bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering large viral DNA genomes using the CRISPR‐Cas9 system
Authors: Suenaga Tadahiro , Kohyama Masako , Hirayasu Kouyuki , Arase Hisashi
Published: July 2014

Manipulation of viral genomes is essential for studying viral gene function and utilizing viruses for therapy. Several techniques for viral genome engineering have been developed. Homologous recombination in virus‐infected cells has traditionally been used to edit viral genomes; however, the frequency of the expected recombination is quite low. Alternatively, large viral genomes have been edited using a bacterial artificial chromosome (BAC) plasmid system. However, cloning of large viral genomes into BAC plasmids is both laborious and time‐consuming. In addition, because it is possible for insertion into the viral genome of drug selection markers or parts of BAC plasmids to affect viral function, artificial genes sometimes need to be removed from edited viruses. Herpes simplex virus (HSV), a common DNA virus with a genome length of 152 kbp, causes labialis, genital herpes and encephalitis. Mutant HSV is a candidate for oncotherapy, in which HSV is used to kill tumor cells. In this study, the clustered regularly interspaced short palindromic repeat‐Cas9 system was used to very efficiently engineer HSV without inserting artificial genes into viral genomes. Not only gene‐ablated HSV but also gene knock‐in HSV were generated using this method. Furthermore, selection with phenotypes of edited genes promotes the isolation efficiencies of expectedly mutated viral clones. Because our method can be applied to other DNA viruses such as Epstein–Barr virus, cytomegaloviruses, vaccinia virus and baculovirus, our system will be useful for studying various types of viruses, including clinical isolates.
FgSKN7 and FgATF1 have overlapping functions in ascosporogenesis, pathogenesis and stress responses in Fusarium graminearum
Authors: Jiang Cong , Zhang Shijie , Zhang Qiang , Tao Yin , Wang Chenfang , Xu Jin‐Rong
Published: July 2014

Fusarium head blight caused by Fusarium graminearum is one of the most destructive diseases of wheat and barley. Deoxynivalenol (DON) produced by the pathogen is an important mycotoxins and virulence factor. Because oxidative burst is a common defense response and reactive oxygen species (ROS) induces DON production, in this study, we characterized functional relationships of three stress‐related transcription factor genes FgAP1, FgATF1 and FgSKN7. Although all of them played a role in tolerance to oxidative stress, deletion of FgAP1 or FgATF1 had no significant effect on DON production. In contrast, Fgskn7 mutants were reduced in DON production and defective in H2O2‐induced TRI gene expression. The Fgap1 mutant had no detectable phenotype other than increased sensitivity to H2O2 and Fgap1 Fgatf1 and Fgap1 Fgskn7 mutants lacked additional or more severe phenotypes than the single mutants. The Fgatf1, but not Fgskn7, mutant was significantly reduced in virulence and delayed in ascospore release. The Fgskn7 Fgatf1 double mutant had more severe defects in growth, conidiation and virulence than the Fgatf1 or Fgskn7 mutant. Instead of producing four‐celled ascospores, it formed eight small, single‐celled ascospores in each ascus. Therefore, FgSKN7 and FgATF1 must have overlapping functions in intracellular ROS signalling for growth, development and pathogenesis in F. graminearum.
Oil Wealth, Ethno‐Religious‐Linguistic Fractionalization and Civil Wars in Africa: Cross‐Country Evidence
Authors: Anyanwu John C.
Published: July 2014

We empirically examine the effect of oil wealth and ethno‐religious‐linguistic fractionalization on civil war prevalence in Africa, by using three different estimation strategies and alternative measures of societal diversity. We show that oil wealth and the three distributional measures of ethnic fractionalization, religious fractionalization and linguistic fractionalization are significant correlates of civil war in Africa. These effects persist as we use an alternative measure of the prevalence of civil war. Thus, while oil wealthy, ethnically and linguistically fractionalized countries are more likely to experience civil violence, religiously fractionalized ones are less likely to experience significant civil violence in the Continent. We also find that countries with large population size, rough (mountainous) terrain and coup‐prone are at greater risk for civil war than those that are more democratic with high per capita income and economic growth.
Speculative Method and Twitter: Bots, Energy and Three Conceptual Characters
Authors: Wilkie Alex , Michael Mike , Plummer-Fernandez Matthew
Published: July 2014

This paper aims to contribute to recent innovations in social scientific methodology that aspire to address the complex, iterative and performative dimensions of method. In particular, we focus on the becoming-with character of social events, and propose a speculative method for engaging with the not-as-yet. This work, being part of a larger project that uses Speculative Design and ethnographic methods to explore energy-demand reduction, specifically considers the ways in which energy-demand reduction features in the Twitter-sphere. Developing and deploying three automated Bots whose function and communications are at best obscure, and not uncommonly nonsensical, we trace some of ways in which they intervene and provoke. Heuristically, we draw on the ‘conceptual characters’ of idiot, parasite and diplomat in order to grasp how the Bots act within Twitter to evoke the instability and emergent eventuations of energy-demand reduction, community and related practices. We conclude by drawing out some of the wider implications of this particular enactment of speculative method.
Effects of Penicillium roqueforti and whey cheese on gross composition, microbiology and proteolysis of mould‐ripened Civil cheese during ripening
Authors: Cakmakci Songul , Hayaloglu Ali A , Dagdemir Elif , Cetin Bulent , Gurses Mustafa , Tahmas‐Kahyaoglu Deren
Published: July 2014

