces (Gaussian normal coordinates), break down at points of shock wave interaction.
Electronic cigarettes: achieving a balanced perspective
Authors: Wagener Theodore L. , Siegel Michael , Borrelli Belinda
Published: April 2012

Concerns have been raised that the advent of electronic cigarettes (e‐cigarettes) may be harmful to public health, and smokers have been advised by important agencies such as the US Food and Drug Administration not to use them. This paper argues that, while more research is needed on the cost–benefit equation of these products and the appropriate level and type of regulation for them, the harms have tended thus far to be overstated relative to the potential benefits. In particular: concern over repeated inhalation of propylene glycol is not borne out by toxicity studies with this compound; risk of accidental poisoning is no different from many household devices and chemicals available in supermarkets; concern that e‐cigarettes may promote continued smoking by allowing smokers to cope with no‐smoking environments is countered by the observation that most smokers use these products to try to quit and their use appears to enhance quitting motivation; concerns over low nicotine delivery are countered by evidence that the products provide significant craving reduction despite this in some cases; and e‐cigarettes may help reduce toxin exposure to non‐smokers.
Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV‐1 infected Thai adults
Authors: Sukasem Chonlaphat , Cressey Tim R. , Prapaithong Pattamawan , Tawon Yardpiroon , Pasomsub Ekawat , Srichunrusami Chutatip , Jantararoungtong Thawinee , Lallement Marc , Chantratita Wasun
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Interindividual variability in efavirenz plasma concentrations is associated with CYP2B6 genetic polymorphisms.

• Twenty‐nine different alleles of the CYP2B6 gene are listed. CYP2B6*6, *9, *16, *26, *27 and *28 carriers are reported to be associated with slower efavirenz oral clearance.

• The allelic variant 516G>T is associated with diminished activity of CYP2B6 and high efavirenz plasma concentrations are associated with an increase risk of neuropsychological toxicity.

WHAT THIS STUDY ADDS

• This study identified three SNPs in the CYP2B6 gene which could potentially act as additional independent predictors of efavirenz plasma concentrations beyond that provided by the CYP2B6 c.516G>T polymorphism.

• The GAC‐CYP2B6 haplotype (G516T/A785G/C21563T) is associated with higher plasma efavirenz concentrations in HIV‐infected Thai adults.

• The CYP2B6 g.18492 T>C polymorphism was significantly associated with lower efavirenz concentrations than those with the homozygous wild‐type.

Aims

To investigate the frequency of CYP2B6 polymorphisms and the influence of haplotype structure on plasma efavirenz concentrations in Thai adults with HIV‐1 infection.

Methods

Genotyping of nine single nucleotide polymorphisms (SNPs, c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T, g.3003T>C, g.18492C>T and g.21563C>T) of CYP2B6 were performed using real‐time PCR‐based allelic discrimination on blood samples from 52 HIV‐infected adults who had received an efavirenz‐based regimen. Plasma efavirenz concentrations were measured by high performance liquid chromatography.

Results

The minor allele frequencies for c.64C>T, c.516G>T, c.785A>G, g.3003C>T, g.18492T>C and g.21563C>T were 0.087, 0.365, 0.413, 0.308 and 0.356, respectively. However, no variant alleles were identified for three SNPs (c.499 C>G, c.1375 A>G and c.1459 C>T). Efavirenz plasma concentrations were significantly associated with c.516G>T (P= 0.0095), c.785A>G (P= 0.0017), g.21563C>T (P= 0.0036) and g.18492C>T (P= 0.0011). The composite CYP2B6 of three SNPs (c.516G ≥ T, c.785A ≥ G and g.21563C ≥ T) genotypes were significantly associated with higher efavirenz concentrations.

