bluuebunny/crossref_metadata_2025 huggingface dataset:
The future of cancer treatment using precision oncogenomics
Authors: Wartman Lukas D.
Published: April 2018

Clinicians should soon have the opportunity to use precision oncogenomics to tailor the optimal cancer treatment to a specific patient. Precision oncogenomics will incorporate different sequencing platforms depending on the goal of the sequencing result. For example, the sequencing strategy used in immuno-oncology for the design of a tumor-specific vaccine may be different than that used by oncologists following a patient for clearance of mutations from circulating tumor DNA in the peripheral blood. I will provide a broad overview of several of the ways that precision oncogenomics is likely to influence the field of oncology over the next several years building off the experience at the Genomics Tumor Board at Washington University in St. Louis and a case of small-cell neuroendocrine carcinoma of the endometrium as examples.
Using Pulsed-Field Gel Electrophoresis to Analyze Schizosaccharomyces pombe Chromosomes and Chromosomal Elements
Authors: Pai Chen-Chun , Walker Carol , Humphrey Timothy C.
Published: April 2018

Pulsed field gel electrophoresis (PFGE) uses alternatively oriented pulsed electrical fields to separate large DNA molecules. Here, we describe PFGE protocols and conditions for separating and visualizing chromosomes between 0.5 and 6 Mb (optimal for analyzing the endogenous fission yeast chromosomes of 5.7, 4.6, and 3.5 Mb), and for shorter chromosomal elements of between 50 and 600 kb, such as the 530 kb Ch16 minichromosome. In addition to determining chromosome size, this technique has a wide range of applications, including determining whether DNA replication or repair is complete, defining the molecular karyotype of cells, analyzing chromosomal rearrangements, assigning genes or constructs to particular chromosomes, and isolating DNA from specific chromosomes.
DNA Double-Strand Break Repair Assay
Authors: Pai Chen-Chun , Blaikley Elizabeth , Humphrey Timothy C.
Published: April 2018

DNA double-strand breaks (DSBs), arising during normal DNA metabolism or following exposure to mutagenic agents such as ionizing radiation can lead to chromosomal rearrangements and genome instability, and are potentially lethal if unrepaired. Therefore, understanding the mechanisms of DSB repair and misrepair, and identifying the factors involved in these processes is of biological as well as medical interest. Here we describe a DSB assay in Schizosaccharomyces pombe that can be used to identify and quantify different repair, misrepair, and failed repair events resulting from a site-specific DSB within the context of a nonessential minichromosome, Ch16. This assay can be used to determine the contribution of most genes or genetic backgrounds to DSB repair and genome stability, and can also provide mechanistic insights into their function.
Isolation of High-Molecular-Weight DNA from Suspension Cultures of Mammalian Cells Using Proteinase K and Phenol
Authors: Green Michael R. , Sambrook Joseph
Published: April 2018

This procedure is the method of choice for purification of mammalian genomic DNA from suspension cultures when large amounts of DNA are required, for example, for Southern blotting. Approximately 200 µg of mammalian DNA, 100–150 kb in length, is obtained from 5 × 107 cultured aneuploid cells (e.g., HeLa cells).
Titration of Lentivirus Vectors
Authors: Sena-Esteves Miguel , Gao Guangping
Published: April 2018

The titer of a lentivirus vector is often expressed in transducing units per milliliter. This is a functional titer that reflects the lentivirus’ ability to transduce a particular cell line under specific conditions. Transduction of other cell lines is likely to be different and will require optimization. 293T cells are used for production of lentivirus stocks, and they can be easily transduced with vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentivirus vectors. Consequently, this cell line is commonly used to determine the functional titer of lentivirus vector stocks produced with this envelope. For lentivirus vectors encoding fluorescent proteins under the control of promoters functional in these cells, titration can be performed using the limiting dilution method or a flow cytometry-based method. For lentivirus vectors lacking a fluorescent marker, or for those carrying promoters that may not be functional in 293T cells, titer can be determined either by real-time polymerase chain reaction (PCR) quantification of viral genomes in genomic DNA from transduced cells or a p24 ELISA-based assay.
Heterologous Protein Expression in the Xenopus Oocyte
Authors: Marchant Jonathan S.
Published: April 2018

The Xenopus oocyte is a specialized single cell of colossal size (>1 mm diameter) that is highly amenable for microinjection and a stalwart model for heterologous expression. Oocytes are easily obtainable, robust in vitro, and faithfully express injected constructs. Their large size translational capacity provides a huge canvas for observing and recording integrated cellular responses—from studies of single molecules within single cells to medium-throughput drug-screening applications. Most eukaryotic promoters suffice for Xenopus expression, and the oocyte can functionally express proteins from many diverse organisms. This protocol provides a basic introduction for scientists keen to perform nuclear microinjections of cDNA constructs. These are easy methods to master, do not require elaborate equipment, and make accessible a wonderful model cell system for studying signaling, transport, cell architecture, and protein function.
Distantly related crops are not better rotation partners for tomato
Authors: Ingerslew Kathryn S. , Kaplan Ian
Published: April 2018

Although crop rotation has been used for centuries to enhance agricultural production, there are surprisingly little data justifying the use of one rotation over another. Growers typically avoid growing plants in succession that belong to the same genus or family, but it is not clear whether closely related crops are indeed poor rotation partners and whether evolutionary history, overall, predicts legacy effects in agricultural soils.

