bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of myo‐inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models
Authors: Tran Ly‐Binh‐An , Cao‐Pham Thanh‐Trang , Jordan Bénédicte F. , Deschoemaeker Sofie , Heyerick Arne , Gallez Bernard
Published: December 2018

Tumour hypoxia is a well‐established factor of resistance in radiation therapy (RT). Myo‐inositol trispyrophosphate (ITPP) is an allosteric effector that reduces the oxygen‐binding affinity of haemoglobin and facilitates the release of oxygen by red blood cells. We investigated herein the oxygenation effect of ITPP in six tumour models and its radiosensitizing effect in two of these models. The evolution of tumour pO2 upon ITPP administration was monitored on six models using 1.2 GHz Electron Paramagnetic Resonance (EPR) oximetry. The effect of ITPP on tumour perfusion was assessed by Hoechst staining and the oxygen consumption rate (OCR) in vitro was measured using 9.5 GHz EPR. The therapeutic effect of ITPP with and without RT was evaluated on rhabdomyosarcoma and 9L‐glioma rat models. ITPP enhanced tumour oxygenation in six models. The administration of 2 g/kg ITPP once daily for 2 days led to a tumour reoxygenation for at least 4 days. ITPP reduced the OCR in six cell lines but had no effect on tumour perfusion when tested on 9L‐gliomas. ITPP plus RT did not improve the outcome in rhabdomyosarcomas. In 9L‐gliomas, some of tumours receiving the combined treatment were cured while other tumours did not benefit from the treatment. ITPP increased oxygenation in six tumour models. A decrease in OCR could contribute to the decrease in tumour hypoxia. The association of RT with ITPP was beneficial for a few 9L‐gliomas but was absent in the rhabdomyosarcomas.
Outcomes following colorectal cancer surgery: Results from a population‐based study in Queensland, Australia, using quality indicators
Authors: Theile David E. , Philpot Shoni , Blake Michael , Harrington John , Youl Philippa H.
Published: December 2018

Rationale, aims and objectives

Colorectal cancer (CRC) is one of the most common cancers diagnosed worldwide, and rates are continuing to rise. Surgery is the primary treatment for CRC, and our aim was to examine clinical outcomes following major resection using a series of established quality indicators and to identify factors associated with poor clinical outcomes.

Method

This population‐based retrospective study included 4321 patients with diagnosed with CRC in 2012 and 2014 in Queensland, Australia, who underwent a major resection. Primary outcomes included in‐hospital mortality, 30‐day unplanned readmission, extended hospital stay (>21 days), and 30‐ and 90‐day mortality. Multivariable logistic regression modelling was conducted to establish factors independently associated with each outcome of interest.

Results

Overall, in‐hospital mortality was 1.5%, 3.0% had an unplanned readmission, 8% had an extended hospital stay, and 30‐ and 90‐day postoperative mortality was 1.6% and 3.1%, respectively. After adjustment, we found that factors such as older age, presence of comorbidities, emergency admission, and stoma formation were significantly associated with poorer outcomes with these findings being consistent across each of the outcomes of interest. In addition to these factors, the risk of 90‐day mortality was significantly elevated for patients with advanced stage disease (OR = 1.95, CI 1.35‐2.82). Sex, primary site, hospital volume, residential location, nor socioeconomic status was found to be associated with any of the outcomes of interest.

Conclusion

Overall, the risk of poorer clinical outcomes for CRC patients in Queensland, Australia, is low. There is however a subgroup of patients at particularly elevated risk of poorer outcomes following CRC. Strategies to reduce the poorer clinical outcomes this group of patients experience should be explored.
Validation of a laser based in‐line aflatoxin sorting technology in Spanish type raw peanut in factory‐scale production conditions
Authors: Liu Jenney Jing , Cai Zhenzhen , Liao Yongcheng , Zhao Lina , Moulin Julie , Hartmann Christoph
Published: December 2018

Aflatoxin (AF) contamination of peanuts represents a significant food safety risk. Developing a rapid and non‐destructive method for in‐line AF detection has received significant attentions. This study confirmed the effectiveness of a laser based in‐line AF sorting technology in a peanut processing factory, with 99% specificity and 75% sensitivity for aflatoxin B1 (AFB1). In total, 80 in‐line sorting trials were undertaken. The accepted samples from 99% trials had AFB1 below 10 μg/kg. In 75% of the trials, the AFB1 content of the rejected material exceeded 10 μg/kg by up to a factor of ca. 20. At a throughput of 2.4–4.0 tons per hour, the rejection rate ranged from 0.7 to 4.7%. No significant differences in AFB1 level and rejection rate were observed among different suppliers nor were there differences among the different quality grades. Overall, the sorter effectively removed AF contaminated peanuts without comprising the line throughput.

