bluuebunny/crossref_metadata_2025 huggingface dataset:
First-passage failure of single-degree-of-freedom nonlinear oscillators with fractional derivative
Authors: Chen Lincong , Li Zhongshen , Zhuang Qingqu , Zhu Weiqiu
Published: September 2012

The first-passage failure of single-degree-of-freedom nonlinear oscillators with fractional derivative under Gaussian white noise excitations is studied. First, the term associated with fractional derivative is approximately equivalent to amplitude-dependent quasi-linear damping and stiffness forces by using the generalized harmonic balance technique and the given system is replaced by an equivalent nonlinear stochastic system without fractional derivative. Then, the equivalent nonlinear stochastic system state is approximately represented by a one-dimensional diffusive process through stochastic averaging. The backward Kolmogorov equation governing the conditional reliability function and the Pontryagin equation governing the conditional mean of first-passage time are established from the averaged Itô equation of the total energy and solved numerically, respectively. Finally, two examples are worked out in detail and the analytical results are validated by those from the Monte Carlo simulation of original systems.
Experimental investigation of hydraulic effects of two-stage fuel injection on fuel-injection systems and diesel combustion in a high-speed optical common-rail diesel engine
Authors: Herfatmanesh Mohammad Reza , Zhao Hua
Published: September 2012

In order to meet the ever more stringent emission standards, significant efforts have been devoted to the research and development of internal combustion engines. The requirements for more efficient and responsive diesel engines have led to the introduction and implementation of multiple injection strategies. However, the effects of such injection modes on the hydraulic systems, such as the high-pressure pipes and fuel injectors, must be thoroughly examined and compensated for since the combustion and the formation of pollutants in direct-injection engines are directly influenced by the spatial and temporal distribution of the injected fuel within the combustion chamber. This study investigated the hydraulic effects of two-stage fuel injection on diesel combustion and emissions. The fuel-injection system was characterised for all the tested strategies through the measurement of the fuel-injection rate and quantity. In particular, the interaction between the two injection events was identified. The effects of two-stage injection, dwell angle and the interactions between two consecutive injection events on the combustion process and the emissions were investigated in a high-speed direct-injection single-cylinder optical diesel engine using heat-release analysis and high-speed fuel spray and combustion visualisation techniques. The results indicated that the two-stage injection strategy has the potential for simultaneous reduction of nitrogen oxide, soot and unburned hydrocarbon emissions. The results suggested that an optimum fuel quantity in the first injection exists, 0–30%, with which simultaneous reduction of nitrogen oxide, soot and unburned hydrocarbon emissions can be achieved with the added benefits of improved engine performance, fuel economy and combustion noise. However, higher soot emissions were produced, mainly due to the interaction between the two consecutive fuel-injection events whereby the fuel sprays during the second injection were injected into burning regions, as well as reduced soot oxidation due to the continuation of the combustion into the expansion stroke.
Experimental investigations of comparative performance, emission and combustion characteristics of a cottonseed biodiesel-fueled four-stroke locomotive diesel engine
Authors: Gautam Anirudh , Agarwal Avinash Kumar
Published: September 2012

A large-bore, four-stroke, medium-speed, compression-ignition railway traction locomotive engine was fueled with cottonseed methyl ester (Biodiesel). The cottonseed methyl ester was stored for 6 months under ordinary storage conditions, and various fuel properties of this seasoned cottonseed methyl ester were evaluated. Various blends of cottonseed methyl ester (B10, B20, B50 and cottonseed methyl ester) were evaluated for engine performance, emissions and combustion characteristics of the locomotive engine compared to baseline diesel. Correlation of the fuel-injection performance parameters with the physical properties of biodiesel has been carried out. The engine was able to operate on cottonseed methyl ester without noticeable power loss. With cottonseed methyl ester, the thermal efficiency decreased marginally by 0.7% and the brake-specific energy consumption increased by 0.1 MJ/kWh at the rated power. Due to the lower calorific value of biodiesel, brake specific fuel consumption (BSFC) increased by 13.4% at eighth engine notch, nitrogen oxide emissions increased by 8% and particulate matter emissions decreased by 32% vis-a-vis mineral diesel. Nitrogen oxide emissions were found to be a function of injection timings, global oxygen/carbon ratios, time of the maximum mean in-cylinder temperatures and apparent heat release. Particulate matter emissions were found to depend on the air–fuel mixture’s oxygen/carbon ratio, fuel bound oxygen and fuel-injection pressure. The experiments were carried out to evaluate the in-cylinder pressure, heat-release rate, cumulative heat release, fuel-injection pressure, needle lift and fuel-injection velocities. Increased fuel-injection pressures (1000 bar compared to 900 bar for mineral diesel), advanced fuel-injection timings, shorter combustion duration, advanced in-cylinder pressures and higher heat-release rates were observed for biodiesel and blends. The findings of the present study have provided further insights into the combustion of biodiesel in locomotive engines.
Multifaceted Problems
Authors: Skitka Linda J.
Published: September 2012