Conclusions

Our data indicate that the GAC‐CYP2B6 haplotype is associated with higher plasma efavirenz concentrations in HIV‐infected Thai adults.
Use and cost of psychotropic drugs among recipients with autism in a state Medicaid fee‐for‐service programme
Authors: Khanna R. , Jariwala K. , West‐Strum D.
Published: April 2012

Background  There has been a significant increase in the prevalence of autism in the USA in the past few decades. The purpose of this study was to provide recent estimates of psychotropic drug use and costs among individuals with autism enrolled in Medicaid programme.

Method  A cross‐sectional analysis of 2007 Mississippi (MS) Medicaid fee‐for‐service (FFS) programme administrative‐claims data was performed. Study sample included recipients (<65 years) who had a medical services claim with a diagnosis of autism in 2007. Psychotropic drug patterns of use and costs were studied. Factors predicting the use of psychotropic drugs were identified using logistic regression analyses. Average number and cost of psychotropic drug claims per recipient were reported. Costs were reported from the perspective of MS Medicaid.

Results  In 2007, there were 1330 recipients with a diagnosis of autism in MS Medicaid FFS programme. Among these recipients, 66.32% had a claim for psychotropic drug during the year. Roughly 39% of recipients with autism had a claim for antipsychotics, 31.58% for stimulants, 19.55% for antidepressants, 19.40% for other psychotropics and 14.81% for anxiolytics/hypnotics/sedatives. Results from regression analyses highlighted variation in psychotropic drug use by demographic and co‐morbid factors. There were a total of 12 618 claims for psychotropic drugs filled by recipients with autism in 2007, at an average of 14 (±12) claims per recipient. The total cost of these claims paid for by MS Medicaid FFS programme was ∼$2 million. Antipsychotics accounted for more than half (∼58%) of the total costs, and had the highest average cost per claim ($291 ± 205).

Conclusions  The results of this study indicate a high use of psychotropic drugs among individuals with autism enrolled in a state Medicaid programme. There is an urgent need to study the risk–benefit profile of these drugs in this growing population. Psychotropic drug use was found to vary by demographic and co‐morbid factors. Among the different classes of psychotropic drugs, antipsychotics were the most commonly used and had the highest cost per claim.
Neuropathology of the hippocampus in FTLD‐Tau with Pick bodies: a study of the BrainNet Europe Consortium
Authors: Kovacs G. G. , Rozemuller A. J. M. , van Swieten J. C. , Gelpi E. , Majtenyi K. , Al‐Sarraj S. , Troakes C. , Bódi I. , King A. , Hortobágyi T. , Esiri M. M. , Ansorge O. , Giaccone G. , Ferrer I. , Arzberger T. , Bogdanovic N. , Nilsson T. , Leisser I. , Alafuzoff I. , Ironside J. W. , Kretzschmar H. , Budka H.
Published: April 2012

G. G. Kovacs, A. J. M. Rozemuller, J. C. van Swieten, E. Gelpi, K. Majtenyi, S. Al‐Sarraj, C. Troakes, I. Bódi, A. King, T. Hortobágyi, M. M. Esiri, O. Ansorge, G. Giaccone, I. Ferrer, T. Arzberger, N. Bogdanovic, T. Nilsson, I. Leisser, I. Alafuzoff, J. W. Ironside, H. Kretzschmar and H. Budka (2013) Neuropathology and Applied Neurobiology39, 166–178

Neuropathology of the hippocampus in FTLD‐Tau with Pick bodies: a study of the BrainNet Europe Consortium

Aims: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurones. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration‐associated protein depositions in the characteristically affected hippocampus. Methods: We evaluated immunoreactivity (IR) for tau (AT8, 3R, 4R), α‐synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease. Results: Mean age at death was 68.2 years (range 49–96). Fifty‐two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of frontotemporal dementia, followed by progressive aphasia, mixed syndromes or early memory disturbance. α‐Synuclein IR was seen only in occasional spherical tau‐positive inclusions, TDP‐43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurones. Aβ IR was observed in 16 cases; however, the overall level of Alzheimer's disease‐related alterations was mainly low or intermediate (n = 3). Furthermore, we identified six cases with unclassifiable tauopathy. Conclusions: (i) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; (ii) even minor deviation from these morphological criteria suggests a different disorder; and (iii) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification.
Isoflurane causes neocortical but not hippocampal‐dependent memory impairment in mice
Authors: FIDALGO A. R. , CIBELLI M. , WHITE J. P. M. , NAGY I. , WAN Y. , MA D.
Published: April 2012

