bluuebunny/crossref_metadata_2025 huggingface dataset:
Imagined Immigration: The Impact of Different Meanings of ‘Immigrants’ in Public Opinion and Policy Debates in Britain
Authors: Blinder Scott
Published: June 2013

Public opinion research on immigration attitudes has largely overlooked the question of how survey respondents understand the term ‘immigrants’. This article investigates latent perceptions of immigrants, termed ‘imagined immigration’, among members of the British public. Using novel survey data, I examine who members of the British public have in mind when they think of immigrants. I find that public perceptions of immigration diverge significantly from the set of people identified as immigrants in government statistics and targeted in policy changes. In particular, public perceptions focus on asylum seekers and permanent arrivals, while mostly ignoring international students, a target of new restrictive immigration policies. I also show that variation in individuals' imagined immigration is strongly associated with individual preferences for reduced immigration, suggesting imagined immigration as a new determinant of anti-immigration policy preferences to consider in future research.
The Salvation Army in Sweden and the Making of Gender — Conversion Narratives 1887–1918
Authors: Lundin Johan A.
Published: June 2013

This article discusses how Swedish Salvationists wrote about femininity and masculinity in conversion narratives during the period 1887–1918; the “breakthrough” of modern Sweden. Through their religious conversion female Salvationists adopted a femininity that demanded the same right to participate in religious life as men. In a similar manner, men in the Salvation Army achieved a changed masculinity through conversion, which allowed them to express feelings and cry in public. Doing so, these Salvationists expressed an unconscious or conscious criticism towards the prevailing values about gender in society.
The ‘Black Metropolis' in the American Urban System of the Early Twentieth Century: Harlem, Bronzeville and Beyond
Authors: Boyd Robert l.
Published: June 2013

By defining and measuring a dimension of the Black Metropolis in terms of occupational representation, this study advances research on the urban black communities of the early twentieth‐century United States. Census data show that: (1) Bronzeville (Chicago) was the premier Black Metropolis overall and the black communities of urban‐industrial centers in the Midwest had locational advantages that rivaled those of Harlem (New York) with respect to the rise of the black professional and entrepreneurial classes; (2) The standing of Harlem as a preeminent Black Metropolis was due mainly to opportunities generated by unique features of New York that aided blacks' entry into an extensive array of artistic, entertainment and mass media occupations; (3) The black community of Washington, DC, was the only substantial Black Metropolis below the Mason‐Dixon Line because of advantages that derived from the city's location above areas of the lower South and from its status as the capital of the US federal government; (4) In general, the northern Black Metropolis was characterized more by opportunities for blacks to participate in politics and public life and to create vital cultural institutions than by opportunities for blacks to economically gain through professions or businesses.
Effect of distillers dried grains with solubles diet supplemented with rumen‐protected lysine and methionine on milk production and milk amino acids in the lactating cow
Authors: Li Wenbo , Chang Qifa , Liu Gang , Shan Anshan , Li Feng
Published: June 2013

This study was to quantify the milk protein and amino acids (AA) in response to rumen‐protected lysine (Lys) and methionine (Met) supplementation in dairy cows fed distillers dried grains with solubles (DDGS) diet. Forty cows were divided into five dietary treatments: soybean meal diet (SM),DDGSdiet andDDGSdiets with 40 g/dayLys (DL), 20 g/ dayMet dry matter (DM) and 20 g/ dayMet plus 40 g/ dayLys (DLM), separately. Compared withSM,DLandDMgroups,DLMgroup increased milk yield, 4% fat‐corrected milk, energy‐corrected milk yield and protein in milk.DDGStreatments increased totalAAand the essentialAAin milk. Results indicated that dietaryDDGSincreased intestinal supplies of Lys and Met.
Quantitative and Qualitative Variation of Fat in Model Vanilla Custard Desserts: Effects on Sensory Properties and Consumer Acceptance
Authors: Tomaschunas Maja , Köhn Ehrhard , Bennwitz Petra , Hinrichs Jörg , Busch‐Stockfisch Mechthild
Published: June 2013

The effects of variation in fat content (0.1% to 15.8%) and type of fat, using different types of milk, dairy cream, or vegetable fat cream, on sensory characteristics and consumer acceptance of starch‐based vanilla model custards were studied. Descriptive analysis with trained panelists and consumer testing with untrained assessors were applied. Descriptive data were related to hedonic data using principal component analysis to determine drivers of liking and disliking. Results demonstrated an increasing effect of fat concerning visual and oral thickness, creamy flavor, and fat‐related texture properties, as well as a decreasing effect concerning yellow color and surface shine. A lack of fat caused moderate intensities in pudding‐like flavor attributes and an intensive jelly texture. Adding a vegetable fat cream led to lower intensities in attributes yellow color, cooked flavor, thick, and jelly texture, whereas intensities in vegetable fat flavor and fat‐related texture properties increased. All consumers favored custards with medium fat contents, being high in pudding‐like and vegetable fat flavor as well as in fat‐related texture attributes. Nonfat custards were rejected due to jelly texture and moderate intensities in pudding‐flavor attributes. High‐fat samples were liked by some consumers, but their high intensities in thickness, white color, and creamy flavor also drove disliking for others.
Garlic Oil Suppressed the Hematological Disorders Induced by Chemotherapy and Radiotherapy in Tumor‐Bearing Mice
Authors: Zeng Tao , Li Yang , Zhang Cui‐Li , Yu Li‐Hua , Zhu Zhen‐Ping , Zhao Xiu‐Lan , Xie Ke‐Qin
Published: June 2013

