bluuebunny/crossref_metadata_2025 huggingface dataset:
Control and yield loss modelling of circular leaf spot of persimmon caused by Mycosphaerella nawae
Authors: Bassimba D.D.M. , Mira J.L. , Sedano M.E. , Vicent A.
Published: February 2017

Symptoms of circular leaf spot of persimmon (CLSP), caused by Mycosphaerella nawae, consisted of necrotic spots on leaves, chlorosis and premature defoliation. Although CLSP is a foliar disease, early fruit maturation and abscission are frequently associated with the presence of lesions on leaves and defoliation, resulting in severe economic losses. Despite their importance for the design of efficient disease management programmes, quantitative relationships between CLSP incidence and yield loss are unknown. Therefore, fungicide efficacy trials were conducted during two consecutive years in Spain to induce different levels of disease severity, defoliation and yield loss. The effects of fungicide treatments on CLSP severity were analysed by ordinal logistic regression models. Relative yield loss values were regressed against the percentage of affected leaves or defoliated obtained at different evaluation dates. The disease had high negative impact and complete yield loss was observed in the absence of effective fungicide treatments. Preventive applications of pyraclostrobin, trifloxy‐strobin and mancozeb provided the best disease control and highest yields, up to 95.77 kg tree−1. An exponential relationship of CLSP incidence and defoliation with yield loss was found. In general, model fit and predictive ability was superior when defoliation, rather than incidence, was used as explanatory variable. The impact of defoliation on yield loss was higher in earliest evaluation dates, suggesting that early leaf abscission may be the main factor contributing to premature fruit drop and subsequent yield loss. Substantial yield losses were observed even with relatively low levels of CLSP incidence and defoliation. Therefore, it was not possible to define a critical action threshold for CLSP management based on foliar symptoms.
Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder
Authors: Wilcox Claire E. , Claus Eric D. , Calhoun Vince D. , Rachakonda Srinivas , Littlewood Rae A. , Mickey Jessica , Arenella Pamela B. , Goodreau Natalie , Hutchison Kent E.
Published: February 2017

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18–55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking‐related or food‐related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood‐oxygen‐level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke − Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, β = −0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke − Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD.
Relevant human tissue resources and laboratory models for use in endometriosis research
Authors: Greaves Erin , Critchley Hilary O.D. , Horne Andrew W. , Saunders Philippa T.K.
Published: February 2017

Endometriosis is characterized by the growth of endometrium‐like tissue outside the uterus, most commonly on the pelvic peritoneum and ovaries. Although it may be asymptomatic in some women, in others it can cause debilitating pain, infertility or other symptoms including fatigue. Current research is directed both at understanding the complex etiology and pathophysiology of the disorder and at the development of new nonsurgical approaches to therapy that lack the unwanted side effects of current medical management. Tools for endometriosis research fall into two broad categories; patient‐derived tissues, and fluids (and cells isolated from these sources) or models based on the use of cells or animals. In this review, we discuss the literature that has reported data from the use of these tools in endometriosis research and we highlight the strengths and weaknesses of each. Although many different models are reported in the literature, hypothesis‐driven research will only be facilitated with careful experimental design and selection of the most appropriate human tissue from patients with and without endometriosis and combinations of physiologically relevant in vitro and in vivo laboratory models.
Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis
Authors: Maspi Nahid , Ghaffarifar Fatemeh , Sharifi Zohreh , Dalimi Abdolhossein , Dayer Mohammad Saaid
Published: February 2017

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF–TSA fusion against cutaneous leishmaniasis pEGFP‐N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3–12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN‐γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF‐TSA, respectively, than in PBS group at 12th week post infection. IFN/IL‐4 and IgG2a/IgG1 ratios indicated that group receiving LeIF–TSA fusion had the highest IFN‐γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN‐γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.
Carbonic anhydrase II: a novel biomarker for pseudomyxoma peritonei
Authors: Järvinen Petrus , Kivelä Antti J. , Nummela Pirjo , Lepistö Anna , Ristimäki Ari , Parkkila Seppo
Published: February 2017