Background

The aim of this study is to investigate the effect of general anaesthesia induced by isoflurane with buprenorphine on hippocampus‐dependent and neocortex‐dependent memory, respectively, in mice, and in addition, to compare the effects of such anaesthesia on these memory processes with the effects induced by lipopolysaccharide (LPS) administration on the same memory processes.

Methods

To assess hippocampus‐dependent memory, isoflurane (for 15 min) after buprenorphine injection, or LPS 100 μg/kg (intraperitoneally) was administered 24 h before or after fear conditioning. The effect of these treatments on hippocampus‐dependent memory was assessed using contextual fear‐conditioning tasks at day 4. To assess neocortex‐dependent memory, isoflurane anaesthesia or LPS was given 72 h after contextual fear conditioning. Neocortex‐dependent memory assessment was performed at day 32.

Results

Unlike LPS injection, isoflurane with buprenorphine‐induced anaesthesia does not impair freezing responses in hippocampus‐dependent fear‐conditioning memory tasks. On anterograde amnesia assessment: 49.67 ± 6.87% for the anaesthesia group and 54.5 ± 4.12% for the control group. On retrograde amnesia assessment: 47.16 ± 8.71% for the anaesthesia group and 54.5 ± 4.12% for control group; P > 0.05. Thus, neither isoflurane nor buprenorphine impair hippocampus‐dependent memory. However, on the neocortex‐dependent memory task, both isoflurane‐induced anaesthesia and LPS‐induced inflammation result in reduced freezing responses: 62.13 ± 5.80% for the anaesthesia group, 74.63 ± 5.69% for the LPS group, and 81.75 ± 3.26% for the control group; P < 0.05 compared with control group.

Conclusion

General anaesthesia induced by isoflurane with buprenorphine may result in impairment of neocortex‐dependent memory in mouse. However, general anaesthesia so induced does not impair hippocampus‐dependent memory in mouse in our experimental conditions.
Influence of multicomponent apheresis on donors’ haematological and coagulation parameters, iron storage and platelet function
Authors: Macher S. , Sipurzynski‐Budraβ S. , Rosskopf K. , Semmelrock M. , Prüller F. , Griesbacher A. , Lanzer G. , Schallmoser K.
Published: April 2012

Background and Objectives  Multicomponent collection (MCC) enables production and processing of various blood components during one apheresis session. In this prospective crossover study, the effects of donating platelets (PLTs) and packed red blood cells (PRBCs) on donor’s blood cell count, coagulation, PLT function and iron state were analysed.

Materials and Methods  Forty‐eight MCCs were performed using two different cell separators (Fenwal Amicus®, CaridianBCT Trima Accel®). Two units of platelet concentrates and one unit of PRBCs were collected during each session. Full blood cell count and iron status were obtained on day 0 before and after apheresis, day 2, day 14 and day 42. PLT function was analysed by aggregometry and rotation thromboelastometry in parallel with coagulation tests before and after MCC and at day 2.

Results  Multicomponent collection was well tolerated without adverse side effects. Blood cell count and iron parameters declined and most of them (haemoglobin, haematocrit, transferrin, transferrin saturation and ferritin) were significantly below baseline values until at least day 42 after donation. Absent iron stores were seen in 31·3% of the donors. In contrast, PLTs significantly exceeded pre‐donation values after 14 days and remained significantly increased for 42 days. After 2 days, coagulation parameters were only slightly (P > 0·05) altered, whereas PLT function was significantly reduced.