Four different types of mould‐ripened Civil cheese were manufactured. A defined (nontoxigenic) strain of a Penicillium roqueforti (SC 509) was used as the secondary starter with and without addition of the whey cheese (Lor); in parallel, secondary starter‐free counterparts were manufactured. Chemical composition, microbiology and proteolysis were studied during the ripening. The incorporation of whey cheese in the manufacture of mould‐ripened Civil cheese altered the gross composition and adversely affected proteolysis in the cheeses. The inoculated P. roqueforti moulds appeared to grow slowly on those cheeses, and little proteolysis was evident in all cheese treatments during the first 90 days of ripening. However, sharp increases in the soluble nitrogen fractions were observed in all cheeses after 90 days. Microbiological analysis showed that the microbial counts in the cheeses were at high levels at the beginning of ripening, while their counts decreased approximately 1–2 log cfu/g towards the end of ripening.
Does preoperative urodynamics improve outcomes for women undergoing surgery for stress urinary incontinence? A systematic review and meta‐analysis
Authors: Rachaneni S , Latthe P
Published: July 2014

Background

Urodynamics is widely used in the investigation of urinary incontinence. The existing evidence questions its add‐on value in improving the outcome of surgical treatment for stress urinary incontinence (SUI).

Objectives

To compare the surgical outcomes in women with SUI or stress‐predominant mixed urinary incontinence (MUI) based on urodynamic diagnoses compared with diagnoses based on office evaluation without urodynamics.

Search strategy

We searched Cochrane, MedLine, Embase, CINAHL, LILACS, metaRegister of Controlled Trials (mRCT) and Google Scholar databases from inception until March 2013.

Selection criteria

We included randomised controlled trials (RCTs) comparing surgical outcomes in women investigated by urodynamics and women who had office evaluation only.

Data collection and analysis

Two independent reviewers (S.R. and P.L.) extracted the data and analysed it using review manager (revman) 5.2 software.

Main results

Of the 388 articles identified, only four RCTs met our criteria. The data from one study are as yet unpublished. In the other three RCTs, the women with SUI or stress‐predominant MUI were randomised either to office evaluation and urodynamics (n = 388) or to office evaluation only (n = 387). There was no statistical difference in the risk ratio (RR) of subjective cure in the two groups (RR 1.02, 95%CI 0.90–1.15, P = 0.79, I2 = 45%), objective cure (RR 1.01, 95%CI 0.93–1.11, P = 0.28, I2 = 20%) or complications such as voiding dysfunction (RR 1.54, 95%CI 0.61–3.89, P = 0.27, I2 = 18%) or urinary urgency (RR 0.80, 95%CI 0.28–2.3, P = 0.19, I2 = 40%).

Authors' conclusions

In women undergoing primary surgery for SUI or stress‐predominant MUI without voiding difficulties, urodynamics does not improve outcomes – as long as the women undergo careful office evaluation.
Cost Savings from Palliative Care Teams and Guidance for a Financially Viable Palliative Care Program
Authors: McCarthy Ian M. , Robinson Chessie , Huq Sakib , Philastre Martha , Fine Robert L.
Published: July 2014

Objectives

To quantify the cost savings of palliative care (PC) and identify differences in savings according to team structure, patient diagnosis, and timing of consult.

Data Sources

Hospital administrative records on all inpatient stays at five hospital campuses from January 2009 through June 2012.

Study Design

The analysis matched PC patients to non‐PC patients (separately by discharge status) using propensity score methods. Weighted generalized linear model regressions of hospital costs were estimated for the matched groups.

Data Collection

Data were restricted to patients at least 18 years old with inpatient stays of between 7 and 30 days. Variables available included patient demographics, primary and secondary diagnoses, hospital costs incurred for the inpatient stay, and when/if the patient had a PC consult.

Principal Findings

We found overall cost savings from PC of $3,426 per patient for those dying in the hospital. No significant cost savings were found for patients discharged alive; however, significant cost savings for patients discharged alive could be achieved for certain diagnoses, PC team structures, or if consults occurred within 10 days of admission.

Conclusions

Appropriately selected and timed PC consults with physician and RN involvement can help ensure a financially viable PC program via cost savings to the hospital.
Efficacy of dipeptidyl‐peptidase‐4 inhibitors and impact on β‐cell function in Asian and Caucasian type 2 diabetes mellitus patients: A meta‐analysis在亚洲人和白种人的2型糖尿病患者中DPP‐4抑制剂的疗效及对β细胞功能的影响：一项meta分析
Authors: Cai Xiaoling , Han Xueyao , Luo Yingying , Ji Linong
Published: July 2014

Background

This work aimed to compare the efficacy of dipeptidyl peptidase‐IV (DPP‐4) inhibitors and their impact on β‐cell function in Asian and Caucasian patients with type 2 diabetes mellitus.

Methods

Databases were systematically searched and qualifying studies that compared DPP‐4 inhibitors with other antidiabetic medications in type 2 diabetes were included.