Altered expression of carbonic anhydrase (CA) II is associated with human carcinogenesis. We analysed CA II protein expression in 89 patients with pseudomyxoma peritonei (PMP) and correlated its association against survival. We determined the expression of CA II by immunohistochemistry and then scored the staining results. The correlations of CA II expression with Peritoneal Cancer Index (PCI) and tumour grade were examined. The effect of CA II and tumour grade on survival was investigated. Positive CA II expression was found in 58 patients (65%) and absent in 31 patients (35%). High‐grade (HG) morphology was associated with a loss of CA II expression (p = 0.048). The mean CA II immunostaining intensity score was 1.00 ± 1.1 (median 1, range 0–3) for HG morphology and 1.54 ± 1.1 (median 2, range 0–3) for low‐grade (LG) morphology. The 5‐year overall survival (OS) for those patients with CA II expression was 80% and 59% for those without (p < 0.001). The 5‐year OS rates for those patients with HG morphology and positive CA II expression was 72% and 31% for those with negative CA II expression (p = 0.044). This study suggests that the expression of CA II acts as independent prognostic biomarker for survival in PMP.
Different subtypes of epithelioid sarcoma and their clinical implication: long‐term multi‐institutional experience with a rare sarcoma
Authors: Kim Chan , Yoo Kwai Han , Kim Min Hwan , Chon Hong Jae , Lee Soon Il , Lee Hyo Jin , Koh Sujin , Lee Ha Yeon , Lee Hye Ran , Kim Kyung Sik , Choi Young Deuk , Rha Sun Young , Lee Su Jin , Kim Hyo Song
Published: February 2017

Epithelioid sarcoma (ES) is a very rare soft‐tissue sarcoma with a high tendency of recurrence and metastasis. We analyzed clinical features of ES and aimed to identify the potential role of radio‐ and chemotherapy in ES. Fifty‐five patients diagnosed with ES between 1997 and 2014 were enrolled from seven tertiary hospitals in Korean Cancer Research Group. The clinical variables were retrospectively reviewed and analyzed. Forty‐six (84%) patients underwent surgical resection of ES, and among them, 27 experienced recurrence. In these patients, resection margin status and adjuvant radiotherapy were independent prognostic factors for longer recurrence‐free survival (RFS), while adjuvant chemotherapy did not influence RFS. Twenty‐two (40%) patients received palliative chemotherapy for metastatic or recurrent ES, and in these patients, palliative chemotherapy was the only independent prognostic factor for longer overall survival. Intriguingly, the clinical benefit of radio‐ and chemotherapy was observable only in proximal ES, but not in extremity ES, indicating that subtypes of ES might respond to radio‐ or chemotherapy differently. Proximal ES seems to benefits more from active anticancer treatment than conventional extremity ES. The aggressive characteristics of proximal ES could be overcome with an optimal multimodal treatment.
The challenge of defining and treating anemia and iron deficiency in pregnancy: A study of New Zealand midwives' management of iron status in pregnancy and the postpartum period
Authors: Calje Esther , Skinner Joan
Published: February 2017

Background

Early recognition and management of low maternal iron status is associated with improved maternal, fetal, and neonatal outcomes. However, existing international guidelines for the testing and management of maternal iron‐deficiency anemia are variable, with no national guideline for New Zealand midwives. Clinical management is complicated by normal physiological hemodilution, and complicated further by the effects of inflammation on iron metabolism, especially in populations with a high prevalence of obesity or infection. This study describes how midwives in one New Zealand area diagnose and treat anemia and iron deficiency, in the absence of established guidelines.

Methods

Data on demographics, laboratory results, and documented clinical management were retrospectively collected from midwives (n=21) and women (n=189), from September to December 2013. Analysis was predominantly descriptive. A secondary analysis of iron status and body mass index (BMI) was undertaken.

Results

A total of 46% of 186 women, with hemoglobin testing at booking, did not have ferritin tested; 86% (of 385) of ferritin tests were not concurrently tested with C‐reactive protein. Despite midwives prescribing iron for 48.7% of second trimester women, 47.1% still had low iron status before birth. Only 22.8% of women had hemoglobin testing postpartum. There was a significant difference between third trimester median ferritin levels in women with BMI ≥25.00 (14 μg/L) and BMI <25.00 (18 μg/L) (P=.05).