Conclusion  Multicomponent collection is an obviously safe procedure; however, the significant long‐term impact on the donor’s blood count and iron store, as well as impaired PLT function, has to be considered in regard to donor safety.
Safety of micafungin in prospective and retrospective clinical trials
Authors: Ullmann Andrew J. , Klaas Wibke
Published: April 2012

Managing fungal diseases remains a major challenge for clinicians despite the improved armamentarium of antifungal agents. This review identified 19 publications reporting safety data on micafungin. Two of these publications were spin off publications, the remaining 17 (15 prospective, two retrospective) were included in the main assessment. Major adverse events reported which occurred in more than 2% in the study populations were infusion‐related, gastro‐intestinal and hepatic (LFT parameters elevations). Micafungin demonstrated significantly less renal events compared with liposomal amphotericin B and less hepatic events compared with voriconazole. Compared with fluconazole no significant treatment‐related adverse events were found except one trial reporting significantly less somnolence but more chills. Micafungin has a similar favourable safety profile in comparison with other echinocandins or fluconazole.
Pneumocystis jirovecii: a peculiar fungus posing particular problems for therapy and prophylaxis
Authors: Hof H.
Published: April 2012

Pneumocystis spp. are peculiar fungi, because they lack ergosterol in their cytoplasmic membrane. Furthermore, they go through various sexual and non‐sexual stages in a living host; the cysts, which are able to survive in the environment, are the infectious agents. The various species are more or less specific for a mammalian host. Pneumocystis jirovecii is pathogenic for humans. Transient colonisation of children and adults with this fungus occurs frequently. As a typical opportunist it can induce an overt disease in immunocompromised patients only. In particular those patients with an impaired cell‐mediated immune system, namely AIDS patients or transplant recipients taking immunosuppressive agents, are affected. The leading clinical feature is a bilateral interstitial pneumonia characterised by progressive dyspnoea, tachypnoea and non‐productive cough. Finally, the interstitial pneumonia will lead to hampered gas exchange resulting in a marked decrease in paO2 and consequently to a rather low haemoglobin saturation. Pneumocystsis spp. do not grow on artificial media. Diagnosis is made by demonstration of fungal cells on microscopy preferentially by immunofluorescence staining or by the highly sensitive PCR method. A standardisation of the molecular methods is still lacking, since different DNA sequences are amplified in each case. Quantification by real‐time PCR can help to differentiate between infection and mere colonisation. Among the common antifungals only the echinocandins are active at least against the cyst forms. The principal therapeutic agents remain, however, antibacterial and anti‐parasitic agents, such as cotrimoxazole, clindamycin, primaquine, pentamidine and atovaquone. In addition, an improvement of the immunosuppression is warranted. Prophylaxis is indicated in those individuals with a prolonged cell‐mediated immunodeficiency.
Distribution of PDIA3 transcript and protein in rat testis and sperm cells
Authors: Zhao XJ , Tang RZ , Wang ML , Guo WL , Liu J , Li L , Xing WJ
Published: April 2012

Contents

Protein disulphide isomerase family A3 (PDIA3) has an activity of thioredoxin, widely expressed in multiple tissues and involved in multiple cellular processes. It was recently found in human and mouse sperm cells and could affect sperm–egg fusion. Therefore, the present investigation aims to identify PDIA3 mRNA and protein in rat testis and sperm cells. Rat PDIA3 cDNA was cloned by RT‐PCR. The cRNA riboprobe was transcribed from PDIA3 cDNA and was used to display PDIA3 mRNA location in rat testes by in situ hybridization. PDIA3 protein distribution was also observed in testis and sperm cells by immunohistochemistry and immunocytochemistry, respectively. The rat PDIA3 transcript and protein were localized in the cells from spermatocytes to the spermatozoa phases of rat testes, mostly in the pachytene spermatocytes. PDIA3 protein was also observed on the intact sperm membrane including the tail. The rat PDIA3 gene is transcribed and translated through the whole spermatogenesis process, and the PDIA3 protein is spread all over the sperm cell membrane. The results provide some primary information about PDIA3 in testis and sperm for further study on PDIA3 function in rat spermatogenesis and sperm–egg fusion.
Narrow‐band imaging on screening of esophageal lesions using an ultrathin transnasal endoscopy
Authors: Kawai Takashi , Takagi Yu , Yamamoto Kei , Hayama Yasutaka , Fukuzawa Mari , Yagi Kenji , Fukuzawa Masakatsu , Kataoka Mikinori , Kawakami Kohei , Itoi Takao , Moriyasu Fuminori , Matsubayashi Jun , Nagao Toshitaka
Published: April 2012