Results

A total of 68 studies were included in the meta‐analysis. Comparison of DPP‐4 inhibitors with placebo in Asian patients showed a decrease in glycosylated hemoglobin (HbA1c) favoring DPP‐4 inhibitors (weighted mean difference [WMD], −0.81%; 95% confidence interval [CI], −0.95% to −0.68%; P < 0.001). Comparison of HbA1c changes between Asian and Caucasian patients showed a significant between‐group difference of −0.18% (95% CI, −0.32% to −0.04%; P = 0.011) when compared with placebo. In Asian patients, the homeostatic model assessment for β‐cell function (HOMA‐β) was increased with DPP‐4 inhibitors compared with placebo (WMD, 7.90; 95% CI, 4.29 to 11.51; P < 0.001), although to a lesser extent in Caucasian patients. Comparisons between Asian and Caucasian patients showed a significant between‐group difference of −4.97 (95% CI, −9.86 to −0.09; P = 0.046) compared with placebo. Body weight increase with DPP‐4 inhibitors compared with placebo was comparable in Asian and Caucasian studies (WMD, 0.37 kg and 0.45 kg and 95% CI, 0.04–0.69 and 0.27–0.62, respectively).

Conclusions

The glucose‐lowering efficacy of DPP‐4 inhibitors was greater in Asian patients than in Caucasian patients, although the effect on β‐cell function was inferior in Asian patients. The effect of DPP‐4 inhibitors on insulin resistance and body weight in Asian patients was comparable with that observed in Caucasian patients.
Weight loss effect of glucagon‐like peptide‐1 mimetics on obese/overweight adults without diabetes: A systematic review and meta‐analysis of randomized controlled trials胰高血糖素样肽‐1类似物对非糖尿病肥胖/超重成人的减重作用：一篇对随机对照试验进行的系统评价及meta分析
Authors: Zhang Fang , Tong Yuzhen , Su Na , Li Yi , Tang Lizhi , Huang Li , Tong Nanwei
Published: July 2014

Background

Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) benefit weight maintenance for diabetic patients. We performed a systematic review to evaluate its weight loss effect on obese/overweight patients without diabetes in randomized controlled trials (RCTs).

Methods

Literature updated to May 5, 2014 from Cochrane Library, MEDLINE, EMBASE and reference lists from relevant articles were identified. RCTs with GLP‐1 mimetics treating obese/overweight adults without diabetes for at least 12 weeks were assessed. Studies lacking primary measurements were excluded. Three authors extracted data independently. Either fixed‐effect or random‐effect models were used to calculate weighted mean differences (WMDs), combined relative risks (RR) and 95% confidence interval (CI) in meta‐analyses. Intertrial heterogeneity across studies was examined by I2 and Q statistics.

Results

A total of 1345 individuals retrieved from eight studies were involved and all included trials were of mild‐to‐moderate bias risks. Participants in GLP‐1RA groups achieved a larger weight loss than those in control groups (−2.85 kg, 95%CI −3.55 to −2.14), and liraglutide may work in a dose‐dependent fashion. GLP‐1RAs also reduced body mass index (BMI) and waist circumferences (WC) and benefited systolic blood pressure and triglyceride regulation. But GLP‐1RAs were associated with increased nausea and vomiting events.

Conclusions

GLP‐1 mimetics induce a weight loss in addition to BMI and WC reduction in obese/overweight adults without diabetes. Further long‐term randomized trials and basic studies are required to investigate the mechanisms.
Cocaine's fall and marijuana's rise: questions and insights based on new estimates of consumption and expenditures in US drug markets
Authors: Caulkins Jonathan P. , Kilmer Beau , Reuter Peter H. , Midgette Greg
Published: July 2014

Aims

Drug policy strategies and discussions often use prevalence of drug use as a primary performance indicator. However, three other indicators are at least as relevant: the number of heavy users, total expenditures and total amount consumed. This paper stems from our efforts to develop annual estimates of these three measures for cocaine (including crack), heroin, marijuana and methamphetamine in the United States.

Methods

The estimates exploit complementary strengths of a general population survey (National Survey on Drug Use and Health) and both survey and urinalysis test result data for arrestees (Arrestee Drug Abuse Monitoring Program), supplemented by many other data sources.

Results

Throughout the 2000s US drug users spent in the order of $100 billion annually on these drugs, although the spending distribution and use patterns changed dramatically. From 2006 to 2010, the amount of marijuana consumed in the United States probably increased by more than 30%, while the amount of cocaine consumed in the United States fell by approximately 50%. These figures are consistent with supply‐side indicators, such as seizures and production estimates. For all the drugs, total consumption and expenditures are driven by the minority of users who consume on 21 or more days each month.

Conclusions

Even for established drugs, consumption can change rapidly. The halving of the cocaine market in five years and the parallel (but independent) large rise in daily/near‐daily marijuana use are major events that were not anticipated by the expert community and raise important theoretical, research, and policy issues.
Relationship between primary colorectal tumour and location of colorectal liver metastases
Authors: Pathak Samir , Palkhi Ebrahim , Dave Rajiv , White Alan , Pandanaboyana Sanjay , Prasad K. Raj , Lodge J. Peter A. , Toogood Giles J.
Published: July 2014

Background

There is conflicting evidence regarding whether streamlining of blood flow within the portal vein influences the anatomical distribution of colorectal liver metastases (CRLM). This study assesses the relationship between primary tumour location and metastases location.