Here, we use a plant–soil feedback framework to test the relationship between species relatedness and crop growth. Using tomato Solanum lycopersicum as our focal crop, we determined how 36 common crop and weed species that vary along a spectrum of phylogenetic relatedness influence tomato growth in subsequent plantings. We also tested whether soil conditioning affects the performance of an above‐ground insect herbivore, the tobacco hornworm Manduca sexta.

Phylogenetic relatedness did not predict plant–soil feedback effects on tomato biomass or hornworm performance; rather, impacts of soil conditioning were highly species‐ or family‐specific. For example, tomatoes growing in soil previously containing plants in the Asteraceae family were notably resistant to caterpillar feeding.

There was also a disconnect between which plant species caused negative feedbacks on tomatoes vs. hornworms (e.g. thistle Cirsium discolor soil had strong negative effects on herbivory but no impact on plant growth). Hence, negative feedbacks on hornworms are likely due to enhanced defence instead of simply reducing leaf availability.

Synthesis and applications. These data demonstrate that, despite being widely recommended by agronomists in most cropping systems, phylogenetic relatedness is a poor predictor for the success of crop pairings in rotation, especially in tomato. Better understanding of species‐specific effects of soil conditioning will lend insight into how polycultures can be better designed to optimize crop growth while reducing susceptibility to insect pests, which is particularly useful on diversified farms that cultivate a variety of crop species.
What Influences Business Academics’ Use of the Association of Business Schools (ABS) List? Evidence From a Survey of UK Academics
Authors: Walker James T. , Fenton Evelyn , Salter Ammon , Salandra Rossella
Published: April 2018

The development of the Association of Business Schools (ABS) list in 2007 and its rapid adoption by UK business schools has had a profound effect on the nature of business and management academics’ ways of working. Using a large‐scale survey of UK business academics, we assess the extent to which individuals use the Academic Journal Guide (AJG/ABS) list in their day‐to‐day professional activities. In particular, we explore how their perceptions of the list, the academic influence of their research, academic rank and organizational context drive the varied use. Building on prior research on the importance of univalent attitudes in predicting behaviour, we find those who haveeitherstrong positive or negative views of the list are more extensive users than those who are ambivalent. We also find that the extent of use of the AJG/ABS list is greatest among those academics who have lower academic influence, in the middle or junior ranks within business schools and in middle and low‐status universities. We explore the implications of these findings for the value of journal rankings and for the management of business schools.
Utility of community‐acquired pneumonia severity scores in guiding disposition from the emergency department: Intensive care or short‐stay unit?
Authors: Williams Julian M , Greenslade Jaimi H , Chu Kevin H , Brown Anthony FT , Lipman Jeffrey
Published: April 2018

Objective

To assess community‐acquired pneumonia severity scores from two perspectives: (i) prediction of ICU admission or mortality; and (ii) utility of low scores for prediction of discharge within 48 h, potentially indicating suitability for short‐stay unit admission.

Methods

Patients with community‐acquired pneumonia were identified from a prospective database of emergency patients admitted with infection. Pneumonia severity index (PSI), CURB‐65, CORB, CURXO, SMARTCOP scores and the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) minor criteria were calculated. Diagnostic accuracy statistics (sensitivity, specificity, predictive values, likelihood ratios and area under receiver operating characteristic curves [AUROC]) were determined for both end‐points.

Results

Of 618 patients admitted with community‐acquired pneumonia judged eligible for invasive therapies, 75 (12.1%) were admitted to ICU or deceased at 30 days, and 87 (14.1%) were discharged within 48 h. All scores effectively stratified patients into categories of risk. For prediction of severe pneumonia, SMARTCOP, CURXO and IDSA/ATS discriminated well (AUROC 0.84–0.87). SMARTCOP and CURXO showed optimal sensitivity (85% [95% confidence interval (CI) 75–92]), while specificity was highest for CORB and CURB‐65 (93% and 94%, respectively). Using lowest risk categories for prediction of discharge within 48 h, only SMARTCOP and CURXO showed specificity >80%. PSI demonstrated highest positive predictive value (31% [95% CI 24–39]) and AUROC (0.74 [95% CI 0.69–0.79]).