Practical applications

The validated in‐line sorting technology can be used in food factories for the control of aflatoxins in food samples such as oilseeds and grains. Furthermore, the technology can be developed for the control of other kinds of mycotoxins.
Aiming for complete safety of first trocar insertion of laparoscopic surgery: usefulness of preoperative ultrasonography of umbilical region
Authors: Nishimura Kazuaki , Yoshimura Kazuaki , Hoshino Kaori , Myoga Mai , Hachisuga Toru
Published: December 2018

Aim

Vascular or intestinal injuries at the time of the first trocar insertion can cause serious complications during laparoscopic surgeries. In this study, we evaluate the usefulness of ultrasound scans of the umbilical region as well as intraumbilical conditions to help prevent serious complications.

Methods

The subjects included 430 cases who underwent laparoscopic gynecologic surgeries. The umbilical ultrasound scan was performed after tracheal intubation to observe the intestinal movements associated with respiration. Structures of the umbilical region as well as peristalsis and the movement of the intestinal tract were observed. Then, the thickness of the subcutaneous fat (between the umbilical skin surface and the rectus fascia) and the preperitoneal fat (between the rectus fascia and the peritoneum) were measured. The relationship between body mass index (BMI), insertion time of the first trocar and ultrasound measurements were analyzed.

Results

The anatomical structures of the umbilical region (the subcutaneous tissue and the preperitoneal fat) were clearly observed in all cases. The BMI score had a significant relationship with subcutaneous fat thickness (r = 0.547), but remarkably not with preperitoneal fat thickness (r = 0.174). There was no significant relationship between BMI and insertion time. However, insertion time of the first trocar had a significant relationship with preperitoneal fat thickness (r = 0.534).

Conclusions

Preoperative ultrasonography of the umbilical region is asimple process, and it is helpful inpreventing serious complications caused by the first trocar insertion. We have found that preperitoneal fat thickness seems to be an important factor in predicting the potential difficulty of the first trocar insertion.
Motherhood Penalties in the U.S., 1986–2014
Authors: Jee Eunjung , Misra Joya , Murray‐Close Marta
Published: December 2018

Objective

This article aims to determine whether the wage penalty for motherhood changed in the United States between 1986 and 2014 and to assess the relative impact of education and experience on the penalty over time.

Background

Mothers earn less than childless women. Although mothers' educational levels and labor market experience have increased over time, most studies do not analyze the motherhood penalty over time.

Method

This article uses ordinary least squares and fixed effects regressions to estimate the motherhood penalty in three time periods (1986–1995, 1996–2004, and 2006–2014) and compares the penalty across time periods. The data used in the analysis are from the U.S. Panel Study of Income Dynamics, one of the only nationally representative data sets that contains a measure of actual labor market experience.

Results

The motherhood penalty remains quite stable over time and may have worsened for mothers with one child. The gross gap in pay between childless women and mothers of two or more children has narrowed only because mothers' have increased their investments in human capital, such as education and workforce experience. Ordinary least squares and fixed effects models provide similar results.

Conclusion

Mothers' human capital investment may not be enough to lower the motherhood wage penalty in the United States.
The deadlock of saying “That is what we already do!” A thematic analysis of mental healthcare professionals’ reactions to using an evidence‐based intervention
Authors: Jørgensen Rikke , Christiansen Jette , Nissen Hanne Becker , Kristoffersen Karin , Zoffmann Vibeke
Published: December 2018

Accessible Summary

What is known on this subject?

There is a need to shed light on healthcare professionals’ reactions to the use of the Guided Self‐Determination method in a mental health hospital to better understand and adjust the implementation process of evidence‐based practice.

Healthcare professionals´ values and beliefs play an important role when implementing evidence‐based practice in real‐world healthcare settings.

What this paper adds to existing knowledge?

The study identifies opposite positions in mental healthcare professionals: being ready or resistant to change when implementing an evidence‐based intervention. The positions are elaborated in four thematic dynamic continuums describing reactions to using the intervention.

In addition, this is the first study to explore mental healthcare professionals´ reactions to using the Guided Self‐Determination method in a mental health context.

What are the implications for practice?

When preparing implementation of an evidence‐based intervention, it is important to consider adaptation of the intervention, the mental healthcare professionals’ acceptability, support from management and participation in supervision.

In future research, it is important to consider collecting data from mental healthcare professionals trained in using an evidence‐based intervention, however not using it in clinical practice, to understand barriers towards evidence‐based practice.

Introduction

Evidence‐based interventions are required in mental health nursing to improve quality and outcome for patients. However, there is a need to shed light on professionals’ reactions to the use of evidence‐based interventions to better understand and adjust the implementation process.

Aim

To explore mental healthcare professionals´ reactions to using the evidence‐based intervention Guided Self‐Determination method in the care of inpatients with severe mental illness.

Method

A qualitative study conducted in relation to an 8 months implementation program. Data collection: 9 qualitative interviews and field notes generated from supervision of the intervention.

Results

Four themes emerged from a thematic analysis: “The expert becomes novice,” “Theory used as a looking glass,” “Guided Self‐Determination perceived as an interruption” and “Becoming an informer of the impact of GSD.”