Inbar and Lammers (2012, this issue) conducted two surveys of a sample of Society for Personality and Social Psychology listserv members to empirically examine two questions: How many social psychologists are politically liberal, and is there evidence that liberal social psychologists are biased against their conservative colleagues and/or research taking a conservative perspective? They conclude that the field is overwhelming liberal, and that there is ample evidence of bias against both conservatives and conservatively motivated research. Biased sampling, conversational norm and question context effects, missing control conditions, and a focus on hypothesis confirmation instead of hypothesis testing, however, undermine the scientific confidence one can place in their findings. Is there liberal bias? Probably. Is the evidence scientifically sound? Not so much. The field needs to adhere to the same standards of scientific rigor when conducting self-critical research as it requires of normal science.
Hindsight Bias
Authors: Roese Neal J. , Vohs Kathleen D.
Published: September 2012

Hindsight bias occurs when people feel that they “knew it all along,” that is, when they believe that an event is more predictable after it becomes known than it was before it became known. Hindsight bias embodies any combination of three aspects: memory distortion, beliefs about events’ objective likelihoods, or subjective beliefs about one’s own prediction abilities. Hindsight bias stems from (a) cognitive inputs (people selectively recall information consistent with what they now know to be true and engage in sensemaking to impose meaning on their own knowledge), (b) metacognitive inputs (the ease with which a past outcome is understood may be misattributed to its assumed prior likelihood), and (c) motivational inputs (people have a need to see the world as orderly and predictable and to avoid being blamed for problems). Consequences of hindsight bias include myopic attention to a single causal understanding of the past (to the neglect of other reasonable explanations) as well as general overconfidence in the certainty of one’s judgments. New technologies for visualizing and understanding data sets may have the unintended consequence of heightening hindsight bias, but an intervention that encourages people to consider alternative causal explanations for a given outcome can reduce hindsight bias.
Stereotypes, Prejudice, and Depression
Authors: Cox William T. L. , Abramson Lyn Y. , Devine Patricia G. , Hollon Steven D.
Published: September 2012

Social psychologists fighting prejudice and clinical psychologists fighting depression have long been separated by the social–clinical divide, unaware that they were facing a common enemy. Stereotypes about others leading to prejudice (e.g., Devine, 1989) and schemas about the self leading to depression (e.g., A. T. Beck, 1967) are fundamentally the same type of cognitive structure. According to the integrated perspective on prejudice and depression, negative stereotypes (i.e., schemas) are activated in a Source, who expresses prejudice toward the Target, causing the Target to experience depression. This linking of prejudice and depression (i.e., “comorbid” prejudice and depression) can occur at the societal level (e.g., Nazis’ prejudice causing Jews’ depression), the interpersonal level (e.g., an abuser’s prejudice causing an abusee’s depression), and the intrapersonal level (e.g., a person’s self-prejudice causing his or her depression). The integrated perspective addresses several longstanding paradoxes, controversies, and questions; generates new areas of inquiry; and spotlights specific methods and findings that have direct cross-disciplinary applications in the battle against prejudice and depression. Ironically, some interventions developed by depression researchers may be especially useful against prejudice, and some interventions developed by prejudice researchers may be especially useful against depression.
Liberal Privilege in Academic Psychology and the Social Sciences
Authors: Jussim Lee
Published: September 2012

This comment is in two parts. The first presents some implications of Inbar and Lammers’ (2012, this issue) findings by making salient many of the advantages and privileges enjoyed by scientists when they extol the moral and intellectual superiority of liberals, liberal beliefs, liberal attitudes, and liberal policy preferences over conservatives, conservative beliefs, conservative attitudes, and conservative policy preferences. The second part of this comment refutes (or, at least, vigorously contests) some of the most common arguments that have attempted to defend social psychology from charges of unscientific and distorting liberal biases.
Applying Production Concepts over Borders: Good Intentions and the Limits of Foreign Culture Understanding
Authors: Linder Christian , Scheuerle Stefan , Seidenstricker Sven
Published: September 2012