Conclusions

Community‐acquired pneumonia severity scores had different strengths; SMARTCOP and CURXO were sensitive with potential to rule out severe disease, while the high specificity of CORB and CURB‐65 facilitated identification of patients at high risk of requirement for ICU. Low severity scores were not useful to identify patients suitable for admission to short‐stay units.
High‐performance work systems as a remedy for growing pains: evidence from South Korean organizations
Authors: Kim Yoon‐Ho , Kim Youngsang , Kim Andrea , Han Kyongji , Lepak David P
Published: April 2018

Drawing on literatures from a contingency perspective of strategic human resource management and a dynamic resource‐based view, this study examines dynamic patterns of investment in high‐performance work systems (HPWS) to support labor productivity of growing organizations. We analyzed a four‐wave panel dataset from 267 establishments in South Korea and found that higher usage of HPWS at a prior point in time and increasing usage of HPWS over time led to consistently improved labor productivity when the employment size of establishments continued to grow. Our theory and findings provide new insight into the dynamic fit between HPWS and organizational performance over time in growing organizations.
Regulation of carbohydrate degradation pathways in Pseudomonas involves a versatile set of transcriptional regulators
Authors: Udaondo Zulema , Ramos Juan‐Luis , Segura Ana , Krell Tino , Daddaoua Abdelali
Published: April 2018

Bacteria of the genus Pseudomonas are widespread in nature. In the last decades, members of this genus, especially Pseudomonas aeruginosa and Pseudomonas putida, have acquired great interest because of their interactions with higher organisms. Pseudomonas aeruginosa is an opportunistic pathogen that colonizes the lung of cystic fibrosis patients, while P. putida is a soil bacterium able to establish a positive interaction with the plant rhizosphere. Members of Pseudomonas genus have a robust metabolism for amino acids and organic acids as well as aromatic compounds; however, these microbes metabolize a very limited number of sugars. Interestingly, they have three‐pronged metabolic system to generate 6‐phosphogluconate from glucose suggesting an adaptation to efficiently consume this sugar. This review focuses on the description of the regulatory network of glucose utilization in Pseudomonas, highlighting the differences between P. putida and P. aeruginosa. Most interestingly, It is highlighted a functional link between glucose assimilation and exotoxin A production in P. aeruginosa. The physiological relevance of this connection remains unclear, and it needs to be established whether a similar relationship is also found in other bacteria.
Uncovering Colonial Legacies: Voices of Indigenous Youth on Child Welfare (Dis)Placements
Authors: Navia Daniela , Henderson Rita Isabel , First Charger Levi
Published: April 2018

Through art and storytelling, Indigenous youth highlight continuity between recent experiences in child welfare systems and Canada's residential schools of the twentieth century. Between mid‐2014 and mid‐2015, twenty Indigenous youth collaborators (eighteen to twenty‐nine years) in Calgary, Canada critiqued how child welfare systems become complicit with assimilationism, perpetuate gendered violence, and contribute to the dispossession of land and resources. Their perspectives demonstrate how settler colonialism continues to shape the lives of Indigenous youth in child welfare (dis)placements.
Increased single‐balloon Foley catheter volume for induction of labor and time to delivery: a systematic review and meta‐analysis
Authors: Schoen Corina N. , Saccone Gabriele , Backley Sami , Sandberg Evelien M. , Gu Ning , Delaney Shani , Berghella Vincenzo
Published: April 2018

Introduction

Induction of labor is a common intervention. The objective was to investigate whether larger Foley catheter volumes for labor induction decrease the total time from induction to delivery.

Material and methods

Randomized controlled trials comparing larger single‐balloon volumes (60–80 mL) during Foley catheter cervical ripening with usual volume (30 mL) in women undergoing labor induction were identified by searching electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) from inception through 2017. The primary outcome was mean time from induction to delivery in hours. Secondary outcomes included time from induction to vaginal delivery, delivery within 24 h, time to Foley expulsion, cesarean section, chorioamnionitis, epidural use, hemorrhage, meconium staining, and neonatal intensive care unit admission. Meta‐analysis was performed using the random effects model of DerSimonian and Laird (PROSPERO CRD42017058885).

Results

Seven randomized controlled trials including 1432 singleton gestations were included in the systematic review. Women randomized to larger volumes of balloon had a significantly shorter time from induction to delivery (mean difference 1.97 h, 95% CI −3.88 to −0.06). There was no difference in cesarean section between groups (16 vs. 18%, relative risk 0.84, 95% CI 0.6–1.17). A larger balloon volume was associated with a nonsignificant decrease in time from induction to delivery in multiparous (mean difference 2.67 h, 95% CI −6.1 to 0.76) and nulliparous women (mean difference 1.82 h, 95% CI −4.16 to 0.53).

Conclusion

Balloon volumes larger than 30 mL during Foley catheter induction reduce total time to delivery by approximately 2 h.
Intrapartum fetal death and doctors: a qualitative exploration
Authors: McNamara Karen , Meaney Sarah , O'Donoghue Keelin
Published: April 2018

Introduction

The death of an infant during a pregnancy is profoundly traumatic, both for the parents and for the involved healthcare professionals. Most research focuses on the impact of antenatal stillbirth with very little research examining the specific impact an intrapartum fetal death has on obstetricians. The aim of this study was to provide an in‐depth qualitative exploration of the attitudes and responses that Irish obstetricians have following direct involvement with an intrapartum fetal death.

Material and methods

Qualitative semi‐structured interviews were used. Interpretative phenomenology was used for data analysis. The setting was a tertiary university maternity unit in Ireland with 8200 deliveries per year. Ten obstetricians were purposively sampled. The main outcome measures were the attitudes and responses of Irish obstetricians following exposure to an intrapartum death.