Discussion

Using the themes may help leaders or researchers predict or discover the support needed by individual professionals.

Implications for practice

When preparing implementation of an evidence‐based intervention, it is important to consider adaptation and acceptability, as well as support from management and participation in supervision. Finally, it is worth to consider collecting data from trained professionals, who did not use the intervention in practice to understand barriers towards evidence‐based practise.
Textural, mechanical, and microstructural properties of restructured pimiento alginate‐guar gels
Authors: Mousavi Seyyed Mohammad Reza , Rafe Ali , Yeganehzad Samira
Published: December 2018

Textural, mechanical, microstructural, and thermal properties of reconstituted pimiento alginate‐guar gels subjected to thermal and mechanical stresses during pasteurization process were investigated. Alginate‐guar gelling system at ratio 2:1 at different calcium chloride concentrations (2–8%) and varying acid conditions including citric and lactic acid 1% were evaluated. Textural profile analysis parameters viz. hardness, springiness, gumminess, cohesiveness, adhesiveness as well as mechanical properties, structural, thermal, and morphological characteristics of pimiento strips were examined. Gel strength and elasticity of pimiento strips were increased at higher calcium levels. Fracturability was decreased clearly revealed the gel system, regain its strength in spite of high pulp content (25%) and can maintain its own structure. Increase in hardness and reduction in springiness showed loss of elasticity, which may be attributed to the gel shrinkage during thermal processing, making it more compact and dense. Therefore, the restructured pimiento strips were completely thermo stable at pasteurization temperature. By increasing alginate and calcium level in the pimiento strip, glass transition temperature was reduced from 112 to 98°C. Fourier transform infrared spectroscopy studies confirmed that the gel network structure at acidic conditions was stable and acid type did not has significant effect on the chemical interactions. The microstructural results showed ellipsoidal and compact structure in which can be an evidence of high elasticity and rigidity of pimiento gels. These results completely approved the high elasticity and rigidity of the pimiento strips and their ability to sustain successfully thermal and mechanical stresses with appreciable textural integrity during processing such as pasteurization.

Practical applications

Restructured pimiento strip for stuffing into cocktail olives is a challenging problem in binary composite hydrogels of alginate and guar gum. The strips should be designed to be strong enough to handle mechanically and cut easily without tearing. Furthermore, it had to withstand to pasteurization process and be flexible to bend like a hairpin into the pit hole of olive. In addition, it also had low syneresis and shrinkage that the strips not fall out of the olive hole during storage. In the view point of marketing and nutritional aspects, it is more advantageous to develop a restructured fruit gel systems several times higher than the limiting 10% pulp because of its weak structure. Therefore, alginate‐gel systems containing 25% pimiento pulp were evaluated at different levels of calcium chloride and thermal processing.
Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure
Authors: Di Lello Federico A. , Ridruejo Ezequiel , Martínez Alfredo P. , Pérez Paula S. , Campos Rodolfo H. , Flichman Diego M.
Published: December 2018

The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV‐infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV‐infected patients from Argentina where HBV‐F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV‐infected patients.
Evaluation of plasma angiopoietin‐2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis
Authors: König Maya , Nentwig Alice , Marti Eliane , Mirkovitch Jelena , Adamik Katja‐Nicole , Schuller Simone
Published: December 2018

Background

Angiopoietin‐2 (Ang‐2) and vascular endothelial growth factor (VEGF) are regulators of endothelial permeability.

Objective

Plasma concentrations of Ang‐2 and VEGF are increased in dogs with systemic inflammatory response syndrome (SIRS) and sepsis and are correlated with disease severity and outcome.

Animals

Healthy dogs (n = 18) and client‐owned dogs with SIRS (n = 34) or sepsis (n = 25).

Methods

Prospective observational study. Ang‐2 and VEGF concentrations in admission plasma samples were compared between healthy dogs and dogs with SIRS or sepsis, and between survivors and non‐survivors. Correlations with the acute patient physiologic and laboratory evaluation (APPLEfast) disease severity score were examined.

Results

Median Ang‐2 was significantly higher in dogs with SIRS (19.3; interquartile range [IQR]: 8.6‐25.7 ng/mL) and sepsis (21.2; IQR: 10.3‐30.1 ng/mL) compared to healthy dogs (7.6; IQR: 6.7‐9.8 ng/mL). Ang‐2 was significantly higher in non‐survivors (24.1; IQR: 11.9‐50.0 ng/mL) than survivors (10.2; IQR: 7.2‐21.5 ng/mL) but did not correlate with the APPLEfast score. Admission Ang‐2 predicted negative outcome in dogs with SIRS and sepsis with reasonable accuracy (area under the curve [AUC]: 0.75, confidence interval [CI]: 0.59‐0.85; sensitivity: 0.5, CI: 0.29‐0.71; specificity: 0.87, CI: 0.75‐0.95); differentiation between sepsis and SIRS was poor (AUC: 0.58). Plasma VEGF was significantly higher in dogs with sepsis (45; IQR: 14‐107.5 pg/mL) than in dogs with SIRS (3.3; IQR: 0‐35.6 pg/mL) or healthy dogs (0; IQR: 0 pg/mL; P = 0.008). VEGF was significantly (P = .0004) higher in non‐survivors (34.5; IQR: 0‐105.7 pg/mL) than in survivors (0; IQR: 0‐55.2 pg/mL). The ability of VEGF to predict a negative outcome was poor.

