bluuebunny/crossref_metadata_2025 huggingface dataset:
A QTL with Major Effect on Reducing Stripe Rust Severity Detected From a Chinese Wheat Landrace
Authors: Zhang H. Y. , Wang Z. , Ren J. D. , Du Z. Y. , Quan W. , Zhang Y. B. , Zhang Z. J.
Published: April 2017

Stripe rust, a devastating disease of wheat worldwide, can be controlled by use of diverse wheat resistance resources. To find new quantitative trait loci (QTL) for resistance to stripe rust, Qing Shumai (a Chinese winter wheat landrace possessing slow rusting resistance) was crossed with the susceptible line Mingxian 169. The parents and 276 recombinant inbred lines (RILs) from the cross were evaluated in five environments involving two locations (Gansu and Shandong provinces, China) and four autumn-sown wheat seasons (2008 to 2012). Disease severities on Qing Shumai were lower than 25%, contrasting with approximately 90% on Mingxian 169. The RILs varied in rust intensity in a continuous and monomodal distribution. A bulked segregant analysis approach using 2,344 simple sequence repeat (SSR) markers mapped a major QTL to the long arm of chromosome 6D (hereby designated as QYr.cau-6DL). An SSR marker (gpw5179, https://wheat.pw.usda.gov/GG2/index.shtml ) was identified as being tightly linked with QYr.cau-6DL. Combination between QYr.cau-6DL and the stripe rust-resistance gene Yr18 was examined using 160 F2:3families of Qing Shumai × RL6058 (a near-isogenic line for Yr18 in the genetic background of the spring wheat Thatcher). The combination elevated the resistance consistently across both winter and spring wheat backgrounds, acting synergistically without undesired epistasis.
Rathayibacter toxicus, Other Rathayibacter Species Inducing Bacterial Head Blight of Grasses, and the Potential for Livestock Poisonings
Authors: Murray Timothy D. , Schroeder Brenda K. , Schneider William L. , Luster Douglas G. , Sechler Aaron , Rogers Elizabeth E. , Subbotin Sergei A.
Published: April 2017

Rathayibacter toxicus, a Select Agent in the United States, is one of six recognized species in the genus Rathayibacter and the best known due to its association with annual ryegrass toxicity, which occurs only in parts of Australia. The Rathayibacter species are unusual among phytopathogenic bacteria in that they are transmitted by anguinid seed gall nematodes and produce extracellular polysaccharides in infected plants resulting in bacteriosis diseases with common names such as yellow slime and bacterial head blight. R. toxicus is distinguished from the other species by producing corynetoxins in infected plants; toxin production is associated with infection by a bacteriophage. These toxins cause grazing animals feeding on infected plants to develop convulsions and abnormal gate, which is referred to as “staggers,” and often results in death of affected animals. R. toxicus is the only recognized Rathayibacter species to produce toxin, although reports of livestock deaths in the United States suggest a closely related toxigenic species may be present. A closely related but undescribed species, Rathayibacter sp. EV, originally isolated from Ehrharta villosa var. villosa in South Africa, is suspected of producing toxin. Many of the diseases caused by Rathayibacter species occur in arid areas and the extracellular polysaccharide they produce is believed to aid in their survival between crops. For example, R. “agropyri” was isolated from infected plant material after being stored for 50 years in a herbarium. Similarly, the anguinid vectors associated with these bacteria form seed galls in infected plants and are capable of surviving for very long periods of time under dry conditions. The addition of R. toxicus to the list of Select Agents has raised concern over its potential introduction and a realization that current diagnostic methods are inadequate to distinguish among Rathayibacter species. In addition, little is known about the Rathayibacter species and their seed gall nematode vectors present in the United States.
Analysis of the Spatial Pattern of Strawberry Angular Leaf Spot in California Nursery Production
Authors: Gigot Christophe , Turechek William , McRoberts Neil
Published: April 2017

In California, angular leaf spot (ALS) is a common disease in strawberry nursery production, and a major concern for nurseries wishing to export plants. As the spatial pattern of a disease can offer insight into pathogen source, mode of dissemination, and how current crop management practices affect epidemic development, an understanding of the spatial pattern of ALS would allow nursery growers to make informed decisions regarding disease management. Ninety-seven field assessments of disease incidence were performed at different nursery locations in 2014 and 2015 to quantify ALS spatial pattern under commercial conditions. Both point-pattern and geostatistical statistical procedures were used to analyze the data. The spatial pattern of ALS was characterized by a high degree of heterogeneity, as indicated by high median values of the beta-binomial distribution’s theta parameter (0.643), and the index of dispersion, D (4.218). The binary power law provided a robust description of the data with estimated slope and intercept parameters significantly greater than 1 and 0, respectively (P < 0.001). Spatial analysis by distance indices (SADIE) detected significant nonrandom spatial arrangements for 64% of the data sets. Analysis of directional disease spread showed a strong spatial association between sampling units along the same planting row. This suggests that recurrent crop operations during the growing season play a significant role in ALS spread and should be taken into account to improve disease control.
Infection Courts in Watermelon Plants Leading to Seed Infestation byFusarium oxysporumf. sp.niveum
Authors: Petkar Aparna , Ji Pingsheng
Published: April 2017

