bluuebunny/crossref_metadata_2025 huggingface dataset:
ERG Status Is Unrelated to PSA Recurrence in Radically Operated Prostate Cancer in the Absence of Antihormonal Therapy
Authors: Minner Sarah , Enodien Malaika , Sirma Hüseyin , Luebke Andreas M. , Krohn Antje , Mayer Pascale S. , Simon Ronald , Tennstedt Pierre , Müller Julia , Scholz Laura , Brase Jan C. , Liu Alvin Y. , Schlüter Hartmut , Pantel Klaus , Schumacher Udo , Bokemeyer Carsten , Steuber Thomas , Graefen Markus , Sauter Guido , Schlomm Thorsten
Published: July 2011

Purpose: About 50% of prostate cancers have TMPRSS2–ERG fusions with concurrent ERG overexpression. The aim of this study was to determine whether clinical differences exist between ERG-positive and ERG-negative cancers in surgically treated patients not exposed to antihormonal therapy. A secondary aim was to search for differences between these tumor classes.

Experimental Design: A tissue microarray containing samples from more than 2,800 prostate cancers with clinical data was analyzed for ERG alterations by immunohistochemistry and FISH. Results were compared with tumor phenotype, biochemical recurrence, and molecular features considered important for prostate cancer. The effect of ERG on androgen receptor (AR)-dependent transcription was analyzed in cell lines.

Results: ERG expression was found in 52.4% of 2,805 cancers with a 95% concordance between ERG expression and ERG gene rearrangement detected by FISH. ERG expression was unrelated to clinical outcome and tumor phenotype. Differences in AMACR, Annexin A3, Bcl2, CD10, ALCAM, chromogranin A, epidermal growth factor receptor, HER2, mTOR, p53, and synaptophysin status were significant but minimal in absolute numbers. The most striking difference was found for AR expression, which was markedly higher in ERG-positive cancers. In vitro studies showed ERG-dependent impairment of AR-mediated transcriptional activity.

Conclusions: The striking similarities between these two types of prostate cancers rules out a major impact of ERG on tumor aggressiveness in early, not hormonally treated cancer. The marked difference in AR levels between ERG-positive and -negative cancers supports a systematic difference in potential response to hormonal therapy as previously observed in clinical trials. Clin Cancer Res; 17(18); 5878–88. ©2011 AACR.
Lapatinib, a Preventive/Therapeutic Agent against Mammary Cancer, Suppresses RTK-Mediated Signaling through Multiple Signaling Pathways
Authors: Li Jixia , Cho Yeon-Yong , Langfald Alyssa , Carper Andria , Lubet Ronald A. , Grubbs Clinton J. , Ericson Marna E. , Bode Ann M.
Published: July 2011

Activation of receptor tyrosine kinases (RTK) plays a key role in the prognosis of mammary cancer. Lapatinib is a small molecule dual RTK inhibitor that targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Identifying the protein targets involved in the effects of lapatinib and other RTK inhibitors might help determine why preventive efficacy varies. In this study, female Sprague-Dawley rats were given methylnitrosourea (MNU) by intravenous injection resulting in the development of multiple estrogen receptor–positive tumors. Treatment with lapatinib beginning 5 days after MNU was highly effective in preventing cancer development. In addition, we treated rats with palpable mammary tumors with lapatinib daily. In these tumor-bearing animals, treatment continued for 42 days and therapeutic results were obtained. Some rats bearing cancers were treated for 5 days, and the resulting lesions were examined for biomarker modulation. Lapatinib effectively suppressed the abundance of HER2, phosphorylated HER2 (Tyr1221/1222), and phosphorylated EGFR (Tyr1173, Tyr1110) compared with tumors from untreated rats. Protein array analyses allowed parallel determination of the effect of lapatinib on the relative levels of protein phosphorylation and proteins associated with apoptosis. These results combined with immunoreactivity data indicated that, in addition to EGFR and HER2, lapatinib treatment was associated with changes in a number of other signaling molecules, including IGF-1R, Akt, and downstream targets such as GSK3, p27, p53, and cyclin D1 presumably leading to impaired proliferation, apoptosis, or cell-cycle arrest. Cancer Prev Res; 4(8); 1190–7. ©2011 AACR.
Phenylbutyl Isoselenocyanate Modulates Phase I and II Enzymes and Inhibits 4-(Methylnitrosamino)-1-(3-Pyridyl)- 1-Butanone–Induced DNA Adducts in Mice
Authors: Crampsie Melissa A. , Jones Nathan , Das Arunangshu , Aliaga Cesar , Desai Dhimant , Lazarus Philip , Amin Shantu , Sharma Arun K.
Published: July 2011