Conclusions and Clinical Importance

Ang‐2 may represent a useful additional prognostic marker in dogs with SIRS.
Child‐directed Dramatic Play as Identity Text in Northern Canadian Indigenous Kindergarten Classrooms
Authors: Peterson Shelley Stagg , Horton Laura
Published: December 2018

In this paper, an Anishnaabe educator and university researcher/former primary teacher make a case for viewing children's dramatic play as multimodal identity texts. Indigenous children in our research study take up an agentic role and construct positive identities in dramatic play, creating narratives that reflect Indigenous cultural practices, as well as some practices of mainstream Canadian society that may be imbued with colonising perspectives. We argue that the Indigenous Cultural classes and follow‐up dramatic play counter the marginalisation of Indigenous knowledge, culture and languages that has occurred with devastating effects on generations of Indigenous families. Our paper is based on video recordings of 4‐ and 5‐year‐old children's dramatic play that were analysed collectively by 12 Indigenous educators in terms of the Indigenous cultural meanings that children created in their play. We conclude with implications for non‐Indigenous teachers, arguing that a case can be made for including child‐led dramatic play in the literacy curriculum when dramatic play narratives are viewed as multimodal identity texts. These texts, which can involve multiple modes including print, draw from children's own cultural and linguistic knowledge and experience.
The future of parentage analysis: From microsatellites to SNPs and beyond
Authors: Flanagan Sarah P. , Jones Adam G.
Published: December 2018

Parentage analysis is a cornerstone of molecular ecology that has delivered fundamental insights into behaviour, ecology and evolution. Microsatellite markers have long been the king of parentage, their hypervariable nature conferring sufficient power to correctly assign offspring to parents. However, microsatellite markers have seen a sharp decline in use with the rise of next‐generation sequencing technologies, especially in the study of population genetics and local adaptation. The time is ripe to review the current state of parentage analysis and see how it stands to be affected by the emergence of next‐generation sequencing approaches. We find that single nucleotide polymorphisms (SNPs), the typical next‐generation sequencing marker, remain underutilized in parentage analysis but are gaining momentum, with 58 SNP‐based parentage analyses published thus far. Many of these papers, particularly the earlier ones, compare the power of SNPs and microsatellites in a parentage context. In virtually every case, SNPs are at least as powerful as microsatellite markers. As few as 100–500 SNPs are sufficient to resolve parentage completely in most situations. We also provide an overview of the analytical programs that are commonly used and compatible with SNP data. As the next‐generation parentage enterprise grows, a reliance on likelihood and Bayesian approaches, as opposed to strict exclusion, will become increasingly important. We discuss some of the caveats surrounding the use of next‐generation sequencing data for parentage analysis and conclude that the future is bright for this important realm of molecular ecology.
Intertemporal substitution in the Spanish economy: Evidence from regional data
Authors: Cutanda Tarín Antonio
Published: December 2018

This paper studies the intertemporal substitution in consumption and leisure for the Spanish economy by estimating the first‐order conditions of an individual optimization model with regional and aggregate data. While first‐order conditions determining intertemporal substitution in consumption show a good econometric fit, and the value we obtain for the intertemporal elasticity of substitution is similar to previously available results, the econometric fit of the intertemporal condition in leisure indicates that the behaviour of the Spanish labour supply over the cycle is more complex than can be explained by the canonical intertemporal choice model.
Health professionals’ perspectives on the discharge process and continuity of care for stroke survivors discharged home in regional Australia: A qualitative, descriptive study
Authors: Kable Ashley , Baker Amanda , Pond Dimity , Southgate Erica , Turner Alyna , Levi Christopher
Published: December 2018

Many stroke patients are discharged home due to advances in treatment approaches and reduced residual disability. The aim of this study was to understand health professionals’ perspectives on the discharge process and continuity of care during the transition between hospital and home for stroke survivors. In this qualitative, descriptive study, we used focus groups with 25 health professionals involved in discharge processes for transition from hospital to home in 2014, in a regional area of Australia. Discontinuity in the discharge process was affected by pressure to discharge patients, discharge medications and associated risks, inadequate or late discharge summaries, and challenges involving carers. Discontinuity in post‐discharge services and follow up was affected by availability of post‐discharge services, number of services arranged at the time of discharge, general practitioner follow up after discharge, delays and waiting lists, carer problems, and long‐term follow up. There were complex organizational barriers to the continuity of care for stroke survivors discharged home. It is important to address these deficits so that stroke survivors and their carers can make the transition home with minimal risk and adequate support following a stroke.
Origin and evolution of the plant immune system
Authors: Han Guan‐Zhu
Published: December 2018