Results

Obstetricians were profoundly and negatively affected by a personal involvement with an intrapartum death. Analysis of the data revealed two superordinate themes; the doctor as a person, and supporting each other. The doctor as person was characterized by two subordinate themes; emotional impact and frustration. Supporting each other was also characterized by two subordinate themes; an unmet need and incidental support and what might work.

Conclusions

Obstetric doctors who are directly involved in an intrapartum death are the second victims of this event and this is something that needs to be acknowledged by the public, by the healthcare system, by the media and by the doctors themselves. The development of effective emotional support interventions for all obstetricians is extremely important.
Transplantation of Cold Stored Porcine Kidneys After Controlled Oxygenated Rewarming
Authors: Gallinat Anja , Lu Jing , von Horn Charlotte , Kaths Moritz , Ingenwerth Marc , Paul Andreas , Minor Thomas
Published: April 2018

The concept of “controlled oxygenated rewarming” (COR) using ex vivo machine perfusion after cold storage was evaluated as tool to improve renal graft function after transplantation. Renal function after 20 min warm ischemia and 21 h cold storage was studied in an auto‐transplant model in pigs (25–30 kg, n = 6 per group). In the study group, preimplant ex vivo machine perfusion for 90 min was added after cold storage, including gentle warming up of the graft to 20°C (COR). Kidneys that were only cold stored for 21 h served as controls. In vivo follow up was one week; the remaining native kidney was removed during transplantation. COR significantly improved cortical microcirculation upon early reperfusion and reduced free radical mediated injury and cellular apoptosis. Post‐transplant kidney function (peak levels in serum) was also largely and significantly improved in comparison to the control group. A weak inverse correlation was found between renal flow during COR and later peak creatinine after transplantation (r2 = 0.5), better values were seen for oxygen consumption, measured during machine perfusion at 20°C (r2 = 0.81). Gentle graft rewarming prior to transplantation by COR improves post‐transplant graft outcome and may also be a valuable adjunct in pretransplant graft assessment.
Political‐economic factors in official reports on rangeland degradation: A critical case study from the Tibet Autonomous Region
Authors: Nyima Yonten
Published: April 2018

A narrative of extremely pervasive rangeland degradation that underlies ongoing state policy on range management and pastoralism widely circulates in scientific reports, policy statements and news reports in China. Adopting a political ecology approach, this paper critically analyses official reports on rangeland degradation through a case study from the Tibet Autonomous Region. It reveals internally inconsistent or contradictory figures and statements regarding the magnitude and extent of rangeland degradation, and points out political‐economic factors influencing official reports on rangeland degradation.
“The show must go on!” Fieldwork, mental health and wellbeing in Geography, Earth and Environmental Sciences
Authors: Tucker Faith , Horton John
Published: April 2018

Fieldwork is central to the identity, culture and history of academic Geography, Earth and Environmental Sciences (GEES). However, in this paper we recognise that, for many academic staff, fieldtrips can be a profoundly challenging “ordeal,” ill‐conducive to wellness or effective pedagogic practice. Drawing on research with 39UKuniversity‐basedGEESacademics who self‐identify as having a mental health condition, we explore how mental health intersects with spaces and expectations of fieldwork in Higher Education. We particularly focus on their accounts of undertaking undergraduate residential fieldtrips and give voice to these largely undisclosed experiences. Their narratives run counter to normative, romanticised celebrations of fieldwork withinGEESdisciplines. We particularly highlight recurrent experiences of avoiding fieldwork, fieldwork‐as‐ ordeal, and “coping” with fieldwork, and suggest that commonplace anxieties within the neoliberal academy – about performance, productivity, fitness‐to‐work, self‐presentation, scrutiny and fear‐of‐falling‐behind – are felt particularly intensely during fieldwork. In spite of considerable work to make fieldwork more accessible to students, we find that field‐based teaching is experienced as a focal site of distress, anxiety and ordeal for manyGEESacademics with common mental health conditions. We conclude with prompts for reflection about how fieldwork could be otherwise.
Vancomycin‐induced acute kidney injury in elderly Chinese patients: a single‐centre cross‐sectional study
Authors: Pan Kun‐ming , Wu Yi , Chen Can , Chen Zhang‐zhang , Xu Jian‐an , Cao Lei , Xu Qing , Wu Wei , Dai Pei‐fang , Li Xiao‐yu , Lv Qian‐zhou
Published: April 2018

Aims

The objective of the present study was to investigate the current situation concerning, and risk factors for, vancomycin (VAN)‐induced acute kidney injury (VI‐AKI) in elderly Chinese patients, to assess outcomes and risk factors in patients who have developed VI‐AKI, in order to provide suggestions for improving the prevention and treatment of this condition in these patients.

Method

We retrospectively identified elderly older inpatients who had received four or more doses of VAN treatment. We compared patients with VI‐AKI with those who received VAN treatment and had not developed AKI (NO‐AKI). We defined VI‐AKI as developing AKI during VAN therapy or within 3 days after withdrawal of VAN.