Although the anticancer effects of garlic and its products have been demonstrated by a variety of studies; however, few studies were conducted to investigate the effects of garlic on the adverse effects of chemo/radiotherapy. In order to clarify the above question and make a more comprehensive understanding of the anticancer effects of garlic, tumor xenograft mice model was established by subcutaneous injection of H22 tumor cells, and was used for the investigation of effects of garlic oil (GO) on the chemo/radiotherapy. In the chemotherapy test, tumor‐bearing mice were treated with cyclophosphamide (CTX) or CTX plus GO (25 or 50 mg/kg bw) for 14 d, while the mice received a single 5 Gy total body radiation or radiation plus GO (25 or 50 mg/kg bw) in radiotherapy test. The results showed that GO did not increase the tumor inhibitory rate of CTX/radiation, which indicated that GO could not enhance the chemo/radiosensitivity of cancer cells. However, the decrease of the peripheral total white blood cells (WBCs) count induced by CTX/radiation was significantly suppressed by GO cotreatment. Furthermore, GO cotreatment significantly inhibited the decrease of the DNA contents and the micronuclei ratio of the bone marrow. Lastly, the reduction of the endogenous spleen colonies induced by CTX/radiation was significantly suppressed by GO cotreatment. These findings support the idea that GO consumption may benefit for the cancer patients receiving chemotherapy or radiotherapy.
Willingness to take drugs to prevent serious chronic diseases (自愿服用药物以预防严重的慢性疾病)
Authors: Jerzak Katarzyna J. , Pallan Shelley , Gerstein Hertzel C.
Published: June 2013

Background

The aim of this study was to determine an individual's willingness to take a preventive therapy for each of two chronic diseases (type 2 diabetes [T2D] and dementia) when provided with varying likelihoods of acquiring the disease.

Methods

After reading a description of two chronic diseases (i.e. T2D and dementia), 345 student volunteers at McMaster University rated their likelihood of taking a drug that could halve their chance of developing each disease, assuming a 1‐year risk of developing the disease of 50%, 25%, and 10%. A five‐point Likert scale was used to collect responses.

Results

Assuming an annual incidence of 50%, 27% of respondents were neither likely nor very likely to take a therapy that halved the annual incidence of T2D and 13% were neither likely nor very likely to take a therapy that halved the annual incidence of dementia. Higher quoted incidence rates of the disease and a personal history of a chronic illness significantly increased willingness to take such therapy.

Conclusions

A high proportion of young educated adults have ambivalent or negative attitudes regarding the use of pharmacological therapy to prevent serious health outcomes even when the absolute 1‐year risk of these outcomes is very high.
Resting energy expenditure in subjects with fibro‐calculous pancreatic diabetes (胰腺纤维钙化性糖尿病患者的静息时能量消耗)
Authors: Behera Kishore Kumar , Joseph Mini , Shetty Sudeep Krishna , Chacko Ashok , Sahoo Manoj Kumar , Mahendri Narayani V , Nair Veena , Nadig Shweta , Thomas Nihal
Published: June 2013

Background

Fibro‐calculous pancreatic diabetes is an indigenous disorder present in populations largely in tropical regions. Energy expenditure through indirect calorimetry has not been studied in this disorder and may provide important clues as to the pathogenesis of diabetes in these patients.

Methods

A total of 51 males in three groups comprising fibrocalculous pancreatic diabetes (FCPD) (group 1; n = 24), type 2 diabetes (group 2; n = 15) and healthy controls (group 3; n = 12) were studied. The body composition was measured using Dual Energy X‐ray Absorptiometry (DEXA) and the REE was estimated using indirect calorimetry. The predicted energy expenditure (PEE) was calculated using three different equations.

Results

Patients in both groups with diabetes had a higher mean waist‐hip ratio than the controls (P = 0.002). However patients with type 2 diabetes alone had a significantly higher mean body mass index (P = 0.012), percentage of fat (P = 0.016) and total fat content (P = 0.031). There was no significant difference in REE among the three groups. After adjustment of body mass index (BMI), the REE was significantly higher in patients with FCPD than in those patients with Type 2 diabetes. PEE correlated poorly with indirect calorimetry.

Conclusions

Energy expenditure in patients with diabetes varies according to the composition and distribution of body fat and is lower in patients with FCPD. Standard predictive equations were not accurate for the assessment of energy expenditure in patients with FCPD. Further research is required to recommend specific nutritional therapy for this group of patients.
The Shugborough Dinner Service and Its Significance for Sino‐British History
Authors: MCDOWALL STEPHEN
Published: June 2013

Tradition has it that the Shugborough dinner service was presented to Commodore Anson (1697‐1762) by the European merchants of Canton in gratitude for his crew's part in extinguishing a fire that threatened the city in 1743, and the service has come to symbolise the ultimate triumph of this courageous and determined commodore over dithering and obstructive Chinese mandarins. This article argues that the link between the dinner service and the fire is actually a twentieth‐century invention, and that its story, as currently presented to us, distorts our understanding both of Canton in 1743 and of mid‐eighteenth‐century Sino‐British relations more generally.
No effect of acute tryptophan depletion on phosphodiesterase inhibition–related improvements of short‐term object memory in maleWistar rats
Authors: van Donkelaar E. L. , Prickaerts J. , Akkerman S. , Rutten K. , Steinbusch H. W. M. , Blokland A.
Published: June 2013

Objective

To further explore the implication of the serotonin (5‐HT) system in the improvement of rat short‐term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE‐I)BAY60‐7550 and the type 5PDE‐I vardenafil, the effect ofPDE2 andPDE5 inhibition upon central amino acid levels, 5‐HT, and related parameters were measured after applying acute tryptophan depletion (ATD).

