bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting violation in abstract pitch patterns with mismatch negativity
Authors: Xiao Xue‐Zhen , Wong Hoi Ki , Wang Yang , Zhao Kunyang , Zeng Ginger Qinghong , Yip Long‐Yin , Wong Geoffrey Chun‐Sung , Tse Chun‐Yu
Published: March 2018

The human brain automatically extracts regularities embedded in environmental auditory events. This study investigated the extraction of abstract patterns by measuring mismatch negativity (MMN). Participants watched a silent subtitled movie and ignored a sequence of auditory events comprising frequent standards and rare deviants presented in the background. Tone triplets with varying pitch (first‐order property) served as the auditory events. The pitch intervals (interval 1 and interval 2) between the tones in a triplet and the ratio of interval 1 and 2 were considered second‐ and third‐order properties, respectively. Both second‐ and third‐order properties of the standards were kept constant in the mixed patterns block, while only the third‐order property was kept constant in the ratio pattern block. Four sets of tone triplets violating the interval and ratio patterns with different deviance levels were presented as deviants in both blocks, and subtracted with physically identical stimuli in a control block to isolate the MMNs. Interval and ratio pattern deviants elicited MMNs in the mixed patterns block while only ratio pattern deviants elicited MMNs in the ratio pattern block. Larger MMNs were elicited by large deviants as compared to small deviants. These results suggest that the change detection system is sensitive to the violation of both second‐ and third‐order abstract patterns. In addition to regularities in the abstract properties of auditory events, regularities in the relationships between abstract properties can also be extracted. This ability plays an important role in music and language perception.
Public Pensions and Collective Bargaining Rights: Evidence from State and Local Governments
Authors: Hoang Trang , Goodman Doug
Published: March 2018

An aging workforce and increasing retirement benefits are ongoing problems for states and municipalities. Unions are often blamed for governments offering too generous pension benefits. This contributes to budgetary pressures in some state and municipal governments. This article analyzes the impact of collective bargaining on pension benefit generosity under different economic conditions. The study finds that the impact of collective bargaining on pension benefits is not consistent over time or across pension plans. Collective bargaining has a positive effect on pension benefits under worsening economic conditions. Additionally, unions indirectly influence pension benefit generosity through campaign donations and unionization intensity. The findings suggest mixed impacts of collective bargaining on different groups of public employees regarding pension contributions. The article concludes with implications for the role of unions in public financial performance and strategic human resource management during fiscal austerity.
Relationships with Arctic indigenous peoples: To what extent has prior informed consent become a norm?
Authors: Hughes Layla
Published: March 2018

‘Indigenous engagement’ refers to a range of relationships with indigenous peoples. Engagement may apply to research activities, government decision making, economic activities, or any other interaction that will bring people into or affect an indigenous community. Free, prior and informed consent (FPIC) is an aspect of indigenous engagement that is gaining increasing recognition in international and domestic law. This article examines the extent to which laws, policies and practices in the Arctic support FPIC. A review of current practices in the Arctic suggests that for the most part, States provide for some degree of prior information sharing and consultation but have yet to implement mechanisms to ensure consent before allowing activities in the Arctic to proceed. At the same time, governance structures in various parts of the Arctic help to fulfil indigenous self‐determination and therefore provide promising alternative means for supporting indigenous human rights.
Multiple breath washout: A new and promising lung function test for patients with idiopathic pulmonary fibrosis
Authors: Nyilas Sylvia , Schreder Theresa , Singer Florian , Poellinger Alexander , Geiser Thomas Kurt , Latzin Philipp , Funke Manuela
Published: March 2018

Background and objective

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease affecting the parenchyma. Nitrogen multiple‐breath washout (N2‐MBW) is a lung function test that measures ventilation inhomogeneity, a biomarker of small airway disease. We assessed clinical properties of N2‐MBW in IPF.

Methods

In this prospective cohort pilot study, 25 IPF patients and 25 healthy controls were assessed at baseline and 10 patients at median 6.2 months later. Outcomes included the lung clearance index (LCI) from N2‐MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), bronchiectasis score from computed tomography scans, the Gender–Age–Physiology (GAP score for IPF) stage and death or lung transplantation (LTx). Study end points were feasibility, repeatability, discriminative capacity and correlation with disease severity and structural lung damage.

Results

All patients were able to perform N2‐MBW. LCI was repeatable and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1–13.8) in IPF versus 7.3 (6.9–8.4) in controls (P < 0.0001). LCI correlated with DLCO corrected for haemoglobin (corrDLCO; r = −0.49, P = 0.016), bronchiectasis score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with FVC. FVC was not related to bronchiectasis. During follow‐up, six patients died and one received LTx. LCI correlated with the latter compound outcome: hazard ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population.

