bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of 18O‐labelled water vapour on the oxygen isotope ratio of water and assimilates in plants at high humidity
Authors: Lehmann Marco M. , Goldsmith Gregory R. , Schmid Lola , Gessler Arthur , Saurer Matthias , Siegwolf Rolf T. W.
Published: September 2017

Our understanding of how temporal variations of atmospheric water vapour and its isotopic composition (δ18OV) influence water and assimilates in plants remains limited, restricting our ability to use δ18O as a tracer of ecophysiological processes.

We exposed oak (Quercus robur) saplings under wet and dry soil moisture conditions to 18O‐depleted water vapour (c. − 200‰) at high relative humidity (c. 93%) for 5 h, simulating a fog event. We then traced the step change in δ18OV into water and assimilates (e.g. sucrose, hexoses, quercitol and starch) in the leaf lamina, main veins and twigs over 24 h.

The immediate δ18OV effect was highest for δ18O of leaf lamina water, but 40% lower on δ18O of main vein water. To a smaller extent, we also observed changes in δ18O of twig xylem water. Depending on the individual assimilation rate of each plant, the 18O‐label was partitioned among different assimilates, with highest changes in δ18O of starch/sucrose and lowest in δ18O of quercitol. Additionally, 18O‐label partitioning and allocation towards leaf starch and twig phloem sugars was influenced by the plant water status.

Our results have important implications for water isotope heterogeneity in plants and for our understanding of how the δ18O signal is incorporated into biomarkers.
The roles of AaMIXTA1 in regulating the initiation of glandular trichomes and cuticle biosynthesis in Artemisia annua
Authors: Shi Pu , Fu Xueqing , Shen Qian , Liu Meng , Pan Qifang , Tang Yueli , Jiang Weimin , Lv Zongyou , Yan Tingxiang , Ma Yanan , Chen Minghui , Hao Xiaolong , Liu Pin , Li Ling , Sun Xiaofen , Tang Kexuan
Published: September 2017

The glandular secretory trichomes (GSTs) on Artemisia annua leaves have the capacity to secrete and store artemisinin, a compound which is the most effective treatment for uncomplicated malaria. An effective strategy to improve artemisinin content is therefore to increase the density of GSTs in A. annua. However, the formation mechanism of GSTs remains poorly understood.

To explore the mechanisms of GST initiation in A. annua, we screened myeloblastosis (MYB) transcription factor genes from a GST transcriptome database and identified a MIXTA transcription factor, AaMIXTA1, which is expressed predominantly in the basal cells of GST in A. annua. Overexpression and repression of AaMIXTA1 resulted in an increase and decrease, respectively, in the number of GSTs as well as the artemisinin content in transgenic plants.

Transcriptome analysis and cuticular lipid profiling showed that AaMIXTA1 is likely to be responsible for activating cuticle biosynthesis. In addition, dual‐luciferase reporter assays further demonstrated that AaMIXTA1 could directly activate the expression of genes related to cuticle biosynthesis.

Taken together, AaMIXTA1 regulated cuticle biosynthesis and prompted GST initiation without any abnormal impact on the morphological structure of the GSTs and so provides a new way to improve artemisinin content in this important medicinal plant.
Positive regulation of AMS by TDF1 and the formation of a TDF1–AMS complex are required for anther development in Arabidopsis thaliana
Authors: Lou Yue , Zhou Hai‐Sheng , Han Yu , Zeng Qiu‐Ye , Zhu Jun , Yang Zhong‐Nan
Published: September 2017

Tapetum development and pollen production are regulated by a complex transcriptional network that consists of a group of tapetum‐specific Arabidopsis transcription factors (TFs). Among these TFs, DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) encodes an R2R3 MYB factor, and ABORTED MICROSPORE (AMS) encodes a basic helix‐loop‐helix (bHLH) factor. However, knowledge regarding the regulatory role of TDF1 in anther development remains limited.

Here, we discovered that TDF1 directly regulates AMS via an AACCT cis‐element. We found the precocious AMS transcript and absence of AMS protein in ams−/− gpTDF1:AMS‐FLAG lines, suggesting the timing of the TDF1‐regulated AMS expression is a prerequisite for AMS functioning.

We found that TDF1 interacts with AMS. Additionally, the TDF1–AMS complex additively promotes the expression of AMS‐regulated genes, suggesting that TDF1 and AMS regulate the downstream genes through a feed‐forward loop.