Successful production concepts are a challenge for every production company. Such concepts are typically seen as free of individual or normative implications. According to common opinion, they follow a strict formal logic in analogy to mathematical algorithms. Optimizing production processes is, at the end of the day, the quest for the perfect non-judgemental formula. The following case shows that this opinion is not applicable. Organizational production structures, even if they follow a strict formal logic, have always to be applied in a certain context. This context is not value free but brings its own understandings, visions, interpretations, and so on. To explain this, the case shows the effort made to transfer a working production concept of a German company to a subsidiary in India. The goal is to illustrate the importance of culture to even rational processes. The focus is on how teamwork is bounded to cultural aspects.
Corporate Social Responsibility: Is It a Matter of Ethics?
Authors: Laeequddin Mohammed , Waheed K. Abdul
Published: September 2012

Recently, there has been an increasing trend of manufacturing organizations adopting the strategy of Corporate Social Responsibility (CSR) and expecting their suppliers, too, to adopt the CSR guidelines developed by them and be accountable. From a supplier’s perspective, it is important to comply with the key customer’s requirements to maintain the business relationships but adopting the customer’s operating principles may not always be feasible and practical. Situations in which disqualifying suppliers who fail to comply with CSR criteria could limit the number of suppliers or create higher dependency relationships on limited number of suppliers adding cost to production. What is ethical to a customer may not necessarily be ethical to its supplier. This is one of such cases, seeking to bring out the ethical dilemma of Mr Kumar, the General Manager of Pack-tech, a medium-sized flexible packaging company based in United Arab Emirates. The questions that are bothering him are as follows: Should he accept and implement the CSR principles of its customers? Should he follow the suggestions of his workers and manipulate the records to show compliance? And, can CSR principles payback the cost of its implementation?
Applicability of Kocks–Mecking approach for tensile work hardening in P9 steel
Authors: Choudhary B K , Christopher J , Samuel E Isaac
Published: September 2012

Work hardening behaviour of P9 steel in the temperature range 300–873 K has been examined in the framework of Kocks–Mecking (K–M) approach. At all temperatures, P9 steel exhibited two-stage work hardening behaviour characterised by a rapid decrease in instantaneous work hardening rate (i.e. θ = d σ/d ϵ, where σ is the true stress and ϵ is the true plastic strain) with stress at low stresses (transient stage) followed by a gradual decrease at high stresses (stage III). Stage III work hardening of P9 steel was adequately described by K–M approach. The variations of work hardening parameters associated with K–M approach for stage III with temperature indicated three distinct temperature regimes. At all temperatures, good correlations between the respective work hardening parameters evaluated using K–M approach and from Voce equation and its derivative have been obtained for P9 steel.
Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial
Authors: Tan King L. , Scott David W. , Hong Fangxin , Kahl Brad S. , Fisher Richard I. , Bartlett Nancy L. , Advani Ranjana H. , Buckstein Rena , Rimsza Lisa M. , Connors Joseph M. , Steidl Christian , Gordon Leo I. , Horning Sandra J. , Gascoyne Randy D.
Published: September 2012

Increased tumor-associated macrophages (TAMs) are reported to be associated with poor prognosis in classic Hodgkin lymphoma (CHL). We investigated the prognostic significance of TAMs in the E2496 Intergroup trial, a multicenter phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally extensive and advanced stage CHL. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tumor tissue and included 287 patients. Patients were randomly assigned into training (n = 143) and validation (n = 144) cohorts. Immunohistochemistry for CD68 and CD163, and in situ hybridization for EBV-encoded RNA were performed. CD68 and CD163 IHC were analyzed by computer image analysis; optimum thresholds for overall survival (OS) were determined in the training cohort and tested in the independent validation cohort. Increased CD68 and CD163 expression was significantly associated with inferior failure-free survival and OS in the validation cohort. Increased CD68 and CD163 expression was associated with increased age, EBV-encoded RNA positivity, and mixed cellularity subtype of CHL. Multivariate analysis in the validation cohort showed increased CD68 or CD163 expression to be significant independent predictors of inferior failure-free survival and OS. We demonstrate the prognostic significance of TAMs in locally extensive and advanced-stage CHL in a multicenter phase 3 randomized controlled clinical trial.
Extensive molecular mapping of TCRα/δ- and TCRβ-involved chromosomal translocations reveals distinct mechanisms of oncogene activation in T-ALL
Authors: Le Noir Sandrine , Ben Abdelali Raouf , Lelorch Marc , Bergeron Julie , Sungalee Stephanie , Payet-Bornet Dominique , Villarèse Patrick , Petit Arnaud , Callens Céline , Lhermitte Ludovic , Baranger Laurence , Radford-Weiss Isabelle , Grégoire Marie-José , Dombret Hervé , Ifrah Norbert , Spicuglia Salvatore , Romana Serge , Soulier Jean , Nadel Bertrand , Macintyre Elizabeth , Asnafi Vahid
Published: September 2012