Discussion

There was a wide range in the midwives' practice. Maternal iron status was difficult to categorize, because of inconsistent testing. This study indicates the need for an evidence‐based clinical guideline for New Zealand midwives and maternity care providers.
Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise
Authors: Slagboom Julien , Kool Jeroen , Harrison Robert A. , Casewell Nicholas R.
Published: February 2017

Snake venoms are mixtures of numerous proteinacious components that exert diverse functional activities on a variety of physiological targets. Because the toxic constituents found in venom vary from species to species, snakebite victims can present with a variety of life‐threatening pathologies related to the neurotoxic, cytotoxic and haemotoxic effects of venom. Of the 1·8 million people envenomed by snakes every year, up to 125 000 die, while hundreds of thousands survive only to suffer with life‐changing long‐term morbidity. Consequently, snakebite is one of the world's most severe neglected tropical diseases. Many snake venoms exhibit strong haemotoxic properties by interfering with blood pressure, clotting factors and platelets, and by directly causing haemorrhage. In this review we provide an overview of the functional activities of haemotoxic venom proteins, the pathologies they cause in snakebite victims and how their exquisite selectivity and potency make them amenable for use as therapeutic and diagnostic tools relevant for human medicine.
The biogeography of tropical reef fishes: endemism and provinciality through time
Authors: Cowman Peter F. , Parravicini Valeriano , Kulbicki Michel , Floeter Sergio R.
Published: February 2017

The largest marine biodiversity hotspot straddles the Indian and Pacific Oceans, driven by taxa associated with tropical coral reefs. Centred on the Indo‐Australian Archipelago (IAA), this biodiversity hotspot forms the ‘bullseye’ of a steep gradient in species richness from this centre to the periphery of the vast Indo‐Pacific region. Complex patterns of endemism, wide‐ranging species and assemblage differences have obscured our understanding of the genesis of this biodiversity pattern and its maintenance across two‐thirds of the world's oceans. But time‐calibrated molecular phylogenies coupled with ancestral biogeographic estimates have provided a valuable framework in which to examine the origins of coral reef fish biodiversity across the tropics. Herein, we examine phylogenetic and biogeographic data for coral reef fishes to highlight temporal patterns of marine endemism and tropical provinciality. The ages and distribution of endemic lineages have often been used to identify areas of species creation and demise in the marine tropics and discriminate among multiple hypotheses regarding the origins of biodiversity in the IAA. Despite a general under‐sampling of endemic fishes in phylogenetic studies, the majority of locations today contain a mixture of potential paleo‐ and neo‐endemic fishes, pointing to multiple historical processes involved in the origin and maintenance of the IAA biodiversity hotspot. Increased precision and sampling of geographic ranges for reef fishes has permitted the division of discrete realms, regions and provinces across the tropics. Yet, such metrics are only beginning to integrate phylogenetic relatedness and ancestral biogeography. Here, we integrate phylogenetic diversity with ancestral biogeographic estimation of lineages to show how assemblage structure and tropical provinciality has changed through time.
Preen oil and bird fitness: a critical review of the evidence
Authors: Moreno‐Rueda Gregorio
Published: February 2017

The uropygial gland is a holocrine complex exclusive to birds that produces an oleaginous secretion (preen oil) whose function is still debated. Herein,Iexamine critically the evidence for the many hypotheses of potential functions of this gland. The main conclusion is that our understanding of this gland is still in its infancy. Even for functions that are considered valid by most researchers, real evidence is scarce. Although it seems clear that preen oil contributes to plumage maintenance, we do not know whether this is due to a role in reducing mechanical abrasion or in reducing feather degradation by keratinophilic organisms. Evidence for a function against pathogenic bacteria is mixed, as preen oil has been demonstrated to act against bacteriain vitro, but notin vivo. Nor is it clear whether preen oil can combat pathogenic bacteria on eggshells to improve hatching success. Studies on the effect of preen oil against dermatophytes are very scarce and there is no evidence of a function against chewing lice. It seems clear, however, that preen oil improves waterproofing, but it is unclear whether this acts by creating a hydrophobic layer or simply by improving plumage structure. Several hypotheses proposed for the function of preen oil have been poorly studied, such as reduction of drag in flight. Similarly, we do not know whether preen oil functions as repellent against predators or parasites, makes birds unpalatable, or functions to camouflage birds with ambient odours. On the other hand, a growing body of work shows the important implications of volatiles in preen oil with regard to social communication in birds. Moreover, preen oil clearly alters plumage colouration. Finally, studies examining the impact of preen oil on fitness are lacking, and the costs or limitations of preen‐oil production also remain poorly known. The uropygial gland appears to have several non‐mutually exclusive functions in birds, and thus is likely to be subject to several selective pressures. Therefore, future studies should consider how the inevitable trade‐offs among different functions drive the evolution of uropygial gland secretions.
Importance of including cultural practices in ecological restoration
Authors: Wehi Priscilla M. , Lord Janice M.
Published: February 2017