Conclusion

N2‐MBW is a feasible, reliable and valid lung function test in IPF. LCI correlates with diffusion impairment, structural airway damage and clinical disease severity. LCI is a promising surveillance tool in IPF that may predict mortality.
Marginal Logistic Regression for Spatially Clustered Binary Data
Authors: Cattelan Manuela , Varin Cristiano
Published: March 2018

Clustered data are often analysed under the assumption that observations from distinct clusters are independent. The assumption may not be correct when the clusters are associated with different locations within a study region, as, for example, in epidemiological studies involving subjects nested within larger units such as hospitals, districts or villages. In such cases, correct inferential conclusions critically depend on the amount of spatial dependence between locations. We develop a modification of the method of generalized estimating equations to detect and account for spatial dependence between clusters in logistic regression for binary data. The approach proposed is based on parametric modelling of the lorelogram as a function of the distance between clusters. Model parameters are estimated by the hybrid pairwise likelihood method that combines optimal estimating equations for the regression parameters and pairwise likelihood for the lorelogram parameters. The methodology is illustrated with an analysis of prevalence disease survey data.
Estimating Material Properties Under Extreme Conditions by Using Bayesian Model Calibration with Functional Outputs
Authors: Brown J. L. , Hund L. B.
Published: March 2018

Dynamic material properties experiments provide access to the most extreme temperatures and pressures attainable in a laboratory setting; the data from these experiments are often used to improve our understanding of material models at these extreme conditions. We apply Bayesian model calibration to dynamic material property applications where the experimental output is a function: velocity over time. This framework can accommodate more uncertainties and facilitate analysis of new types of experiments relative to techniques traditionally used to analyse dynamic material experiments. However, implementation of Bayesian model calibration requires more sophisticated statistical techniques, because of the functional nature of the output as well as parameter and model discrepancy identifiability. We propose a novel Bayesian model calibration process to simplify and improve the estimation of the material property calibration parameters. Specifically, we propose scaling the likelihood function by an effective sample size rather than modelling the auto-correlation function to accommodate the functional output. Additionally, we propose sensitivity analyses by using the notion of 'modularization' to assess the effect of experiment-specific nuisance input parameters on estimates of the physical parameters. The Bayesian model calibration framework proposed is applied to dynamic compression of tantalum to extreme pressures, and we conclude that the procedure results in simple, fast and valid inferences on the material properties for tantalum.
The Role of Secondary Outcomes in Multivariate Meta-Analysis
Authors: Copas John B. , Jackson Dan , White Ian R. , Riley Richard D.
Published: March 2018

Univariate meta-analysis concerns a single outcome of interest measured across a number of independent studies. However, many research studies will have also measured secondary outcomes. Multivariate meta-analysis allows us to take these secondary outcomes into account and can also include studies where the primary outcome is missing. We define the efficiency E as the variance of the overall estimate from a multivariate meta-analysis relative to the variance of the overall estimate from a univariate meta-analysis. The extra information gained from a multivariate meta-analysis of n studies is then similar to the extra information gained if a univariate meta-analysis of the primary effect had a further n(1−E)/E studies. The variance contribution of a study's secondary outcomes (its borrowing of strength) can be thought of as a contrast between the variance matrix of the outcomes in that study and the set of variance matrices of all the studies in the meta-analysis. In the bivariate case this is given a simple graphical interpretation as the borrowing-of-strength plot. We discuss how these findings can also be used in the context of random-effects meta-analysis. Our discussion is motivated by a published meta-analysis of 10 antihypertension clinical trials.
Assessment of palliative care needs of patients/families living with cancer in a developing country
Authors: Ndiok Akon , Ncama Busisiwe
Published: March 2018

Purpose

The study seeks to assess the care needs of oncology in‐patients and clinic attendees or families in two tertiary health institutions.

Methods

This was a descriptive study which utilised a quantitative survey questionnaire of all cancer patients diagnosed between January 2014 and September 2016 (n = 547) with the return rate (n = 455) representing 82%. The questionnaire explored assessment of palliative care need. These instruments were used, because patients with cancer and their families are reluctant to talk about the disease. Using a questionnaire was therefore the best means of obtaining their full participation. The data were analysed using descriptive statistics to identify the highest need of patients with cancer patients. The study was approved by the two participating hospitals and the Human and Social Sciences Research Ethics of University of KwaZulu‐Natal.

Findings

The study found that most common needs of patients were information on possibilities of treatment and side effects (92.8%), diagnosis (91.6%), testing (91.1%) and physical symptoms (90.9%). There were also other needs, such as psychological, spiritual and financial needs, related to factors causing distress to patients and their families following diagnosis of cancer.

Conclusions

This article focused on needs as expressed by patients and families and offers a useful guide to develop a model for integration of palliative care activities. The findings reveal that patients who are undergoing follow‐up care and cancer treatment or investigation are clearly concerned about receiving information on a range of cancer issues. We therefore conclude that patients are able to deal with the disease more effectively when hospitals set up a palliative care team or unit to carry out proper assessment of patients living with cancer.
Should we look beyond Kt/V urea in assessing dialysis adequacy?
Authors: Jones Clare B. , Bargman Joanne M.
Published: March 2018