Chromosomal translocations involving the TCR loci represent one of the most recurrent oncogenic hallmarks of T-cell acute lymphoblastic leukemia (T-ALL) and are generally believed to result from illegitimate V(D)J recombination events. However, molecular characterization and evaluation of the extent of recombinase involvement at the TCR-oncogene junction has not been fully evaluated. In the present study, screening for TCRβ and TCRα/δ translocations by FISH and ligation-mediated PCR in 280 T-ALLs allowed the identification of 4 previously unreported TCR-translocated oncogene partners: GNAG, LEF1, NKX2-4, and IL2RB. Molecular mapping of genomic junctions from TCR translocations showed that the majority of oncogenic partner breakpoints are not recombinase mediated and that the regulatory elements predominantly used to drive oncogene expression differ markedly in TCRβ (which are exclusively enhancer driven) and TCRα/δ (which use an enhancer-independent cryptic internal promoter) translocations. Our data also imply that oncogene activation takes place at a very immature stage of thymic development, when Dδ2-Dδ3/Dδ3-Jδ1 and Dβ-Jβ rearrangements occur, whereas the bulk leukemic maturation arrest occurs at a much later (cortical) stage. These observations have implications for T-ALL therapy, because the preleukemic early thymic clonogenic population needs to be eradicated and its disappearance monitored.
QuartetS-DB: a large-scale orthology database for prokaryotes and eukaryotes inferred by evolutionary evidence
Authors: Yu Chenggang , Desai Valmik , Cheng Li , Reifman Jaques
Published: September 2012

Background

The concept of orthology is key to decoding evolutionary relationships among genes across different species using comparative genomics. QuartetS is a recently reported algorithm for large-scale orthology detection. Based on the well-established evolutionary principle that gene duplication events discriminate paralogous from orthologous genes, QuartetS has been shown to improve orthology detection accuracy while maintaining computational efficiency.

Description

QuartetS-DB is a new orthology database constructed using the QuartetS algorithm. The database provides orthology predictions among 1621 complete genomes (1365 bacterial, 92 archaeal, and 164 eukaryotic), covering more than seven million proteins and four million pairwise orthologs. It is a major source of orthologous groups, containing more than 300,000 groups of orthologous proteins and 236,000 corresponding gene trees. The database also provides over 500,000 groups of inparalogs. In addition to its size, a distinguishing feature of QuartetS-DB is the ability to allow users to select a cutoff value that modulates the balance between prediction accuracy and coverage of the retrieved pairwise orthologs. The database is accessible at https://applications.bioanalysis.org/quartetsdb.

Conclusions

QuartetS-DB is one of the largest orthology resources available to date. Because its orthology predictions are underpinned by evolutionary evidence obtained from sequenced genomes, we expect its accuracy to continue to increase in future releases as the genomes of additional species are sequenced.
Serotonin immunoreactive interneurons in the brain of the Remipedia: new insights into the phylogenetic affinities of an enigmatic crustacean taxon
Authors: Stemme Torben , Iliffe Thomas M , Bicker Gerd , Harzsch Steffen , Koenemann Stefan
Published: September 2012

Background

Remipedia, a group of homonomously segmented, cave-dwelling, eyeless arthropods have been regarded as basal crustaceans in most early morphological and taxonomic studies. However, molecular sequence information together with the discovery of a highly differentiated brain led to a reconsideration of their phylogenetic position. Various conflicting hypotheses have been proposed including the claim for a basal position of Remipedia up to a close relationship with Malacostraca or Hexapoda. To provide new morphological characters that may allow phylogenetic insights, we have analyzed the architecture of the remipede brain in more detail using immunocytochemistry (serotonin, acetylated α-tubulin, synapsin) combined with confocal laser-scanning microscopy and image reconstruction techniques. This approach allows for a comprehensive neuroanatomical comparison with other crustacean and hexapod taxa.

Results

The dominant structures of the brain are the deutocerebral olfactory neuropils, which are linked by the olfactory globular tracts to the protocerebral hemiellipsoid bodies. The olfactory globular tracts form a characteristic chiasm in the center of the brain. InSpeleonectes tulumensis, each brain hemisphere contains about 120 serotonin immunoreactive neurons, which are distributed in distinct cell groups supplying fine, profusely branching neurites to 16 neuropilar domains. The olfactory neuropil comprises more than 300 spherical olfactory glomeruli arranged in sublobes. Eight serotonin immunoreactive neurons homogeneously innervate the olfactory glomeruli. In the protocerebrum, serotonin immunoreactivity revealed several structures, which, based on their position and connectivity resemble a central complex comprising a central body, a protocerebral bridge, W-, X-, Y-, Z-tracts, and lateral accessory lobes.