Results

A total of 647 out of 862 elderly inpatients were included in the study. Among those excluded, in 89.3% of cases (192/215) this was because of lack of data on serum creatinine (SCr). Among included patients, 32.5% (210/647) of patients received therapeutic drug monitoring (TDM) during VAN therapy. In 66.9% of cases (424/634), there was insufficient TDM, and in 3.9% (25/634) this was appropriate. A total of 102 patients had confirmed VI‐AKI, with an incidence of 15.8% (102/647). Multiple logistic regression analysis revealed that hyperuricaemia [odds ratio (OR) = 3.045; P = 0.000)], mechanical ventilation (OR = 1.906; P = 0.022) and concomitant vasopressor therapy (OR = 1.919; P = 0.027) were independent risk factors for VI‐AKI; higher serum albumin (OR = 0.885; P = 0.000) was determined to be an independent protective factor for VI‐AKI.

Conclusions

For the elderly Chinese patients treated with VAN, there was insufficient monitoring of SCr, too little use of VAN TDM, and lower rate of patients whose VAN though serum concentrations were not obtained at the correct time. We recommend that hospital managers increase investment in clinical pharmacists, to strengthen professional management. Patients with concomitant hyperuricaemia and on mechanical ventilation and vasopressor therapy should be paid more attention, and a higher serum albumin was determined to be an independent protective factor for VI‐AKI.
Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients
Authors: Lin Xiao‐bin , Li Zi‐wei , Yan Miao , Zhang Bi‐kui , Liang Wu , Wang Feng , Xu Ping , Xiang Da‐xiong , Xie Xu‐biao , Yu Shao‐jie , Lan Gong‐bin , Peng Feng‐hua
Published: April 2018

Aims

The aims of the present study were to characterize the pharmacokinetics of voriconazole in renal transplant recipients and to identify factors significantly affecting pharmacokinetic parameters. We also aimed to explore the optimal dosing regimens for patients who developed invasive fungal infections.

Methods

A total of 105 patients (342 concentrations) were included prospectively in a population pharmacokinetic analysis. Nonlinear mixed‐effects models were developed using Phoenix NLME software. Dosing simulations were performed based on the final model.

Results

A one‐compartment model with first‐order absorption and elimination was used to characterize voriconazole pharmacokinetics. Population estimates of clearance, volume of distribution and oral bioavailability were 2.88 l·h−1, 169.3 l and 58%, respectively. The allele frequencies of cytochrome P450 gene (CYP) 2C19*2, *3 and *17 variants were 29.2%, 5.2% and 0.5%, respectively. CYP2C19 genotype had a significant effect on the clearance. Voriconazole trough concentrations in poor metabolizers were significantly higher than in intermediate metabolizers and extensive metabolizers alike. The volume of distribution increased with increased body weight. The oral bioavailability was substantially lower within 1 month after transplantation but increased with postoperative time. Dosing simulations indicated that during the early postoperative period, poor metabolizers could be treated with 150 mg intravenously or 250 mg orally twice daily; intermediate metabolizers with 200 mg intravenously or 350 mg orally twice daily; and extensive metabolizers with 300 mg intravenously twice daily.

Conclusions

Using a combination of CYP2C19 genotype and postoperative time to determine the initial voriconazole dosing regimens followed by therapeutic drug monitoring could help to advance individualized treatment in renal transplantation patients with invasive fungal infections.
The role of temporal patterns in students' behavior for predicting course performance: A comparison of two blended learning courses
Authors: van Leeuwen Anouschka , Bos Nynke , van Ravenswaaij Heleen , van Oostenrijk Jurgen
Published: April 2018

In higher education, many studies have tried to establish which student activities predict achievement in blended courses, with the aim of optimizing course design. In this paper, we examine whether taking into account temporal patterns of student activity and instructional conditions of a course help to explain course performance. A course with a flipped classroom model (FCM) and a course with an enhanced hybrid model (EHM) were compared. The results show that in both cases, a regular pattern of activity is more effective than low activity. In the FCM, initial low activity is detrimental, whereas in the EHM the strategy of cramming later on in the course can still lead to higher course performance. In the FCM, a combination of face‐to‐face and online activity led to sufficient course performance, whereas in the EHM, face‐to‐face or online activity on its own could lead to sufficient course performance. This study offers a methodological and empirical contribution to exploring the role of patterns of activity and instructional conditions for course performance.
Low‐dose‐rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse
Authors: Laing Robert , Uribe Jennifer , Uribe‐Lewis Santiago , Money‐Kyrle Julian , Perna Carla , Chintzoglou Stylianos , Khaksar Sara , Langley Stephen E.M.
Published: April 2018

Objectives

To report clinical outcomes of 125I low‐dose‐rate prostate brachytherapy (LDR‐PB) as monotherapy or combined with androgen‐deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high‐risk localised prostate cancer.