ContentsSummary70I.Introduction70II.Ancient associations between plants and microbes72III.Evolutionary dynamics of plant–pathogen interactions74IV.Evolutionary signature of plant–pathogen interactions74V.Origin and evolution of RLK proteins75VI.Origin and evolution of NLR proteins77VII.Origin and evolution of SA signaling78VIII.Origin and evolution of RNA‐based defense79IX.Perspectives79Acknowledgements80References80

Microbes have engaged in antagonistic associations with plants for hundreds of millions of years. Plants, in turn, have evolved diverse immune strategies to combat microbial pathogens. The conflicts between plants and pathogens result in everchanging coevolutionary cycles known as ‘Red Queen’ dynamics. These ancient and ongoing plant–pathogen interactions have shaped the evolution of both plant and pathogen genomes. With the recent explosion of plant genome‐scale data, comparative analyses provide novel insights into the coevolutionary dynamics of plants and pathogens. Here, we discuss the ancient associations between plants and microbes as well as the evolutionary principles underlying plant–pathogen interactions. We synthesize and review the current knowledge on the origin and evolution of key components of the plant immune system. We also highlight the importance of studying algae and nonflowering land plants in understanding the evolution of the plant immune system.
Recombinant growth differentiation factor 11 impairs fracture healing through inhibiting chondrocyte differentiation
Authors: Zheng Rixin , Xie Liang , Liu Weiqing , Guo Yuchen , Wang Yuan , Wu Yunshu , Liu Yuting , Luo Hongke , Kang Ning , Yuan Quan
Published: December 2018

Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor‐β (TGF‐β) superfamily, has been reported to have the capacity to reverse age‐related pathologic changes and regulate organ regeneration after injury; however, the role of GDF11 in fracture healing and bone repair is still unclear. Here, we established a fracture model in 12‐week‐old male mice to observe two healing states: the cartilaginous callus and bony callus formation phases. Our results showed that recombinant GDF11 (rGDF11) injection inhibits cartilaginous callus maturation and hard callus formation, thereby impairing fracture healing in vivo. In vitro, rGDF11 administration inhibited chondrocyte differentiation and maturation by phosphorylating SMAD2/3 protein and inhibiting RUNX2 expression. Notably, inhibition of TGF‐β activity by a SMAD‐specific inhibitor attenuated GDF11 effects. Thus, our study demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation.
The effect of mindfulness meditation on sleep quality: a systematic review and meta‐analysis of randomized controlled trials
Authors: Rusch Heather L. , Rosario Michael , Levison Lisa M. , Olivera Anlys , Livingston Whitney S. , Wu Tianxia , Gill Jessica M.
Published: December 2018

There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced‐based sleep treatments) and nonspecific active controls (such as time/attention‐matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At posttreatment and follow‐up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 (95% CI –0.43 to 0.49)) and (ES –0.14 (95% CI –0.62 to 0.34)), respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at postintervention (ES 0.33 (95% CI 0.17–0.48)) and at follow‐up (ES 0.54 (95% CI 0.24–0.84)). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.
Peripheral retinal findings in populations with macular disease are similar to healthy eyes
Authors: Nivison‐Smith Lisa , Milston Rebecca , Chiang Jaclyn , Ly Angelica , Assaad Nagi , Kalloniatis Michael
Published: December 2018

Purpose

Recent evidence suggests several macular diseases are associated with peripheral retinal changes. This study investigated the number, type and management consequences of peripheral retinal findings detected in patients attending a referral only, eye‐care clinic, the Centre for Eye Health(CFEH) with macular disease.

Methods

Records of 537 patients attending CFEH for a macular assessment were included in the study. Subjects were classified as having age‐related macular degeneration (AMD), epiretinal membrane (ERM), central serous chorioretinopathy (CSCR), inherited macular dystrophy or no macular disease. Data extracted included reason for referral, macular findings, peripheral findings (based on examination by ultra‐widefield scanning laser ophthalmoscopy), diagnosis and management.

Results

After age‐matching, the number of peripheral findings in subjects with AMD, ERM or CSCR was not significant different to normal subjects. The most common finding for all cohorts were non‐specific, degenerative changes such as drusen or pigmentation (61–72%) except inherited macular dystrophy subjects who had mostly vascular findings (30%; p < 0.05). Subjects with AMD and ERM with peripheral findings were significantly more likely to be reviewed or referred to an ophthalmologist than discharged back to their community eye care provider compared to subjects without findings. However only 8% of subjects had altered management based specifically on peripheral findings suggesting the macular findings in most subjects dictated their management. For those with a change, it was significant (upgrade to referral to an ophthalmologist). Peripheral findings also flagged 5% of subjects with vascular findings for referral to their general practitioner (GP).