Method

Wistar rats were orally administered saline or a protein–carbohydrate mixture with or without tryptophan (TRP).TRP‐depleted animals additionally received an oral vehicle injection or thePDEinhibitorsBAY60–7550 or vardenafil at a dose known to improve object memory performance.

Results

AlthoughATDsignificantly decreasedTRPlevels in the hippocampus 2 h after administration, 5‐HTlevels appeared only moderately affected, without any changes observed in the amount of 5‐HIAAor 5‐HTturnover rate. Moreover, no effects ofPDEinhibition upon 5‐HTor related parameters were observed.

Conclusion

Changes in 5‐HTneurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability ofPDEinhibitors to improve short‐term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underliesATD‐induced object memory deficits, most likely due to decrease inNOsynthesis.
‘HAPI’ life model for the new older generation in Korea
Authors: Kim Jeeyeon
Published: June 2013

Aim

The aim of this study was to estimate the overall success of services at Gangnam Senior Plaza (GSP), determine the effect of GSP on users, and ascertain local demand for services.

Methods

A 4‐week survey including 1188 participants aged over 50 years old was conducted. Participants included 498 GSP members and 690 older non‐members (Gangnam residents). Six GSP members were interviewed to substantiate the survey findings.

Results

Survey findings indicated high level of user satisfaction in terms of accessibility to services and facilities, availability of community services and educational programs, staff friendliness and facility cleanliness. GSP service delivery can be further improved by involving highly educated and experienced older people.

Conclusion

Health promotion, education and recreation activities inspiring a vibrant lifestyle have been recognised as the success factors for GSP service delivery. Thus, GSP can be considered a model for other welfare services in South Korea.
Perfusion index in the very preterm infant
Authors: Kinoshita Meredith , Hawkes Colin Patrick , Ryan C Anthony , Dempsey Eugene Michael
Published: June 2013

Aim

Perfusion Index (PI) is a quantifiable measurement of peripheral perfusion and may be a useful adjunct to the assessment of circulatory status in the newborn. (i) To assess reproducibility of PI and (ii) To determine whether there is a difference between simultaneously obtained limb measurements of PI in newborns <32 weeks GA in the transitional period.

Methods

Perfusion Index was measured in newborns <32 weeks during the first 48 h of life. To examine reproducibility, the pulse oximetry probe was replaced on the same limb consecutively by the same operator. Upper and lower limbs were then simultaneously evaluated over a 5‐min period. Heart rate, blood pressure, birth weight, ventilation requirement, inotrope use, lactate, PCO2 and CRIB‐II score were also recorded.

Results

Thirty infants were assessed. Intraclass correlation coefficient for reproducibility in the same limb was high (r value = 0.982 p < 0.001). Measurements obtained in the right upper limb were consistently higher than either lower limb. The median (IQR) PI for the entire cohort was 0.70 (0.29–1.35). No correlation existed between gestational age, birth weight, CRIB scores, systolic and diastolic blood pressure, mean blood pressure and median PI values.

Conclusion

Perfusion Index measurement is reproducible, and values are highest in the right upper limb. Wide differences between right upper and lower limb readings are most likely related to transitional circulatory changes.
Visigothic Jewellery: A Technical Study of Glass Used as Gems in Belt Buckles from a Spanish Necropolis
Authors: Ventolà L. , Vendrell‐Saz M. , Giráldez P.
Published: June 2013

In this work, we studied coloured and colourless glass used as gems in Visigothic buckles possibly originating from the necropolises of Torredonjimeno, Duraton or Castilltierra in Spain. Scanning electron microscopy (SEM) with energy‐dispersive analysis (EDS) and observations made with an optical microscope in reflected and transmission mode were performed in order to establish the composition, origin of the colour and decay process of these glass pieces. The chemical analysis of ancient glass can provide relevant information regarding the manufacturing approach used during a specific period. The results revealed the presence of various transition metal elements used as chromophore elements, as well as some metallic backing foils used to improve the colour of pieces of almost colourless glass.
A genetic algorithm based global search strategy for population pharmacokinetic/pharmacodynamic model selection
Authors: Sale Mark , Sherer Eric A.
Published: June 2013

The current algorithm for selecting a population pharmacokinetic/pharmacodynamic model is based on the well‐established forward addition/backward elimination method. A central strength of this approach is the opportunity for a modeller to continuously examine the data and postulate new hypotheses to explain observed biases. This algorithm has served the modelling community well, but the model selection process has essentially remained unchanged for the last 30 years. During this time, more robust approaches to model selection have been made feasible by new technology and dramatic increases in computation speed. We review these methods, with emphasis on genetic algorithm approaches and discuss the role these methods may play in population pharmacokinetic/pharmacodynamic model selection.
CYP3A activity in severe liver cirrhosis correlates with Child–Pugh and model for end‐stage liver disease (MELD) scores
Authors: Albarmawi Albader , Czock David , Gauss Annika , Ehehalt Robert , Lorenzo Bermejo Justo , Burhenne Jürgen , Ganten Tom M. , Sauer Peter , Haefeli Walter E.
Published: June 2013

Aims

Impaired liver function often necessitates drug dose adjustment to avoid excessive drug accumulation and adverse events, but a marker for the extent of the required adjustment is lacking. The aim of this study was to investigate whether Child–Pugh (CP) and model for end‐stage liver disease (MELD) scores correlate with drug clearance.