Since the advent of maintenance dialysis therapy, our interpretation of what adequate dialysis really is has broadened and become more controversial. This is not only due to our changing and aging dialysis population but also to our evolving knowledge base. As nephrologists, we strive to achieve both quality and (often) quantity of life for our patients and we feel reassured when we have a quantifiable marker to show for our efforts. However, we suggest that adequate dialysis reaches far beyond the realms of attaining a particular biochemical result. Dialysis adequacy should encompass a more comprehensive assessment of patient well‐being. This metric could comprise quality of life and patient‐specified goals, sufficient small solute and middle molecule clearance, optimal blood pressure control, and effective bone‐mineral balance, all in the context of minimizing mortality and morbidity, and a livable dialysis regimen for the patient.
Tectonically controlled initiation of contemporaneous deep‐water channel systems along a Late Cretaceous continental margin, western British Columbia, Canada
Authors: Englert Rebecca G. , Hubbard Stephen M. , Coutts Daniel S. , Matthews William A.
Published: March 2018

Submarine channel‐systems are globally prevalent on continental margins and their deposits record the transfer of significant volumes of sediment from continental catchments to deep‐water environments. These deposits contain signals of past events that can provide critical insight into the geological history of an area, including the long‐term (>1 Ma) controls on sedimentation. Well‐exposed outcrops of the Late Cretaceous Nanaimo Group, British Columbia, Canada, provide an opportunity to investigate long‐term sediment‐routing in a tectonically active setting. This study combines detrital zircon geochronology with stratigraphic analysis to establish a robust, basin‐wide palaeogeographic framework that constrains the timing and distribution of coarse‐grained sediment transport and deposition in the Nanaimo forearc basin. Three south‐west trending submarine conduits are documented along a 135 km long strike‐oriented transect, parallel to the north‐west/south‐east trending basin. Composite conduit deposits are 350 to 700 m thick, 4 to 16 km wide, and record substantial delivery of coarse‐grained detritus (up to boulder‐sized clasts) within submarine channel‐levée systems. Maximum depositional ages derived from detrital zircon datasets constrain contemporaneous sediment transfer and deposition at each conduit location, which spanned between 73·5 ± 1·3 Ma to 69·1 ± 1·1 Ma around the Campanian–Maastrichtian boundary. Submarine conduits are spaced at 40 km and 70 km, and were likely connected to fluvial drainage systems sourced in uplifted catchments. Widespread, coarse‐grained deposits suggest that surface uplift associated with concurrent regional events (such as deformation and/or magma emplacement) along the North American margin may have promoted sediment delivery to the deep‐water basin. Comparisons to modern and ancient analogues support palaeogeographic interpretations, as well as the interpretation that pervasive coarse‐grained deep‐water sediment delivery was linked to tectonic activity. The integrated stratigraphic–geochronological approach used provides unique insight into the influence of regional tectonics on continental margin physiography and the nature of deep‐water sediment dispersal.
Understanding the Pathways from Depression to Suicidal Risk from the Perspective of the Interpersonal–Psychological Theory of Suicide
Authors: Kang Nan , You Jianing , Huang Jiyi , Ren Yaxuan , Lin Min‐pei , Xu Sian
Published: March 2018

Suicide is a major public health concern, especially in adolescence. Identifying risk factors for suicide is important to effectively prevent such behavior. Depression is one of the most widely examined risk factors for suicidal risk. How depression and suicidal risk are related, however, is still not clear. This study tested a model with three key constructs of the interpersonal–psychological theory of suicidal behavior (IPTS)—perceived burdensomeness, thwarted belongingness, and nonsuicidal self‐injury (NSSI)—as mediators in the relationship between depression and suicidal risk among Chinese adolescents. Chinese high school students (N = 1,074; 54.2% male; Mage = 13.87 years, SD = 1.48) completed questionnaires assessing all study variables. Results suggested that perceived burdensomeness and NSSI partially mediated the relationship between depression and suicidal risk. Findings of this study emphasize the importance of the IPTS framework in understanding the possible mechanisms underlying the relationship between depression and suicidal risk, and suggest a possible avenue for suicide interventions.
The effect of Nordic hamstring exercise training volume on biceps femoris long head architectural adaptation
Authors: Presland J. D. , Timmins R. G. , Bourne M. N. , Williams M. D. , Opar D. A.
Published: March 2018

The aim of this study was to determine the time course of architectural adaptations in the biceps femoris long head (BFLH) following high or low volume eccentric training. Twenty recreationally active males completed a two week standardized period of eccentric Nordic hamstring exercise (NHE) training, followed by four weeks of high (n = 10) or low volume (n = 10) training. Eccentric strength was assessed pre‐ and post intervention and following detraining. Architecture was assessed weekly during training and after two and four weeks of detraining. After six weeks of training, BFLH fascicles increased significantly in the high (23% ± 7%, P < .001, d = 2.87) and low volume (24% ± 4%, P < .001, d = 3.46) groups, but reversed following two weeks of detraining (high volume: −17% ± 5%, P < .001, d = −2.04; low volume: −15% ± 3%, P < .001, d = −2.56) after completing the intervention. Both groups increased eccentric strength after six weeks of training (high volume: 28% ± 20%, P = .009, d = 1.55; low volume: 34% ± 14%, P < .001, d = 2.09) and saw no change in strength following a four week period of detraining (high volume: −7% ± 7%, P = .97, d = −0.31; low volume: −2% ± 5%, P = .99, d = −0.20). Both low and high volume NHE training stimulate increases in BFLH fascicle length and eccentric knee flexor strength. Architectural adaptations reverted to baseline levels within two weeks after ceasing training, but eccentric strength was maintained for at least four weeks. These observations provide novel insight into the effects of training volume and detraining on BFLH architecture and may provide guidance for the implementation of NHE programs.
The prevalence of Achilles and patellar tendon injuries in Australian football players beyond a time‐loss definition
Authors: Docking S. I. , Rio E. , Cook J. , Orchard J.W. , Fortington L. V.
Published: March 2018