Background and Aim:  Ultrathin transnasal endoscopy, used extensively in Japan, is considered to have inferior image quality and suction performance, and questionable diagnostic performance. So the aim of the present study was to compare the diagnostic performance of white light (WL) examination and non‐magnified narrow‐band imaging (NBI) examination in screening for esophageal disorders with ultrathin transnasal endoscopy.

Methods:  A prospective case study of 105 consecutive patients screened for upper gastrointestinal disorders at a single clinic in Tokyo Medical University Hospital. All subjects were diagnosed using WL, NBI and Lugol‐staining examinations. Areas ≥ 5 mm clearly not a Lugol‐staining lesion were defined as esophageal disorders and the rates of detection of the two examination methods (WL vs NBI) were compared.

Results:  For WL examination, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy (concordance rate) for esophageal disorders were 19.6%, 98.1%, 90.9%, 55.4%, and 59.2%, respectively, versus 60.8% 96.2%, 93.9%, 71.4%, and 78.6% for NBI.

Conclusion:  A useful level of diagnostic performance for esophageal disorders can be achieved with non‐magnified narrow‐band NBI ultrathin transnasal endoscopy.
Multiple‐antibiotic‐resistant Helicobacter pylori infection eradicated with a tailor‐made quadruple therapy
Authors: Nakajima Shigemi , Inoue Hisayuki , Inoue Tetsuya , Maruoka Yuri
Published: April 2012

In 2008, a 44‐year‐old woman with mild epigastralgia diagnosed as having Helicobacter pylori‐positive chronic gastritis without peptic ulcer underwent eradication therapy with lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) for 7 days, but it failed, so treatment with rabeprazole, AMPC, and metronidazole (MNZ) for another 7 days was given, but it also failed. She was then prescribed a modified, 14‐day sequential therapy of LPZ and AMPC with an increased dose of CAM followed by MNZ supplement, but the infection was still not eradicated. The H. pylori was cultured and examined for antibiotic susceptibility with the agar dilution method and was found to be resistant to CAM, MNZ, and levofloxacin, and non‐sensitive to AMPC, namely multiple‐antibiotic‐resistant, although sensitive to minocycline. The CYP2C19 genotype of the patient was an extensive metabolizer (G681A: G/A, G636A: G/G). In 2010, she gave informed consent for a 14‐day, tailor‐made, modified classical (or modified high‐dose PPI + AMPC) quadruple therapy comprising 30 mg LPZ, 500 mg AMPC and 500 mg bismuth subnitrate, qid, and 100 mg minocycline, bid. Two months later, her urea breath test was negative. Histology and bacterial culture were still negative 1 year after the therapy. She did not have any adverse events during or after the novel therapy, nor did she feel any further epigastralgia.
Hemopexin is upregulated in rat intestinal mucosa injured by indomethacin
Authors: Takagi Tomohisa , Naito Yuji , Okada Hitomi , Takaoka Megumi , Oya‐Ito Tomoko , Yamada Shinya , Hirai Yasuko , Mizushima Katsura , Yoshida Naohisa , Kamada Kazuhiro , Katada Kazuhiro , Uchiyama Kazuhiko , Ishikawa Takeshi , Handa Osamu , Yagi Nobuaki , Konishi Hideyuki , Kokura Satoshi , Ichikawa Hiroshi , Yoshikawa Toshikazu
Published: April 2012

Background and Aims:  Recent advancements in capsule endoscopy and double‐balloon endoscopy have revealed that non‐steroidal anti‐inflammatory drugs (NSAIDs), such as indomethacin, can induce small intestinal mucosal damage. However, the precise pathogenesis and therapeutic strategy have not been fully revealed. The aim of the present study was to determine the upregulated proteins in the small intestine exposed to indomethacin.