EPXB5, encoding a beta‐expansin family protein, is another direct target of TDF1, and it is highly expressed in the tapetum and pollen grains. The TDF1–AMS complex acts in concert to activate EXPB5 expression through a feed‐forward loop. The identification of the regulatory pathway between TDF1 and AMS provides an interlocked feed‐forward loop circuit that precisely regulates the transcriptional cascades that support anther development.
Cytosolic glyceraldehyde‐3‐phosphate dehydrogenases play crucial roles in controlling cold‐induced sweetening and apical dominance of potato (Solanum tuberosum L.) tubers
Authors: Liu Tengfei , Fang Hui , Liu Jun , Reid Stephen , Hou Juan , Zhou Tingting , Tian Zhendong , Song Botao , Xie Conghua
Published: September 2017

Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is an important enzyme that functions in producing energy and supplying intermediates for cellular metabolism. Recent researches indicate that GAPDHs have multiple functions beside glycolysis. However, little information is available for functions of GAPDHs in potato. Here, we identified 4 putative cytosolic GAPDH genes in potato genome and demonstrated that the StGAPC1, StGAPC2, and StGAPC3, which are constitutively expressed in potato tissues and cold inducible in tubers, encode active cytosolic GAPDHs. Cosuppression of these 3 GAPC genes resulted in low tuber GAPDH activity, consequently the accumulation of reducing sugars in cold stored tubers by altering the tuber metabolite pool sizes favoring the sucrose pathway. Furthermore, GAPCs‐silenced tubers exhibited a loss of apical dominance dependent on cell death of tuber apical bud meristem (TAB‐meristem). It was also confirmed that StGAPC1, StGAPC2, and StGAPC3 interacted with the autophagy‐related protein 3 (ATG3), implying that the occurrence of cell death in TAB‐meristem could be induced by ATG3 associated events. Collectively, the present research evidences first that the GAPC genes play crucial roles in diverse physiological and developmental processes in potato tubers.
Combined transcriptomic and proteomic analysis constructs a new model for light‐induced anthocyanin biosynthesis in eggplant (Solanum melongena L.)
Authors: Li Jing , Ren Li , Gao Zhen , Jiang Mingmin , Liu Yang , Zhou Lu , He Yongjun , Chen Huoying
Published: September 2017

Light is a key environmental factor affecting anthocyanin biosynthesis. Our previous study demonstrated that “Lanshan Hexian” is a light‐sensitive eggplant cultivar, but its regulatory mechanism is unknown. Here, delphinidin‐3‐[4‐(cis‐p‐coumaroyl)‐rhamnosyl‐glucopyranoside]‐5‐glucopyranoside and delphinidin‐3‐[4‐(trans‐p‐coumaroyl)‐rhamnosyl‐glucopyranoside]‐5‐glucopyranoside were identified as the main anthocyanin components in Lanshan Hexian by ultra‐performance liquid chromatography‐tandem mass spectrometry. Three time points of anthocyanin accumulation, including the start point (0 day), fastest point (5 days), and highest point (12 day), were investigated by using ribonucleic acid sequencing and iTRAQ technology. The corresponding correlation coefficients of differentially expressed genes, and differentially expressed proteins were 0.6936, 0.2332, and 0.6672. Anthocyanin biosynthesis was a significantly enriched pathway, and CHI, F3H, 3GT, 5GT, and HY5 were regulated at both transcriptional and translational levels. Moreover, some transcription factors and photoreceptors may participate in light‐induced anthocyanin biosynthesis like the known transcription factors MYB113 and TT8. The transient expression assay indicated that SmMYB35, SmMYB44, and a SmMYB86 isoform might involve in the light‐induced anthocyanin biosynthesis pathway. Finally, a regulatory model for light‐induced anthocyanin biosynthesis in eggplant was constructed. Our work provides a new direction for the study of the molecular mechanisms of light‐induced anthocyanin biosynthesis in eggplant.
Dog skin parasite load, TLR‐2, IL‐10 and TNF‐α expression and infectiousness
Authors: Pereira‐Fonseca D. C. M. , Oliveira‐Rovai F. M. , Rodas L. A. C. , Beloti C. A. C. , Torrecilha R. B. P. , Ito P. K. R. K. , Avanço S. V. , Cipriano R. S. , Utsunomiya Y. T. , Hiramoto R. M. , Calvo‐Bado L. , Courtenay O. , Machado G. F. , Lima V. M. F. , Nunes C. M.
Published: September 2017