Little is known about the prevalence and associated of morbidity of tendon problems. With only severe cases of tendon problems missing games, players that have their training and performance impacted are not captured by traditional injury surveillance. The aim of this study was to report the prevalence of Achilles and patellar tendon problems in elite male Australian football players using the Oslo Sports Trauma Research Centre (OSTRC) overuse questionnaire, compared to a time‐loss definition. Male athletes from 12 professional Australian football teams were invited to complete a monthly questionnaire over a 9‐month period in the 2016 pre‐ and competitive season. The OSTRC overuse injury questionnaire was used to measure the prevalence and severity of Achilles and patellar tendon symptoms and was compared to traditional match‐loss statistics. A total of 441 participants were included. Of all participants, 21.5% (95% CI: 17.9‐25.6) and 25.2% (95% CI 21.3‐29.4) reported Achilles or patellar tendon problems during the season, respectively. Based on the traditional match‐loss definition, a combined 4.1% of participants missed games due to either Achilles or patellar tendon injury. A greater average monthly prevalence was observed during the pre‐season compared to the competitive season. Achilles and patellar tendon problems are prevalent in elite male Australian football players. These injuries are not adequately captured using a traditional match‐loss definition. Prevention of these injuries may be best targeted during the off‐ and pre‐season due to higher prevalence of symptoms during the pre‐season compared to during the competitive season.
Trends in time‐loss injuries during the 2011‐2016 South African Rugby Youth Weeks
Authors: Sewry N. , Verhagen E. , Lambert M. , van Mechelen W. , Marsh J. , Readhead C. , Viljoen W. , Brown J.
Published: March 2018

Youth rugby is a popular sport in South Africa (SA) with a high injury incidence. The annual SA Rugby Youth Week tournaments attract the top age‐group players in the country providing a sample of players for reliable injury surveillance. The aim of the study was to analyze the changes in time‐loss injury rates at the SA Rugby Youth Week tournaments between 2011 and 2016, differences between age‐groups, and to investigate associated injury risk factors. All confirmed time‐loss injuries at the 4 age‐group tournaments (under‐13, under‐16, and 2 under‐18) from 2011 to 2016 were recorded. Injury incidence densities (IID) for years, tournaments, and injury risk factors were calculated and Poisson regression analyses were performed to determine differences. Time‐loss injuries (n = 494) were reported over 24 240 exposure hours, with an overall IID of 20.4 (18.6‐22.2) injuries per 1000 player hours. The year 2013 had a significantly lower IID compared to 2011. Injury risk decreased with increasing age; under‐13 and under‐16 had significantly higher IID compared to under‐18 Craven Week. Tackling was the phase of play at highest risk, with an IID of 7.4 (6.3‐8.5) injuries per 1000 player hours. Central/peripheral nervous system (CNS/PNS) and, therefore, the head/neck were the most commonly occurring injuries/location injured. In conclusion, within the SA Rugby tournament structure, the older players had a decreased rate of injury. The tackle event was still the phase of play with the highest injury incidence regardless of age. This increase in incidence is largely due to an increase in CNS/PNS injuries.
Visual attention to members of own and other groups: Preferences, determinants, and consequences
Authors: Kawakami Kerry , Friesen Justin , Vingilis‐Jaremko Larissa
Published: March 2018

Many current and past theories of social categorization acknowledge and even underline the critical role that visual processing plays in intergroup misperceptions and biases, yet research that directly measures or manipulates these processes is limited. In the present paper, we reviewed the current literature on visual attention to own and other group faces. First, we explored the development of preferential attention in face processing. Next, we examined these processes in adults and show different patterns of attention for own and other group faces. Although we briefly consider cross‐cultural variations, the focus of this review is on within‐culture differences in visual attention. In particular, we explore preferential attention to specific features on own versus other group faces and to their overall faces. We also discuss potential determinants for differential attention such as experience, threat, individuation and a desire to know in‐groups, and liking. Finally, we explore the implications of differential attention to own and other groups. These consequences range from reduced recognition of other group faces, to impaired identification of emotional expressions, to impeded interaction intentions, and to increased discrimination. Together our analyses provide strong evidence for differences in attention to the faces and eyes of own versus other group members and their role in intergroup biases.
Root and Phrasal Diminutive Markers in Gan Chinese
Authors: Li Xuping , Liu Hongyong
Published: March 2018