Fusarium wilt incited by Fusarium oxysporum f. sp. niveum is a seed-transmitted disease that causes significant yield loss in watermelon production. The pathogen may infect watermelon seeds latently, which can be an important inoculum source and contribute to severe disease outbreak. However, information regarding infection courts of F. oxysporum f. sp. niveum leading to infestation of watermelon seeds is limited. To determine how seeds in watermelon fruit can be infested by F. oxysporum f. sp. niveum during the watermelon growing season, greenhouse and field experiments were conducted in 2014 and 2015 where watermelon flowers and immature fruit were inoculated with F. oxysporum f. sp. niveum. Seeds were extracted from mature watermelon fruit, and infestation of watermelon seeds was determined by isolation of F. oxysporum f. sp. niveum and further confirmed by real-time polymerase chain reaction (PCR) analysis. Inoculation of the pericarp of immature fruit resulted in 17.8 to 54.4% of infested seeds under field conditions and 0.6 to 12.8% of infested seeds under greenhouse conditions when seeds were not surface disinfested prior to isolation. Seed infestation was also detected in 0 to 4.5% of the seeds when seeds were surface disinfested prior to isolation. Inoculation of pistil resulted in 0 to 7.2% and 0 to 18.3% of infested seeds under greenhouse and field conditions when seeds were surface disinfested or not disinfested before isolation, respectively. Inoculation of peduncle resulted in 0.6 to 6.1% and 0 to 10.0% of infested seeds in the greenhouse and field experiments when seeds were surface disinfested or not disinfested before isolation, respectively. Seed infestation was also detected in all the experiments using real-time PCR assay when pericarp or pistil was inoculated, and in three of four experiments when peduncle was inoculated, regardless of whether seeds were surface disinfested or not disinfested. Pericarp and peduncle of immature watermelon fruit and pistil of watermelon flowers could be potential infection courts for F. oxysporum f. sp. niveum leading to infestation of seeds in asymptomatic watermelon fruit.
Predicting receptor functionality of signaling lymphocyte activation molecule for measles virus hemagglutinin by docking simulation
Authors: Suzuki Yoshiyuki
Published: April 2017

Predicting susceptibility of various species to a virus assists assessment of risk of interspecies transmission. Evaluation of receptor functionality may be useful in screening for susceptibility. In this study, docking simulation was conducted for measles virus hemagglutinin (MV‐H) and immunoglobulin‐like variable domain of signaling lymphocyte activation molecule (SLAM‐V). It was observed that the docking scores for MV‐H and SLAM‐V correlated with the activity of SLAM as an MV receptor. These results suggest that the receptor functionality may be predicted from the docking scores of virion surface proteins and cellular receptor molecules.
Microbial community function in the bleaching disease of the marine macroalgae Delisea pulchra
Authors: Zozaya‐Valdés Enrique , Roth‐Schulze Alexandra J. , Egan Suhelen , Thomas Torsten
Published: April 2017

Disease is increasingly viewed as a major factor impacting the health of both natural and cultured populations of marine organisms, including macroalgae. The red macroalga Delisea pulchra suffers from a bleaching disease resulting from host stress and infection by opportunistic bacterial pathogens. However, how pathogens cause the disease and how the entire macro algal‐associated community is involved in the process is unclear. Here, we perform a metagenomic analysis of microbial communities associated with diseased and healthy D. pulchra across multiple bleaching events. Analysis of reconstructed 16S rRNA gene sequences showed that bacteria belonging to the families Rhodobacteraceae, Saprospiraceae and Flavobacteriaceae, including bacteria previously implicated in algal bleaching, to be enriched in diseased D. pulchra. Genes with predicted functions related to chemotaxis, motility, oxidative stress response, vitamin biosynthesis and nutrient acquisition were also prevalent in microbiomes of bleached algae, which may have a role in pathogenicity. Reconstruction of genomes that were abundant on bleached samples revealed that no single organism contains all bleaching‐enriched functional genes. This observation indicates that potential virulence traits are distributed across multiple bacteria and that the disease in D. pulchra may result from a consortium of opportunistic pathogens, analogous to dysbiotic or polymicrobial diseases.
Traditional processing, composition, microbial quality and sensory characteristics of Eshabwe (ghee sauce)
Authors: Mukisa Ivan Muzira , Kiwanuka Bernard Junior
Published: April 2017