Conclusions

The brain of Remipedia shows several plesiomorphic features shared with other Mandibulata, such as deutocerebral olfactory neuropils with a glomerular organization, innervations by serotonin immunoreactive interneurons, and connections to protocerebral neuropils. Also, we provided tentative evidence for W-, X-, Y-, Z-tracts in the remipedian central complex like in the brain of Malacostraca, and Hexapoda. Furthermore, Remipedia display several synapomorphies with Malacostraca supporting a sister group relationship between both taxa. These homologies include a chiasm of the olfactory globular tract, which connects the olfactory neuropils with the lateral protocerebrum and the presence of hemiellipsoid bodies. Even though a growing number of molecular investigations unites Remipedia and Cephalocarida, our neuroanatomical comparison does not provide support for such a sister group relationship.
Transcriptomic profiling of proteases and antiproteases in the liver of sexually mature hens in relation to vitellogenesis
Authors: Bourin Marie , Gautron Joël , Berges Magali , Hennequet-Antier Christelle , Cabau Cédric , Nys Yves , Réhault-Godbert Sophie
Published: September 2012

Background

Most egg yolk precursors are synthesized by the liver, secreted into the blood and transferred into oocytes, to provide nutrients and bioactive molecules for the avian embryo. Three hundred and sixteen distinct proteins have been identified in egg yolk. These include 37 proteases and antiproteases, which are likely to play a role in the formation of the yolk (vitellogenesis), as regulators of protein metabolism. We used a transcriptomic approach to define the protease and antiprotease genes specifically expressed in the hen liver in relation to vitellogenesis by comparing sexually mature and pre-laying chickens showing different steroid milieu.

Results

Using a 20 K chicken oligoarray, a total of 582 genes were shown to be over-expressed in the liver of sexually mature hens (1.2 to 67 fold-differences). Eight of the top ten over-expressed genes are known components of the egg yolk or perivitelline membrane. This list of 582 genes contains 12 proteases and 3 antiproteases. We found that “uncharacterized protein LOC419301/similar to porin” (GeneID:419301), an antiprotease and “cathepsin E-A-like/similar to nothepsin” (GeneID:417848), a protease, were the only over-expressed candidates (21-fold and 35-fold difference, respectively) that are present in the egg yolk. Additionally, we showed the 4-fold over-expression of “ovochymase-2/similar to oviductin” (GeneID:769290), a vitelline membrane-specific protease.

Conclusions

Our approach revealed that three proteases and antiproteases are likely to participate in the formation of the yolk. The role of the other 12 proteases and antiproteases which are over-expressed in our model remains unclear. At least 1/3 of proteases and antiproteases identified in egg yolk and vitelline membrane proteomes are expressed similarly in the liver regardless of the maturity of hens, and have been initially identified as regulators of haemostasis and inflammatory events. The lack of effect of sex steroids on these genes expressed in the liver but the products of which are found in the yolk suggests that these may be passively incorporated into the yolk rather than actively produced for that purpose. These results raise the question of the biological significance of egg yolk proteases and antiproteases, and more generally of all minor proteins that have been identified in egg yolk.
Determinants of periodontal health in pregnant women and association with infants’ anthropometric status: a prospective cohort study from Eastern Uganda
Authors: Wandera Margaret , Åstrøm Anne N , Okullo Isaac , Tumwine James K
Published: September 2012

Background

Preterm-low birth weight delivery is a major cause of infant morbidity and mortality in sub Saharan Africa and has been linked to poor periodontal health during pregnancy. This study investigated predisposing and enabling factors as determinants of oral health indicators in pregnancy as well as the association between periodontal problems at 7 months gestational age and the infants’ anthropometric status.

Method

A community –based prospective cohort study was conducted in Mbale, Eastern Uganda between 2006 and 2008. Upon recruitment, 713 pregnant women completed interviews and a full mouth oral clinical examination using the CPITN (Community Periodontal Index of Treatment Need) and OHI-S (Simplified Oral Hygiene) indices. A total of 593 women were followed up with anthropometric assessments of their infants 3 weeks after delivery. Multiple logistic regression analyses were used to identify independent determinants of periodontal problems and use of dental services during pregnancy. Analysis of covariance (ANCOVA) was used to investigate the relationship between periodontal problems and the child’s anthropometric status in terms of wasting, underweight and stunting.

Results

A total of 67.0% women presented with periodontal problems, 12.1% with poor oral hygiene, 29.8% with recent dental visit and 65.0% with periodontal symptoms. Of the infants, 2.0% were wasted, 6.9% were underweight and 10.0% were stunted. The odds ratio of having CPI > 0 increased with increased maternal age and single marital status, and was lower in primiparous women and those who used mosquito bed nets. Mean wasting scores discriminated between mothers with CPI = 0 and CPI > 0 as well as between mothers with good and poor OHI-S scores.