Previous analyses of diminutives made a dichotomy between derivational and inflectional diminutives, and we found that such a distinction does not cover all the possibilities that diminutives may be in world languages. This article presents a case study of two diminutive markers, namely, ‐li and ‐tsiʔ, in Yichun Gan, a Sinitic language. The diminutive marker ‐tsiʔ is typologically significant in being cross‐categorial at the phrasal level. It can be attached to different types of phrases, ranging from noun phrases, classifier phrases, adjective phrases and verb phrases. These two diminutive markers are characterized with distinct distributions and semantic interpretations, based on which, we propose that the diminutive ‐li works at the root level and functions as a root nominalizer, and ‐tsiʔ operates at the phrasal level and is a phrasal diminutive modifier.
Molecular phylogeny of moth flies (Diptera, Psychodidae, Psychodinae) revisited, with a revised tribal classification
Authors: KVIFTE GUNNAR MIKALSEN
Published: March 2018

Classification of Psychodinae has been a hotly contested topic in the taxonomic literature, with multiple mutually incompatible classifications proposed. Three main points of contention can be identified: (i) the validity of Maruinini Enderlein as a tribe‐level taxon and whether it forms a monophyletic group; (ii) the placement of subtribe Trichopsychodina Ježek – specifically whether it belongs with Psychoda Latreille in Psychodini or with Paramormia Enderlein and Telmatoscopus Eaton in Paramormiini Enderlein or Mormiini Enderlein; and (iii) whether Mormia Enderlein is more closely related to Brunettia Annandale or Paramormia Enderlein and Telmatoscopus Eaton. In the present paper, these questions are investigated using a molecular phylogeny of sequences compiled from all previous molecular phylogenies relevant to Psychodinae, as well as some hitherto unpublished sequences. The resulting matrix comprised 5406 base pairs from six markers for 32 taxa, and when analysed using Bayesian inference it yielded a well‐resolved tree which was unambiguous for all previously contentious points: Maruinini sensu lato (including Setomimini) was resolved as a valid taxon, Trichopsychodina is rendered paraphyletic by Psychodini, and Mormia is not closely related to Brunettia, but instead closer to Telmatoscopus and Paramormia. A revised tribal classification of Psychodinae is proposed, recognizing the tribes Psychodini, Brunettiini, Maruinini and Pericomaini as well as 17 unplaced genera.
A novel HLA class I allele: HLA‐A*11:01:49
Authors: Zheng J. W. , Shen W. , Sun Y. , Xie J. H. , Xiang D.
Published: March 2018

The HLA‐A*11:01:49 allele differs from A*11:01:01:01 by one synonymous nucleotide substitution at position 837.
General practice tasters for foundation doctors
Authors: Sales Bryony , Masding Mike , Scallan Samantha
Published: March 2018

Background

General practice (GP) is currently not viewed positively as a career choice, compared with other specialties, with GP training programmes struggling to fill posts. Opportunities to change this mindset in the early years of training are limited. Trainees may find themselves applying for entry into GP specialty training just 3–4 months after completing Foundation Year 1 (FY1), yet there are few GP attachments during FY1 that can provide experience of primary care and positively inform career choice.

Context

To help ameliorate the current crisis in GP, recruitment and retention initiatives are needed to provide relevant experience of GP early in medical careers so that more doctors can make an informed decision to choose GP as a career.

Innovation

FY1 doctors have been given the opportunity to shadow final‐year GP specialty trainees (GPST3) in clinical practice (for between 3 and 5 days). The voluntary scheme has run successfully since 2014. This paper describes the taster programme and its evaluation. The programme has been positively received by both FY1s and GPST3 mentors. The GPST3s are enthusiastic about GP, which appeared to ‘rub off’ on the FY1s. FY1s find it helpful to have a trainee's perspective, gaining an overview of what to expect, including the opportunities available to them.

General practice is currently not viewed positively as a career choice

Implications

Using GPST3 trainees as mentors for FY1 doctors is educational for both groups and can have a positive impact on GP recruitment. The taster demonstrated how varied GP is, and challenged some negative perceptions of primary care. GPST3s gained confidence in their knowledge about GP and greater insight into educational roles.
Plasmodium falciparum infection transmitted by transfusion: A cause of hemophagocytic syndrome after bone marrow tranplantation in a non‐endemic country
Authors: Ladeb Saloua , Ben Abdejlil Nour , Fakhfakh Najla , Lakhal Amel , Belloumi Dorra , Ben Hamed Leila , Kallel Aicha , Torjman Lamia , El Fatimi Rym , Hmida Slama , Kallel Kalthoum , Ben Othman Tarek
Published: March 2018

A 27‐year‐old man with severe aplastic anemia underwent bone marrow transplantation from his HLA identical brother in July 2016. Conditioning included ATGAM 30 mg/kg for 3 days and Cyclophosphamide 50 mg/kg for 4 days. The patient received several platelet and red blood cell transfusions before and after the conditioning. The patient received broad spectrum antibiotics and caspofungin because persistant febrile neutropenia without bacteriological or mycological documentation. Hemophagocytic syndrome was diagnosed on day +12. Steroids at 1 mg/kg were started on day +12. Fever resolved the same day but resumed 3 days later associated to intravascular hemolysis with no schizocytes on blood smears and negative DAT. Thick blood film smears performed on day +26 revealed Plasmodium falciparum parasites (parasitemia = 20%). Except the level of parasitemia, there were no signs of gravity. Quinine was started on day 26 at a loading dose of 15 mg/kg followed by 8 mg/kg three times a day for 20 doses. Fever vanished after 2 days. Parasitemia cleared in 3 days and remained negative thereafter. Investigations revealed that the patient was transfused by a red cell unit harvested in a voluntary donor native of a malaria endemic country. PCR for P. falciparum performed in this donor in the frame of investigations was positive. The patient is alive with a normal blood count 1 year after BMT.
Efficient in planta gene targeting in Arabidopsis using egg cell‐specific expression of the Cas9 nuclease of Staphylococcus aureus
Authors: Wolter Felix , Klemm Jeannette , Puchta Holger
Published: March 2018