Ecosystems worldwide have a long history of use and management by indigenous cultures. However, environmental degradation can reduce the availability of culturally important resources. Ecological restoration aims to repair damage to ecosystems caused by human activity, but it is unclear how often restoration projects incorporate the return of harvesting or traditional life patterns for indigenous communities. We examined the incorporation of cultural use of natural resources into ecological restoration in the context of a culturally important but protected New Zealand bird; among award‐winning restoration projects in Australasia and worldwide; and in the peer‐reviewed restoration ecology literature. Among New Zealand's culturally important bird species, differences in threat status and availability for hunting were large. These differences indicate the values of a colonizing culture can inhibit harvesting by indigenous people. In Australasia among award‐winning ecological restoration projects, <17% involved human use of restored areas beyond aesthetic or recreational use, despite many projects encouraging community participation. Globally, restoration goals differed among regions. For example, in North America, projects were primarily conservation oriented, whereas in Asia and Africa projects frequently focused on restoring cultural harvesting. From 1995 to 2014, the restoration ecology literature contained few references to cultural values or use. We argue that restoration practitioners are missing a vital component for reassembling functional ecosystems. Inclusion of sustainably harvestable areas within restored landscapes may allow for the continuation of traditional practices that shaped ecosystems for millennia, and also aid project success by ensuring community support.
How economic contexts shape calculations of yield in biodiversity offsetting
Authors: Carver L. , Sullivan S.
Published: February 2017

We examined and analyzed methods used to create numerical equivalence between sites affected by development and proposed conservation offset sites. Application of biodiversity offsetting metrics in development impact and mitigation assessments is thought to standardize biodiversity conservation outcomes, sometimes termed yield by those conducting these calculations. The youth of biodiversity offsetting in application, however, means little is known about how biodiversity valuations and offset contracts between development and offset sites are agreed on in practice or about long‐term conservation outcomes. We examined how sites were made commensurable and how biodiversity gains or yields were calculated and negotiated for a specific offset contract in a government‐led pilot study of biodiversity offsets in England. Over 24 months, we conducted participant observations of various stages in the negotiation of offset contracts through repeated visits to 3 (anonymized) biodiversity offset contract sites. We conducted 50 semistructured interviews of stakeholders in regional and local government, the private sector, and civil society. We used a qualitative data analysis software program (DEDOOSE) to textually analyze interview transcriptions. We also compared successive iterations of biodiversity‐offsetting calculation spreadsheets and planning documents. A particular focus was the different iterations of a specific biodiversity impact assessment in which the biodiversity offsetting metric developed by the U.K.’s Department for Environment, Food and Rural Affairs was used. We highlight 3 main findings. First, biodiversity offsetting metrics were amended in creative ways as users adapted inputs to metric calculations to balance and negotiate conflicting requirements. Second, the practice of making different habitats equivalent to each other through the application of biodiversity offsetting metrics resulted in commensuration outcomes that may not provide projected conservation gains. Third, the pressure of creating value for money diminished projected conservation yields.
Four cases of pediatric deep‐seated/subcutaneous pyogenic granuloma: Review of literature and differential diagnosis
Authors: Putra Juan , Rymeski Beth , Merrow Arnold C. , Dasgupta Roshni , Gupta Anita
Published: February 2017

Background

Pyogenic granulomas are benign, reactive, typically superficial vascular lesions that can be idiopathic or arise secondary to trauma, underlying vascular malformations, infections, physiologic or pathologic endocrine changes, and hormone therapy. Deep‐seated/subcutaneous pyogenic granulomas (DSPG) are rarely seen in any age group. Pediatric DSPGs can be a clinical and pathologic challenge because these lesions mimic other vascular lesions, including kaposiform hemangioendothelioma, infantile hemangiomas and vascular malformations.

Methods

Retrospective search of DSPG excised at Cincinnati Children's Hospital Medical center between June 2010 and June 2011 was conducted. Clinical information was obtained from patient charts and histologic slides were retrieved and reviewed.

Results

Of the 106 cases of pyogenic granuloma, 4 (3.8%) were diagnosed as DSPG. We report the details of those 4 cases and compare them with the other pediatric DSPG cases reported in the literature. We also review the histologic differential diagnosis of DSPG in pediatric population.