Methods

Midazolam was used as a CYP3A probe and its pharmacokinetics were analyzed in 24 patients with mild to severe liver cirrhosis (n = 4, 10 and 10 with CP class A, B and C, respectively) and six patients without liver disease.

Results

Both scores correlated well with unbound midazolam clearance (CLu), unbound midazolam fraction and half‐life (all P < 0.01), whereas the unbound steady‐state volume of distribution was not significantly changed. In patients with severe liver cirrhosis unbound midazolam clearance was only 14% of controls (CP C: CLu = 843 ± 346 l h−1, MELD ≥ 15: CLu = 805 ± 474 l h−1, controls: CLu = 5815 ± 2649 l h−1, P < 0.01).

Conclusion

The correlation with unbound midazolam clearance suggests that either score predicts the metabolic capacity of CYP3A, the most relevant drug metabolizing enzyme subfamily in humans.
Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics
Authors: Kuru Timur H. , Wadhwa Karan , Chang Richard Tsung Meng , Echeverria Lina Maria Carmona , Roethke Matthias , Polson Alexander , Rottenberg Giles , Koo Brendan , Lawrence Edward M. , Seidenader Jonas , Gnanapragasam Vincent , Axell Richard , Roth Wilfried , Warren Anne , Doble Andrew , Muir Gordon , Popert Rick , Schlemmer Heinz‐Peter , Hadaschik Boris A. , Kastner Christof
Published: June 2013

Objectives

To define terms and processes and agree on a minimum dataset in relation to transperineal prostate biopsy procedures and enhanced prostate diagnostics.

To identify the need for further evaluation and establish a collaborative research practice.

Patients and Methods

A 19‐member multidisciplinary panel rated 66 items for their appropriateness and their definition to be incorporated into the international databank using the Research and Development/University of California Los Angeles Appropriateness Method.

The item list was developed from interviews conducted with healthcare professionals from urology, radiology, pathology and engineering.

Results

The panel agreed on 56 items that were appropriate to be incorporated into a prospective database.

In total, 10 items were uncertain and were omitted. These items were within the categories: definitions (n = 2), imaging (n = 1), surgical protocols (n = 2) and histology (n = 5).

Conclusions

The components of a minimum dataset for transperineal prostate biopsy have been defined.

This provides an opportunity for multicentre collaborative data analysis and technique development.

The findings of the present study will facilitate prospective studies into the application and outcome of transperineal prostate biopsies.
Rationally Designed Sulfamides as Glutamate Carboxypeptidase II Inhibitors
Authors: Choy Cindy J. , Fulton Melody D. , Davis Austen L. , Hopkins Mark , Choi Joseph K. , Anderson Marc O. , Berkman Clifford E.
Published: June 2013

Glutamate carboxypeptidase II (GCPII) is a membrane‐bound cell surface peptidase. There is significant interest in the inhibition of GCPII as a means of neuroprotection, while GCPII inhibition as a method to treat prostate cancer remains a topic of further investigation. The key zinc‐binding functional group of the well‐characterized classes of GCPII inhibitors (phosphonates and phosphoramidates) is tetrahedral and negatively charged at neutral pH, while glutamyl urea class of inhibitors possesses a planar and neutral zinc‐binding group. This study explores a new class of GCPII inhibitors, glutamyl sulfamides, which possess a putative net neutral tetrahedral zinc‐binding motif. A small library containing six sulfamides was prepared and evaluated for inhibitory potency against purified GCPII in an enzymatic assay. While most inhibitors have potencies in the micromolar range, one showed promising sub‐micromolar potency, with the optimal inhibitor in this series being aspartyl–glutamyl sulfamide (2d). Lastly, computational docking was used to develop a tentative binding model on how the most potent inhibitors interact with the ligand‐binding site of GCPII.
The prognostic significance of APC gene mutation and miR‐21 expression in advanced‐stage colorectal cancer
Authors: Chen T.‐H. , Chang S.‐W. , Huang C.‐C. , Wang K.‐L. , Yeh K.‐T. , Liu C.‐N. , Lee H. , Lin C.‐C. , Cheng Y.‐W.
Published: June 2013

Aim

Colorectal cancer (CRC) is the second commonest cause of cancer death in Taiwan. Although numerous genes have been associated with tumorigenesis in colorectal cancer, only a few have been validated and used as biomarkers for predicting clinical outcome. The aim of this study was to analyse the association of APC gene mutation and miR‐21 expression with clinical outcome in CRC patients.