Eshabwe is a traditional Ugandan condiment produced from butter or ghee. The traditional formula, proximate composition, microbial quality and sensory characteristics of Eshabwe have previously not been reported. The purpose of this study was to describe the processing and to determine the sensory characteristics, proximate composition and microbial quality of Eshabwe. Ten commercial processors of Eshabwe were interviewed. Samples of Eshabwe obtained from processors were analysed for proximate composition and microbial quality. A lexicon for the sensory attributes of Eshabwe was developed using quantitative descriptive analysis. Eshabwe is prepared by whipping butter or ghee (1 kg) with boiled water (560 ± 0.13 mL), rock salt (37.8 ± 0.13 g) and sodium chloride (5.6 ± 0.09 g). Eshabwe has a shelf life of 3–5 days at room temperature, 3 months under refrigeration and over 6 months under frozen storage. Eshabwe contains 43.10 ± 0.15% dry matter, 1.99 ± 0.13% ash, 0.49 ± 0.02% crude protein, 32.87 ± 0.93% fat and 3.93 ± 0.05 Kcal/g. The total aerobic counts (6.56 ± 0.03 log cfu/mL), yeasts and moulds (2.26 ± 0.02 log cfu/mL) and coliforms (3.16 × 103 MPN/mL) were in excess of microbial specifications. A lexicon of 15 descriptors for the sensory attributes of Eshabwe was developed. Eshabwe processing should be standardised to ensure consistent quality and consumer safety.
Posterior ankle labral changes at MRI: A preliminary study
Authors: Khan Nasir , Sahota Navdeep , Shepel Michael L , Obaid Haron
Published: April 2017

Introduction

The transverse ligament in the ankle joint has been described as a labrum‐like structure in a previous cadaveric study. The purpose of this study is to assess the spectrum of abnormal changes related to this structure on imaging/MRI, and correlate these findings with other ankle joint findings and patient symptoms.

Method

A retrospective observational review of 172 ankle MRI scans was carried out independently by two fellowship trained musculoskeletal Radiologists. Correlation between abnormal labral changes, other ankle joint findings and patient symptomatology was performed.

Results

Abnormal labral changes were seen in 26% of the MRI scans (n = 44/172) and included signal change, contour abnormality with heterogeneous signal change, linear fluid filled clefts, multidirectional fluid filled clefts, and a macerated labrum. There was a statistically significant association between abnormal labral changes and the presence of Stieda process/os trigonum (P = 0.001), talocrural joint osteoarthritis (P = 0.0003), paralabral cysts (P = 0.0001), imaging features of posterior impingement (P = 0.01), and both medial (P = 0.005) and lateral (P = 0.01) ankle ligament injuries. However, there was no statistically significant association between abnormal labral changes and patient symptoms.

Conclusion

The posterior ankle labrum can develop a spectrum of abnormal MRI appearances in patients with other ankle joint abnormalities. Although this study showed no correlation between patients’ symptoms and posterior ankle labral changes, larger studies are needed to examine the biomechanical alterations that may arise from these labral changes.
Establishment of an inferior vena cava filter database and interventional radiology led follow‐up – retrieval rates and patients lost to follow‐up
Authors: Klinken Sven , Humphries Charlotte , Ferguson John
Published: April 2017

Introduction

To evaluate the rates of inferior vena cava (IVC) filter retrieval and the number of patient's lost to follow‐up, before and after the establishment of an IVC filter database and interventional radiology (inserting physician) led follow‐up.

Methods

On the 1st of June 2012, an electronic interventional radiology database was established at our Institution. In addition, the interventional radiology team took responsibility for follow‐up of IVC filters. Data were prospectively collected from the database for all patients who had an IVC filter inserted between the 1st June 2012 and the 31st May 2014. Data on patients who had an IVC filter inserted between the 1st of June 2009 to the 31st of May 2012 were retrospectively reviewed. Patient demographics, insertion indications, filter types, retrieval status, documented retrieval decisions, time in situ, trackable events and complications were obtained in the pre‐database (n = 136) and post‐database (n = 118) cohorts.

Results

Attempted IVC filter retrieval rates were improved from 52.9% to 72.9% (P = 0.001) following the establishment of the database. The number of patients with no documented decision (lost to follow‐up) regarding their IVC filter reduced from 31 of 136 (23%) to 0 of 118 patients (P = < 0.001). There was a non‐significant reduction in IVC filter dwell time in the post‐database group (113 as compared to 137 days, P = 0.129).

Conclusion

Following the establishment of an IVC filter database and interventional radiology led follow‐up, we demonstrate a significant improvement in the attempted retrieval rates of IVC filters and the number of patient's lost to follow‐up.
The effects of local cold application on fibromyalgia pain
Authors: Yilmaz Naside , Kiyak Emine
Published: April 2017

Aim

This study was conducted to evaluate the effects of local cold application on pain when applied to the trapezius muscles of patients with fibromyalgia.

Method

A one‐group, pre‐test/post‐test, pre‐experimental model was applied in this study, which was conducted with 55 fibromyalgia patients who presented to a rheumatology outpatient clinic. A 10‐min cold application was administered to one trapezius muscle of each patient. The participants’ pain was evaluated, in total, four times (before the cold application and 10 min, 1.5 h and 24 h after the cold application). The visual analogue scale (VAS) for pain was used to collect data for the study, and Friedman and Wilcoxon tests were used to assess the data.