Lung cancer remains one of the most preventable forms of cancer with about 90% of cases attributed to cigarette smoking. Over the years, the development of chemopreventive agents that could inhibit, delay, or reverse the lung carcinogenesis process has been an active field of research, however, without much attainment. Through extensive structure–activity relationship studies, we recently identified a novel agent phenylbutyl isoselenocyanate (ISC-4), designed on the basis of naturally occurring isothiocyanates well known for their lung cancer prevention properties, as a potential chemopreventive agent. In this study, we used A/J mice to evaluate the lung cancer chemopreventive potential of ISC-4. A single intragastric dose of 1.25 μmol ISC-4 resulted in a time-dependent increase of selenium levels in serum, liver, and lung, suggesting that ISC-4 is orally bioavailable, a key requirement for a chemopreventive agent. This dose also resulted in a time-dependent inhibition of microsomal cytochrome P450 (Cyp450) activity and delayed increases in phase II UDP-glucuronyl transferase (Ugt) and glutathione-S-transferase (Gst) activity. ISC-4 was able to induce mRNA expression of Cyp, Ugt, and Gst enzyme isoforms in liver, but in lung, it inhibited Cyp isoforms while inducing Ugt and Gst isoforms. In addition, ISC-4 effectively inhibited methyl–DNA adduct formation in mice fed diet supplemented with ISC-4 for two weeks and then treated with the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. These results suggest that ISC-4 is a strong candidate for development as a chemopreventive agent. Cancer Prev Res; 4(11); 1884–94. ©2011 AACR.
Prevalence, Presentation and Clinical Evolution of Graves’ Disease in Children and Adolescents with Type 1 Diabetes Mellitus
Authors: Lombardo F. , Messina M.F. , Salzano G. , Rabbone I. , Lo Presti D. , Calcaterra V. , Aversa T. , De Luca F. , Wasniewska M.
Published: July 2011

Aims: To ascertain the prevalence of Graves’ disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B). Results: Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups. Conclusions: GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM.
Effect of Pomegranate Juice on Insulin Secretion and Sensitivity in Patients with Obesity
Authors: González-Ortiz Manuel , Martínez-Abundis Esperanza , Espinel-Bermúdez María C. , Pérez-Rubio Karina G.
Published: July 2011

Aim: To evaluate the effect of pomegranate juice on insulin secretion and sensitivity in patients with obesity. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 20 obese, adult volunteer subjects. After random allocation of the intervention, 10 patients received 120 ml of pomegranate juice or placebo while in a fasted state for 1 month. Glucose, uric acid, creatinine, lipid profile, and insulin were measured at baseline, and glucose and insulin were also measured at 30, 60, 90, and 120 min. The area under the curve of glucose and insulin, total insulin secretion, and insulin sensitivity was calculated. Results: There was a significant increase in weight, body mass index, and fat mass in the placebo group after the intervention. Insulin secretion and insulin sensitivity were not modified with administration of pomegranate juice. There was a significant difference in changes from baseline in fat mass between groups (1.1 ± 1.1% vs. –1.4 ± 3.0%, p = 0.010; placebo and pomegranate groups, respectively). Conclusion: Pomegranate juice administration for 1 month did not modify insulin secretion and sensitivity in patients with obesity; however, the natural evolution to increased weight and adiposity was halted.
Resting Metabolic Rate in Elite Rowers and Canoeists: Difference between Indirect Calorimetry and Prediction
Authors: Carlsohn Anja , Scharhag-Rosenberger Friederike , Cassel Michael , Mayer Frank
Published: July 2011

Background: Athletes may differ in their resting metabolic rate (RMR) from the general population. However, to estimate the RMR in athletes, prediction equations that have not been validated in athletes are often used. The purpose of this study was therefore to verify the applicability of commonly used RMR predictions for use in athletes. Methods: The RMR was measured by indirect calorimetry in 17 highly trained rowers and canoeists of the German national teams (BMI 24 ± 2 kg/m2, fat-free mass 69 ± 15 kg). In addition, the RMR was predicted using Cunningham (CUN) and Harris-Benedict (HB) equations. A two-way repeated measures ANOVA was calculated to test for differences between predicted and measured RMR (α = 0.05). The root mean square percentage error (RMSPE) was calculated and the Bland-Altman procedure was used to quantify the bias for each prediction. Results: Prediction equations significantly underestimated the RMR in males (p < 0.001). The RMSPE was calculated to be 18.4% (CUN) and 20.9% (HB) in the entire group. The bias was 133 kcal/24 h for CUN and 202 kcal/24 h for HB. Conclusions: Predictions significantly underestimate the RMR in male heavyweight endurance athletes but not in females. In athletes with a high fat-free mass, prediction equations might therefore not be applicable to estimate energy requirements. Instead, measurement of the resting energy expenditure or specific prediction equations might be needed for the individual heavyweight athlete.
Percutaneous Closure of Left Ventricular Pseudoaneurysm
Authors: Dudiy Yuriy , Jelnin Vladimir , Einhorn Bryce N. , Kronzon Itzhak , Cohen Howard A. , Ruiz Carlos E.
Published: July 2011

Background—

Left ventricular pseudoaneurysm is a rare but serious complication from myocardial infarction and cardiac surgery. Although standard treatment is surgical intervention, percutaneous closure of left ventricular pseudoaneurysm has become an option for high-risk surgical candidates. Experience with percutaneous treatment is limited to a few single case reports. This is the first series of percutaneous treatment of the left ventricular pseudoaneurysms.