Visceral leishmaniosis is a zoonotic disease that is transmitted by Lutzomyia longipalpis sandflies. Dogs are the main peri‐urban reservoir of the disease, and progression of canine leishmaniosis is dependent on the type of immune response elaborated against the parasite. Type 1 immunity is characterized by effective cellular response, with production of pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α). In contrast, Type 2 immunity is predominantly humoral, associated with progression of the disease and mediated by anti‐inflammatory cytokines such as interleukin 10 (IL‐10). Although seemly important in the dynamics of leishmaniosis, other gene products such as toll‐like receptor 2 (TRL‐2) and inducible nitric oxide synthase (iNOS) exert unclear roles in the determination of the type of immune response. Given that the dog skin serves as a micro‐environment for the multiplication of Leishmania spp., we investigated the parasite load and the expression of TLR‐2, iNOS, IL‐10 and TNF‐α in the skin of 29 infected and 8 control dogs. We found that increased parasite load leads to upregulation of TLR‐2, IL‐10 and TNF‐α, indicating that abundance of these transcripts is associated with infection. We also performed a xenodiagnosis to demonstrate that increased parasitism is a risk factor for infectiousness to sandflies.
Integrated drought responses of black poplar: how important is phenotypic plasticity?
Authors: Garavillon‐Tournayre Marie , Gousset‐Dupont Aurélie , Gautier Florian , Benoit Pierrick , Conchon Pierre , Souchal Romain , Lopez David , Petel Gilles , Venisse Jean‐Stéphane , Bastien Catherine , Label Philippe , Fumanal Boris
Published: September 2017

Climate change is expected to increase drought frequency and intensity which will threaten plant growth and survival. In such fluctuating environments, perennial plants respond with hydraulic and biomass adjustments, resulting in either tolerant or avoidant strategies. Plants' response to stress relies on their phenotypic plasticity. The goal of this study was to explore physiology of young Populus nigra in the context of a time‐limited and progressive water deficit in regard to their growth and stress response strategies. Fourteen French 1‐year‐old black poplar genotypes, geographically contrasted, were subjected to withholding water during 8 days until severe water stress. Water fluxes (i.e. leaf water potentials and stomatal conductance) were analyzed together with growth (i.e. radial and longitudinal branch growth, leaf senescence and leaf production). Phenotypic plasticity was calculated for each trait and response strategies to drought were deciphered for each genotype. Black poplar genotypes permanently were dealing with a continuum of adjusted water fluxes and growth between two extreme strategies, tolerance and avoidance. Branch growth, leaf number and leaf hydraulic potential traits had contrasted plasticities, allowing genotype characterization. The most tolerant genotype to water deficit, which maintained growth, had the lowest global phenotypic plasticity. Conversely, the most sensitive and avoidant genotype ceased growth until the season's end, had the highest plasticity level. All the remaining black poplar genotypes were close to avoidance with average levels of traits plasticity. These results underpinned the role of plasticity in black poplar response to drought and calls for its wider use into research on plants' responses to stress.
Sparse Approximations of Fractional Matérn Fields
Authors: Roininen Lassi , Lasanen Sari , Orispää Mikko , Särkkä Simo
Published: September 2017

We consider fast lattice approximation methods for a solution of a certain stochastic non‐local pseudodifferential operator equation. This equation defines a Matérn class random field. We approximate the pseudodifferential operator with truncated Taylor expansion, spectral domain error functional minimization and rounding approximations. This allows us to construct Gaussian Markov random field approximations. We construct lattice approximations with finite‐difference methods. We show that the solutions can be constructed with overdetermined systems of stochastic matrix equations with sparse matrices, and we solve the system of equations with a sparse Cholesky decomposition. We consider convergence of the truncated Taylor approximation by studying band‐limited Matérn fields. We consider the convergence of the discrete approximations to the continuous limits. Finally, we study numerically the accuracy of different approximation methods with an interpolation problem.
Serum IL‐15 and IL‐15Rα levels are decreased in lean and obese physically active humans
Authors: Pérez‐López A. , Valadés D. , Vázquez Martínez C. , de Cos Blanco A. I. , Bujan J. , García‐Honduvilla N.
Published: September 2017