Results

The patients’ pain mean score before (6.45, SD:1.27) the cold applications was found to be significantly higher than the scores noted 10 min (2.75, SD:1.73), 1.5 h (2.45, SD:1.29), and 24 h (3.36, SD:1.30) after the application (P < 0.001).

Conclusion

The study found that local cold applications performed on the trapezius muscles of patients with fibromyalgia significantly decreased their pain. With its discovery of a new method of pain control in fibromyalgia patients, this study will significantly contribute to science and will serve as a guide for pain management, especially in nursing practice. Further studies to evaluate the maximum effect duration and effect mechanisms of local cold applications to the trapezius muscles of FM patients are indicated.
Nicotine‐induced molecular alterations are modulated by GABAB receptor activity
Authors: Varani Andres P. , Pedrón Valeria T. , Aon Amira J. , Höcht Christian , Acosta Gabriela B. , Bettler Bernhard , Balerio Graciela N.
Published: April 2017

It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward effect; nevertheless, the mechanism implicated is not well known. In this regard, we evaluated the involvement of GABAB receptors on the behavioral, neurochemical, biochemical and molecular alterations associated with the rewarding effects induced by NIC in mice, from a pharmacological and genetic approach. NIC‐induced rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by conditioned place preference (CPP) paradigm. CPP has three phases: preconditioning, conditioning and postconditioning. GABAB receptor antagonist 2‐hydroxysaclofen (0.25, 0.5 and 1 mg/kg; intraperitoneally, ip) or the GABAB receptor agonist baclofen (3 mg/kg; ip) was injected before NIC during the conditioning phase. GABAB1 knockout (GABAB1KO) mice received NIC during the conditioning phase. Vehicle and wild‐type controls were employed. Neurochemical (dopamine, serotonin and their metabolites), biochemical (nicotinic receptor α4β2, α4β2nAChRs) and molecular (c‐Fos) alterations induced by NIC were analyzed after the postconditioning phase by high‐performance liquid chromatography (HPLC), receptor‐ligand binding assays and immunohistochemistry, respectively, in nucleus accumbens (Acb), prefrontal cortex (PFC) and ventral tegmental area (VTA). NIC induced rewarding effects in the CPP paradigm and increased dopamine levels in Acb and PFC, α4β2nAChRs density in VTA and c‐Fos expression in Acb shell (AcbSh), VTA and PFC. We showed that behavioral, neurochemical, biochemical and molecular alterations induced by NIC were prevented by baclofen. However, in 2‐hydroxysaclofen pretreated and GABAB1KO mice, these alterations were potentiated, suggesting that GABAB receptor activity is necessary to control alterations induced by NIC‐induced rewarding effects. Therefore, the present findings provided important contributions to the mechanisms implicated in NIC‐induced rewarding effects.
Excessive heat‐associated gingival necrosis: a case report
Authors: Barnes PL , Rossi‐Fedele G
Published: April 2017

Heat‐delivery devices have been associated with relatively high temperatures. Previous basic research studies suggest that the risk for periodontal tissues is negligible, as the presence of the root filling materials, amongst other factors, reduce the risk of overheating. This report describes the case of a 45 year old male, who was undergoing restorative treatment in a multi‐specialty dental practice. As part of his overall treatment planning, orthograde root canal retreatment for his maxillary left incisor teeth was deemed necessary, due to chronic apical periodontitis. Following cold lateral compaction, the coronal portion of the core material was severed using a System B Heat Source (Kerr Dental, Orange, CA, USA), with the patient reporting pain as well as a burning sensation. The following day the patient was seen by a periodontist and gingival necrosis in relation to the central incisor was found. The most likely cause of the complication was considered to be excessive heat during the operative procedure. The patient was followed up for a 2‐year period and the soft tissues returned to their original condition without the need for periodontal treatment.
How can we restrict the sale of sports and energy drinks to children? A proposal for a World Health Organization‐sponsored framework convention to restrict the sale of sports and energy drinks
Authors: Jean G
Published: April 2017

High‐sugar drinks, including fruit drinks, soft drinks, sports drinks and energy drinks, are of no nutritional value and contribute to the burden of dental disease in all age groups. The manufacturers of sports and energy drinks have elected to target children in their marketing campaigns and promote a misleading association between their products, healthy lifestyles and sporting prowess. The World Health Organization (WHO) has acknowledged that strategies aimed at prevention of dental disease are the only economically viable options for managing the oral health of children in low‐ and middle‐income countries. Developed nations will also be advantaged by preventive programmes given that the cost of providing dental care to those who cannot pay draws valuable resources away from more pressing health issues. The Convention on the Rights of the Child (CRC) obligates governments to develop legislation to protect the health of children. A framework convention modelled on the existing Framework Convention for Tobacco Control, supported by the WHO, would assist governments to proactively legislate to restrict the sale of sports and energy drinks to children. This article will consider how a framework convention would be an advantage with reference to the strategies used by sports and energy drink manufacturers in Australia.
Environmental influences on the bioluminescence display of the glow‐worm, Arachnocampa flava (Diptera: Keroplatidae)
Authors: Merritt David J , Patterson Rachell
Published: April 2017