Methods and Results—

This is a retrospective analysis of 9 procedures of percutaneous repair of left ventricular pseudoaneurysm in 7 consecutive patients (ages 51 to 83 years, 6 men) completed in our Structural Heart Disease center from June 2008 to December 2010. All patients were considered as a high risk for surgery because of multiple comorbidities. Multiple imaging modalities were used before, during, and after the procedures to improve success and efficacy. The left ventricular pseudoaneurysms of all 7 patients were successfully repaired. Fluoroscopy time on average was 36.5±24.0 minutes (range, 12.4 to 75.7 minutes). All patients were followed up for a period ranging from 3 to 32 months after the procedure. Each patient improved by at least 1 New York Heart Association functional class, and 4 patients improved by 2 classes.

Conclusions—

Transcatheter closure of the left ventricular pseudoaneurysm is a feasible alternative for high-risk surgical candidates. The use of multiple imaging modalities is required for a detail planning and execution of the procedure.
Climatological Variations in North Atlantic Tropical Cyclone Tracks
Authors: Colbert Angela J. , Soden Brian J.
Published: July 2011

This study investigates the relationship between tropical cyclone (TC) tracks and climatological variations in large-scale environmental parameters associated with the TC steering flow. By using the Atlantic Ocean hurricane database for 1950–2010, TCs that form in the main development region (MDR) are categorized into one of three track types: straight moving, recurving landfall, or recurving ocean. As expected, the straight-moving storms are associated with a westward extension and strengthening of the subtropical high, whereas the recurving ocean storms are associated with a weakening of the high. The presence of El Niño conditions in the tropical Pacific Ocean is shown to be associated with a weakening of the high, an increase in the percentage of recurving ocean TCs, and a decrease in the percentage of recurving landfall TCs. Positive phases of the Atlantic Meridional Mode are associated with an increase in the percentage of recurving ocean TCs and a decrease in the percentage of straight-moving TCs. Synthetic tracks are simulated for each storm using a beta and advection model. Sensitivity experiments using both observed and uniformly seeded genesis locations indicate that the path of straight-moving TCs is largely a reflection of their tendency to form in the southwestern portion of the MDR rather than of differences in steering flow. These experiments also suggest that the shift in TC tracks associated with El Niño/La Niña conditions is largely attributable to changes in the steering flow, whereas the track changes associated with variations in the Atlantic Meridional Mode are due to a systematic shift in genesis location.
Tornado Maintenance Investigated with High-Resolution Dual-Doppler and EnKF Analysis
Authors: Marquis James , Richardson Yvette , Markowski Paul , Dowell David , Wurman Joshua
Published: July 2011

Dual-Doppler wind synthesis and ensemble Kalman filter analyses produced by assimilating Doppler-on-Wheels velocity data collected in four tornadic supercells are examined in order to further understand the maintenance of tornadoes. Although tornado-scale features are not resolved in these analyses, larger-scale processes involved with tornado maintenance are well represented.

The longest-lived tornado is maintained underneath the midlevel updraft within a zone of low-level horizontal convergence along a rear-flank gust front for a considerable time, and dissipates when horizontally displaced from the midlevel updraft. The shortest-lived tornado resides in a similar zone of low-level convergence briefly, but dissipates underneath the location of the midlevel updraft when the updraft becomes tilted and low-level convergence is displaced several kilometers from the tornado. This suggests that a location beneath the midlevel updraft is not always a sufficient condition for tornado maintenance, particularly in the presence of strongly surging outflow. Tornadoes in two other storms persist within a band of low-level convergence in the outflow air (a possible secondary rear-flank gust front), suggesting that tornado maintenance can occur away from the main boundary separating the outflow air and the ambient environment.