Method

In total, 195 colorectal cancer patients were enrolled in a single medical centre between 2003 and 2007. APC gene mutation and expression of APC and miR‐21 were analysed by direct DNA sequencing and real‐time reverse transcription polymerase chain reaction. The primary outcome included 5‐year overall survival and univariate (Kaplan–Meier) and multivariate (Cox regression) analyses of prognostic factors.

Results

The results showed that 66 (33.8%) of 195 tumour tissues contained an APC mutation. The predominant APC gene variations were deletion mutations (50.0%). APC gene expression was low in CRC and negatively correlated with miR‐21 expression and gene mutation. In advanced‐stage cancer, patients with APC mutation/high miR‐21 had poorer overall survival rates than those with APC mutation/low miR‐21, APC wild‐type/high miR‐21 and APC wild‐type/low miR‐21.

Conclusion

In Taiwan, downregulation of the APC gene in CRC correlated with gene mutation and miR‐21 upregulation. APC mutation and miR‐21 expression could be used to predict the clinical outcome of CRC, especially in patients with advanced disease.
Comparison of three‐dimensional high‐resolution manometry and endoanal ultrasound in the diagnosis of anal sphincter defects
Authors: Vitton V. , Ben Hadj Amor W. , Baumstarck K. , Behr M. , Bouvier M. , Grimaud J.‐C.
Published: June 2013

Aim

Three‐dimensional high‐resolution anorectal manometry (3D HRAM) is a new technique that can simultaneously provide physiological and topographical data. Our aim was to assess whether it can identify anal sphincter defects by comparing it with endoanal ultrasonography (EUS) considered as the gold standard.

Method

An anal defect on 3D HRAM was defined as a continuous circumferential area over which the pressure was < 10 mmHg during the measurement of anal resting and voluntary contraction pressure. Inter‐observer agreement was also assessed.

Results

A total of 100 patients (93 females) with a mean age of 53.5 ± 15.3 years were included. The positive diagnosis of an anal sphincter defect using 3D HRAM and EUS was in agreement (59.3%) (κ = 0.419) of the time for the internal anal sphincter (IAS) and (55.9%) (κ = 0.461) for the external anal sphincter (EAS). The inter‐observer agreement for a diagnosis of an anal sphincter defect was (100%) (κ = 0.937) for the IAS and (95%) (κ = 0.751) for the EAS. The intra‐class correlation coefficient for the extent of the defect was 0.853 for the IAS and 0.651 for the EAS.

Conclusion

The preliminary results demonstrate some level of agreement in the diagnosis of anal sphincter defects between 3D HRAM and EUS but insufficient for 3D HRAM to be adequately reliable using the criteria chosen. The excellent inter‐observer agreement, however, demonstrates that 3D HRAM is reproducible and provides a new dimension for the evaluation of sphincter function.
Phospho‐mTOR is not upregulated in metastatic SDHB paragangliomas
Authors: Ghayee Hans K. , Giubellino Alessio , Click Arielle , Kapur Payal , Christie Alana , Xie Xian‐Jin , Martucci Victoria , Shay Jerry W. , Souza Rhonda F. , Pacak Karel
Published: June 2013

Background

Pheochromocytomas (PCCs)/paragangliomas (PGLs) are neuroendocrine tumours that may cause arrhythmia and death if untreated. Treatment for patients with metastatic tumours is lacking. As new PCC/PGL susceptibility genes are discovered that are associated with the mTOR pathway, treatment targets focusing on this pathway are being intensively explored.

Design

Twenty‐one human PCC/PGLs were analysed from two tertiary care centres. Immunohistochemistry (IHC) analysis was performed for phospho‐mTOR (pmTOR), phospho‐S6K (pS6K), phosphoinositide 3‐kinase (PI3K), phospho‐4EBP1 (p4EBP1), HIF1α and MIB‐1 in 6 metastatic SDHB PCC/PGLs, 15 nonmetastatic PCC/PGLs, (including 1 TMEM127 PCC and 1 nonmetastatic SDHB PGL) and 6 normal adrenal medullas. The product of the intensity of stain and percentage of cells stained was calculated as an H score.

Results

Using a two‐sample t‐test and paired t‐test, pmTOR and pS6K had significantly higher H scores in nonmetastatic PCC/PGLs than in metastatic SDHB PCC/PGLs. HIF1α had significantly higher H scores in metastatic SDHB PCC/PGLs compared with nonmetastatic PCC/PGLs and normal adrenal medulla. No difference in H scores was seen with p4EBP1, PI3K and MIB‐1 when comparing metastatic SDHB PCC/PGLs and nonmetastatic PCC/PGLs. Significantly higher difference in pS6K was seen in normal adrenal medullas compared to nonmetastatic PCC/PGLs and metastatic SDHB PCC/PGLs.

Conclusion

The present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/PGLs may not achieve good therapeutic efficacy in patients.
Variation in duration of untreated psychosis in an 18‐year perspective
Authors: ten Velden Hegelstad Wenche , Joa Inge , Barder Helene , Evensen Julie , Haahr Ulrik , Johannessen Jan O. , Langeveld Johannes , Melle Ingrid , Opjordsmoen Stein , Røssberg Jan Ivar , Rund Bjørn Rishovd , Simonsen Erik , Vaglum Per , McGlashan Thomas , Friis Svein , Larsen Tor K.
Published: June 2013

Aim

The Scandinavian TIPS project engineered an early detection of psychosis programme that sought to reduce the duration of untreated psychosis (DUP) through early detection teams and extensive information campaigns since 1997. In 1997–2000, DUP was reduced from 26 to 4.5 weeks median. The programme was continued beyond the initial project in modified forms for over 13 years. The aim of this study was to track the vicissitudes of DUP over an 18‐year period (1993–2010) with differing early detection efforts in a defined catchment area.