Glow‐worms are the larvae of fungus gnats that use bioluminescence to lure night‐flying insects to their webs. They are found in still, humid environments such as rainforest gullies, the vicinity of waterfalls or inside caves. Arachnocampa flava is endemic to south‐east Queensland where it is the focus of night‐time tourism at a number of subtropical rainforest locations. For management of tourist populations as well as understanding the natural dynamics of the bioluminescence display, previous studies of A. flava used photographic imaging or quadrat‐based counts to assess the number of larvae glowing. Here, time‐lapse digital photography with an SLR camera is employed in a rainforest gully to image a glow‐worm colony at 10 min intervals. Recordings took place between April and December of 2010. Blocks of continuous recording lasted 13–35 continuous days. This sampling frequency revealed the nightly bioluminescence intensity profile and the influence of some environmental conditions. On nights without rainfall, larvae initiated glowing soon after dusk, rapidly rose to a peak intensity and then progressively decreased their intensity through to dawn when they douse in response to approaching dawn. Bioluminescence output increased substantially on nights when rainfall was recorded. Use of a tipping‐bucket rain gauge at the site showed that larvae increased their intensity and the number glowing increased immediately when rain began falling. Moonlight around the time of a full moon inhibited larval bioluminescence output. The time‐lapse photographic method proved to be a useful monitoring tool that has revealed correlations between climate and season and the intensity of the glow‐worm display.
Characteristics and outcomes of ALK+ non‐small cell lung cancer patients in Korea
Authors: Lim Sung Hee , Yoh Kyung Ah , Lee Jong Seok , Ahn Myung‐ju , Kim Yu Jung , Kim Se Hyun , Zhang Jie , Patel Dony , Swallow Elyse , Kageleiry Andrew , Galebach Philip , Lee Dongyeol , Stein Karen , Degun Ravi , Park Keunchil
Published: April 2017

Aim

This study aimed to describe characteristics, treatment patterns and survival among Korean patients diagnosed with locally advanced or metastatic anaplastic lymphoma kinase (ALK)+ non‐small cell lung cancer (NSCLC).

Methods

A retrospective patient chart review was conducted in major cancer centers in Korea in 2014–2015. Participating physicians reviewed patient charts and reported characteristics, treatment patterns, clinician‐defined progression‐free survival (PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC patients. PFS and OS were estimated using Kaplan–Meier analysis.

Results

Physicians reported on 55 ALK+ NSCLC patients. Median age at locally advanced or metastatic NSCLC diagnosis was 60 years. Most patients (82%) received initial chemotherapy; 13% received an ALK inhibitor in the first line; 62% received an ALK inhibitor by the end of follow‐up. Of the 30 patients who received crizotinib, 83% discontinued and 13% died during crizotinib therapy. Median PFS on crizotinib was 6.7 months. Of those who discontinued, 32% switched to chemotherapy, 16% switched to a different ALK inhibitor and 52% received no further therapy. After discontinuing crizotinib, median OS was 6.0 months overall, and 3.4 months among patients who did not receive a second‐generation ALK inhibitor.

Conclusion

In this study of locally advanced or metastatic ALK+ NSCLC patients in Korea, roughly one‐third did not receive an ALK inhibitor. Among patients who discontinued crizotinib, over half received no further antineoplastic therapy and OS was poor, particularly among patients without second‐generation ALK inhibitor use. These findings suggest a need for greater access to effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.
Feasibility and utility of portable ultrasound during retrieval of sick preterm infants
Authors: Browning Carmo Kathryn , Lutz Tracey , Greenhalgh Mark , Berry Andrew , Kluckow Martin , Evans Nick
Published: April 2017

Aim

Document the incidence of haemodynamic pathology in critically ill preterm newborns requiring transport.

Method

A transport neonatologist performed cardiac and cerebral ultrasound before and after transportation of infants born ≤30 weeks gestation.

Results

Forty‐four newborns were studied in 2008–2015; of them, 21 were transported by road, 19, by helicopter and four, by fixed wing: median birthweight, 1130 g (680–1960 g) and median gestation, 27 weeks (23–30); 30 of 44 were male babies. Antenatal steroid course was complete in two babies. Ultrasound in the referring hospital was at a mean of two hours: 47 minutes (00:15–7:00) of age. Low systemic blood flow was common: 50% had right ventricular output <150mL/kg/min and 23%, a superior vena cava flow <50mL/kg/min. at stabilisation. Cranial US: 10 Grade I IVH, 2 Grade II IVH, 1 Grade IV IVH and 32 normal scans pretransport. After transport, three further Grade I IVH were reported. Mortality was higher in the babies with low systemic blood flow: 4 of 12 (33%) died vs 1 of 31 (6%) in the normal flow group (OR = 7.2, 95% CI: 1.1 to 47, p = 0.022).