Conclusions

Socio-demographic factors and information about oral health were associated with oral health indicators in pregnant women. Second, the height- for- age status at 3 weeks postpartum was worse in infants of mothers having periodontal problems and poor oral hygiene during pregnancy. Efforts to prevent oral diseases during pregnancy should be part of the local state and national health policy agenda in Uganda.
Validity of self-reported use of sulphadoxine-pyrimethamine intermittent presumptive treatment during pregnancy (IPTp): a cross-sectional study
Authors: Namusoke Fatuma , Ntale Muhammad , Wahlgren Mats , Kironde Fred , Mirembe Florence
Published: September 2012

Background

Malaria in pregnancy is a major health problem that can cause maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra-uterine stunting. The WHO recommends use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic areas. Towards monitoring and assessing IPTp coverage in the population, the Roll Back Malaria Partnership recommends the use of self-reported data. The aim of this study was to assess the validity of self-reported IPTp by testing for sulphadoxine in maternal blood at delivery.

Methods

Two hundred and four pregnant women were consented and enrolled in a cross-sectional study in Mulago National Referral Hospital in Kampala Uganda. - Participants who reported a history of taking sulpha-containing drugs like co-trimoxazole , those who were not sure of dates relating to last menstrual period or who took IPTp within the first 20 weeks of gestation were excluded from the study. Data on demographic characteristics, obstetric history, and delivery outcome were collected. At birth, maternal venous blood was taken off aseptically and used to make thick blood smears for malaria parasites and plasma for determining sulphadoxine using high performance liquid chromatography (HPLC).

Results

Of 120 participants who self reported to have used IPTp, 35 (29.2%) tested positive for sulphadoxine by HPLC, while 63 (75%) of 84 patients who reported not having used IPTp tested negative for sulphadoxine. Participants possessing post-primary education were more likely to have reported using IPTp. The low agreement (kappa coefficient = 0.037) between self-report and actual presence of the drug in the blood casts doubt on the validity of self-reported data in estimating IPTp coverage.

Conclusions

The results of this study question the accuracy of self-reported data in estimating IPTp coverage in the population. More studies on validity of self reported data are recommended. Since the validity of IPTp self reports is vital for guiding policy on malaria control in pregnancy, ways should be sought to improve accuracy of the information from such reports.
Neurocognitive Function and CNS Integrity in Adult Survivors of Childhood Hodgkin Lymphoma
Authors: Krull Kevin R. , Sabin Noah D. , Reddick Wilburn E. , Zhu Liang , Armstrong Gregory T. , Green Daniel M. , Arevalo Alejandro R. , Krasin Matthew J. , Srivastava Deo Kumar , Robison Leslie L. , Hudson Melissa M.
Published: September 2012

Purpose

Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL.

Patients and Methods

In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations.

Results

Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E′; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E′]; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DLcocorr; P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E′, although impaired sustained attention and naming speed were associated with DLcocorr. Neurocognitive performance was associated with academic and vocational functioning.

Conclusion

These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.
Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen
Authors: Van Cutsem Eric , Tabernero Josep , Lakomy Radek , Prenen Hans , Prausová Jana , Macarulla Teresa , Ruff Paul , van Hazel Guy A. , Moiseyenko Vladimir , Ferry David , McKendrick Joe , Polikoff Jonathan , Tellier Alexia , Castan Rémi , Allegra Carmen
Published: September 2012

Purpose

Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab.

Patients and Methods

Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival.

Results

Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti–vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities.

Conclusion

Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.
Isoorientin Reverts TNF-α-Induced Insulin Resistance in Adipocytes Activating the Insulin Signaling Pathway
Authors: Alonso-Castro Angel Josabad , Zapata-Bustos Rocio , Gómez-Espinoza Guadalupe , Salazar-Olivo Luis A.
Published: September 2012

Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.
Chemerin, a Novel Regulator of Follicular Steroidogenesis and Its Potential Involvement in Polycystic Ovarian Syndrome
Authors: Wang Qi , Kim Ji Young , Xue Kai , Liu Jia-yin , Leader Arthur , Tsang Benjamin K.
Published: September 2012

Polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome associated with follicle growth arrest, minimal granulosa cell proliferation, dysregulated sex hormone profile, hyperthecosis, and insulin resistance. Using a 5α-dihydrotestosterone (DHT)-induced rat model that recapitulates the reproductive and metabolic phenotypes of human PCOS, we have examined the steroidogenic capability of granulosa cells from DHT-treated rats. Gene expression of several key steroidogenic enzymes including p450 side-chain cleavage enzyme (p450scc), aromatase, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenase-17β, and hydroxysteroid dehydrogenase-3β were markedly lower in DHT-treated rats than the controls, although the responsiveness of their granulosa cells to FSH was higher. Expression of the adipokine chemerin and its receptor, chemokine receptor-like 1, was evident in control and DHT-treated rats, with significantly higher ovarian mRNA abundances and protein contents of chemerin and its receptor. Recombinant chemerin decreases basal estradiol secretion in granulosa cells from DHT-treated rats. When the inhibitory role of chemerin on steroidogenesis was further examined in vitro, chemerin suppressed FSH-induced progesterone and estradiol secretion in cultured preantral follicles and granulosa cells. Chemerin also inhibits FSH-induced aromatase and p450scc expression in granulosa cells. Overexpression of nuclear receptors NR5a1 and NR5a2 promotes p450scc and aromatase expression, respectively, which is suppressed by chemerin. These findings suggest that chemerin is a novel negative regulator of FSH-induced follicular steroidogenesis and may contribute to the pathogenesis of PCOS.
Phosphodiesterase Type 5 Inhibition Reverts Prostate Fibroblast-to-Myofibroblast Trans-Differentiation
Authors: Zenzmaier Christoph , Kern Johann , Sampson Natalie , Heitz Martin , Plas Eugen , Untergasser Gerold , Berger Peter
Published: September 2012

Phosphodiesterase type 5 (PDE5) inhibitors have been demonstrated to improve lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). Because BPH is primarily driven by fibroblast-to-myofibroblast trans-differentiation, this study aimed to evaluate the potential of the PDE5 inhibitor vardenafil to inhibit and reverse trans-differentation of primary human prostatic stromal cells (PrSC). Vardenafil, sodium nitroprusside, lentiviral-delivered short hairpin RNA-mediated PDE5 knockdown, sodium orthovanadate, and inhibitors of MAPK kinase, protein kinase G, Ras homolog family member (Rho) A, RhoA/Rho kinase, phosphatidylinositol 3 kinase and protein kinase B (AKT) were applied to PrSC treated with basic fibroblast growth factor (fibroblasts) or TGFβ1 (myofibroblasts) in vitro, in chicken chorioallantoic membrane xenografts in vivo, and to prostatic organoids ex vivo. Fibroblast-to-myofibroblast trans-differentiation was monitored by smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels. Vardenafil significantly attenuated TGFβ1-induced PrSC trans-differentiation in vitro and in chorioallantoic membrane xenografts. Enhancement of nitric oxide/cyclic guanosine monophosphate signaling by vardenafil, sodium nitroprusside, or PDE5 knockdown reduced smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels and restored fibroblast-like morphology in trans-differentiated myofibroblast. This reversal of trans-differentiation was not affected by MAPK kinase, protein kinase G, RhoA, or RhoA/Rho kinase inhibition, but vardenafil attenuated phospho-AKT levels in myofibroblasts. Consistently, phosphatidylinositol 3 kinase or AKT inhibition induced reversal of trans-differentiation, whereas the tyrosine phosphatase inhibitor sodium orthovanadate abrogated the effect of vardenafil. Treatment of prostatic organoids with vardenafil ex vivo reduced expression of myofibroblast markers, indicating reverse remodeling of stroma towards a desired higher fibroblast/myofibroblast ratio. Thus, enhancement of the nitric oxide/cyclic guanosine monophosphate signaling pathway by vardenafil attenuates and reverts fibroblast-to-myofibroblast trans-differentiation, hypothesizing that BPH patients might benefit from long-term therapy with PDE5 inhibitors.
cAMP-Mediated and Metabolic Amplification of Insulin Secretion Are Distinct Pathways Sharing Independence of β-Cell Microfilaments
Authors: Mourad Nizar I. , Nenquin Myriam , Henquin Jean-Claude
Published: September 2012