Circulating IL‐15 presence is required to stimulate anti‐adipogenic effects of the IL‐15/IL‐15Rα axis in adipose tissue. Although exercise increases blood IL‐15 expression post‐exercise, it remains inconclusive whether physical activity can alter the baseline concentrations of this cytokine. The aim of this study was to determine whether physical activity regulates circulating IL‐15 and IL‐15Rα in lean and obese individuals. Two hundred and seventy‐six participants were divided into five groups according to physical activity (PA), body mass and type 2 diabetes mellitus (T2DM) diagnosis: (a) lean PA (N = 25); (b) lean non‐PA (N = 28); (c) obese PA (N = 64); (d) obese non‐PA (N = 79); and (e) obese non‐PA with T2DM (N = 80). Serum IL‐15 and IL‐15Rα, blood glucose/lipid profile and body composition were measured. Serum IL‐15 and IL‐15Rα decreased in PA participants compared to non‐PA (P < .05), while IL‐15 and IL‐15Rα increased in obese with T2DM compared to obese without T2DM (P < .05). No differences were observed between lean non‐PA and obese PA. Serum IL‐15Rα was associated with fasting glucose (R2 = .063), insulin (R2 = .082), HbA1c (R2 = .108), and HOMA (R2 = .057) in obese participants. Circulating IL‐15 and IL‐15Rα are reduced in lean and obese participants who perform physical activity regularly (≥180 min/week), suggesting a regulative role of physical activity on the circulating concentrations of IL‐15 and IL‐15Rα at baseline. Moreover, the relationship observed between IL‐15Rα and glucose profile may indicate a role of the alpha receptor in glucose metabolism.
Can alternating temperatures be used to estimate base temperature for seed germination?
Authors: Masin R , Onofri A , Gasparini V , Zanin G
Published: September 2017

Modelling weed seedling emergence pattern appears to be a promising approach in the development of effective weed management programmes based on the selection of optimal timing of control operations. Thermal and hydrothermal time models propose that seed germination rates are proportional to the amount by which temperature and water potential exceed threshold values for these environmental factors. Hence, base temperature for seed germination is a fundamental biological parameter for the prediction of weed emergence. A series of laboratory experiments were conducted to estimate base temperature in three weed species belonging to the Asteraceae family, predominant in conservation tillage fields in north‐eastern Italy. The traditional method based on germination assays at constant temperatures was compared with a method based on assays at alternating temperatures. The latter might represent an alternative to the former for those species which do not germinate or only poorly under constant temperatures. Base temperature was estimated by regressing the reciprocal of the median germination time on temperature comparing two functions, a broken‐stick and an exponential‐type model. Both models showed good fit to all data in the whole temperature range and in almost all cases provided similar estimates of base temperature. The main result is that, for the weed species examined in this study, the use of alternating temperatures for base temperature estimation appears to be possible. However, further research is required to test if the use of germination assays performed at alternating temperatures can be a suitable method to estimate base temperature of species that have too low germination at constant temperatures.
A Framework for Understanding of Bilingual Education in Turkey: A Mixed Method Approach
Authors: Ozfidan Burhan , Burlbaw Lynn M.
Published: September 2017

This study seeks to identify the obstacles and opportunities involved in setting up a bilingual education system and to identify the challenges and benefits associated with the daily experience of maintaining a bilingual education model. This study discusses the benefits of developing a bilingual education program and what these programs can offer regarding concerns related to the lives of minority people in Turkey. Explanatory sequential mixed method was used for this study. The first phase of this study was a survey that measured the perspectives of educators regarding potential bilingual education curricula in Turkey. The second phase comprised a qualitative data collection process to expand on the findings of quantitative results. For quantitative data collection, 140 participants responded the survey instrument. Participants included 96 males and 44 females. For qualitative data collection, eight participants were interviewed. Both quantitative and qualitative data reflected the benefits of a bilingual education program. First, minority students who are taught by means of a bilingual education program can protect their linguistic knowledge, cultural heritage, ethnic, and religious identity. Second, they can increase their understanding of linguistic and cultural diversity. Third, school attendance at the primary school level could be increased. Fourth, a bilingual program could contribute to the reduction of inequalities.
Laminar‐specific encoding of texture elements in rat barrel cortex
Authors: Allitt Benjamin J. , Alwis Dasuni S. , Rajan Ramesh
Published: September 2017

Key points

For rats texture discrimination is signalled by the large face whiskers by stick‐slip events.

Neural encoding of repetitive stick‐slip events will be influenced by intrinsic properties of adaptation.

We show that texture coding in the barrel cortex is laminar specific and follows a power function.

Our results also show layer 2 codes for novel feature elements via robust firing rates and temporal fidelity.

We conclude that texture coding relies on a subtle neural ensemble to provide important object information.