In at least one case, tilting of horizontal vorticity occurs near the tornado along the secondary gust front, as evidenced by three-dimensional vortex line arching. This observation suggests that a relatively cold secondary rear-flank downdraft may assist with tornado maintenance through the baroclinic generation and tilting of horizontal vorticity, despite the fact that parcels composing them would be more negatively buoyant than the preceding outflow air.
Unemployment trap or high job turnover? Ethnic penalties and labour market transitions in Italy
Authors: Fullin Giovanna
Published: July 2011

This article aims at analysing the trajectories of immigrants in the Italian labour market, focusing on yearly transitions from unemployment to employment and vice versa. Regression models show that, controlling for age, educational attainment and region, immigrant workers lose their jobs more often than natives but, once being unemployed they have more probabilities of finding a job than natives. As the probabilities of both transitions can be affected by characteristics of the initial status as well, the two transitions have been analysed separately. For the risk of losing a job, the segregation of immigrants in the secondary labour market seems to be the main reason of their penalization, but also the main reason of their advantage in job seeking, since their unemployment spells are shorter than those of natives, although at the cost of accepting worse working conditions. Analyses are based on the yearly transition matrices of Italian Labour Force Surveys, from 2005 to 2008.
Foreign military intervention and women’s rights
Authors: Peksen Dursun
Published: July 2011

A large body of scholarly work has been devoted to the possible consequences of foreign military intervention for the target state. This literature, however, tends to be state-centric and mostly neglects the insight from gender-specific theoretical and empirical perspectives. The purpose of this article is to examine the extent to which military intervention affects women’s rights. It is argued that unilateral interventions are prone to diminishing women’s status by encouraging the persistence or creation of repressive regimes and contributing to political disorder in the target state. If the use of armed forces ever helps or causes no damage to women’s well-being, it will likely be during interventions led by intergovernmental organizations (IGOs). This is because IGO interventions are unlikely to protect or support an authoritarian, patriarchal political system. Furthermore, such multilateral missions will increase international awareness of women’s status along with other human rights issues in the target society, thereby creating more pressure on the government to enforce women’s rights. To empirically substantiate these arguments, three different indicators that tap socio-economic and political aspects of women’s status are used, including the indices of women’s economic, political, and social rights from the Cingranelli-Richards database. The results indicate that while women’s political and economic status suffer most during unilateral US interventions, IGO interventions are likely to have a positive influence on women’s political rights. Non-US unilateral interventions, on the other hand, are unlikely to cause any major change in women’s status. Finally, military interventions in general have no major statistically significant impact on women’s social rights.
Does trade prevent or promote interstate conflict initiation?
Authors: Li Quan , Reuveny Rafael
Published: July 2011

Competing theories argue, respectively, that more trade reduces, increases, or does not affect interstate military conflict. We offer a new general theory on how trade affects conflict, which encompasses the liberal logic and the neo-Marxist/neo-mercantilist mechanism of asymmetric dependence and offers alternative explanations to the effects predicted by the bargaining and classical realist approaches. If a country expects its conflict toward a target to reduce the price of its import from or increase the price of its export to a target, it has an economic incentive to initiate conflict, and vice versa. These expectations can vary across trade flow directions and economic sectors. Using our model, we predict the effects of increases in exports and imports in five sectors on military conflict initiation. Statistical analysis of directed dyads from 1970 to 1997 largely supports our predictions. Rises in the initiator’s imports of agriculture/fishery, energy, and chemical/mineral goods and exports of miscellaneous consumption goods reduce the likelihood of conflict initiation; rises in the initiator’s exports of energy and both imports and exports of manufactured goods increase the likelihood. We evaluate implications for the literature and public policy.
Bullets and votes: Public opinion and terrorist strategies
Authors: Criado Henar
Published: July 2011

There is an increasing number of analyses of the effects of terrorism, especially its impact on public opinion. Most of these analyses are focused on the effects of terrorist strategies and attacks on public opinion in general. This article analyzes an important but usually neglected question in this literature: the effects of terrorist strategies on the vote for parties that support the terrorist organization. It uses data referred to the case of the Basque terrorist group ETA and its attached political movement. ETA is one of the most enduring terrorist groups in the world, and during the last three decades, its strategy has combined violence with the convening of truces. The article shows how terrorist strategies, especially the convening of truces and negotiating with the government, significantly increase public support for the terrorist organization. Once the terrorist group has declared a truce and negotiations with the government are under way, the terrorists’ constituency has an incentive to increase its mobilization in favour of the terrorist group. With higher levels of support, the terrorist group has a stronger bargaining position, and, therefore, it becomes more likely to attain its demands.
Armed conflict, 1946–2010
Authors: Themnér Lotta , Wallensteen Peter
Published: July 2011

In 2010, UCDP recorded 30 active armed conflicts (i.e. with a minimum of 25 battle-related deaths). This is a substantial reduction in relation to the 36 conflicts registered for 2009. A drop of this magnitude has only been reported four times previously in the post-1946 period. However, only in two of these instances was this part of a general downward trend. Thus no major inferences should be drawn, except perhaps that the reduction in conflicts in Africa seems to be part of a trend. At 30 in 2010, the number of active conflicts is at its lowest level since 2003. Furthermore, the number of wars (1,000 or more battle-related deaths) declined from six in 2009 to four in 2010. The most intense war in terms of fatalities was in Afghanistan. Eight of the armed conflicts listed for 2009 were not active in 2010, but during the year two new conflicts erupted – Mauritania and Tajikistan – both involving rebel groups that had previously fought in neighbouring countries. Only two peace agreements were concluded during the year. While this is one more than 2009, it is decidedly below the annual average for the post-Cold War period.
Salience and the Social Meaning of Declarative Contours
Authors: Podesva Robert J.
Published: July 2011