Methods

Patients were identified using a prospectively maintained database, and those with known site of primary colorectal tumour and hemiliver involvement were included. Site of metastases and segments affected were confirmed via review of the radiology reports. The location of primary colonic tumour was confirmed via review of clinical correspondence letters.

Results

A total of 2364 metastases were identified in 891 patients. Of these, 379 metastases were in the right lobe and 156 in the left lobe, with 356 having bilobar disease. There was no significant relationship between the distribution of CRLM and the site of primary disease (left colon versus right colon) (P = 0.819). However, when the segmental location of the metastases was considered, there is a statistically significant difference between the number of right‐sided CRLM compared with left‐sided CRLM (P < 0.001).

Conclusions

Right‐sided CRLM is more likely regardless of the primary location. Portal streaming may have an effect, although the natural anatomical ‘angulation’, particularly of the left portal vein branch is more likely to play a role.
System review and meta‐analysis on photodynamic therapy in central serous chorioretinopathy
Authors: Ma Jinlan , Meng Nana , Xu Xiaoyi , Zhou Fang , Qu Yi
Published: July 2014

Purpose

To evaluate the effect of photodynamic therapy (PDT) on central serous chorioretinopathy (CSC) compared with laser therapy and intravitreal injection of anti‐vascular endothelial growth factor (anti‐VEGF) drugs, and to find the maximum treatment effect with minimal dose and fluence of PDT.

Methods

A systematic electronic search was conducted in Feb 2013 in PubMed, Embase, ISI Web of Knowledge and the Cochrane library. The main outcome factors were compared in best‐corrected visual acuity (BCVA), central macular thickness (CMT) and resolution of subretinal fluid (SRF). Meta‐analysis was performed when it is appropriate. The comparisons were designed into four groups: group 1, PDT versus laser photocoagulation; group 2, PDT versus intravitreal injection of anti‐VEGF drugs; group 3, half‐dose verteporfin PDT versus placebo; group 4, half‐fluence PDT versus full‐fluence PDT.

Results

We retrieved nine reports of studies including a total of 319 patients. In group 1, the summary result indicated that PDT was superior in resolution of SRF (p = 0.005) than laser photocoagulation. In group 2, PDT could resolute SRF (p = 0.007) and decrease CMT (p = 0.002) more rapidly than intravitreal injection of anti‐VEGF drugs. In group 3, half‐dose PDT was effective in improving BCVA (p < 0.00001), decreasing CMT (p = 0.001) and resolving SRF (p < 0.001). In group 4, half‐fluence PDT was effective and could significantly decrease the hypoxic damage which was caused by PDT (p < 0.001).

Conclusion

PDT is a promising therapy for CSC patients and the parameters of PDT can be adjusted to obtain the maximum treatment effect with minimal adverse effects.
Orthodontic widening of the palate may provide a cure for selected children with therapy‐resistant enuresis
Authors: Nevéus Tryggve , Leissner Lena , Rudblad Stig , Bazargani Farhan
Published: July 2014

Aim

According to a number of small case series, orthodontic treatment may have anti‐enuretic effects. Thus, we evaluated whether widening of the palate can alleviate enuresis and whether prognostic information can be gained from examining children's nocturnal respiration and nasal airway dimensions.

Methods

Children with therapy‐resistant enuresis underwent polysomnography, focusing on nocturnal respiration, and had their nasal airways examined. Rapid maxillary expansion was performed, widening the maxilla by approximately 0.5 cm. The dental appliance was removed after 6 months. Enuresis frequency was evaluated four times: at baseline, with the orthodontic apparatus in situ, after completed maxillary expansion and 1 year post‐treatment.

Results

Of the 34 children recruited, one dropped out due to oral discomfort. The numbers of wet nights per week on the four assessment occasions were 5.48 ± 1.48, 5.12 ± 1.73, 3.09 ± 2.49 and 2.63 ± 2.81; p < 0.001. The proportions of responders, intermediate responders and non‐responders during treatment were 21.2%, 27.3% and 51.5%, respectively. Responders were found to have a lower enuresis frequency at baseline (p = 0.001) and to have larger nasal airway dimensions (p = 0.01).

Conclusion

Orthodontic widening of the palate may be curative in a subgroup of children with therapy‐resistant enuresis.
Determination of the binding mode for the cyclopentapeptide CXCR4 antagonist FC131 using a dual approach of ligand modifications and receptor mutagenesis
Authors: Thiele S , Mungalpara J , Steen A , Rosenkilde M M , Våbenø J
Published: July 2014

Background and Purpose

The cyclopentapeptide FC131 (cyclo(‐L‐Arg1‐L‐Arg2‐L‐2‐Nal3‐Gly4‐D‐Tyr5‐)) is an antagonist at the CXC chemokine receptor CXCR4, which plays a role in human immunodeficiency virus infection, cancer and stem cell recruitment. Binding modes for FC131 in CXCR4 have previously been suggested based on molecular docking guided by structure–activity relationship (SAR) data; however, none of these have been verified by in vitro experiments.

Experimental Approach

Heterologous 125I‐12G5‐competition binding and functional assays (inhibition of CXCL12‐mediated activation) of FC131 and three analogues were performed on wild‐type CXCR4 and 25 receptor mutants. Computational modelling was used to rationalize the experimental data.