Conclusion

Our results suggest that these lesions may not be as rare as inferred by literature, but, rather, underdiagnosed.
Do city–county mergers in China promote local economic development?
Authors: Tang Wei , Hewings Geoffrey J.D.
Published: February 2017

Municipal mergers have become a worldwide phenomenon in the past few decades, primarily advanced to exploit economies of scale. While most evaluations of municipal mergers have focused on the efficiency of local public goods provision, it is rare in the literature to explore how such mergers promote economic growth in a developing country context. This research investigates the economic consequences of a policy experiment of city–county mergers (che xian she qu) in China during the period 2000–2004. Using comprehensive datasets at city, county and firm levels, we present evidence that the merger significantly increases local economic development, and the magnitude of the effect depends on local endowments related to agglomeration forces. The results are robust to a number of different model specifications. We further verify that improved transport infrastructure and urban agglomeration economies after merger are potential contributors to the positive merger effects.
RNAi feeding bioassay: development of a non‐transgenic approach to control Asian citrus psyllid and other hemipterans
Authors: Andrade Eduardo C. , Hunter Wayne B.
Published: February 2017

RNA interference (RNAi) involves a natural mechanism of gene regulation and an antiviral defense system in eukaryotic cells, resulting in sequence‐specific degradation of RNAs. Recent studies demonstrated the feasibility of using RNAi‐based strategies to reduce insect pests or increase the health of beneficial insects. This technology permits the development of strategies to control a single insect species, with possibly no negative effects on non‐target species, like honey bees or parasitoids. Focus on the development of topically applied RNAi‐based approaches to manage insect pests and pathogens may provide environmentally sound products for use across all agriculture production systems. Herein presented are methods to develop RNAi‐based control to the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), vector of citrus Huanglongbing (HLB). Described is an RNAi feeding bioassay, called in plant system (iPS), which uses vegetative new‐growth citrus flush to deliver double‐strand RNA (dsRNA) to ACP during natural feeding. The iPS demonstrated delivery of non‐specific dsRNA in ACP 72 h post feeding. Feeding on flushes treated with dsRNA targeting ACP Arginine Kinase (dsAK), caused relative transcript knockdown and psyllid mortality. Increasing the dose of dsAK or use of dsRNA triggers made to different regions of the AK mRNA did not increase psyllid mortality. The iPS bioassay provides an easy system for use across many plants to successfully deliver dsRNA to ACP and other hemipteran insects for research or RNAi development.
Description of veterinary events and risk factors for fatality in National Hunt flat racing Thoroughbreds in Great Britain (2000–2013)
Authors: Allen S. E. , Rosanowski S. M. , Stirk A. J. , Verheyen K. L. P.
Published: February 2017

Background

No large‐scale studies have described veterinary events occurring in National Hunt (NH) flat racing or investigated risk factors for fatality in this race type.

Objectives

To describe injuries and conditions requiring veterinary attendance on race day and to determine risk factors for racehorse fatality in NH flat racing in Great Britain.

Study design

Retrospective cohort study (2000–2013).

Methods

Information from all NH flat races held over the study period, including horse, race and veterinary event report details, was combined. Veterinary events were described by type and anatomical structure(s) affected. Incidence per 1000 starts were calculated for all veterinary events and by event group, and stratified by certain horse‐ and race‐level variables. Risk factors for fatality were determined using multivariable logistic regression modelling.

Results

Over the 14‐year study period, 544 veterinary events were recorded, providing an overall incidence of 13.0 events per 1000 starts. The most common events were bone injuries (23.5%) and tendon or ligament injuries (16.4%). A fatal outcome was recorded for 117 horses (21.5% of all events), resulting in an incidence of 2.9 deaths per 1000 starts. Odds of fatality were 4.33 (95% confidence interval [CI] 1.59–11.82; P = 0.02) times higher in races restricted to conditional jockeys compared to those that were not. Horses starting in their first race experienced 1.44 (95% CI 1.00–2.08; P = 0.05) times the odds of death compared to those that had raced before.

Main limitations

Classification of veterinary events frequently relied upon presumptive diagnosis.