Most studies exploring the social meaning of variation have focused on phonological variables at the segmental level. This article investigates the social meaning of intonational variation in the speech of three gay professionals. To examine how intonational meanings can be exploited as symbolic resources, this study takes an intraspeaker approach, inspecting declarative intonation patterns across three situations per speaker. The analysis reveals that speakers exhibit systematic patterns of variation on either of two levels—the frequency with which variants are employed or their phonetic manifestations—depending on the salience of variants. The social significance of these patterns is inferred by situating them in their discourse and ethnographic contexts. Importantly, intonational meaning surfaces in both the choice of a variant and its phonetic rendering. The categorical choice of a variant conveys pragmatic meaning, while the variant’s phonetic realization reflects the strength of its social meaning.
Responsiveness of Goal Attainment Scaling in comparison to two standardized measures in outcome evaluation of children with cerebral palsy
Authors: Steenbeek Duco , Gorter Jan Willem , Ketelaar Marjolijn , Galama Krys , Lindeman Eline
Published: July 2011

Objectives: To assess the responsiveness of Goal Attainment Scaling compared with the Pediatric Evaluation of Disability Inventory (PEDI) and the 66-item Gross Motor Function Measure (GMFM-66) in multidisciplinary rehabilitation practice.

Design: Observational study. Pretest–posttest design.

Subjects/patients: Twenty-three children with cerebral palsy, aged 2–13 years.

Methods: Goal Attainment Scaling, PEDI and GMFM-66 assessments were performed before and after six months of treatment. Physical, occupational and speech therapists constructed and scored 6-point Goal Attainment Scaling scales meeting predetermined criteria, describing the main functional goal per discipline. The contents of the three measures were compared using International Classification of Functioning, Disability and Health child and youth version (ICF-CY) codes. Spearman’s rho correlations between Goal Attainment Scaling change scores per discipline and change scores obtained with the PEDI functional skills scales and GMFM-66 were calculated. Complete goal attainment was compared with significant change in terms of the standardized measures.

Results: Twenty per cent of the Goal Attainment Scaling items were not covered by items of the PEDI or the GMFM-66. Inconclusive correlations were found between Goal Attainment Scaling and PEDI change scores ( r 0.28–0.64). Even after exclusion of the non-corresponding items, correlations were moderate ( r 0.57–0.73). Of 39/64 Goal Attainment Scaling scales scored as complete goal attainment, 16 individual PEDI scores did not show change on the corresponding scale. Low correlation was found between Goal Attainment Scaling change scores and GMFM-66 change scores.

Conclusion: Goal Attainment Scaling, PEDI and GMFM-66 were complementary in their ability to measure individual change over time in children with cerebral palsy. Using only the standardized instruments could have caused many individual rehabilitation goals actually attained being missed in the outcome evaluation.
Can an Entrepreneurial Personality Compensate for a Boring Job?
Authors: D’Souza Pearl , Mulla Zubin R.
Published: July 2011

We examined the relationship between entrepreneurial orientation and employee engagement by studying 101 Indian managers across three companies. In addition, we studied the moderating role of three job characteristics (autonomy, skill variety and task feedback) on the relationship between entrepreneurial orientation and employee engagement. The results of this study show that individuals who score high on entrepreneurial orientation are likely to score high on employee engagement. In addition, we found that individuals high on entrepreneurial orientation experienced high engagement levels when their jobs were characterised by low levels of autonomy, low levels of skill variety and high levels of task feedback. The findings indicate that a proactive personality does compensate for some non-motivating elements of job design.
Effect of Entrepreneur Network and Entrepreneur Self-efficacy on Subjective Performance
Authors: Prajapati Keerti , Biswas Saswata Narayan
Published: July 2011

The article presents results of a study on the impact of entrepreneurial demographic characteristics (age, experience and education), entrepreneurial network structure (size, density and centrality), entrepreneurial network types (competitive and supportive) and entrepreneurial self-efficacy on subjective performance. The sample consisted of 148 micro and small enterprises in a textile handicraft and handloom cluster in Kutch, Gujarat, India. Regression analysis results suggested that size, density, centrality, entrepreneur self-efficacy, competitive network and supportive network predicted subjective performance significantly and together they accounted for about 56 per cent of the variance in the dependent variable. However, the unique contribution of the demographic variables and supportive network was not significant. Results are explained in the light of the theory of social capital and the entrepreneur cognitive theory. The research has implications for policymaking, research and entrepreneurship training and education.
Managerial Resourcefulness
Authors: Doğan Selen , Şahin Faruk
Published: July 2011