Key Results

The Arg2 and 2‐Nal3 side chains of FC131 interact with residues in TM‐3 (His113, Asp171) and TM‐5 (hydrophobic pocket) respectively. Arg1 forms charge‐charge interactions with Asp187 in ECL‐2, while D‐Tyr5 points to the extracellular side of CXCR4. Furthermore, the backbone of FC131 interacts with the chemokine receptor‐conserved Glu288 via two water molecules. Intriguingly, Tyr116 and Glu288 form a H‐bond in CXCR4 crystal structures and mutation of either residue to Ala abolishes CXCR4 activity.

Conclusions and Implications

Ligand modification, receptor mutagenesis and computational modelling approaches were used to identify the binding mode of FC131 in CXCR4, which was in agreement with binding modes suggested from previous SAR studies. Furthermore, insights into the mechanism for CXCR4 activation by CXCL12 were gained. The combined findings will facilitate future design of novel CXCR4 antagonists.
Fluvial deposition during transition from flexural to dynamic subsidence in the Cordilleran foreland basin: Ericson Formation, Western Wyoming, USA
Authors: Leary Ryan , DeCelles Peter , Gehrels George , Morriss Matthew
Published: July 2014

The Ericson Formation was deposited in the distal foredeep of the Cordilleran foreland basin during Campanian time. Isopach data show that it records early dynamic subsidence and the onset of basin partitioning by Laramide uplifts. The Ericson Formation is well exposed around the Rock Springs uplift, a Laramide structural dome in southwestern Wyoming; the formation is thin, regionally extensive, and does not display the wedge‐shaped geometry typical of foredeep deposits. Sedimentation in this area was controlled both by activity in the thrust belt and by intraforeland tectonics. The Ericson Formation is ideally situated both spatially and temporally to study the transition from Sevier to Laramide (thin‐ to thick‐skinned) deformation which corresponded to the shift from flexural to dynamic subsidence and the demise of the Cretaceous foreland basin system. We establish the depositional age of the Ericson Formation as ca. 74 Ma through detrital zircon U–Pb analysis. Palaeocurrent data show a generally southeastward transport direction, but northward indicators near Flaming Gorge Reservoir suggest that the intraforeland Uinta uplift was rising and shedding sediment northward by late Campanian time. Petrographic data and detrital zircon U–Pb ages indicate that Ericson sediment was derived from erosion of Proterozoic quartzites and Palaeozoic and Mesozoic quartzose sandstones in the Sevier thrust belt to the west. The new data place temporal and geographic constraints on attempts to produce geodynamic models linking flat‐slab subduction of the oceanic Farallon plate to the onset of the Laramide orogenic event.
Structure–activity Relationship Studies of Microbiologically Active Thiosemicarbazides Derived from Hydroxybenzoic Acid Hydrazides
Authors: Plech Tomasz , Paneth Agata , Kaproń Barbara , Kosikowska Urszula , Malm Anna , Strzelczyk Aleksandra , Stączek Paweł
Published: July 2014

Forty‐five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram‐positive and Gram‐negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram‐positive bacteria, whereas only two derivatives had the ability to inhibit the growth of Gram‐negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially at the N4–terminus of thiosemicarbazide skeleton, determines the antibacterial activity. Unfortunately, in opposition to what we expected, only one of the tested compounds inhibited the activity of the topoIV enzyme, and none of them was active against DNA gyrase.
“I Know You Don't Know I Know…” Children Use Second‐Order False‐Belief Reasoning for Peer Coordination
Authors: Grueneisen Sebastian , Wyman Emily , Tomasello Michael
Published: July 2014

Numerous studies have investigated children's abilities to attribute mental states, but few have examined their ability to recruit these abilities in social interactions. Here, 6‐year‐olds (N = 104) were tested on whether they can use first‐ and second‐order false‐belief understanding to coordinate with peers. Children adjusted their decisions in a coordination game in response to either their partner's erroneous belief or their partner's erroneous belief about their own belief—a result that contrasts with previous findings on the use of higher order “theory of mind” (TOM) reasoning at this age. Six‐year‐olds are thus able to use their higher order TOM capacities for peer coordination, which marks an important achievement in becoming competent social collaborators.
Monoracial and Biracial Children: Effects of Racial Identity Saliency on Social Learning and Social Preferences
Authors: Gaither Sarah E. , Chen Eva E. , Corriveau Kathleen H. , Harris Paul L. , Ambady Nalini , Sommers Samuel R.
Published: July 2014

Children prefer learning from, and affiliating with, their racial in‐group but those preferences may vary for biracial children. Monoracial (White, Black, Asian) and biracial (Black/White, Asian/White) children (N = 246, 3–8 years) had their racial identity primed. In a learning preferences task, participants determined the function of a novel object after watching adults (White, Black, and Asian) demonstrate its uses. In the social preferences task, participants saw pairs of children (White, Black, and Asian) and chose with whom they most wanted to socially affiliate. Biracial children showed flexibility in racial identification during learning and social tasks. However, minority‐primed biracial children were not more likely than monoracial minorities to socially affiliate with primed racial in‐group members, indicating their in‐group preferences are contextually based.
The effects of the novel SHIP1 activator AQX‐1125 on allergen‐induced responses in mild‐to‐moderate asthma
Authors: Leaker B. R. , Barnes P. J. , O'Connor B. J. , Ali F. Y. , Tam P. , Neville J. , Mackenzie L. F. , MacRury T.
Published: July 2014

Background

SH2‐containing inositol‐5′‐phosphatase 1 (SHIP1) is an endogenous inhibitor of the phosphoinositide‐3‐kinase pathway that is involved in the activation and chemotaxis of inflammatory cells. AQX‐1125 is a first‐in‐class, oral SHIP1 activator with a novel anti‐inflammatory mode of action.