Texture discrimination by rats is exquisitely guided by fine‐grain mechanical stick‐slip motions of the face whiskers as they encounter, stick to and slip past successive texture‐defining surface features such as bumps and grooves. Neural encoding of successive stick‐slip texture events will be shaped by adaptation, common to all sensory systems, whereby receptor and neural responses to a stimulus are affected by responses to preceding stimuli, allowing resetting to signal novel information. Additionally, when a whisker is actively moved to contact and brush over surfaces, that motion itself generates neural responses that could cause adaptation of responses to subsequent stick‐slip events. Nothing is known about encoding in the rat whisker system of stick‐slip events defining textures of different grain or the influence of adaptation from whisker protraction or successive texture‐defining stick‐slip events. Here we recorded responses from halothane‐anaesthetized rats in response to texture‐defining stimuli applied to passive whiskers. We demonstrate that: across the columnar network of the whisker‐recipient barrel cortex, adaptation in response to repetitive stick‐slip events is strongest in uppermost layers and equally lower thereafter; neither whisker protraction speed nor stick‐slip frequency impede encoding of stick‐slip events at rates up to 34.08 Hz; and layer 2 normalizes responses to whisker protraction to resist effects on texture signalling. Thus, within laminar‐specific response patterns, barrel cortex reliably encodes texture‐defining elements even to high frequencies.
Ixodid Ticks Diversity and Seasonal Dynamic on Cattle in North, Middle and South of Iraq
Authors: Shanan Salam Muhemmad Hussein , Abbas‎‏ Salah F. , Mohammad Mohammad K.
Published: September 2017

A survey was conducted from January 2015 to December 2015 in 12 provinces in Iraq to identify and classify the seasonal distributions of the major hard ticks species (Ixodidae) found on cattle in the north, middle and south of Iraq. A total of 17,156 adult hard ticks were collected from 3,812 indigenous cattle. Sampling was repeated from the same provinces every month to determine the seasonal diversity. Five species belonging to two genera (Hyalomma and Rhipicephalus) were identified; the most abundant ticks were Hyalomma anatolicum 41.72%, Rhipicephalus turanicus 24.60%, Hyalomma turanicum 16.65%, Hyalomma scupense 13.26% and Rhipicephalus annulatus 3.67%. There were differences between each province related to the environment as well with the previous studies.
Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest
Authors: Perry Dorothy A. , Salvin Joshua W. , Romfh Padraic , Chen Peili , Krishnamurthy Kalyani , Thomson Lindsay M. , Polizzotti Brian D. , McGowan Francis X. , Vakhshoori Daryoosh , Kheir John N.
Published: September 2017

Monitoring of mitochondrial redox states of the epicardium predicts impending myocardial dysfunction and cardiac arrest.
The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
Authors: Shmakov Sergey A. , Sitnik Vassilii , Makarova Kira S. , Wolf Yuri I. , Severinov Konstantin V. , Koonin Eugene V.
Published: September 2017

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR “dark matter.” We performed a comprehensive analysis of the spacers from all CRISPR-
cas
loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes.

IMPORTANCE
The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers match any sequences in the current databases, and of these, only a minority correspond to known parasitic elements. We show that nearly all spacers with matches originate from viral or plasmid genomes that are either free or have been integrated into the host genome. We further demonstrate that spacers with no matches have the same properties as those of identifiable origins, strongly suggesting that all spacers originate from mobile elements.
Cell Cycle Inhibition To Treat Sleeping Sickness
Authors: Epting Conrad L. , Emmer Brian T. , Du Nga Y. , Taylor Joann M. , Makanji Ming Y. , Olson Cheryl L. , Engman David M.
Published: September 2017

African trypanosomiasis is caused by infection with the protozoan parasiteTrypanosoma brucei. During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes,T. bruceihas a cell cycle involving thede novosynthesis of DNA regulated by ribonucleotide reductase (RNR), which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy. We hypothesized that inhibition of RNR by genetic or pharmacological means would impair parasite growthin vitroand prolong the survival of infected animals. Our results demonstrate that RNR inhibition is highly effective in suppressing parasite growth bothin vitroandin vivo. These results support drug discovery efforts targeting the cell cycle, not only for African trypanosomiasis but possibly also for other infections by eukaryotic pathogens.

IMPORTANCEThe development of drugs to treat infections with eukaryotic pathogens is challenging because many key virulence factors have closely related homologues in humans. Drug toxicity greatly limits these development efforts. For pathogens that replicate at a high rate, especially in the blood, an alternative approach is to target the cell cycle directly, much as is done to treat some hematologic malignancies. The results presented here indicate that targeting the cell cycle via inhibition of ribonucleotide reductase is effective at killing trypanosomes and prolonging the survival of infected animals.
Role of ultrasound biomicroscopy in diagnosis of ocular toxocariasis
Authors: Chen Qian , Gu Junxiang , Jiang Rui , Zhou Min , Chang Qing
Published: September 2017

Purpose

To investigate ultrasound biomicroscopy (UBM) characteristics of patients with ocular toxocariasis (OT) and to explore the role of UBM in the diagnosis and differential diagnosis of OT.

Design

Cross-sectional study.

Methods

78 eyes of 77 patients clinically consistent with OT and confirmed by serum and/or intraocular antibodies in a single tertiary centre (Fudan University Eye and ENT Hospital, Shanghai) between July 2009 and July 2016 were included in the study. UBM was performed, and the outcomes were analysed.