Research has suggested the importance of managerial competencies in predicting managerial success. Managerial resourcefulness implies the use of cognitive self-regulatory competencies to cope well with environmental challenges in an organisational setting. However, measures of managerial resourcefulness are scarce. This study reports on the validation of a new Managerial Resourcefulness Questionnaire (MRQ) in the Turkish context. The MRQ was validated using three samples of Turkish managers and yielded sound psychometric properties for an eight-factorial structure consisting of 50 items. The results provided empirical evidence for reliability, measurement invariance and discriminant validity of the MRQ. Significant correlations between the MRQ and several measures were also found, which together provided evidence for its construct validity. Implications for future research and practice are discussed.
Learning From Looking at Sound
Authors: Thibeault Matthew D.
Published: July 2011

This article details the use of multimedia spectrogram displays for visualizing and understanding music. A section on foundational considerations presents similarities and differences between Western musical scores and spectrograms, in particular the benefit in avoiding Western notation when using music from a culture where representation through the use of a score may misrepresent that culture. Four examples from the author’s own teaching and research detail applications of multimedia spectrograms. A tutorial provides guidance for generating spectrograms using the free program Audacity. The article closes with three extension projects suitable for classroom teachers to use with their students.
Review Series: Old age: Pneumonia in old age
Authors: Malin Adam
Published: July 2011

At the end of the 19th century William Osler noted key differences in the presentation of pneumonia in the elderly. His observational perspicuity has withstood the passage of time. The following article pays deference to this Canadian physician, summarizing not only differences in clinical presentation but also including an update on epidemiology, aetiology and management.
A Review of Assessment Tools for Diagnosis of Autism Spectrum Disorders
Authors: Klose Laurie McGarry , Plotts Cynthia , Kozeneski Nicole , Skinner-Foster Jacqueline
Published: July 2011

This paper provides a review of widely used measures for assessing Autism Spectrum Disorders, including the Autism Diagnostic Interview–Revised, Autism Diagnostic Observation Schedule, Psychoeducational Profile–Third Edition, Gilliam Autism Rating Scale–Second Edition, and Childhood Autism Rating Scale–Second Edition. Each measure is evaluated in terms of its usefulness for diagnosis and screening with respect to IDEA eligibility criteria, clinical diagnostic criteria, and current understanding of best practices.
Motivated information processing during intergroup competition
Authors: Wittchen Marion , Dick Rolf van , Hertel Guido
Published: July 2011

Group work in organizations usually involves the existence of more than one group, which can lead to intergroup competition either implicitly or based on explicit competitive incentives. In this paper, a model of task-related effort in multigroup settings is developed, relating findings on intergroup competition to current research on motivation and information processing in groups. Increased effort during intergroup competition is explained based on (a) the degree of deliberate and systematic information retrieval and processing, and (b) the degree of collective self-construal within the groups. Implications for using and dealing with intergroup competition in organizations are discussed.
Safety of drugs used in the treatment of osteoporosis
Authors: McGreevy Cora , Williams David
Published: July 2011

A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years’ duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and timing of therapy. Strontium should be used with caution in patients with renal impairment and its use has been associated with venous thromboembolism. The role of HRT and SERMs in the treatment of postmenopausal osteoporosis is restricted as a result of an increased risk of stroke, venous thromboembolism and breast cancer. Postmarketing experience with denusomab is limited but a number of potential safety concerns including osteonecrosis of the jaw are emerging. All of these drugs have been proven to reduce fractures. The decision to use a drug to reduce fracture risk should be based on risk–benefit analysis of the drug and its suitability for individual patients.
Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks
Authors: Czeizel Andrew E. , Bártfai Zoltán , Bánhidy Ferenc
Published: July 2011

The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’).
Friending the Virgin
Authors: Friedlander Larry
Published: July 2011

This article looks at how previous practice of portraiture prepared the way for self-presentation on social networking sites. A portrait is not simply an exercise in the skillful or “realistic” depiction of a subject. Rather, it is a rhetorical exercise in visual description and persuasion and a site of intricate communicative processes. A long evolution of visual culture, intimately intertwined with evolving notions of identity and society, was necessary to create the conditions for the particular forms of self-representation we encounter on Facebook. Many of these premodern strategies prefigure ones we encounter on Facebook. By delineating the ways current practices reflect earlier ones, we can set a baseline from which we can isolate the precise novelty of current practice in social networking sites.
Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells
Authors: Istvanffy Rouzanna , Kröger Monika , Eckl Christina , Gitzelmann Sylke , Vilne Baiba , Bock Franziska , Graf Steffi , Schiemann Matthias , Keller Ulrich B. , Peschel Christian , Oostendorp Robert A. J.
Published: July 2011