Insulin secretion is triggered by an increase in the cytosolic calcium concentration ([Ca2+]c) in β-cells. Ca2+-induced exocytosis of insulin granules can be augmented by metabolic amplification (unknown signals generated through glucose metabolism) or neurohormonal amplification (in particular cAMP mediated). Functional actin microfilaments are not required for metabolic amplification, but their possible role in cAMP-mediated amplification is unknown. It is also uncertain whether cAMP (generated in response to glucose) is implicated in metabolic amplification. These questions were addressed using isolated mouse islets. cAMP levels were increased by phosphodiesterase inhibition (with isobutylmethylxanthine) and adenylate-cyclase stimulation (with forskolin or glucagon-like peptide-1, 7-36 amide). Raising cAMP levels had no steady-state impact on actin polymerization in control islets. Neither disruption (depolymerization by latrunculin) nor stabilization (polymerization by jasplakinolide) of actin microfilaments was counteracted by cAMP. Both changes increased both phases of glucose- or tolbutamide-induced insulin secretion but did not prevent further amplification by cAMP. These large changes in secretion were not caused by changes in [Ca2+]c, which was only slightly increased by cAMP. Both phases of insulin secretion were larger in response to glucose than tolbutamide, although [Ca2+]c was lower. This difference in secretion, which reflects metabolic amplification, was independent of microfilaments, was not attributable to differences in cAMP, and persisted in presence of dibutyryl-cAMP or when cAMP levels were variably raised by isobutylmethylxanthine + forskolin or glucagon-like peptide-1, 7-36 amide. We conclude that metabolic and cAMP-mediated amplification of insulin secretion are distinct pathways that accelerate acquisition of release competence by insulin granules that can access exocytotic sites without intervention of microfilaments.
Polycystic Ovary-Like Abnormalities (PCO-L) in Women with Functional Hypothalamic Amenorrhea
Authors: Robin G. , Gallo C. , Catteau-Jonard S. , Lefebvre-Maunoury C. , Pigny P. , Duhamel A. , Dewailly D.
Published: September 2012

Context:

In the general population, about 30% of asymptomatic women have polycystic ovary-like abnormalities (PCO-L), i.e. polycystic ovarian morphology (PCOM) at ultrasound and/or increased anti-Müllerian hormone (AMH) serum level. PCOM has also been reported in 30–50% of women with functional hypothalamic amenorrhea (FHA).

Objective:

The aim of this study was to verify whether both PCOM and excessive AMH level indicate PCO-L in FHA and to elucidate its significance.

Design:

We conducted a retrospective analysis using a database and comparison with a control population.

Setting:

Subjects received ambulatory care in an academic hospital.

Patients:

Fifty-eight patients with FHA were compared to 217 control women with nonendocrine infertility and body mass index of less than 25 kg/m2.

Interventions:

There were no interventions.

Main Outcome Measures:

We measured serum testosterone, androstenedione, FSH, LH, AMH, and ovarian area values. The antral follicle count (AFC) was used as a binary variable (i.e. negative or positive) because of the evolution of its sensitivity over the time of this study. The ability of these variables (except AFC) to detect PCO-L in both populations was tested by cluster analysis.

Results:

One cluster (cluster 2) suggesting PCO-L was detected in the control population (n = 52; 24%), whereas two such clusters were observed in the FHA population (n = 22 and n = 6; 38 and 10%; clusters 2 and 3, respectively). Cluster 2 in FHA had similar features of PCO-L as cluster 2 in controls, with higher prevalence of positive AFC (70%) and PCOM (70%), higher values of ovarian area and higher serum AMH (P < 0.0001 for all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in FHA was peculiar, with frankly elevated AMH levels. In the whole population (controls + FHA), PCO-L was significantly associated with lower FSH values (P < 0.0001).

Conclusion:

PCO-L in FHA is a frequent and usually incidental finding of unclear significance, as in controls. The association of PCO-L with hypothalamic amenorrhea should not lead to a mistaken diagnosis of PCOS.
Breast compression in mammography: pressure distribution patterns
Authors: Dustler Magnus , Andersson Ingvar , Brorson Håkan , Fröjd Patrik , Mattsson Sören , Tingberg Anders , Zackrisson Sophia , Förnvik Daniel
Published: September 2012

Background

Breast compression is important in mammography in order to improve image quality, better separate tissue components, and reduce absorbed dose to the breast. In this study we use a method to measure and visualize the distribution of pressure over a compressed breast in mammography.

Purpose

To measure and describe the pressure distribution over the breast as a result of applied breast compression in mammography.

Material and Methods

One hundred and three women aged 40.7-74.3 years (median, 48.9 years) invited for mammographic screening consented to take part in this study. They were subjected to two additional breast compressions of the left breast (standard force and approximately 50% reduction). Pressure images of the compressed breast were obtained using force sensing resistor (FSR) sensors placed underneath the compression plate. Subjects rated their experience of pain on a visual analogue scale (VAS).

Results

Four pressure patterns were identified, fitting 81 of the 103 breasts, which were grouped accordingly. The remaining 22 breasts were found to correspond to a combination of any two patterns. Two groups (43 breasts) showed pressure mainly over the juxtathoracic part of the breast, had significantly greater breast thickness ( P = 0.003) and had a lower mean pressure over dense tissue ( P < 0.0001) than those with more evenly distributed pressure. Reducing compression force increased average breast thickness by 1.8 mm ( P < 0.0001).

Conclusion

The distribution of pressure differed greatly between breasts. In a large proportion of breasts the compression plate did not provide optimal compression of the breast, the compression force being absorbed in juxtathoracic structures.