Conclusions

Overall, the percentage and distribution of peripheral retinal findings in some macular diseases was similar to normal subjects. However, subjects with peripheral findings appeared to have significant differences in management. Considering some common findings, such as peripheral drusen may be relevant to AMD pathogenesis and therefore affect management of this disease, assessment of the peripheral retina should not be overlooked when the clinical focus is on the posterior pole.
Recognition acuity in children measured using The Auckland Optotypes
Authors: Hamm Lisa M , Anstice Nicola S , Black Joanna M , Dakin Steven C
Published: December 2018

Purpose

Sloan letters displayed by the Electronic Visual Acuity (EVA) system are the gold standard for recognition acuity measurement in research settings. However, letters are not always appropriate for children. The Auckland Optotypes (TAO) are a new, open‐access set of 10 pictograms available in regular and vanishing formats. We sought to assess feasibility of using both formats of TAO for measuring visual acuity (VA) in children using a Bayesian adaptive staircase, in a community setting.

Methods

We tested 121 children (5–12 years old) with both formats of TAO, a handheld flipchart vision screener (Parr vision test), as well as the gold standard EVA. We measured feasibility of the three comparison tests in three ways. First, using limits of agreement (LoA) with EVA, second, calculating area under the receiver operating characteristic curve (AUC), and finally, investigating trial‐by‐trial responses.

Results

Agreement between tests was within test‐retest reliability of EVA measures (LoATAOregular = ±0.14, LoATAOvanishing = ±0.15, LoAParr = ±0.16 logMAR). TAO tests were highly effective at identifying children with vision impairment (AUCTAOregular = 0.96, AUCTAOvanishing = 0.95), whereas Parr was less effective (AUCParr = 0.82). In 5–6 year old children there was an enhanced advantage of TAO (AUCTAOregular = 0.97, AUCTAOvanishing = 0.98) over Parr (AUCParr = 0.75). Although each child completed 16 trials, approximately 10 trials were sufficient to achieve excellent LoA, and six trials sufficient for accurate screening.

Conclusion

Threshold VA assessment and vision screening are feasible using both vanishing and regular formats of TAO.
Cold chain and virus‐free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes
Authors: Daniell Henry , Rai Vineeta , Xiao Yuhong
Published: December 2018

To prevent vaccine‐associated paralytic poliomyelitis, WHO recommended withdrawal of Oral Polio Vaccine (Serotype‐2) and a single dose of Inactivated Poliovirus Vaccine (IPV). IPV however is expensive, requires cold chain, injections and offers limited intestinal mucosal immunity, essential to prevent polio reinfection in countries with open sewer system. To date, there is no virus‐free and cold chain‐free polio vaccine capable of inducing robust mucosal immunity. We report here a novel low‐cost, cold chain/poliovirus‐free, booster vaccine using poliovirus capsid protein (VP1, conserved in all serotypes) fused with cholera non‐toxic B subunit (CTB) expressed in lettuce chloroplasts. PCR using unique primer sets confirmed site‐specific integration of CTB‐VP1 transgene cassettes. Absence of the native chloroplast genome in Southern blots confirmed homoplasmy. Codon optimization of the VP1 coding sequence enhanced its expression 9–15‐fold in chloroplasts. GM1‐ganglioside receptor‐binding ELISA confirmed pentamer assembly of CTB‐VP1 fusion protein, fulfilling a key requirement for oral antigen delivery through gut epithelium. Transmission Electron Microscope images and hydrodynamic radius analysis confirmed VP1‐VLPs of 22.3 nm size. Mice primed with IPV and boosted three times with lyophilized plant cells expressing CTB‐VP1co, formulated with plant‐derived oral adjuvants, enhanced VP1‐specific IgG1, VP1‐IgA titres and neutralization (80%–100% seropositivity of Sabin‐1, 2, 3). In contrast, IPV single dose resulted in <50% VP1‐IgG1 and negligible VP1‐IgA titres, poor neutralization and seropositivity (<20%, <40% Sabin 1,2). Mice orally boosted with CTB‐VP1co, without IPV priming, failed to produce any protective neutralizing antibody. Because global population is receiving IPV single dose, booster vaccine free of poliovirus or cold chain offers a timely low‐cost solution to eradicate polio.
Expression of the Arabidopsis WRINKLED 1 transcription factor leads to higher accumulation of palmitate in soybean seed
Authors: Vogel Pamela A. , Bayon de Noyer Shen , Park Hyunwoo , Nguyen Hanh , Hou Lili , Changa Taity , Khang Hoang Le , Ciftci Ozan N. , Wang Tong , Cahoon Edgar B. , Clemente Tom Elmo
Published: December 2018