Gene targeting (GT), the programmed change of genomic sequences by homologous recombination (HR), is still a major challenge in plants. We previously developed an in planta GT strategy by simultaneously releasing from the genome a dsDNA donor molecule and creating a double‐stranded break (DSB) at a specific site within the targeted gene. Using Cas9 form Streptococcus pyogenes (SpCas9) under the control of a ubiquitin gene promoter, we obtained seeds harbouring GT events, although at a low frequency. In the present research we tested different developmentally controlled promotors and different kinds of DNA lesions for their ability to enhance GT of the acetolactate synthase (ALS) gene of Arabidopsis. For this purpose, we used Staphylococcus aureus Cas9 (SaCas9) nuclease and the SpCas9 nickase in various combinations. Thus, we analysed the effect of single‐stranded break (SSB) activation of a targeted gene and/or the HR donor region. Moreover, we tested whether DSBs with 5′ or 3′ overhangs can improve in planta GT. Interestingly, the use of the SaCas9 nuclease controlled by an egg cell‐specific promoter was the most efficient: depending on the line, in the very best case 6% of all seeds carried GT events. In a third of all lines, the targeting occurred around the 1% range of the tested seeds. Molecular analysis revealed that in about half of the cases perfect HR of both DSB ends occurred. Thus, using the improved technology, it should now be feasible to introduce any directed change into the Arabidopsis genome at will.
Silencing Arabidopsis CARBOXYL‐TERMINAL DOMAIN PHOSPHATASE‐LIKE 4 induces cytokinin‐oversensitive de novo shoot organogenesis
Authors: Fukudome Akihito , Goldman Jared S. , Finlayson Scott A. , Koiwa Hisashi
Published: March 2018

De novo shoot organogenesis (DNSO) is a post‐embryonic development programme that has been widely exploited by plant biotechnology. DNSO is a hormonally regulated process in which auxin and cytokinin (CK) coordinate suites of genes encoding transcription factors, general transcription factors, and RNA metabolism machinery. Here we report that silencing Arabidopsis thaliana carboxyl‐terminal domain (CTD) phosphatase‐like 4 (CPL4RNAi) resulted in increased phosphorylation levels of RNA polymerase II (pol II) CTD and altered lateral root development and DNSO efficiency of the host plants. Under standard growth conditions, CPL4RNAi lines produced no or few lateral roots. When induced by high concentrations of auxin, CPL4RNAi lines failed to produce focused auxin maxima at the meristem of lateral root primordia, and produced fasciated lateral roots. In contrast, root explants of CPL4RNAi lines were highly competent for DNSO. Efficient DNSO of CPL4RNAi lines was observed even under 10 times less the CK required for the wild‐type explants. Transcriptome analysis showed that CPL4RNAi, but not wild‐type explants, expressed high levels of shoot meristem‐related genes even during priming on medium with a high auxin/CK ratio, and during subsequent shoot induction with a lower auxin/CK ratio. Conversely, CPL4RNAi enhanced the inhibitory phenotype of the shoot redifferentiation defective2–1 mutation, which affected snRNA biogenesis and formation of the auxin gradient. These results indicated that CPL4 functions in multiple regulatory pathways that positively and negatively affect DNSO.
More than just sugars: Conserved oligomeric Golgi complex deficiency causes glycosylation‐independent cellular defects
Authors: Blackburn Jessica B. , Kudlyk Tetyana , Pokrovskaya Irina , Lupashin Vladimir V.
Published: March 2018

The conserved oligomeric Golgi (COG) complex controls membrane trafficking and ensures Golgi homeostasis by orchestrating retrograde vesicle trafficking within the Golgi. Human COG defects lead to severe multisystemic diseases known as COG‐congenital disorders of glycosylation (COG‐CDG).

To gain better understanding of COG‐CDGs, we compared COG knockout cells with cells deficient to 2 key enzymes, Alpha‐1,3‐mannosyl‐glycoprotein 2‐beta‐N‐acetylglucosaminyltransferase and uridine diphosphate‐glucose 4‐epimerase (GALE), which contribute to proper N‐ and O‐glycosylation. While all knockout cells share similar defects in glycosylation, these defects only account for a small fraction of observed COG knockout phenotypes. Glycosylation deficiencies were not associated with the fragmented Golgi, abnormal endolysosomes, defective sorting and secretion or delayed retrograde trafficking, indicating that these phenotypes are probably not due to hypoglycosylation, but to other specific interactions or roles of the COG complex.