Pleiotrophin (Ptn) is strongly expressed by stromal cells which maintain HSCs. However, in vivo, Ptn deficiency does not alter steady-state hematopoiesis. However, knockdown of Ptn (PtnKD) in stromal cells increases production of hematopoietic progenitors as well as HSC activity in cocultures, suggesting that Ptn may have a role in HSC activation. Indeed, transplantations of wild-type (Ptn+/+) HSCs into Ptn−/− mice show increased donor cell production in serial transplantations and dominant myeloid regeneration caused by Ptn-dependent regulation of HSC repopulation behavior. This regulation of Lin−Kit+Sca1+ function is associated with increased proliferation and, on a molecular level, with up-regulated expression of cyclin D1 (Ccnd1) and C/EBPα (Cepba), but reduced of PPARγ. The known HSC regulator β-catenin is, however, not altered in the absence of Ptn. In conclusion, our results point to different Ptn-mediated regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration. Moreover, our results support the idea that microenvironmental Ptn regulates hematopoietic regeneration through β-catenin–independent regulation of Ccnd1 and Cebpa.
How I treat extramedullary acute myeloid leukemia
Authors: Bakst Richard L. , Tallman Martin S. , Douer Dan , Yahalom Joachim
Published: July 2011

Extramedullary (EM) manifestations of acute leukemia include a wide variety of clinically significant phenomena that often pose therapeutic dilemmas. Myeloid sarcoma (MS) and leukemia cutis (LC) represent 2 well-known EM manifestations with a range of clinical presentations. MS (also known as granulocytic sarcoma or chloroma) is a rare EM tumor of immature myeloid cells. LC specifically refers to the infiltration of the epidermis, dermis, or subcutis by neoplastic leukocytes (leukemia cells), resulting in clinically identifiable cutaneous lesions. The molecular mechanisms underlying EM involvement are not well defined, but recent immunophenotyping, cytogenetic, and molecular analysis are beginning to provide some understanding. Certain cytogenetic abnormalities are associated with increased risk of EM involvement, potentially through altering tissue-homing pathways. The prognostic significance of EM involvement is not fully understood. Therefore, it has been difficult to define the optimal treatment of patients with MS or LC. The timing of EM development at presentation versus relapse, involvement of the marrow, and AML risk classification help to determine our approach to treatment of EM disease.
Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells
Authors: Suzuki Yuko , Yasui Hideki , Brzoska Tomasz , Mogami Hideo , Urano Tetsumei
Published: July 2011

In a previous study, we demonstrated unique secretory dynamics of tissue plasminogen activator (tPA) in which tPA was retained on the cell surface in a heavy chain–dependent manner after exocytosis from secretory granules in vascular endothelial cells. Here, we examined how retained tPA expresses its enzymatic activity. Retained tPA effectively increased the lysine binding site–dependent binding of plasminogen on the cell surface and pericellular area; this was abolished by inhibition of enzymatic activity of either tPA or plasmin, which suggests that de novo generation of carboxyl-terminal lysine as a consequence of degradation of surface/pericellular proteins by plasmin is essential. Retained tPA initiated zonal clot lysis of a fibrin network that had been formed on vascular endothelial cells, which was preceded by the binding of plasminogen to the lysis front. Our results provide evidence that secreted and retained tPA is essential for maintaining both high fibrinolytic activity and effective clot lysis on the vascular endothelial cell surface.
Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS)
Authors: Mailankody Sham , Pfeiffer Ruth M. , Kristinsson Sigurdur Y. , Korde Neha , Bjorkholm Magnus , Goldin Lynn R. , Turesson Ingemar , Landgren Ola
Published: July 2011

Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n = 8740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed between 1986 and 2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and nonhematologic malignancies for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem cell transplantation [HDM-ASCT]) and 2000 (introduction of immunomodulatory drugs [IMiDs]), respectively. MM patients had an 11.51-fold (95% confidence interval: 8.19-15.74) increased risk of acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS); risk was very similar before/after 1995 and 2000, respectively. MGUS patients had an 8.01-fold (5.40-11.43) increased risk of AML/MDS. Risk was confined to IgG/IgA, while no IgM MGUS patients developed AML/MDS; patients with monoclonal-protein (M-protein) concentrations > 1.5 g/dL (SIR = 11.12; 3.61-25.96) had higher risk than those < 1.5 g/dL (SIR = 4.67; 1.71-10.16). An excess risk of nonmelanoma skin cancer was observed subsequent to both MM (SIR = 2.22; 1.74-2.80) and MGUS (SIR = 3.30; 2.76-3.90). Our novel observations of an excess risk for AML/MDS following IgG/IgA (but not IgM) MGUS, and the highest risk associated with M-protein concentrations > 1.5 g/dL, support a role for nontreatment-related factors in plasma cell dyscrasias. AML/MDS risk following MM was the same before/after the introduction of HDM-ASCT. Longer follow-up is needed to characterize second tumor risks in the IMiD era.
miRTar: an integrated system for identifying miRNA-target interactions in human
Authors: Hsu Justin Bo-Kai , Chiu Chih-Min , Hsu Sheng-Da , Huang Wei-Yun , Chien Chia-Hung , Lee Tzong-Yi , Huang Hsien-Da
Published: July 2011