Soybean (Glycine max [L.] Merr.) is a commodity crop highly valued for its protein and oil content. The high percentage of polyunsaturated fatty acids in soybean oil results in low oxidative stability, which is a key parameter for usage in baking, high temperature frying applications, and affects shelf life of packaged products containing soybean oil. Introduction of a seed‐specific expression cassette carrying the Arabidopsis transcription factor WRINKLED1 (AtWRI1) into soybean, led to seed oil with levels of palmitate up to approximately 20%. Stacking of the AtWRI1 transgenic allele with a transgenic locus harbouring the mangosteen steroyl‐ACP thioesterase (GmFatA) resulted in oil with total saturates up to 30%. The creation of a triple stack in soybean, wherein the AtWRI1 and GmFatA alleles were combined with a FAD2‐1 silencing allele led to the synthesis of an oil with 28% saturates and approximately 60% oleate. Constructs were then assembled that carry a dual FAD2‐1 silencing element/GmFatA expression cassette, alone or combined with an AtWRI1 cassette. These plasmids are designated pPTN1289 and pPTN1301, respectively. Transgenic events carrying the T‐DNA of pPTN1289 displayed an oil with stearate levels between 18% and 25%, and oleate in the upper 60%, with reduced palmitate (<5%). While soybean events harboring transgenic alleles of pPTN1301 had similar levels of stearic and oleate levels as that of the pPTRN1289 events, but with levels of palmitate closer to wild type. The modified fatty acid composition results in an oil with higher oxidative stability, and functionality attributes for end use in baking applications.
State Biotechnology and Genomic Development: Critical Resources and Barriers
Authors: Chao Chia‐An , Myers Nathan
Published: December 2018

This article describes the development of an index of state biotechnology and genomic development and the cluster analysis used to group U.S. states based on their level of development in each area. Multivariate analysis of variance (MANOVA) is then used to test hypotheses regarding statistically significant differences between the biotechnology/genomic development clusters and variables related to states’ workforce, investment in research and development (R&D), and policy environment. The authors find statistically significant results in the areas of workforce education, migration of knowledge workers, industrial and nonindustrial R&D, and policy to promote the development of the biotechnology industry. While the MANOVA for policies placing limits on the development of biotechnology policy did not yield statistical significance, the authors argue that the finding deserves further study as it may indicate some states' willingness to strike a more sustainable balance between support and regulation.

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Effect of prepubertal nutrition on cellular apoptosis and proliferation in at term placenta of Anglo‐Nubian goats
Authors: Turiello María P. , Cristofolini Andrea L. , Fiorimanti Mariana R. , Diaz Tomás , Cavaglieri Lilia R. , Merkis Cecilia I.
Published: December 2018

Contents

The aim of this study was to evaluate the effect of feed restriction with or without monensin supplementation, followed by a re‐feeding period on cellular apoptosis and proliferation in at term placenta of Anglo‐Nubian goats. To evaluate the induction of apoptosis through the intrinsic pathway, proteins Bax and Bcl‐2 were determinated. The apoptosis was related with the cell proliferation indices through Ki67 determination. The treatments were applied for 250 days and were (a) ad libitum feeding (control; n = 5); (b) restricted feeding at 70% of control (restricted; n = 7); and (c) restricted with monensin supplementation (monensin; n = 7). After treatments, all the animals were fed to support their requirements. After parturition, 27 placentas were gathered. The placental cellular structure was studied by high‐resolution light microscopy and transmission electron microscopy; the cellular proliferation was determined by Ki67 index, and Bax and Bcl‐2 proteins were localized by immunohistochemical analysis. Differences in cell proliferation through the Ki67 index were found in monensin group placentas. Monensin supplementation stimulated the placental cell proliferation reversing the effect of feed restriction during the peripuberal period. A significant increase of Bcl‐2 in placentas of restricted group was found, and it would provide a protective effect on the placental structure. A lack of the Bcl‐2 protective effect was observed in control and monensin group placentas, probably meaning that the observed apoptosis would be induced through the intrinsic signalling pathway. A balance between apoptosis and cell proliferation is necessary to maintain tissue homoeostasis during caprine placental development.
Does regulation matter? A cross‐national analysis of the impact of gun policies on homicide and suicide rates
Authors: Hurka Steffen , Knill Christoph
Published: December 2018

In this contribution, we evaluate the effectiveness of firearm regulations in curbing the number of homicides and suicides committed both with and without firearms. We develop a gun control index that enables us to compare the restrictiveness of firearm regulations across time and space. We model the effects of gun control on figures of (gun) homicide and (gun) suicide gained from public health records in 16 West European countries between 1980 and 2010. We thus shift the analytical focus away from the United States, which can be considered an extreme case in many ways and analyze the effects of gun control in a least likely setting: a world region in which gun control is comparably strict to begin with. Our analysis demonstrates that stricter gun control entails a strong and robust negative effect not only on homicides and suicides committed with firearms, but also on overall homicide and suicide rates.
Analytical solution of gravity tunnels through an inhomogeneous Earth
Authors: Isermann Stefan
Published: December 2018

A piecewise linear approximation of the Preliminary reference Earth model (PREM) is used for the Earth's velocity profile. The analytical solution derived for the motion on the shortest path and the path of fastest descent corresponds to the direct numerical integration of the PREM. This explains why traversal times can be approximated by the assumption of constant gravity, while the gravity of the Earth is certainly not constant.
Laboratory demonstration of acoustic source localization in two dimensions
Authors: Lamelas Frank , Swaminathan Sudha
Published: December 2018