Importantly, these COG deficiency specific phenotypes were also apparent in COG7‐CDG patient fibroblasts, proving the human disease relevance of our CRISPR knockout findings. The knowledge gained from this study has important implications, both for understanding the physiological role of COG complex in Golgi homeostasis in eukaryotic cells, and for better understanding human diseases associated with COG/Golgi impairment.
Sorting of Arabidopsis NRAMP3 and NRAMP4 depends on adaptor protein complex AP4 and a dileucine‐based motif
Authors: Müdsam Christina , Wollschläger Paul , Sauer Norbert , Schneider Sabine
Published: March 2018

Adaptor protein complexes mediate cargo selection and vesicle trafficking to different cellular membranes in all eukaryotic cells. Information on the role of AP4 in plants is still limited. Here, we present the analyses of Arabidopsis thaliana mutants lacking different subunits of AP4. These mutants show abnormalities in their development and in protein sorting. We found that growth of roots and etiolated hypocotyls, as well as male fertility and trichome morphology are disturbed in ap4. Analyses of GFP‐fusions transiently expressed in mesophyll protoplasts demonstrated that the tonoplast (TP) proteins MOT2, NRAMP3 and NRAMP4, but not INT1, are partially sorted to the plasma membrane (PM) in the absence of a functional AP4 complex. Moreover, alanine mutagenesis revealed that in wild‐type plants, sorting of NRAMP3 and NRAMP4 to the TP requires an N‐terminal dileucine‐based motif. The NRAMP3 or NRAMP4 N‐terminal domain containing the dileucine motif was sufficient to redirect the PM localized INT4 protein to the TP and to confer AP4‐dependency on sorting of INT1. Our data show that correct sorting of NRAMP3 and NRAMP4 depends on both, an N‐terminal dileucine‐based motif as well as AP4.
Lipid packing defects and membrane charge control RAB GTPase recruitment
Authors: Kulakowski Guillaume , Bousquet Hugo , Manneville Jean‐Baptiste , Bassereau Patricia , Goud Bruno , Oesterlin Lena K.
Published: March 2018

Specific intracellular localization of RAB GTPases has been reported to be dependent on protein factors, but the contribution of the membrane physicochemical properties to this process has been poorly described. Here, we show that three RAB proteins (RAB1/RAB5/RAB6) preferentially bind in vitro to disordered and curved membranes, and that this feature is uniquely dependent on their prenyl group. Our results imply that the addition of a prenyl group confers to RAB proteins, and most probably also to other prenylated proteins, the ability to sense lipid packing defects induced by unsaturated conical‐shaped lipids and curvature. Consistently, RAB recruitment increases with the amount of lipid packing defects, further indicating that these defects drive RAB membrane targeting. Membrane binding of RAB35 is also modulated by lipid packing defects but primarily dependent on negatively charged lipids. Our results suggest that a balance between hydrophobic insertion of the prenyl group into lipid packing defects and electrostatic interactions of the RAB C‐terminal region with charged membranes tunes the specific intracellular localization of RAB proteins.
Blood donors' preferences for blood donation for biomedical research
Authors: Raivola Vera , Snell Karoliina , Pastila Satu , Helén Ilpo , Partanen Jukka
Published: March 2018

BACKGROUND

Increasing numbers of blood donors are recruited to participate in biomedical research. As blood services depend on voluntary donors, successful recruitment calls for a better understanding of donors' expectations and attitudes toward the use of samples in research.

STUDY DESIGN AND METHODS

Sixty‐one semistructured interviews were conducted with blood donors at eight Finnish Red Cross Blood Service donation sites in Finland. The 10‐ to 30‐minute interviews included open‐ended questions about donors' views on blood donation for patients and for biomedical research. Central motives to donate blood for patients were identified against which views on research use were compared to see how these reflections differed.

RESULTS

Six central motives for donating blood for patients were identified among donors. The interviewees were, in general, willing to donate blood for research, but considered research donation more likely if it could be easily integrated into their usual blood donation habits. Biomedical research was perceived as important but its social benefits were more abstract than a direct help to patients.

CONCLUSIONS

Familiarity and reciprocity were key to the relationship between the blood service and blood donors. Donation for research introduces a new, more complex context to blood donation. Challenge to recognize concrete outcomes and benefits of donation may affect willingness to donate for research. Transparent communication of the role of the blood service in research and of the beneficiaries of the research is essential in maintaining trust. These results will help blood services in their planning to recruit blood donors for research projects.
Trends in hepatitis B and hepatitis C seroprevalence among blood donors – Haiti, 2005‐2014
Authors: Jean Baptiste A. E. , Chevalier M. S. , Polo E. , Noel E. , Hulland E. N. , Archer W. R.
Published: March 2018

Background and Objectives

Data on the seroprevalence of viral hepatitis are limited in Haiti; consequently, the epidemiology is poorly described. This study aims to provide a descriptive analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence of blood donations in Haiti.

Materials and Methods

Using Haiti's National Blood Safety Program and Haitian Red Cross reports from 2005 to 2014, we analysed the results of screening tests of donor serum samples to assess HBV and HCV seroprevalence among adults aged 17 to 65 years.