Methods:  Indomethacin (10 mg/kg) was administered subcutaneously to male Wistar rats to induce small intestinal damage and the severity of the intestinal injury was evaluated by measuring the area of visible ulcerative lesions. The intestinal mucosal tissue samples were collected and then analyzed by two‐dimensional gel electrophoresis, with matrix‐assisted laser desorption/ionization time‐of‐flight spectrometer peptide mass fingerprinting being used to determine the differentially expressed proteins between normal and injured intestinal mucosa.

Results:  Among several protein spots showing differential expression, one, hemopexin (HPX), was identified as upregulated in indomethacin‐induced injured intestinal mucosa using the MASCOT search engine.

Conclusion:  HPX was identified as upregulated protein in the small intestine exposed to indomethacin. HPX may be responsible for the development of the intestinal inflammation induced by NSAIDs.
Utility of preoperative chemoradiotherapy for advanced esophageal carcinoma
Authors: Kuroda Junko , Yoshida Masashi , Kitajima Masaki , Yanagisawa Akio , Matsubara Toshiki , Yamaguchi Toshiharu , Osamura Yoshiyuki , Ohta Keiichirou , Kubota Keisuke , Beck Yoshifumi , Yamashita Yuichi
Published: April 2012

Background and Aims:  The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three‐field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three‐field lymphadenectomy.

Methods:  A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3–T4 or, < cT3 with multiple lymph node metastasis. ≧ T2 of 95 cases were treated by surgery alone (NACRT [−] case). The effect of NACRT was evaluated by histological examination and corrected with the clinicopathologic factors, including postoperative prognosis. After reports JCOG9907, we treated eight cases with neoadjuvant chemotherapy at stages II and III. We examined Musashi‐1 staining for these eight cases.

Results:  Histological good response to NACRT group showed good prognosis. Lymph node metastasis is a predictive factor for prognosis. In this additional study, Musashi‐1 was positive after neoadjuvant chemotherapy in three cases. The histological response was grade 1 in all of them and recurrence was observed within a short period of time. Two cases of grade 3 were negative staining to Musashi‐1 and showed no recurrence.

Conclusions:  This study shows that NACRT plus surgery with three‐field lymphadenectomy is a feasible therapeutic approach for the cases with multiple lymph node metastases. Prognosis was significantly better in cases with marked histological improvement. It is important to find the predictive factors of histological improvement. Musashi‐1 might be a candidate maker for histological response and prognosis, and further studies are needed to prove it.
Endoscopic characteristics of short‐segment Barrett's esophagus, focusing on squamous islands and mucosal folds
Authors: Ishimura Norihisa , Amano Yuji , Uno Goichi , Yuki Takafumi , Ishihara Shunji , Kinoshita Yoshikazu
Published: April 2012

Background and Aim:  Endoscopic definitions of Barrett's esophagus (BE) vary among countries, mainly because of the difficulty in diagnosing short‐segment BE (SSBE) endoscopically. The aim of this study was to investigate whether the endoscopic identification of squamous islands and the specific position of columnar epithelium helps improve the diagnosis of SSBE.

Methods:  First, we prospectively enrolled 100 consecutive patients with SSBE and evaluated the number of identified squamous islands in the columnar epithelium with different modalities: white light (WL), narrow band imaging (NBI), and iodine chromoendoscopy. Second, in another group of 100 consecutive patients with tongue‐like SSBE, the correlation of the location of Barrett's mucosa to the esophageal longitudinal folds (ridge or valley) was evaluated endoscopically.