Method

The DUP of all patients meeting criteria for first episode psychosis was measured 1993–1994 and from 1997 to 2010 in a naturalistic long‐term study. DUP values of all patients were included, irrespective of patients' participation in a clinical follow‐up study, yielding a highly representative sample.

Results

DUP varied across studies with differing information campaign intensity and content. These variations will be described and explored.

Conclusions

Early detection campaigns should have a stable focus and high intensity level. Future research should further elucidate pathways to care in order to establish principal targets for information campaigns.
Prospective study of the course of delusional themes in first‐episode non‐affective psychosis
Authors: Ellersgaard Ditte , Mors Ole , Thorup Anne , Jørgensen Per , Jeppesen Pia , Nordentoft Merete
Published: June 2013

Aim

The stability of delusional themes in psychotic disorders is only sparsely lit. The study aims to investigate the stability of delusional themes over a period of time in patients with first‐episode non‐affective psychosis.

Methods

The data were drawn from a randomized controlled trial of 547 first‐episode patients with schizophrenia spectrum disorders, the OPUS trial. A subsample of 411 patients met our inclusion criteria. They were interviewed at the time of first treatment contact, and at years 1, 2 and 5 after onset. The delusional themes of the 411 patients were classified by applying principal component analysis to the patients' scores on 12 items of delusions from the Scale for the Assessment of Positive Symptoms in Schizophrenia, SAPS. The course of the patients' predominant delusional themes was analysed afterwards.

Results

The 12 delusional themes from SAPS were converted into five groups using principal component analysis. At all three follow ups there were almost equal proportions of patients with the predominant delusion being from the same group of delusional themes as at baseline and of patients with the predominant delusion being from another group of delusional themes than at baseline.

Conclusions

The predominant delusional theme at the time of first treatment contact was seen to be only of some predictive value to the predominant delusional theme at the later follow‐up points in patients with first‐episode non‐affective psychosis. This stresses the importance of a systematic assessment of different delusional themes in the continued monitoring of early signs of psychotic relapse and at each psychotic episode.
Attitudes of patients and clinicians in relation to the at‐risk state for psychosis
Authors: Welsh Patrick , Tiffin Paul A.
Published: June 2013

Aim

In the last decade, advances have been made in identifying young people who may be at relatively high risk (HR) of developing psychosis. Given the controversial and experimental nature of the HR concept, the attitudes and experiences of mental health professionals and patients are likely to influence practice in this area. Previous work has been published that has speculated on the potential risks and advantages of identifying and intervening within the HR state. However, few have attempted to capture the attitudes and experiences of patients and professionals towards this concept. This article provides, via the collation of existing research reports, a reflection on the views, attitudes and experiences of these key stakeholders.

Methods

A narrative review of the literature was undertaken focussing upon the following key areas: mental health professionals’ attitudes towards the HR concept, patients’ attitudes towards the HR concept, attitudes of patients towards potential treatments and attitudes of professionals towards HR treatments.

Results

Relatively few published studies focusing on the attitudes and experiences of patients and mental health professionals exist. However, there is some evidence that both professionals and affected individuals view the HR concept as worthy of diagnosis and intervention. Expressed treatment preferences appear to vary, dependent on the group of individuals surveyed.

Conclusions

Further systematic studies of patient and professional preferences, in relation to identification and intervention, are desirable in order to explore the way that the HR denotation is personally interpreted and the extent to which it affects patient and practitioner behaviour.
Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification
Authors: Wolfe Devin M. , Lee Ju‐hyun , Kumar Asok , Lee Sooyeon , Orenstein Samantha J. , Nixon Ralph A.
Published: June 2013

Autophagy is a lysosomal degradative process which recycles cellular waste and eliminates potentially toxic damaged organelles and protein aggregates. The important cytoprotective functions of autophagy are demonstrated by the diverse pathogenic consequences that may stem from autophagy dysregulation in a growing number of neurodegenerative disorders. In many of the diseases associated with autophagy anomalies, it is the final stage of autophagy–lysosomal degradation that is disrupted. In several disorders, including Alzheimer's disease (AD), defective lysosomal acidification contributes to this proteolytic failure. The complex regulation of lysosomal pH makes this process vulnerable to disruption by many factors, and reliable lysosomal pH measurements have become increasingly important in investigations of disease mechanisms. Although various reagents for pH quantification have been developed over several decades, they are not all equally well suited for measuring the pH of lysosomes. Here, we evaluate the most commonly used pH probes for sensitivity and localisation, and identify LysoSensor yellow/blue‐dextran, among currently used probes, as having the optimal profile of properties for measuring lysosomal pH. In addition, we review evidence that lysosomal acidification is defective in AD and extend our original findings, of elevated lysosomal pH in presenilin 1 (PS1)‐deficient blastocysts and neurons, to additional cell models of PS1 and PS1/2 deficiency, to fibroblasts from AD patients with PS1 mutations, and to neurons in the PS/APP mouse model of AD.
Aging and neurogenesis in the adult forebrain: what we have learned and where we should go from here
Authors: Hamilton Laura K. , Joppé Sandra E. , M. Cochard Loїc , Fernandes Karl J. L.
Published: June 2013