Results

A total of 198 758 donor samples were screened from 2005 to 2014, of which 0·56% were positive for antibody to hepatitis C virus (anti‐HCV) and 3·80% were positive for hepatitis B surface antigen. Over the 10‐year study period, anti‐HCV seroprevalence among blood donors increased by 31% from 0·66% to 0·86% (95% CI: 1·01–1·70); however, this trend was not uniform over time, with a significant decrease from 0·66% in 2005 to 0·39% in 2009 (95% CI: 0·43–0·82) and 0·43% in 2012 (95% CI: 0·50–0·90). Conversely, HBV decreased significantly by 13% from 3·95% in 2005 to 3·42% in 2014 (95% CI: 0·77–0·97), a trend that was also observed in 2012 and 2013.

Conclusion

The significant, uniform decrease in HBV seroprevalence in more recent years may represent the positive impact of public health interventions in preventing the transmission of blood‐borne infections. More research is needed to understand why the trends in HCV transmission are non‐uniform and to investigate the significant increase in more recent years.
Characterization of the nonpoint source pollution into river at different spatial scales
Authors: Wang Kang , Lin Zhongbing
Published: March 2018

The objectives of this study were to investigate the effects of rainfall and underlying surface conditions on nonpoint source (NPS) pollution loads and to identify the uncertainty in NPS pollution loads at different spatial scales in the Fuxi River basin, China. Data on monitored daily flow rates and concentrations of ammonium nitrogen, total nitrogen, total phosphorus and permanganate index at the sub‐basin and basin scales were collected for a period from 2013 to 2015. Dynamic time warping distance and information measures were used to characterize pollution loads and determine the uncertainties. The results indicate that, at both sub‐basin and basin scales, NPS pollution loads increased nonlinearly with rainfall until it reached 38.4 mm, and subsequently, the NPS pollution loads stabilized. The underlying surface conditions affected the NPS pollution loads more profoundly than rainfall. Additionally, the uncertainty in NPS pollution loads increased with the spatial scales.
Defining the habitat niche of Alopecurus myosuroides at the field scale
Authors: Metcalfe H , Milne A E , Webster R , Lark R M , Murdoch A J , Kanelo L , Storkey J
Published: March 2018

The distribution of Alopecurus myosuroides (black‐grass) in fields is patchy. The locations of these patches can be influenced by the environment. This presents an opportunity for precision management through patch spraying. We surveyed five fields on various types of soil using a nested sampling design and recorded both A. myosuroides seedlings in autumn and seed heads in summer. We also measured soil properties at those sampling locations. We found that the patches of seed heads within a field were smaller than the seedling patches, suggesting that techniques for patch spraying based on maps of heads in the previous season could be inherently risky. We also found that the location of A. myosuroides patches within fields can be predicted through their relationship with environmental properties and that these relations are consistent across fields on different soil types. This improved understanding of the relations between soil properties and A. myosuroides seedlings could allow farmers to use pre‐existing or suitably supplemented soil maps already in use for the precision application of fertilisers as a starting point in the creation of herbicide application maps.
A four‐season longitudinal study of enterohaemorrhagic Escherichia coli in beef cow–calf herds in Mississippi and Nebraska
Authors: Schneider L. G. , Lewis G. L. , Moxley R. A. , Smith D. R.
Published: March 2018

Our objective was to describe the probability of detecting seven serogroups of enterohaemorrhagic Escherichia coli (EHEC‐7) of public health importance in faecal samples from beef cow–calf herds and to test for factors associated with their detection. Fresh faecal samples (n = 85) from two Mississippi and two Nebraska herds were collected in each of four seasons. Samples were tested for each EHEC‐7 serogroup by a molecular screening assay. Separate management groups within herds were sampled, and group‐level factors were recorded. To measure the effects of factors on faecal shedding of EHEC‐7, separate multivariable logistic regression models were used, accounting for the random effect of clustering by group within farm. Statistical significance was set α = 0.05. Fifty‐nine samples (4.3%) were positive for EHEC O26, and Nebraska samples were more likely to be positive than Mississippi samples (OR = 12.4, 95% CI: 1.1, 139.2). Forty‐four samples (3.2%) were positive for EHEC O45. Odds for detection were greater in the summer than all other seasons combined (OR = 4.2, 95% CI: 1.3, 14.0), and odds decreased if a precipitation event occurred (OR = 0.07, 95% CI: 0.006, 0.8). EHEC O103 was detected in 66 samples (4.9%) with increased probability to be detected at increased temperature. EHEC O111 was detected in 71 samples (5.2%), and 43 samples (3.2%) were positive for EHEC O145. Both EHEC O111 and O145 were associated separately with season, with greater probability for detection in the summer. Eighteen (1.3%) and 68 (5.0%) samples were positive for EHEC O121 and EHEC O157, respectively. We failed to detect significant explanatory factors associated with probability to detect EHEC O121 or O157. Factors that vary by time and place, such as precipitation, ambient temperature, region and season, are uniquely associated with the probability to detect EHEC‐7 in fresh faeces collected from cow–calf herds.