Conclusion

Point‐of‐care ultrasound during the retrieval of preterm infants confirms a high incidence of haemodynamic pathology. The use of ultrasound during transport may provide an opportunity for earlier targeted circulatory support.
A general empirical model for renal drug handling in pharmacokinetic analyses
Authors: Wright Daniel F. B. , Duffull Stephen B.
Published: April 2017

Dose adjustment in renal insufficiency is generally based on the assumption that renal drug clearance is related linearly to glomerular filtration rate. The theory underpinning this model is the intact nephron hypothesis, which says that impaired renal function is caused by a reduction in the number of complete (intact) nephrons. The purpose of the present commentary is to propose a general empirical model for renal drug handling. We will explore models for renal function under two scenarios: one that aligns with the intact nephron hypothesis, and one that relaxes the assumptions of this hypothesis. We propose that a nonlinear, non‐intact nephron model will allow for differences in renal drug handling, while incorporating the intact nephron hypothesis model as a special case.
Assisted Dying & Disability
Authors: Riddle Christopher A.
Published: April 2017

This article explores at least two dominant critiques of assisted dying from a disability rights perspective. In spite of these critiques, I conclude that assisted dying ought to be permissible. I arrive at the conclusion that if we respect and value people with disabilities, we ought to permit assisted dying. I do so in the following manner. First, I examine recent changes in legislation that have occurred since the Royal Society of Canada Expert Panel on End‐of‐Life Decision‐Making report, published in this journal. I suggest that these changes are likely to only strengthen opposition to assisted dying from disability rights activists and people with disabilities. Second, I focus on respect for people with disabilities and in particular, respect for their autonomy and decision‐making abilities. Third, I explore the opposition to assisted dying that focuses on risk and the vulnerability of people with disabilities. Here I suggest that this risk ought not to be of special concern. Ultimately, I conclude that upholding respect for the disabled requires the legalization of assisted dying, rather than the denial of access in a misguided effort to protect people with disabilities.
Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia
Authors: Ho Gwendolyn , Jonas Brian A. , Li Qian , Brunson Ann , Wun Ted , Keegan Theresa H. M.
Published: April 2017

Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999–2000; 16·8%, 2011–2012) across all age groups, but was higher in older patients (6·9%, 15–39, 11·4%, 40–54, 18·6% 55–65, and 35·8%, >65 years). Major bleeding [Odds ratio (OR) 1·5, 95% confidence interval (CI) 1·3–1·9], liver failure (OR 1·9, 95% CI 1·1–3·1), renal failure (OR 2·4, 95% CI 2·0–2·9), respiratory failure (OR 7·6, 95% CI 6·2–9·3) and cardiac arrest (OR 15·8, 95% CI 8·7–28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute‐designated cancer centres was associated with lower early mortality (OR 0·5, 95% CI 0·4–0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality.
Cortactin, a Lyn substrate, is a checkpoint molecule at the intersection of BCR and CXCR4 signalling pathway in chronic lymphocytic leukaemia cells
Authors: Martini Veronica , Gattazzo Cristina , Frezzato Federica , Trimarco Valentina , Pizzi Marco , Chiodin Giorgia , Severin Filippo , Scomazzon Edoardo , Guzzardo Vincenza , Saraggi Deborah , Raggi Flavia , Martinello Leonardo , Facco Monica , Visentin Andrea , Piazza Francesco , Brunati Anna Maria , Semenzato Gianpietro , Trentin Livio
Published: April 2017

Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP‐9) and the motility of neoplastic cells. Cortactin knockdown, by siRNA, induced a reduction in MMP‐9 release as well as a decrease of migration capability of leukaemic B cells in vitro, also after chemotactic stimulus. Furthermore, Cortactin phosphorylation was lowered by the Src kinase‐inhibitor PP2 with a consequent decrease of MMP‐9 release in culture medium. An impaired migration, as compared to control experiments without Cortactin knockdown, was observed following CXCL12 triggering. Reduced Cortactin expression and phosphorylation were also detected both in vivo and in vitro after treatment with Ibrutinib, a Btk inhibitor. Our results highlight the role of Cortactin in CLL as a check‐point molecule between the BCR and CXCR4 signalling pathways.
Detailed immunophenotyping of B‐cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection
Authors: Theunissen Prisca M. J. , Sedek Lukasz , De Haas Valerie , Szczepanski Tomasz , Van Der Sluijs Alita , Mejstrikova Ester , Nováková Michaela , Kalina Tomas , Lecrevisse Quentin , Orfao Alberto , Lankester Arjan C. , van Dongen Jacques J. M. , Van Der Velden Vincent H. J. ,   the EuroFlow Consortium
Published: April 2017