Objective

To evaluate the effects of AQX‐1125 on airway responses to allergen challenge in mild‐to‐moderate asthmatic patients.

Methods

A randomized, double‐blind, placebo‐controlled, two‐way crossover study was performed in 22 steroid‐naïve mild‐to‐moderate asthmatics with a documented late‐phase response to inhaled allergen (LAR). AQX‐1125 (450 mg daily) or placebo was administered orally for 7 days. Allergen challenge was performed on day 6 (2 h postdose), followed by methacholine challenge (day 7), and induced sputum collection and fractional exhaled nitric oxide (FeNO).

Results

AQX‐1125 significantly attenuated the late‐phase response compared with placebo (FEV1 4–10 h: mean difference 150 mL, 20%; P = 0.027) and significantly increased the minimum FEV1 during LAR (mean difference 180 mL; P = 0.014). AQX‐1125 had no effect on the early‐phase response. AQX‐1125 showed a trend in reduction of sputum eosinophils, neutrophils and macrophages although this did not achieve significance as there were only 11 paired samples for analysis. There was no effect on methacholine responsiveness or FeNO. Pharmacokinetic data showed AQX‐1125 was rapidly absorbed with geometric mean Cmax and AUC0–24 h values of 1417 ng/mL and 16 727 h ng/mL, respectively. AQX‐1125 was well tolerated, but mild GI side‐effects (dyspepsia, nausea and abdominal pain) were described in 4/22 subjects on active treatment. These side‐effects were mild self‐limiting, required no further treatment and did not lead to discontinuation of therapy.

Conclusion and Clinical Relevance

AQX‐1125, a novel oral SHIP1 activator, significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX‐1125 was safe and well tolerated and merits further investigation in inflammatory disorders.
Should all patients with acromegaly receive somatostatin analogue therapy before surgery and, if so, for how long?
Authors: Jacob Jubbin J. , Bevan John S.
Published: July 2014

Current guidelines do not recommend the routine use of somatostatin analogue pretreatment prior to surgery in patients with growth hormone‐secreting pituitary tumours. In theory, presurgical use of somatostatin analogues should improve metabolic control and reduce soft tissue swelling, leading to improved anaesthetic outcomes. Shrinkage of tumours prior to surgery might also improve surgical remission rates. Hence, this article addresses the question: Should all patients with acromegaly receive a somatostatin analogue prior to surgery? Clinical trials published before December 2013 were reviewed, although literature in this area remains relatively deficient. We conclude: (i) On the basis of limited data available, somatostatin analogue pretreatment does not improve anaesthetic or immediate postoperative outcomes (i.e. hospital stay, rates of surgical complications and postoperative pituitary dysfunction). (ii) Somatostatin analogues should be considered in all patients with growth hormone‐secreting macroadenomas, including invasive macroadenomas, when the overall surgical remission rate for macroadenomas at the treating centre is below 50%. Four recent RCTs have demonstrated increased rates of surgical remission using such an approach. (iii) When deemed appropriate, patients should be treated with somatostatin analogues for at least 3 months before surgery; there is currently no evidence that treatment beyond 6 months provides any additional benefit. Patients with minimally invasive macroadenomas are those most likely to benefit in terms of improved surgical remission.
Mandatory Critical Points of 2D Uncertain Scalar Fields
Authors: Günther David , Salmon Joseph , Tierny Julien
Published: July 2014

This paper introduces a novel, non‐local characterization of critical points and their global relation in 2D uncertain scalar fields. The characterization is based on the analysis of the support of the probability density functions (PDF) of the input data. Given two scalar fields representing reliable estimations of the bounds of this support, our strategy identifies mandatory critical points: spatial regions and function ranges where critical points have to occur in any realization of the input. The algorithm provides a global pairing scheme for mandatory critical points which is used to construct mandatory join and split trees. These trees enable a visual exploration of the common topological structure of all possible realizations of the uncertain data. To allow multi‐scale visualization, we introduce a simplification scheme for mandatory critical point pairs revealing the most dominant features. Our technique is purely combinatorial and handles parametric distribution models and ensemble data. It does not depend on any computational parameter and does not suffer from numerical inaccuracy or global inconsistency. The algorithm exploits ideas of the established join/split tree computation. It is therefore simple to implement, and its complexity is output‐sensitive. We illustrate, evaluate, and verify our method on synthetic and real‐world data.
InSpectr: Multi‐Modal Exploration, Visualization, and Analysis of Spectral Data
Authors: Amirkhanov Artem , Fröhler Bernhard , Kastner Johann , Gröller Eduard , Heinzl Christoph
Published: July 2014