Results

Mean age of the patients included was 12.8±10.3 years. Positive UBM findings were observed in 72 of 78 eyes (92.3%). The primary imaging feature was peripheral granulomas (66 eyes; 84.6%), of which 78.5% were adjacent to the nasal or temporal side of horizontal meridian and 79.7% located on the surface of the ciliary body, presenting as olivary foci on radical section and botuliform foci on coronal section. Moreover, 12 of the peripherally involved eyes were accompanied with posterior pole granulomas, which could be termed ‘combined type’. Other UBM findings included vitreous strands (53 eyes; 67.9%), peripheral tractional retinal detachment (41 eyes; 52.6%) and tractional cyclodialysis (32 eyes; 41.0%).

Conclusions

The utilisation of UBM verifies the existence of the combined subtype (with both peripheral and posterior pole granulomas) and improves the detection rate of peripheral granulomas, which is of great importance to the diagnosis and differential diagnosis of OT.
Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis
Authors: Krogh Jesper , Hjorthøj Carsten , Speyer Helene , Gluud Christian , Nordentoft Merete
Published: September 2017

Objectives

To assess the benefits and harms of exercise in patients with depression.

Design

Systematic review

Data sources

Bibliographical databases were searched until 20 June 2017.

Eligibility criteria and outcomes

Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.

Results

Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.

Conclusions

Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.

Systematic review registration

The protocol was published in the journalSystematic Reviews: 2015; 4:40.
Integrated management of atrial fibrillation including tailoring of anticoagulation in primary care: study design of the ALL-IN cluster randomised trial
Authors: van den Dries Carline J , Oudega Ruud , Elvan Arif , Rutten Frans H , van de Leur Sjef J C M , Bilo Henk J G , Hoes Arno W , Moons Karel G M , Geersing Geert-Jan
Published: September 2017

Introduction

In our ageing society, we are at the merge of an expected epidemic of atrial fibrillation (AF). AF management requires an integrated approach, including rate or rhythm control, stroke prevention with anticoagulation and treatment of comorbidities such as heart failure or type 2 diabetes. As such, primary care seems to be the logical healthcare setting for the chronic management of patients with AF. However, primary care has not yet played a dominant role in AF management, which has been in fact more fragmented between different healthcare providers. This fragmentation might have contributed to high healthcare costs. To demonstrate the feasibility of managing AF in primary care, studies are needed that evaluate the safety and (cost-)effectiveness of integrated AF management in primary care.

Methods and analysis

The ALL-IN trial is a multicentre, pragmatic, cluster randomised, non-inferiority trial performed in primary care practices in a suburban region in the Netherlands. We aim to include a minimum of 1000 patients with AF aged 65 years or more from around 18 to 30 practices. Duration of the study is 2 years. Practices will be randomised to either the intervention arm (providing integrated AF management, involving a trained practice nurse and collaboration with secondary care) or the control arm (care as usual). The primary endpoint is all-cause mortality. Secondary endpoints are cardiovascular mortality, (non)-cardiovascular hospitalisation, major adverse cardiac events, stroke, major bleeding, clinically relevant non-major bleeding, quality of life and cost-effectiveness.

Ethics and dissemination

The protocol was approved by the Medical Ethical Committee of the Isala Hospital Zwolle, the Netherlands. Patients in the intervention arm will be asked informed consent for participating in the intervention. Results are expected in 2019 and will be disseminated through both national and international journals and conferences.

Trial registration number

This trial is registered at the Netherlands Trial Register (NTR5532).
Controlling Nutritional Status (CONUT) score as a predictor of all-cause mortality in elderly hypertensive patients: a prospective follow-up study
Authors: Sun Xiaonan , Luo Leiming , Zhao Xiaoqian , Ye Ping
Published: September 2017

Objectives

The aim of this study was to elucidate the impact of nutritional status on survival per Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI) in patients with hypertension over 80 years of age.

Design

Prospective follow-up study.

Participants

A total of 336 hypertensive patients over 80 years old were included in this study.

Outcome measures

All-cause deaths were recorded as Kaplan-Meier curves to evaluate the association between CONUT and all-cause mortality at follow-up. Cox regression models were used to investigate the prognostic value of CONUT and GNRI for all-cause mortality in the 90-day period after admission.