In the brains of adult vertebrates, including humans, neurogenesis occurs in restricted niches where it maintains cellular turnover and cognitive plasticity. In virtually all species, however, aging is associated with a significant decline in adult neurogenesis. Moreover, an acceleration of neurogenic defects is observed in models of Alzheimer's disease and other neurodegenerative diseases, suggesting an involvement in aging‐ and disease‐associated cognitive deficits. To gain insights into when, how and why adult neurogenesis decreases in the aging brain, we critically reviewed the scientific literature on aging of the rodent subventricular zone, the neurogenic niche of the adult forebrain. Our analysis revealed that deficits in the neurogenic pathway are largely established by middle age, but that there remains striking ambiguity in the underlying mechanisms, especially at the level of stem and progenitor cells. We identify and discuss several challenging issues that have contributed to these key gaps in our current knowledge. In the future, addressing these issues should help untangle the interactions between neurogenesis, aging and aging‐associated diseases.
Alterations in hippocampal network oscillations and theta–gamma coupling arise before Aβ overproduction in a mouse model of Alzheimer's disease
Authors: Goutagny Romain , Gu Ning , Cavanagh Chelsea , Jackson Jesse , Chabot Jean‐Guy , Quirion Rémi , Krantic Slavica , Williams Sylvain
Published: June 2013

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by memory impairments. Brain oscillatory activity is critical for cognitive function and is altered in AD patients. Recent evidence suggests that accumulation of soluble amyloid‐beta (Aβ) induces reorganization of hippocampal networks. However, whether fine changes in network activity might be present at very early stages, before Aβ overproduction, remains to be determined. We therefore assessed whether theta and gamma oscillations and their cross‐frequency coupling, which are known to be essential for normal memory function, were precociously altered in the hippocampus. Electrophysiological field potential recordings were performed using complete hippocampal preparations in vitro from young transgenic CRND8 mice, a transgenic mouse model of AD. Our results indicate that a significant proportion of 1‐month‐old TgCRND8 mice showed robust alterations of theta–gamma cross‐frequency coupling in the principal output region of the hippocampus, the subiculum. In addition we showed that, compared to controls, these mice expressed negligible levels of Aβ. Finally, these network alterations were not due to genetic factors as 15‐day‐old animals did not exhibit theta–gamma coupling alterations. Thus, initial alterations in hippocampal network activity arise before Aβ accumulation and may represent an early biomarker for AD.
Calorie restriction alleviates the age‐related decrease in neural progenitor cell division in the aging brain
Authors: Park June‐Hee , Glass Zachary , Sayed Kasim , Michurina Tatyana V. , Lazutkin Alexander , Mineyeva Olga , Velmeshev Dmitry , Ward Walter F. , Richardson Arlan , Enikolopov Grigori
Published: June 2013

Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age‐related cognitive deficits. Restriction of calorie intake and prolonged treatment with rapamycin have been shown to extend the lifespan of animals and delay the onset of the age‐related decline in tissue and organ function. Using a reporter line in which neural stem and progenitor cells are marked by the expression of green fluorescent protein (GFP), we examined the effect of prolonged exposure to calorie restriction (CR) or rapamycin on hippocampal neural stem and progenitor cell proliferation in aging mice. We showed that CR increased the number of dividing cells in the dentate gyrus of female mice. The majority of these cells corresponded to nestin–GFP‐expressing neural stem or progenitor cells; however, this increased proliferative activity of stem and progenitor cells did not result in a significant increase in the number of doublecortin‐positive newborn neurons. Our results suggest that restricted calorie intake may increase the number of divisions that neural stem and progenitor cells undergo in the aging brain of females.
A dual‐porous, inverse model of water retention to study biological and hydrological interactions in soil
Authors: Laudone G. M. , Matthews G. P. , Gregory A. S. , Bird N. R. A. , Whalley W. R.
Published: June 2013

The deterministic modelling of bio‐hydrological processes in soil requires a void structure model that is explicitly dual‐porous containing fully and separately characterized macroporosity and microporosity. It should also contain information that relates the positioning of microporosity relative to macroporosity. An example of such a process is the production of nitrous oxide, in which bacteria in microporous ‘hot‐spots’ are supplied with nutrients and gases through a macroporous pathway. We present a precision void‐structure model that satisfies these two criteria, namely explicit macroporosity and microporosity, and their positional relationship. To demonstrate the construction of the model, we describe the modelling of a single soil, namely Warren soil from Rothamsted Research's Woburn Experimental Farm in Bedfordshire, UK, although the modelling approach is applicable to a wide range of soils and other dual porous solids. The model is capable of fitting several fundamental properties of soil, namely water retention, aggregate size distribution, and porosity of the microporous and macroporous zones. It comprises a dendritic critical percolation path, around which are clustered the microporous regions. The saturated hydraulic conductivity of the dual‐porous network is of the correct order of magnitude for a soil of the same density and texture as the Warren sample. Finally, we demonstrate how the preferential flow pathway in the resulting structure differs from the critical percolation pathway, and that only 4.6% by volume of the unclogged macroporosity contributes to the fluid flow through the structure.
Setting Standards for English Foreign Language Assessment: Methodology, Validation, and a Degree of Arbitrariness
Authors: Tiffin‐Richards Simon P. , Anand Pant Hans , Köller Olaf
Published: June 2013