This paper addresses the increasing demand in industry for methods to analyze and visualize multimodal data involving a spectral modality. Two data modalities are used: high‐resolution X‐ray computed tomography (XCT) for structural characterization and low‐resolution X‐ray fluorescence (XRF) spectral data for elemental decomposition. We present InSpectr, an integrated tool for the interactive exploration and visual analysis of multimodal, multiscalar data. The tool has been designed around a set of tasks identified by domain experts in the fields of XCT and XRF. It supports registered single scalar and spectral datasets optionally coupled with element maps and reference spectra. InSpectr is instantiating various linked views for the integration of spatial and non‐spatial information to provide insight into an industrial component's structural and material composition: views with volume renderings of composite and individual 3D element maps visualize global material composition; transfer functions defined directly on the spectral data and overlaid pie‐chart glyphs show elemental composition in 2D slice‐views; a representative aggregated spectrum and spectra density histograms are introduced to provide a global overview in the spectral view. Spectral magic lenses, spectrum probing and elemental composition probing of points using a pie‐chart view and a periodic table view aid the local material composition analysis. Two datasets are investigated to outline the usefulness of the presented techniques: a 3D virtually created phantom with a brass metal alloy and a real‐world 2D water phantom with insertions of gold, barium, and gadolinium. Additionally a detailed user evaluation of the results is provided.
Comparative Blood Flow Visualization for Cerebral Aneurysm Treatment Assessment
Authors: van Pelt R. , Gasteiger R. , Lawonn K. , Meuschke M. , Preim B.
Published: July 2014

A pathological vessel dilation in the brain, termed cerebral aneurysm, bears a high risk of rupture, and is associated with a high mortality. In recent years, incidental findings of unruptured aneurysms have become more frequent, mainly due to advances in medical imaging. The pathological condition is often treated with a stent that diverts the blood flow from the aneurysm sac back to the original vessel. Prior to treatment, neuroradiologists need to decide on the optimal stent configuration and judge the long‐term rupture risk, for which blood flow information is essential. Modern patient‐specific simulations can model the hemodynamics for various stent configurations, providing important indicators to support the decision‐making process. However, the necessary visual analysis of these data becomes tedious and time‐consuming, because of the abundance of information. We introduce a comprehensive comparative visualization that integrates morphology with blood flow indicators to facilitate treatment assessment. To deal with the visual complexity, we propose a details‐on‐demand approach, combining established medical visualization techniques with innovative glyphs inspired by information visualization concepts. In an evaluation we have obtained informal feedback from domain experts, gauging the value of our visualization.
Illustrative Visualization of Molecular Reactions using Omniscient Intelligence and Passive Agents
Authors: Le Muzic M. , Parulek J. , Stavrum A.K. , Viola I.
Published: July 2014

In this paper we propose a new type of a particle systems, tailored for illustrative visualization purposes, in particular for visualizing molecular reactions in biological networks. Previous visualizations of biochemical processes were exploiting the results of agent‐based modeling. Such modeling aims at reproducing accurately the stochastic nature of molecular interactions. However, it is impossible to expect events of interest happening at a certain time and location, which is impractical for storytelling. To obtain the means of controlling molecular interactions, we propose to govern passive agents with an omniscient intelligence, instead of giving to the agents the freedom of initiating reaction autonomously. This makes it possible to generate illustrative animated stories that communicate the functioning of the molecular machinery. The rendering performance delivers for interactive framerates of massive amounts of data, based on the dynamic tessellation capabilities of modern graphics cards. Finally, we report an informal expert feedback we obtained from the potential users.
Methods for Compensating Contrast Effects in Information Visualization
Authors: Mittelstädt S. , Stoffel A. , Keim D. A.
Published: July 2014

Color, as one of the most effective visual variables, is used in many techniques to encode and group data points according to different features. Relations between features and groups appear as visual patterns in the visualization. However, optical illusions may bias the perception at the first level of the analysis process. For instance, in pixel‐based visualizations contrast effects make pixels appear brighter if surrounded by a darker area, which distorts the encoded metric quantity of the data points. Even if we are aware of these perceptual issues, our visual cognition system is not able to compensate these effects accurately. To overcome this limitation, we present a color optimization algorithm based on perceptual metrics and color perception models to reduce physiological contrast or color effects. We evaluate our technique with a user study and find that the technique doubles the accuracy of users comparing and estimating color encoded data values. Since the presented technique can be used in any application without adaption to the visualization itself, we are able to demonstrate its effectiveness on data visualizations in different domains.
Visualizing Proximity‐Based Spatiotemporal Behavior of Museum Visitors using Tangram Diagrams
Authors: Lanir J. , Bak P. , Kuflik T.
Published: July 2014

For museum curators it is imperative to learn, analyze, and understand the behavior patterns of the visitors in their museum. Recent developments in the field of indoor positioning systems make the acquisition and availability of visitor behavior data more attainable. However, the analysis of such data remains a challenge due to its noisiness, complexity and sheer size. The current paper applies information visualization techniques to analyze this data and make it more accessible to museum curators and personnel. We first provide a detailed description of the application domain including an analysis of the curators' information needs and a description of how a dataset on visitors' spatiotemporal behavior could be acquired. In order to address the curators' needs, we designed a visualization to encode and convey the information based on a newly adjusted visual glyph that we call Tangram Diagrams. We thereby focus on the adaptability of the technique to a particular domain, rather than on the novelty aspects of the technique itself. We have evaluated our design decisions empirically, and conducted an expert study to describe the insights gained and the value of the information obtained from the visualization. The contribution of this work is twofold. First, we apply information visualization to the museum domain and discuss how it extends to general indoor spatiotemporal behavior analysis. Second, we show how a visual glyph metaphor can be applied in different ways and contexts to efficiently encode multi‐faceted information.
Glyphs for Exploring Crowd‐sourced Subjective Survey Classification
Authors: Kachkaev A. , Wood J. , Dykes J.
Published: July 2014