Background

MicroRNAs (miRNAs) are small non-coding RNA molecules that are ~22-nt-long sequences capable of suppressing protein synthesis. Previous research has suggested that miRNAs regulate 30% or more of the human protein-coding genes. The aim of this work is to consider various analyzing scenarios in the identification of miRNA-target interactions, as well as to provide an integrated system that will aid in facilitating investigation on the influence of miRNA targets by alternative splicing and the biological function of miRNAs in biological pathways.

Results

This work presents an integrated system, miRTar, which adopts various analyzing scenarios to identify putative miRNA target sites of the gene transcripts and elucidates the biological functions of miRNAs toward their targets in biological pathways. The system has three major features. First, the prediction system is able to consider various analyzing scenarios (1 miRNA:1 gene, 1:N, N:1, N:M, all miRNAs:N genes, and N miRNAs: genes involved in a pathway) to easily identify the regulatory relationships between interesting miRNAs and their targets, in 3'UTR, 5'UTR and coding regions. Second, miRTar can analyze and highlight a group of miRNA-regulated genes that participate in particular KEGG pathways to elucidate the biological roles of miRNAs in biological pathways. Third, miRTar can provide further information for elucidating the miRNA regulation, i.e., miRNA-target interactions, affected by alternative splicing.

Conclusions

In this work, we developed an integrated resource, miRTar, to enable biologists to easily identify the biological functions and regulatory relationships between a group of known/putative miRNAs and protein coding genes. miRTar is now available at http://miRTar.mbc.nctu.edu.tw/.
IsoformEx: isoform level gene expression estimation using weighted non-negative least squares from mRNA-Seq data
Authors: Kim Hyunsoo , Bi Yingtao , Pal Sharmistha , Gupta Ravi , Davuluri Ramana V
Published: July 2011

Background

mRNA-Seq technology has revolutionized the field of transcriptomics for identification and quantification of gene transcripts not only at gene level but also at isoform level. Estimating the expression levels of transcript isoforms from mRNA-Seq data is a challenging problem due to the presence of constitutive exons.

Results

We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms. Validations based on in silico simulation of mRNA-Seq and qRT-PCR experiments with real mRNA-Seq data showed that IsoformEx could accurately estimate transcript expression levels. In comparisons with published methods, the transcript expression levels estimated by IsoformEx showed higher correlation with known transcript expression levels from simulated mRNA-Seq data, and higher agreement with qRT-PCR measurements of specific transcripts for real mRNA-Seq data.

Conclusions

IsoformEx is a fast and accurate algorithm to estimate transcript expression levels and gene expression levels, which takes into account short exons and alternative exons with a weighting scheme. The software is available at http://bioinformatics.wistar.upenn.edu/isoformex.
Islands beneath islands: phylogeography of a groundwater amphipod crustacean in the Balearic archipelago
Authors: Bauzà-Ribot Maria M , Jaume Damià , Fornós Joan J , Juan Carlos , Pons Joan
Published: July 2011

Background

Metacrangonyctidae (Amphipoda, Crustacea) is an enigmatic continental subterranean water family of marine origin (thalassoid). One of the species in the genus,Metacrangonyx longipes, is endemic to the Balearic islands of Mallorca and Menorca (W Mediterranean). It has been suggested that the origin and distribution of thalassoid crustaceans could be explained by one of two alternative hypotheses: (1) active colonization of inland freshwater aquifers by a marine ancestor, followed by an adaptative shift; or (2) passive colonization by stranding of ancestral marine populations in coastal aquifers during marine regressions. A comparison of phylogenies, phylogeographic patterns and age estimations of clades should discriminate in favour of one of these two proposals.

Results

Phylogenetic relationships withinM. longipesbased on three mitochondrial DNA (mtDNA) and one nuclear marker revealed five genetically divergent and geographically structured clades. Analyses of cytochrome oxidase subunit 1 (cox1) mtDNA data showed the occurrence of a high geographic population subdivision in both islands, with current gene flow occurring exclusively between sites located in close proximity. Molecular-clock estimations dated the origin ofM. longipesprevious to about 6 Ma, whereas major cladogenetic events within the species took place between 4.2 and 2.0 Ma.

Conclusions

M. longipesdisplayed a surprisingly old and highly fragmented population structure, with major episodes of cladogenesis within the species roughly correlating with some of the major marine transgression-regression episodes that affected the region during the last 6 Ma. Eustatic changes (vicariant events) -not active range expansion of marine littoral ancestors colonizing desalinated habitats-explain the phylogeographic pattern observed inM. longipes.