Cut‐scores were set by expert judges on assessments of reading and listening comprehension of English as a foreign language (EFL), using the bookmark standard‐setting method to differentiate proficiency levels defined by the Common European Framework of Reference (CEFR). Assessments contained stratified item samples drawn from extensive item pools, calibrated using Rasch models on the basis of examinee responses of a German nationwide assessment of secondary school language performance. The results suggest significant effects of item sampling strategies for the bookmark method on cut‐score recommendations, as well as significant cut‐score judgment revision over cut‐score placement rounds. Results are discussed within a framework of establishing validity evidence supporting cut‐score recommendations using the widely employed bookmark method.
Phosphatidylinositol 3‐kinases inhibitor LY294002 potentiates the cytotoxic effects of doxorubicin, vincristine, and etoposide in a panel of cancer cell lines
Authors: Badinloo Marzieh , Esmaeili‐Mahani Saeed
Published: June 2013

Many novel therapeutic approaches to overcome chemoresistance have involved targeting specific signaling pathways such as the phosphatidylinositol 3‐kinase (PI3K) pathway. PI3K is a known stress response pathway which is involved in the regulation of cell survival, apoptosis, and growth. Inhibition of this pathway may possibly restore or augment the effectiveness of chemotherapy. Using three human malignant cell lines, we examined the effects of LY294002 (PI3K inhibitor) on chemotherapeutic agent‐induced apoptosis and cytotoxicity. An antimicrotubule agent vincristine, a topoisomerase II inhibitor etoposide, and a DNA cross‐linking agent doxorubicin were used accompanied with LY294002. Cell viability was determined by MTT assay, and the induction of apoptosis was assessed by immunoblotting of caspase‐3. Blocking the PI3K/Akt cascade with a PI3K inhibitor LY294002 (10 μM) increased the cytotoxic effect of vincristine and doxorubicin on SK‐OV‐3 cell line. Furthermore, LY294002 showed a greater promoting effect in etoposide‐ and doxorubicin‐induced cytotoxicity on MDA‐MB‐468 and A549 cells. The quantity of cleaved caspase‐3 in cancer cells that had combination therapy was increased compared with that in the cells treated with each drug alone. We suggest that inhibitors of the PI3K/Akt pathway in combination with chemotherapeutic agents may induce cell death effectively and be a potent modality to treat various types of cancer. The effectiveness of such combination therapy is depending to the used cell line and class of anticancer drug.
Increased temperature reduces herbivore host‐plant quality
Authors: Bauerfeind Stephanie S. , Fischer Klaus
Published: June 2013

Globally increasing temperatures may strongly affect insect herbivore performance, as their growth and development is directly linked to ambient temperature as well as host‐plant quality. In contrast to direct effects of temperature on herbivores, indirect effects mediated via thermal effects on host‐plant quality are only poorly understood, despite having the potential to substantially impact performance and thereby to alter responses to the changing climatic conditions. We here use a full‐factorial design to explore the direct (larvae were reared at 17 °C or 25 °C) and indirect effects (host plants were reared at 17 °C or 25 °C) of temperature on larval growth and life‐history traits in the temperate‐zone butterfly Pieris napi. Direct temperature effects reflected the common pattern of prolonged development and increased body mass at lower temperatures. At the higher temperature, efficiency of converting food into body matter was much reduced being accompanied by an increased food intake, suggesting compensatory feeding. Indirect temperature effects were apparent as reduced body mass, longer development time, an increased food intake, and a reduced efficiency of converting food into body matter in larvae feeding on plants grown at the higher temperature, thus indicating poor host‐plant quality. The effects of host‐plant quality were more pronounced at the higher temperature, at which compensatory feeding was much less efficient. Our results highlight that temperature‐mediated changes in host‐plant quality are a significant, but largely overlooked source of variation in herbivore performance. Such effects may exaggerate negative effects of global warming, which should be considered when trying to forecast species' responses to climate change.
‘DAS ES TEUTSCHE ZUNG VERNIMPT’: ZUR ÜBERSETZUNGSLITERATUR TIROLS UM 1400
Authors: Harris Nigel
Published: June 2013

The achievement of Vienna (and particularly of its University) in spreading the culture of late‐medieval Latinity via translations into German is well known. Much less thoroughly explored, however, is the role played by contemporary Tyrolean translators in building a bridge between their German audiences and a variety of important products of medieval Latin, French, and Italian literature. This article foregrounds three South Tyrolean translations, by Michel Velser, Hans Vintler, and Ulrich Putsch, and refers also to the anonymous Tiroler Petrarca‐Übersetzung. All of these were composed between roughly 1390 and 1430, and transmit versions of texts that had enjoyed enormous popularity in the Romance lands. The piece focuses especially on questions of translation technique and of reception. It concludes that there is no firm evidence on which to postulate the existence of a concerted Tyrolean ‘school’ of translators or the involvement of a particular influential patron, but demonstrates that the cultural ‘bridge’ built by these Tyrolean authors was a significant and multi‐faceted one, which as such merits far more investigation. It also provides further evidence to support medievalists’ increasing awareness that medieval books were often in practice owned and read by rather different people from those whom their authors had envisaged.