Patients and Methods

Analysis of clinical outcomes from a prospective cohort of patients treated with LDR‐PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse‐free survival (RFS), overall survival (OS), prostate cancer‐specific survival (PCSS), and metastases‐free survival (MFS), were analysed together with patient‐reported symptom scores and physician‐reported adverse events.

Results

The NICE and NCCN criteria identified 267 and 202 high‐risk patients, respectively. NICE‐defined patients had significantly lower pre‐treatment PSA levels, Gleason scores <7, and a greater proportion of patients who received LDR‐PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log‐rank P = 0.637), and OS 93% and 94%, respectively (log‐rank P = 0.481). All of the survival estimates were similar between LDR‐PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment‐related toxicity was also similar between the treatment methods.

Conclusion

LDR‐PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR‐PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high‐risk factors.
Bird mixed‐species flock formation is driven by low temperatures between and within seasons in a Subtropical Andean‐foothill forest
Authors: Mangini G. Giselle , Areta Juan Ignacio
Published: April 2018

According to both the predation avoidance and foraging efficiency hypotheses, birds within mixed flocks increase their foraging efficiency and/or can spend more time feeding and less time looking out for predators. These hypotheses predict that birds in mixed flocks obtain benefits. Thus, mixed flock formation could serve as a strategy to cope with difficult conditions imposed on birds such as climatic conditions that ultimately result in a change in predation pressure or food resources. We evaluate the hypotheses that forming part of a flock confers benefits to its members and the associated prediction that birds will take advantage of these benefits and flock more often under cold and dry weather conditions between and within seasons to cope with such conditions. We surveyed the presence of mixed flocks, flocking propensity, number of species and individuals in mixed flocks in the Subtropical Yungas foothill of Argentina, to examine seasonality, flocking behavior of birds and their responses to two climatic variables: temperature and humidity. Bird species presented a higher flocking propensity and mixed flocks occurred more frequently during the dry and cold seasons than during the more benign seasons, and lower values of temperature within seasons triggered the flocking behavior. Although effects between seasons were expected, birds also showed a short‐term response to small changes in temperature within seasons. These results strengthen the ideas proposed by the foraging hypothesis. Although benefits derived from flocking have yet to be determined, whatever they are should be understood in the context of seasonal variation in life‐history traits.
Preventing Unintentional Injuries to Young Children in the Home: Understanding and Influencing Parents’ Safety Practices
Authors: Morrongiello Barbara A.
Published: April 2018

Unintentional injuries are the leading cause of preventable deaths for children in most industrialized countries. In this article, I consider research on how parents prevent home injuries to children under 6 years and discuss an intervention aimed at improving parents’ home‐safety practices. Parents of young children use three types of home‐safety practices: teaching about safety, modifying the environment, and supervising. Relying predominantly on teaching increases young children's risk of injury, whereas modifying the environment and supervising protect children and predict fewer injuries. Drawing on evidence about factors that motivate parents’ safety practices, an intervention was developed to improve supervision: The Supervising for Home Safety program positively changed parents’ appraisals about injury and supervision practices. Developing evidence‐based injury‐prevention programs is an effective way to address this national public‐health issue.
Development of Multifaceted Risk Taking and the Relations to Sex Steroid Hormones: A Longitudinal Study
Authors: Peper Jiska S. , Braams Barbara R. , Blankenstein Neeltje E. , Bos Marieke G.N. , Crone Eveline A.
Published: April 2018

Risk taking is a multidimensional construct. It is currently unclear which aspects of risk‐taking change most during adolescence and if/how sex hormones contribute to risk‐taking tendencies. This study applied a longitudinal design with three time‐points, separated by 2 years, in participants aged 8–29 years (670 observations). The Balloon Analogue Risk Task, a delay discounting task, and various self‐report questionnaires were administered, to measure aspects of risk taking. Longitudinal analyses demonstrated mostly nonlinear age‐related patterns in risk‐taking behavior and approach‐related personality characteristics (peaking in late adolescence). Increased testosterone and estradiol were found to increase risk‐taking behavior and impulsive personality, but decrease avoidance‐like personality. This study demonstrates that risk taking is most pronounced in mid‐to‐late adolescence and suggests that sex hormones accelerate this maturational process.
Clinical implications of food allergen thresholds
Authors: Graham F. , Eigenmann P. A.
Published: April 2018

Food allergy has increased in recent decades and has a major impact on patients’ quality of life. There is currently no treatment in routine clinical practice, and patients are often faced with accidental reactions. Precautionary allergen labelling (PAL) has been used by the food industry to attempt to minimize this risk, although not standardized and often ambiguous. Estimating the risk of reacting to traces in foods is complicated by heterogeneous amounts of allergens in foods with precautionary labelling and individual variability in reaction thresholds. In recent years, oral food challenge studies have shown that low individual reaction thresholds do not necessarily correlate with severe reactions, and current understanding of thresholds is evolving with novel low‐dose challenge protocols better adapted to estimate them. Future tools to provide a better estimation of minimal eliciting doses, including basophil activation tests, may improve our management of food‐allergic patients.
Combined use of xenogeneic bone substitute material covered with a native bilayer collagen membrane for alveolar ridge preservation: A randomized controlled clinical trial
Authors: Jung Ronald E. , Sapata Vitor M. , Hämmerle Christoph H. F. , Wu Hui , Hu Xiu‐lian , Lin Ye
Published: April 2018

Aim

The aim of this split‐mouth randomized controlled study was to evaluate radiographic dimensional changes after tooth extraction in posterior sites treated with a ridge preservation technique or left for spontaneous healing.