A high-resolution table-top experiment in source localization is carried out using four USB microphones. We show that the acoustic source location can be determined with an accuracy of 1 cm if timing measurements are carried out as follows. First, the sound source is a noise pulse played through a cell-phone speaker, ensuring the presence of high-frequency components and an easily identified abrupt onset of the sound signal. Second, we normalize the clock rates of the four computers used with the microphones. The position of the source is calculated using an analytical expression which depends on the microphone layout and the arrival times of the sound signal at the four microphones. The experiment can be carried out in an undergraduate laboratory.
Assessing Program Learning Outcomes: A Tale of Self-Discovery
Authors: Denicoló Glenda
Published: December 2018

Learning assessment at two-year colleges is growing, but not much has been published about it yet. In general, our smaller classrooms, diverse student population, high proportion of adjunct faculty, and academic freedom in teaching methods and tools set the stage for a different approach to assessment than at four-year institutions. This is the story of how faculty at Suffolk County Community College (SCCC) are working through a long-term assessment plan.
Universities 'held hostage' in Nicaragua's political crisis
Authors: Wade Lizzie
Published: December 2018

Intensifying oppression paralyzes teaching and research.
NK cell–mediated cytotoxicity contributes to tumor control by a cytostatic drug combination
Authors: Ruscetti Marcus , Leibold Josef , Bott Matthew J. , Fennell Myles , Kulick Amanda , Salgado Nelson R. , Chen Chi-Chao , Ho Yu-jui , Sanchez-Rivera Francisco J. , Feucht Judith , Baslan Timour , Tian Sha , Chen Hsuan-An , Romesser Paul B. , Poirier John T. , Rudin Charles M. , de Stanchina Elisa , Manchado Eusebio , Sherr Charles J. , Lowe Scott W.
Published: December 2018

Small molecules spark NK cell response

Immunotherapy is a powerful treatment for certain cancers. Yet for those patients that do not respond, simultaneous strategies that mobilize the immune system and directly target malignant cells may be more effective. Ruscetti
et al.
report that combining two clinically approved cancer drugs promoted immune surveillance and killing of KRAS-mutant lung tumors in mice (see the Perspective by Cornen and Vivier). The two small molecules—a mitogen-activated protein kinase inhibitor and a cyclin-dependent kinase 4/6 inhibitor—induced natural killer (NK) cell recruitment and elimination of senescent lung cancer cells, which did not occur when either agent was used alone.

Science
, this issue p.
1416
; see also p.
1355
ATP-dependent force generation and membrane scission by ESCRT-III and Vps4
Authors: Schöneberg Johannes , Pavlin Mark Remec , Yan Shannon , Righini Maurizio , Lee Il-Hyung , Carlson Lars-Anders , Bahrami Amir Houshang , Goldman Daniel H. , Ren Xuefeng , Hummer Gerhard , Bustamante Carlos , Hurley James H.
Published: December 2018

Membrane scission by ESCRTs

The ESCRT protein complexes are essential for cell division, the release of HIV from infected cells via budding, and other cell processes involving the scission of narrow membrane necks from their inner surface. The unusual inside-directed membrane cutting has made it hard to recapitulate this reaction and understand its mechanism. Schöneberg
et al.
encapsulated ESCRTs inside lipid vesicles and used optical tweezers to pull out membrane nanotubes. In the presence of adenosine triphosphate, clusters of ESCRTs generated force and constricted the nanotube, eventually severing it. This approach provides a window into the molecular mechanisms involved in the activities of ESCRTs.

Science
, this issue p.
1423
Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
Authors: Tokatlian Talar , Read Benjamin J. , Jones Christopher A. , Kulp Daniel W. , Menis Sergey , Chang Jason Y. H. , Steichen Jon M. , Kumari Sudha , Allen Joel D. , Dane Eric L. , Liguori Alessia , Sangesland Maya , Lingwood Daniel , Crispin Max , Schief William R. , Irvine Darrell J.
Published: December 2018

HIV glycans and nanoparticle vaccines

Synthetic nanoparticles have attracted widespread interest for vaccine design, but how the immune system generates a response to multimeric nanoparticles remains unclear. Tokatlian
et al.
studied immunity generated by HIV envelope antigens arranged in either multivalent nanoparticle forms or as single monomers (see the Perspective by Wilson). The nanoparticle HIV immunogens triggered greater antibody responses compared with the monomeric forms. Glycosylation appeared key for enhanced humoral immunity because it spurred binding to mannose-binding lectin, complement fixation, and antigen trafficking to follicular dendritic cells. The findings highlight how the innate immune system recognizes HIV nanoparticles and the importance of antigen glycosylation in the design of next-generation nano-based vaccines.

Science
, this issue p.
649
; see also p.
584