Results:  It was possible to detect squamous islands in 48, 71, and 75 patients by WL, NBI, and iodine chromoendoscopy, respectively. The detection rate of squamous islands by NBI or iodine chromoendoscopy was significantly superior to that by WL. Tongue‐like SSBEs were predominantly found on the ridge of mucosal folds (71%), similar to the location of mucosal breaks (84%).

Conclusions:  Squamous islands in the columnar epithelium were efficiently observed by NBI or iodine chromoendoscopy. SSBE was found more frequently on the ridges but not in the valleys of esophageal longitudinal mucosal folds. NBI endoscopic observation focusing on columnar epithelium with squamous islands on the ridges of distal esophageal folds may improve endoscopic detection of SSBE.
Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non‐risk allele colorectal cancer associated with insulin growth factor 2 receptor expression
Authors: Takahashi Yusuke , Mimori Koshi , Yamamoto Ken , Watanabe Masahiko , Tanaka Jun‐Ichi , Kudo Shin‐Ei , Sugihara Ken‐Ichi , Hase Kazuo , Mochizuki Hidetaka , Kusunoki Masato , Yamada Kazutaka , Shimada Yasuhiro , Moriya Yoshihiro , Mori Masaki
Published: April 2012

Background and Aim:  The incidence of both diabetes mellitus and hyperlipidemia is increasing and they are risk factors for colorectal cancer (CRC). On the other hand, the carcinogenic significance of the single nucleotide polymorphism (SNP), rs6983267 at 8q24, in CRC has been reported. The association between the SNP genotype and genes associated with diabetes or hyperlipidemia was investigated in cases of CRC.

Methods:  In 107 cases of CRC diagnosed in eight institutes from 2003 to 2008, array‐CGH and cDNA microarray was performed and the data analyzed from two groups subdivided according to SNP genotype.

Results:  In the array‐CGH data, we selected 38 genes related to diabetes or fat metabolism, and of these 10 had a correlation coefficient between the genome copy number at 8q24 locus and that of each gene. Of the 10 genes, insulin growth factor 2 receptor (IGF2R) was the only one with an expression level significantly associated with the 8q24 genotype. IGF2R expression was significantly lower in non‐risk allele than in risk allele cases (P = 0.012). There was neither a diabetes‐ nor a fat metabolism‐related gene that was significantly associated with CRC cases with the risk allele at 8q24.

Conclusions:  SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non‐risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC.
Intestinal cancers occurring in patients with Crohn's disease
Authors: Kamiya Toru , Ando Takafumi , Ishiguro Kazuhiro , Maeda Osamu , Watanabe Osamu , Hibi Satoshi , Mimura Shunya , Ujihara Masaki , Hirayama Yutaka , Nakamura Masanao , Miyahara Ryoji , Ohmiya Naoki , Goto Hidemi
Published: April 2012

Background and Aims:  The number of patients with Crohn's disease (CD) and the number of cases of intestinal cancer associated with CD have both been increasing in Japan. However, the number of reported cases is lower than for ulcerative colitis‐associated cancer. The aim of this study was to identify the clinical picture of CD‐associated intestinal cancer in a consecutive series of patients with CD and to stress the importance of surveillance.

Methods:  We enrolled 174 consecutive patients (130 men, 44 women, mean age 25 years) diagnosed with CD and investigated the development of intestinal cancer from October 1998 to July 2010. There were 104 cases of the ileocolitis type, 47 of ileitis, and 23 of colitis.

Results:  Intestinal cancer developed in two male patients (1.5% of the total), whose respective ages at onset of CD were 41 and 19 years, and 55 and 37 years at onset of cancer. Both cases were of ileocolitis‐type CD; one cancer developed in the rectum and the other in the small bowel, and both were accompanied by severe stricture. Histopathological results revealed well and moderately differentiated adenocarcinoma, respectively.