Materials and Methods

In a total of 18 patients, tooth extraction in posterior sites of the upper and lower jaw was performed in a split‐mouth design. The post‐extraction sockets were randomly assigned to the following two treatment modalities: deproteinized bovine bone mineral (DBBM) with 10% collagen (DBBM‐C) covered with a native bilayer collagen membrane (NBCM) (test group) and spontaneous healing (control group). Cone beam computed tomography (CBCT) scans were performed after extractions, 3 and 6 months later. The following parameters were measured: the height of the buccal bone plate (BH), height of the palatal bone plate (PH), horizontal width of the extraction socket at 1 mm, 3 mm, and 5 mm (HW‐1, HW‐3, HW‐5), and the horizontal width (thickness) of the buccal bone plate at 1 mm, 3 mm, and 5 mm (BHP‐1, BHP‐3, BHP‐5). Statistical analysis was performed applying a nonparametric Wilcoxon signed‐rank test.

Results

The CBCT analysis showed a bone loss compared to baseline in test and control group. The measurements which have reached statistically significant differences at 6 months were BH (test: −2.31% vs control: −13.11%), PH (test: −2.07% vs control: −15.32%), HW‐1 (test: −17.14% vs control: −32.47%), and HW‐3 (test: −11.65% vs control: −28.47%).

Conclusions

The posterior ridge preservation technique using DBBM‐C covered with a NBCM is a valid approach reducing the amount of the radiographic loss in alveolar ridge dimensions.
Specific barrier response profiles after experimentally induced skin irritation in vivo
Authors: Soltanipoor Maryam , Stilla Tasja , Riethmüller Christoph , Thyssen Jacob P. , Sluiter Judith K. , Rustemeyer Thomas , Fischer Tobias W. , Kezic Sanja , Angelova‐Fischer Irena
Published: April 2018

Background

Recently, natural moisturizing factors (NMFs) and corneocyte surface topography were suggested as biomarkers for irritant dermatitis.

Objectives

To investigate how exposure to different irritants influences corneocyte surface topography, NMF levels and the barrier function of human skin in vivo.

Methods

Eight healthy adult volunteers were exposed to aqueous solutions of 60% n‐propanol, 0.5% sodium lauryl sulfate (SLS), 0.15% sodium hydroxide, and 2.0% acetic acid, and distilled water, in a repeated irritation test over a period of 96 hours. Erythema, transepidermal water loss (TEWL), skin hydration, the dermal texture index (DTI) and NMF levels were measured at baseline, and after 24 and 96 hours.

Results

SLS and sodium hydroxide had the most pronounced effects on erythema and TEWL. Although n‐propanol caused only slight changes in TEWL and erythema, it showed pronounced effects on skin hydration, NMF levels, and the DTI. NMF was the only parameter that was significantly altered by all investigated irritants. The changes in the DTI were inversely associated with NMF levels and skin hydration.

Conclusion

Skin barrier impairment and the inflammatory response are irritant‐specific, emphasizing the need for a multiparametric approach to the study of skin irritation. NMF levels seem to be the most sensitive parameter in detecting irritant‐induced skin barrier alterations.
Presenteeism in a Dutch hand eczema population—a cross‐sectional survey
Authors: Oosterhaven Jart A. F. , Flach Peter A. , Bültmann Ute , Schuttelaar Marie L. A.
Published: April 2018

Background

Presenteeism (attending work despite complaints and ill health, which should prompt rest and absence) has been overlooked in the field of hand eczema.

Objectives

To examine the 1‐year prevalence of presenteeism related to hand eczema in a population of hand eczema patients who visited a tertiary referral centre. Secondary objectives: to identify intrinsic/extrinsic reasons for presenteeism and to evaluate associated factors.

Methods

This was a cross‐sectional questionnaire study. Presenteeism was defined as “going to work despite feeling you should have taken sick leave because of hand eczema”. Respondents answered questions about socio‐demographic factors, clinical features, occupational characteristics, and hand eczema related to occupational exposure.

Results

Forty‐one per cent (141/346) of patients who had both worked and had hand eczema during the past 12 months reported presenteeism. The most often reported reasons were: “Because I do not want to give in to my impairment/weakness” (46%) and “Because I enjoy my work” (40%). Presenteeism was associated with: mean hand eczema severity; absenteeism because of hand eczema; improvement of hand eczema when away from work; and high‐risk occupations.