Results

Hypertensive patients with higher CONUT scores exhibited higher mortality within 90 days after admission (1.49%, 6.74%, 15.38%, respectively, χ2=30.92, p=0.000). Surviving patients had higher body mass index (24.25±3.05 vs 24.25±3.05, p=0.012), haemoglobin (123.78±17.05 vs 115.07±20.42, p=0.040) and albumin levels, as well as lower fasting blood glucose (6.90±2.48 vs 8.24±3.51, p=0.010). Higher GRNI score (99.42±6.55 vs 95.69±7.77, p=0.002) and lower CONUT (3.13±1.98 vs 5.14±2.32) both indicated better nutritional status. Kaplan-Meier curves indicated that survival rates were significantly worse in the high-CONUT group compared with the low-CONUT group (χ1=13.372, p=0.001). Cox regression indicated an increase in HR with increasing CONUT risk (from normal to moderate to severe). HRs (95% CI) for 3-month mortality was 1.458 (95% CI 1.102 to 1.911). In both respiratory tract infection and ‘other reason’ groups, only CONUT was a sufficiently predictor for all-cause mortality (HR=1.284, 95% CI 1.013 to 1.740, p=0.020 and HR=1.841, 95% CI 1.117 to 4.518, p=0.011). Receiver operating characteristic showed that CONUT higher than 3.0 was found to predict all-cause mortality with a sensitivity of 77.8% and a specificity of 64.7% (area under the curve=0.778, p<0.001).

Conclusion

Nutritional status assessed via CONUT is an accurate predictor of all-cause mortality 90 days postadmission. Evaluation of nutritional status may provide additional prognostic information in hypertensive patients.
Adherence and dosing interval of subcutaneous antitumour necrosis factor biologics among patients with inflammatory arthritis: analysis from a Canadian administrative database
Authors: Bhoi Peter , Bessette Louis , Bell Mary J , Tkaczyk Cathy , Nantel Francois , Maslova Karina
Published: September 2017

Objectives

Subcutaneous tumour necrosis factor alpha TNFαinhibitors (SC-TNFis) such as golimumab (GLM), adalimumab (ADA), etanercept (ETA) and certolizumab pegol (CZP) have been used for many years for the treatment of inflammatory arthritis. Non-adherence to therapy is an important modifiable factor that may compromise patient outcomes. The aim of this analysis was to compare adherence and dosing interval of SC-TNFis in the treatment of people with inflammatory arthritis.

Design

We used the IMS Brogan database combining both Canadian private and public drug plan databases of Ontario and Quebec. Target drugs included SC-TNFis for inflammatory arthritis. The index period was from 1 January 2010 to 30 June 2012 and patients were followed for 24 months through 30 June 2014. Inclusion criteria were adult patients newly prescribed a SC-TNFis with at least three prescriptions and retained on therapy at 24 months.

Dosing regimens as per the product monographs were used to compare actual versus expected drug utilisation. The mean possession ratio was used as a marker for adherence. Patients who scored >80% were considered adherent. The average days between units was estimated by taking the total days on therapy and divided by the number of units the patient received.

Results

4035 patients were included: 683 (16.9%), 1400 (34.7%), 1765 (43.7%) and 187 (4.6%) were treated with GLM, ADA, ETA and CZP, respectively. The proportion of adherent patients in the GLM cohort (n=595/683, 87%, p<0.0001) was greater compared with ADA (n=1044/1400, 75%), ETA (n=1285/1765, 73%) and CZP-treated patients (132/187, 71%). In addition, the number of patients receiving biological drug at a shorter dosing interval was similar between cohorts, and was 5%, 6%, 12% and 4% in GLM (≤26 days), ADA (≤12 days), ETA (≤6 days) and CZP-treated patients (≤12 days), respectively.

Conclusions

In this real-life administrative database, GLM had better adherence compared with other SC-TNFis.
How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study
Authors: Chu Hongling , Zeng Lin , Fetters Micheal D , Li Nan , Tao Liyuan , Shi Yanyan , Zhang Hua , Wang Xiaoxiao , Li Fengwei , Zhao Yiming
Published: September 2017

Objectives

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research.

Setting

The setting for this research was a major academic institution in Beijing, China.

Participants

The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts.

Methods

Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research.

Results

Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly.

Conclusion

These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers.
Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: protocol for an observational study
Authors: Malla Lucas , Perera-Salazar Rafael , McFadden Emily , English Mike
Published: September 2017

Introduction

WHO treatment guidelines are widely recommended for guiding treatment for millions of children with pneumonia every year across multiple low-income and middle-income countries. Guidelines are based on synthesis of available evidence that provides moderate certainty in evidence of effects for forms of pneumonia that can result in hospitalisation. However, trials have included fewer children from Africa than other settings, and it is suggested that African children with pneumonia have higher mortality. Thus, despite improving access to recommended treatments and deployment with high coverage of childhood vaccines, pneumonia remains one of the top causes of mortality for children in Kenya. Establishing whether there are benefits of alternative treatment regimens to help reduce mortality would require pragmatic clinical trials. However, these remain relatively expensive and time consuming. This protocol describes an approach to using secondary analysis of a new, large observational dataset as a potentially cheaper and quicker way to examine the comparative effectiveness of penicillin versus penicillin plus gentamicin in treatment of indrawing pneumonia. Addressing this question is important, as although it is now recommended that this form of pneumonia is treated with oral medication as an outpatient, it remains associated with non-trivial mortality that may be higher outside trial populations.