Flow cytometric detection of minimal residual disease (MRD) in children with B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) requires immunophenotypic discrimination between residual leukaemic cells and B‐cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow‐based 8‐colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP‐ALL. We identified pre‐B‐I cells that expressed low or dim CD34 levels, in contrast to the classical CD34high pre‐B‐I cell immunophenotype. These CD34−dim pre‐B‐I cells were relatively abundant in regenerating BM (11–85% within pre‐B‐I subset), while hardly present in healthy control BM (9–13% within pre‐B‐I subset; P = 0·0037). Furthermore, we showed that some of the BCP‐ALL diagnosis immunophenotypes (23%) overlapped with CD34−dim pre‐B‐I cells. Our results indicate that newly identified CD34−dim pre‐B‐I cells can be mistaken for residual BCP‐ALL cells, potentially resulting in false‐positive MRD outcomes. Therefore, regenerating BM, in which CD34−dim pre‐B‐I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements.
Young people's beliefs about the risk of bowel cancer and its link with physical activity
Authors: Newby Katie V. , Cook Chloe , Meisel Susanne F. , Webb Thomas L. , Fisher Bernadette , Fisher Abi
Published: April 2017

Objectives

The primary objective was to explore young people's risk appraisals of bowel cancer, including whether they had a coherent understanding of the protective effects of physical activity (PA). A secondary objective was to examine whether the illness risk representations (IRRs) framework could be used to understand beliefs underlying bowel cancer risk appraisals.

Design

Qualitative.

Methods

Framework analysis of semi‐structured interviews with 19 people aged 14–17 years.

Results

Participants judged their risk of getting bowel cancer as low. This was based on a lack of family history of cancer and their current lifestyle behaviours, which were viewed as having a protective effect, or because they planned on making change to their lifestyle in the future when disease risk became more relevant. Participants were not aware of, and struggled to understand, the link between PA and bowel cancer. They also lacked knowledge of the effects of, or treatments for, bowel cancer. Beliefs underlying judgements about the risk of bowel cancer fitted the IRR framework reasonably well.

Conclusions

The present research suggests that interventions designed to increase PA with a view to reducing the risk of bowel cancer should aim to make the future risk of bowel cancer feel more tangible, help young people to understand the full range of consequences, explain how and why preventative behaviours such as PA are effective in reducing risk, and emphasize that the typical late presentation of symptoms, and therefore investigation by health care services, reduces treatability.

Statement of contribution

What is already known on this subject?

Physical activity (PA) performed throughout the lifespan can have a protective effect on bowel cancer, but levels of PA are low among young people.

Changing beliefs about the risk of getting bowel cancer may be a useful strategy in motivating PA.

What does this study add?

Increased understanding of how young people think about bowel cancer and the relationship between PA and cancer.

Identification of strategies for increasing young adults’ appraisals of the likelihood and severity of bowel cancer.

Evidence to support the validity of illness risk representations framework.
Fluvial architecture in actively deforming salt basins: Chinle Formation, Paradox Basin, Utah
Authors: Hartley Adrian , Evenstar Laura
Published: April 2017

Determining the response of fluvial systems to syn‐sedimentary halokinesis is important for reconstructing the palaeogeography of salt basins, determining the history of salt movement and predicting development and architecture of sandstone bodies for subsurface fluid extraction. To assess both the influence of salt movement on fluvial system development and the use of lithostratigraphic correlation schemes in salt basins we have analysed the Triassic Chinle Formation in the Paradox Basin, Utah. Results indicate that sandstone body development proximal to salt bodies should be considered at two scales: intra‐ (local) and inter‐ (regional) mini‐basin scale. At the intra‐mini basin or local scale, conformable packages of up to 12 m deep meandering fluvial channel deposits and associated overbank deposits are developed, which may thin, pinch‐out or become truncated towards salt highs. When traced down the axis of a mini‐basin, individual stories extend for a few hundred metres, and form part of amalgamated channel‐belt packages up to 60 m thick that can be traced for at least 25 km parallel to palaeoflow. Where salt movement outpaces sediment accumulation, progressive low angle unconformities are developed along the flanks of salt highs. Significantly, in mini‐basins with high sand supply, sandstone bodies are present across salt highs where they show increased amalgamation, decrease in thickness due to truncation and no change in internal sandstone body character. At inter mini‐basin or regional scale, spatial and temporal variations in accommodation space generated by differential salt movement strongly influence facies distributions and facies correlation lengths. Broad lithostratigraphic packages (5–50 m thick) can be correlated within mini‐basins, but correlation of these units between adjacent mini‐basins is problematic. Knowledge of fluvial system development at a regional scale is critical as, fluvial sediment distribution is focussed by topography generated by growing salt bodies, such that adjacent mini‐basins can have significant differences in sandstone body thickness, distribution and lateral extent. The observations from the Chinle Formation indicate that lithostratigraphic‐based correlation schemes can only be applied within mini‐basins and cannot be used to correlate between adjacent mini‐basins or across a salt mini‐basin province. The key to predicting sandstone body development is an understanding of the timing of salt movement and reconstructing fluvial drainage system development.
Prolonged breastfeeding for 24 months or more and mental health at 6 years of age: evidence from the 2004 Pelotas Birth Cohort Study, Brazil
Authors: Delgado Carlos Alberto , Munhoz Tiago N. , Santos Iná S. , Barros Fernando C. , Matijasevich Alicia
Published: April 2017

Background

There is scarce and conflicting evidence on medium‐ to long‐term effects of prolonged breastfeeding on child behavior.