Conclusions

In this study, presenteeism was common and predominantly observed in patients with more severe hand eczema and occupational exposure. The most frequently reported reasons for presenteeism were of an intrinsic nature.
Outcome of pediatric heart transplantation in blood culture positive donors in the United States
Authors: Amdani Shahnawaz M. , Du Wei , Aggarwal Sanjeev
Published: April 2018

Active donor infection at the time of organ procurement poses a potential infection risk and may increase post‐transplant morbidity and mortality in recipients. Our hypothesis was that pediatric heart transplant recipients from blood culture positive donors (BCPD) would have increased morbidity and mortality compared to non‐blood culture positive donors (NBCPD). A retrospective analysis of pediatric heart transplant recipients using the organ procurement and transplant network (OPTN) between 1987 and 2015 was conducted. Recipient as well as donor data were analyzed. Propensity score matching with 1:2 ratios was performed for recipient variables. Post‐transplant morbidity and mortality were compared for recipients of BCPD and NBCPD. Among 9618 heart transplant recipients, 450 (4.7%) were from culture positive donors. Recipients of BCPD had longer duration of listing as Status 1; diagnosis of congenital heart disease or restrictive cardiomyopathy and required support (IV inotropes, Inhaled NO and LVAD) prior to transplant. Post‐transplant survival between the 2 groups was not different. Propensity‐matched recipients had similar length of stay; stroke rate; need for dialysis; pacemaker implantation and treated rejection episodes in the first year post‐transplant. Careful acceptance of BCPD may have the potential to increase availability of donor hearts in the pediatric population.
Self‐organization of human iPS cells into trophectoderm mimicking cysts induced by adhesion restriction using microstructured mesh scaffolds
Authors: Okeyo Kennedy O. , Tanabe Maiko , Kurosawa Osamu , Oana Hidehiro , Washizu Masao
Published: April 2018

Cellular dynamics leading to the formation of the trophectoderm in humans remain poorly understood owing to limited accessibility to human embryos for research into early human embryogenesis. Compared to animal models, organoids formed by self‐organization of stem cells in vitro may provide better insights into differentiation and complex morphogenetic processes occurring during early human embryogenesis. Here we demonstrate that modulating the cell culture microenvironment alone can trigger self‐organization of human induced pluripotent stem cells (hiPSCs) to yield trophectoderm‐mimicking cysts without chemical induction. To modulate the adhesion microenvironment, we used the mesh culture technique recently developed by our group, which involves culturing hiPSCs on suspended micro‐structured meshes with limited surface area for cell adhesion. We show that this adhesion‐restriction strategy can trigger a two‐stage self‐organization of hiPSCs; first into stem cell sheets, which express pluripotency signatures until around day 8–10, then into spherical cysts following differentiation and self‐organization of the sheet‐forming cells. Detailed morphological analysis using immunofluorescence microscopy with both confocal and two‐photon microscopes revealed the anatomy of the cysts as consisting of a squamous epithelial wall richly expressing E‐cadherin and CDX2. We also confirmed that the cysts exhibit a polarized morphology with basal protrusions, which show migratory behavior when anchored. Together, our results point to the formation of cysts which morphologically resemble the trophectoderm at the late‐stage blastocyst. Thus, the mesh culture microenvironment can initiate self‐organization of hiPSCs into trophectoderm‐mimicking cysts as organoids with potential application in the study of early embryogenesis and also in drug development.
Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome study
Authors: Casey C. , McGinty A. , Holmes V. A. , Hill A. J. , Patterson C. C. , Young I. S. , McCance D. R.
Published: April 2018

Aims

To measure total 25‐hydroxyvitamin D levels in women in mid‐pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25‐hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers.

Methods

A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24–32 weeks’ gestation, as part of the HAPO study. 25‐hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C‐peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed.

Results

The median (interquartile range) 25‐hydroxyvitamin D concentration during pregnancy was 38.6 (24.1–60.7) nmol/l, with 65.8% of women being vitamin D‐deficient (≤50 nmol/l). In regression analysis, the association between maternal 25‐hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient –0.017 (95% CI –0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25‐hydroxyvitamin D and β‐cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25‐hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis.

Conclusions

These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25‐hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.
Teaching Line Balancing through Active and Blended Learning*
Authors: Bayley Tiffany , Hurst Ada
Published: April 2018

The design of balanced assembly lines, especially when considering workforce, material, and cycle time factors, is an important managerial decision‐making activity in manufacturing firms. Numerous active learning activities are available to assist instructors in teaching assembly line balancing to students. While effective in improving student engagement, they require considerable planning and expense on the part of instructors, and they may be difficult to implement in inflexible teaching spaces and lecture‐oriented curricula. We present a new approach to teaching line balancing using online videos depicting an assembly process. Students design an assembly line by determining themselves how to separate and time tasks, rather than by modifying an existing configuration. To save valuable classroom time, students complete a portion of the activity outside of class. This blended learning approach allows for all students to be engaged in the activity, both in and out of class. Furthermore, a controlled study showed that compared to the traditional lecture format, it better equips students to address less tangible aspects of line balancing, such as ergonomic and workforce factors, material handling considerations, and changing cycle time. With the online content for this activity completely developed and available, other instructors can easily implement this approach within their courses.