Methods and analysis

We will use a large observational dataset that captures data on all admissions to 13 Kenyan county hospitals. These data represent the findings of clinicians in practice and, because the system was developed for large observational research, pose challenges of non-random treatment allocation and missing data. To overcome these challenges, this analysis will use a rigorous approach to study design, propensity score methods and multiple imputation to minimise bias.

Ethics and dissemination

The primary data are held by hospitals participating in the Kenyan Clinical Information Network project with de-identifed data shared with the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme for agreed analyses. The use of data for the analysis described received ethical clearance from the KEMRI scientific and ethical review committee. The findings of this analysis will be published.
Measuring the preference towards patient-centred communication with the Chinese-revised Patient–Practitioner Orientation Scale: a cross-sectional study among physicians and patients in clinical settings in Shanghai, China
Authors: Wang Jie , Zou Runyu , Fu Hua , Qian Haihong , Yan Yueren , Wang Fan
Published: September 2017

Objectives

To adapt the Patient–Practitioner Orientation Scale (PPOS), to a Chinese context, and explore the preference towards patient-centred communication among physicians and patients with the Chinese-revised Patient–Practitioner Orientation Scale (CR-PPOS).

Design

A cross-sectional questionnaire-based study.

Setting

Clinical settings from eight medical units, including four community hospitals and four general hospitals, in Shanghai, China.

Participants

1018 participants, including 187 physicians and 831 patients, completed this study in two successive stages.

Outcome measurements

Psychometric properties of the CR-PPOS and participants’ score on the CR-PPOS.

Results

Compared with the original PPOS, the 11-item CR-PPOS obtained better psychometric indices. Physicians and patients scored differently on both the total CR-PPOS and its two subscales. Compared with physicians, the scores of patients were more influenced by their personal characteristics, such as age and education.

Conclusions

The CR-PPOS is a better instrument in a Chinese context than the original translated version. The divergence in the extent to which patient-centred communication is preferred among Chinese physicians and patients should be noted. Adapting physicians’ communication strategy to patients’ preferences based on their personal characteristics can be a viable approach towards improving clinical efficiency.
Development of the Huddle Observation Tool for structured case management discussions to improve situation awareness on inpatient clinical wards
Authors: Edbrooke-Childs Julian , Hayes Jacqueline , Sharples Evelyn , Gondek Dawid , Stapley Emily , Sevdalis Nick , Lachman Peter , Deighton Jessica
Published: September 2017

Background

‘Situation Awareness For Everyone’ (SAFE) was a 3-year project which aimed to improve situation awareness in clinical teams in order to detect potential deterioration and other potential risks to children on hospital wards. The key intervention was the ‘huddle’, a structured case management discussion which is central to facilitating situation awareness. This study aimed to develop an observational assessment tool to assess the team processes occurring during huddles, including the effectiveness of the huddle.

Methods

A cross-sectional observational design was used to psychometrically develop the ‘Huddle Observation Tool’ (HOT) over three phases using standardised psychometric methodology. Huddles were observed across four NHS paediatric wards participating in SAFE by five researchers; two wards within specialist children hospitals and two within district general hospitals, with location, number of beds and length of stay considered to make the sample as heterogeneous as possible. Inter-rater reliability was calculated using the weighted kappa and intraclass correlation coefficient.

Results

Inter-rater reliability was acceptable for the collaborative culture (weighted kappa=0.32, 95% CI 0.17 to 0.42), environment items (weighted kappa=0.78, 95% CI 0.52 to 1) and total score (intraclass correlation coefficient=0.87, 95% CI 0.68 to 0.95). It was lower for the structure and risk management items, suggesting that these were more variable in how observers rated them. However, agreement on the global score for huddles was acceptable.

Conclusion

We developed an observational assessment tool to assess the team processes occurring during huddles, including the effectiveness of the huddle. Future research should examine whether observational evaluations of huddles are associated with other indicators of safety on clinical wards (eg, safety climate and incidents of patient harm), and whether scores on the HOT are associated with improved situation awareness and reductions in deterioration and adverse events in clinical settings, such as inpatient wards.