Method

A population‐based birth cohort study started in 2004 in the city of Pelotas, Southern Brazil. Children were followed up at 3, 12, 24, and 48 months and 6 years of age. Breastfeeding duration was determined based on information collected around the time of weaning. Psychiatric disorders were assessed using the Development and Well‐Being Assessment (DAWBA). Children who were never breastfed were excluded from the analysis. Crude and adjusted analyses were performed using Poisson regression with robust variance.

Results

Data on breastfeeding and mental health at the age of 6 years were available for 3377 children. Prevalence of breastfeeding for 24–35 months and ≥36 months was 16.1% (95% CI: 14.8–17.3) and 8.1% (95% CI: 7.2–9.1), respectively. Prevalence of psychiatric disorders among those who were breastfed for <24 months, 24–35 months and ≥36 months was 12.4% (95% CI: 11.1–13.7), 13.1% (95% CI: 10.4–16.2) and 12.3% (95% CI: 8.7–16.8), respectively. No association was found between breastfeeding for 24 months or more and psychiatric disorders among children aged 6 years both in the crude and adjusted analyses.

Conclusions

In this cohort there was no association between breastfeeding for 24 months or more and an increased prevalence of psychiatric disorders at the age of 6 years. Studies analyzing the medium‐ and long‐term effects of prolonged breastfeeding for 2 years or more are scarce and further research is needed regarding this practice.
Toward the rational design of macrolide antibiotics to combat resistance
Authors: Pavlova Anna , Parks Jerry M. , Oyelere Adegboyega K. , Gumbart James C.
Published: April 2017

Macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild‐type, A2058G‐mutated, and singly or doubly A2058‐methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from their crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole‐analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole‐analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives.
Stakeholders' views of the introduction of assistive technology in the classroom: How family‐centred is Australian practice for students with cerebral palsy?
Authors: Karlsson P. , Johnston C. , Barker K.
Published: April 2017

Background

With family‐centred care widely recognized as a cornerstone for effective assistive technology service provision, the current study was undertaken to investigate to what extent such approaches were used by schools when assistive technology assessments and implementation occurred in the classroom.

Method

In this cross‐sectional study, we compare survey results from parents (n = 76), school staff (n = 33) and allied health professionals (n = 65) with experience in the use of high‐tech assistive technology. Demographic characteristics and the stakeholders' perceived helpfulness and frequency attending assessment and set‐up sessions were captured. To evaluate how family‐centred the assistive technology services were perceived to be, the parents filled out the Measure of Processes of Care for Caregivers, and the professionals completed the Measure of Processes of Care for Service Providers. Descriptive statistics and one‐way analysis of variance were used to conduct the data analysis.

Results

Findings show that parents are more involved during the assessment stage than during the implementation and that classroom teachers are often not involved in the initial stage. Speech pathologists in particular are seen to be to a great extent helpful when implementing assistive technology in the classroom. This study found that family‐centred service is not yet fully achieved in schools despite being endorsed in early intervention and disability services for over 20 years. No statistically significant differences were found with respect to school staff and allied health professionals' roles, their years of experience working with students with cerebral palsy and the scales in the Measure of Processes of Care for Service Providers.

Conclusion

To enhance the way technology is matched to the student and successfully implemented, classroom teachers need to be fully involved in the whole assistive technology process. The findings also point to the significance of parents' involvement, with the support of allied health professionals, in the process of selecting and implementing assistive technology in the classroom.
The Role of Family Characteristics for Students’ Academic Outcomes: A Person‐Centered Approach
Authors: Häfner Isabelle , Flunger Barbara , Dicke Anna‐Lena , Gaspard Hanna , Brisson Brigitte M. , Nagengast Benjamin , Trautwein Ulrich
Published: April 2017

Using data from 1,571 ninth‐grade students (Mage = 14.62) from 82 academic track schools in Germany and their predominantly Caucasian middle‐class parents, configurations of different family characteristics reported by parents were investigated. Latent profile analyses considering academic involvement, family interest, parents’ self‐concept, child's need for support, and parents’ time and energy identified average, indifferent, motivated and engaged, motivated and disengaged, and involved families. Cross‐sectional and longitudinal associations with students’ motivational (self‐concept, effort, and interest) and achievement outcomes (achievement test and grades) in math were analyzed. Students from families classified as motivated and disengaged showed higher initial levels motivation and achievement. Over 5 months, these students also showed an increase in self‐concept and higher achievement than students from other family types.