The findings drawn from opinion survey responses are usually made by producing summary charts or conducting statistical analysis. Both involve data aggregation and filtering as exploring the unaggregated data has traditionally been impractical or error‐prone for large numbers of responses. We propose the use of glyphs with parallel coordinate plots to show all survey responses in a single view and design an interactive visual analytics tool around the representation to explore the data. We use this software for a ‘photo content assessment’ survey, where 359 participants classify 900 images by seven criteria. The proposed approach allows all 8,434 responses (49,285 answers to questions in total) to be represented in a single view and helps analysts to both clean the data and understand the nature of the survey responses. We describe the construction of the survey response glyphs and the interface to the interactive visual analytics software and generalise the design principles that arise from the approach. We apply the tool to two other datasets to evaluate the technique and to confirm its wider applicability for surveys with Likert scale responses.
Vertical components of head‐shaking nystagmus in vestibular neuritis, Meniere's disease and migrainous vertigo
Authors: Kim C.H. , Shin J.E. , Song C.I. , Yoo M.H. , Park H.J.
Published: July 2014

Objectives

To describe vertical and horizontal components of head‐shaking nystagmus (HSN) in various vestibular disorders.

Design

Retrospective case review.

Setting

Tertiary care academic referral centre.

Participants

Head‐shaking nystagmus was assessed in 66 vestibular neuritis (VN) patients at acute (<7 days) and follow‐up (2 months), and 65 Meniere's disease (MD) and 76 migrainous vertigo (MV) in interictal period.

Main outcome measures

Head‐shaking nystagmus was categorised as pure horizontal, pure vertical or mixed. Horizontal HSN was classified as monophasic or biphasic and paretic or recovery. Vertical HSN was classified as upbeat or downbeat.

Results

Abnormal HSN (pathologic monophasic, biphasic or delayed‐peak HSN) showed different positive rates depending on the vestibular disorders and compensation (94% in acute VN; 89% in FU VN; 78% in MD; 50% in MV). Paretic HSN with the nystagmus towards the lesioned side was the most common type in VN and MD; however, recovery HSN with the nystagmus towards the intact side could be rarely observed especially in patients with MD or compensated VN. Vertical nystagmus could be combined with horizontal HSN, and upbeat HSN was observed in most (83%) of the patients with acute VN, but downbeat HSN was common in follow‐up VN (83%), MD (97%) and MV (85%). Weak perverted HSN, which is assumed to be a central nystagmus, was rarely observed in MD and MV (6–9%), but not in VN.

Conclusions

Head‐shaking nystagmus (HSN) in horizontal plane is a valuable tool in the assessment of vestibular imbalance. Common observation of upbeat HSN in acute VN and downbeat HSN in follow‐up VN, MD and MV suggests that vertical components are possibly related to the involvement of vestibular apparatus and compensation. Weak perverted HSN and delayed‐peak HSN were rarely observed in MD and MV, and never observed in VN, suggesting that it is possibly related to either asymmetrically impaired vertical canals or misorientation of the velocity‐storage system.
The Need to Disentangle Key Concepts from Ecosystem‐Approach Jargon
Authors: WAYLEN K. A. , HASTINGS E. J. , BANKS E. A. , HOLSTEAD K. L. , IRVINE R. J. , BLACKSTOCK K. L.
Published: July 2014

The ecosystem approach—as endorsed by the Convention on Biological Diversity (CDB) in 2000—is a strategy for holistic, sustainable, and equitable natural resource management, to be implemented via the 12 Malawi Principles. These principles describe the need to manage nature in terms of dynamic ecosystems, while fully engaging with local peoples. It is an ambitious concept. Today, the term is common throughout the research and policy literature on environmental management. However, multiple meanings have been attached to the term, resulting in confusion. We reviewed references to the ecosystem approach from 1957 to 2012 and identified 3 primary uses: as an alternative to ecosystem management or ecosystem‐based management; in reference to an integrated and equitable approach to resource management as per the CBD; and as a term signifying a focus on understanding and valuing ecosystem services. Although uses of this term and its variants may overlap in meaning, typically, they do not entirely reflect the ethos of the ecosystem approach as defined by the CBD. For example, there is presently an increasing emphasis on ecosystem services, but focusing on these alone does not promote decentralization of management or use of all forms of knowledge, both of which are integral to the CBD's concept. We highlight that the Malawi Principles are at risk of being forgotten. To better understand these principles, more effort to implement them is required. Such efforts should be evaluated, ideally with comparative approaches, before allowing the CBD's concept of holistic and socially engaged management to be abandoned or superseded. It is possible that attempts to implement all 12 principles together will face many challenges, but they may also offer a unique way to promote holistic and equitable governance of natural resources. Therefore, we believe that the CBD's concept of the ecosystem approach demands more attention.

La Necesidad de Desenredar Conceptos Clave del Argot Ambiente‐Estrategia