Conclusions:  Intestinal cancer developed in patients with ileocolitis‐type CD of more than 10 years' duration. Our findings suggest that patients with chronic, widespread CD should be under cancer surveillance.
Association of prostate‐specific antigen doubling time and cancer in men undergoing repeat prostate biopsy
Authors: Moreira Daniel M , Gerber Leah , Thomas Jean‐Alfred , Bañez Lionel L , McKeever Madeline G , Freedland Stephen J
Published: April 2012

Objectives:  To analyze the association between prostate‐specific antigen doubling time with prostate cancer risk and grade among men with prostate‐specific antigen levels ≥4.0 ng/mL undergoing repeat prostate biopsy.

Methods:  A total of 286 patients with prostate‐specific antigen ≥4 ng/mL and available prostate‐specific antigen doubling time data, who underwent repeat prostate biopsy from 1996–2009, were included in this analysis. Prostate‐specific antigen doubling time was divided into three groups: >9 years, 3–9 years and <3 years. Multivariate analyses of prostate‐specific antigen doubling time with cancer risk and grade (≤3 + 4 vs≥4 + 3) were carried out using logistic regression adjusting for prebiopsy prostate‐specific antigen, race, age, digital rectal examination, year of biopsy and number of prior negative biopsies.

Results:  The median prostate‐specific antigen doubling time before biopsy was 4.5 years (interquartile range = 2.5–10). Shorter prostate‐specific antigen doubling time was associated with higher prostate‐specific antigen (P < 0.001), but it was unrelated to age, digital rectal examination or race. Shorter prostate‐specific antigen doubling time as a continuous variable was associated with greater prostate cancer risk in both uni‐ (hazard ratio = 0.99, 95% confidence interval = 0.98–0.99, P = 0.001) and multivariate analysis (hazard ratio = 0.99, 95% confidence interval = 0.98–0.99, P = 0.004). The prevalence of cancer among prostate‐specific antigen doubling time groups (>9, 3–9, <3 years) was 17%, 37% and 40%, respectively. Shorter prostate‐specific antigen doubling time groups were associated with higher cancer risk (P = 0.001). Stratified by grade, short prostate‐specific antigen doubling time as a continuous variable significantly predicted both low‐ (P = 0.010) and high‐grade disease (P = 0.049). The inclusion of prostate‐specific antigen doubling time groups in a multivariate model to predict biopsy positivity increased its accuracy from 0.69 to 0.74.

Conclusion:  Prostate‐specific antigen doubling time seems to provide further cancer risk assessment in men undergoing repeat biopsy for prostate‐specific antigen ≥4.0 ng/mL. If validated in future studies, the present findings support the use of prostate‐specific antigen doubling time in the risk stratification of this patient population.
Unmet needs of people with end‐stage chronic obstructive pulmonary disease: recommendations for change in Australia
Authors: Crawford G. B. , Brooksbank M. A. , Brown M. , Burgess T. A. , Young M.
Published: April 2012

Background

Chronic obstructive pulmonary disease (COPD) is an increasing cause of mortality. However, people with COPD are unlikely to receive care that meets the needs of themselves or their carers at the end of life.

Aims

To explore the needs of people with end‐stage COPD in South Australia and develop recommendations for a model of care.

Methods

Three related studies were undertaken: in Study 1, 15 people with advanced COPD and their carers were interviewed twice, 6 months apart; Study 2 investigated views of an Expert Panel and Study 3 conducted focus groups and interviews with service providers and community groups to examine service availability and accessibility.

Results

This project demonstrated that the needs of people with COPD are not being met. There was an absence of a coordinated pathway for support. Care was fragmented, episodic and reactive. The role of carers was poorly recognised. Health professionals identified the lack of a clear transition to an end‐stage and significant barriers to obtaining support for activities of daily living. Communication issues were identified in all studies, including the absence of advance care planning conversations.

Conclusions

A flexible model of care is needed that assists people with COPD to navigate the health system. This should be patient centred and coordinated across primary, acute and community sectors. Neither respiratory nor palliative care services alone can adequately support people with COPD. The integration of a multidisciplinary palliative approach within a chronic disease management strategy will be central for the best care for people living with advanced COPD.