Conclusions

This study provides a benchmark for the ongoing surveillance of veterinary events in NH flat racing. These results support the phasing out of NH flat races restricted to conditional jockeys and highlight the need for further work to establish why NH flat racing Thoroughbreds competing in their first race are at increased risk for death.
Social Capital and Entrepreneurship: Does the Relationship Hold in Deprived Urban Neighbourhoods?
Authors: Williams Nick , Huggins Robert , Thompson Piers
Published: February 2017

The aim of this paper is to examine the relationship between social capital and entrepreneurship in deprived urban neighbourhoods (DUNs). While there is a great deal of research on social capital, its usage and value in deprived areas is an under‐researched topic. Drawing on survey data, it is found that social capital in the form of network ties within a DUN is linked to how entrepreneurship develops in these places. The breadth and variety of network ties that individuals are able to identify as sources of advice is related to the probability of considering an entrepreneurial career, and is even more strongly related to the conversion of entrepreneurial intentions into full engagement. If entrepreneurship is to be harnessed in DUNs a starting point is the enhancement of initiatives for developing social capital incorporating local businesses, residents, and local government agencies.
Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3
Authors: Kakumu Erina , Nakanishi Seiya , Shiratori Hiromi M. , Kato Akari , Kobayashi Wataru , Machida Shinichi , Yasuda Takeshi , Adachi Naoko , Saito Naoaki , Ikura Tsuyoshi , Kurumizaka Hitoshi , Kimura Hiroshi , Yokoi Masayuki , Sakai Wataru , Sugasawa Kaoru
Published: February 2017

In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV‐DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones. Treatment of cells with histone deacetylase inhibitors retarded recruitment of XPC to sites of UV‐induced DNA damage and the subsequent repair process. Biochemical studies showed novel multifaceted interactions of XPC with histone H3, which were profoundly impaired by deletion of the N‐terminal tail of histone H3. In addition, histone H1 also interacted with XPC. Importantly, acetylation of histone H3 markedly attenuated the interaction with XPC in vitro, and local UV irradiation of cells decreased the level of H3K27ac in the damaged areas. Our results suggest that histone deacetylation plays a significant role in the process of DNA damage recognition for nucleotide excision repair and that the localization and functions of XPC can be regulated by acetylated states of histones.
Pharmacokinetics of a novel extended half‐life glycoPEGylated factor IX, nonacog beta pegol (N9‐GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials
Authors: Tiede A. , Abdul‐Karim F. , Carcao M. , Persson P. , Clausen W. H. O. , Kearney S. , Matsushita T. , Negrier C. , Oldenburg J. , Santagostino E. , Young G.
Published: February 2017

Introduction

Nonacog beta pegol (N9‐GP) is a glycoPEGylated recombinant factor IX (FIX) with an extended half‐life developed for routine prophylaxis and the prevention and treatment of bleeding episodes in patients with haemophilia B.

Aim

The aim of this study was to evaluate the pharmacokinetics (PK) of N9‐GP.

Methods

Data from 41 previously treated haemophilia B patients, enrolled globally (16 adolescents/adults and 25 children; FIX activity ≤0.02 IU mL−1) with no history of FIX inhibitors, were included. N9‐GP was administered once‐weekly as 10 IU kg−1 or 40 IU kg−1 in adolescents/adults and 40 IU kg−1 in children. Blood was sampled up to 168 h (1 week) post dose. Standard PK was estimated on the basis of plasma FIX activity vs. time (PK profiles) using non‐compartmental methods. Furthermore, a population PK analysis and FIX activity predictions were performed.

Results

Incremental recoveries were 0.02 (IU mL−1)/(IU kg−1) in both adolescents/adults and children. The extended half‐life resulted in mean trough levels of 0.27 IU mL−1 for adolescents/adults and 0.17 IU mL−1 for children at steady‐state after weekly dosing at 40 IU kg−1. The population PK analysis confirmed a mono‐exponential decay in FIX activity and allowed for predictions of FIX activity for adolescents/adults above 0.15 IU mL−1 at all times and 6.4 days week−1 in children.

Conclusion

N9‐GP has the potential to shift previously treated haemophilia B patients from a severe/moderate disease state into a mild‐ or non‐haemophilic range for most of the dosing interval, which is expected to reduce the number of bleeding episodes.
CGRP and its receptors
Authors: Hay Debbie L. , Walker Christopher S.
Published: February 2017

The calcitonin gene‐related peptide (CGRP) neuropeptide system is an important but still evolving target for migraine. A fundamental consideration for all of the current drugs in clinical trials and for ongoing development in this area is the identity, expression pattern, and function of CGRP receptors because this knowledge informs safety and efficacy considerations. In recent years, only the calcitonin receptor‐like receptor/receptor activity‐modifying protein 1 (RAMP1) complex, known as the CGRP receptor, has generally been considered relevant. However, CGRP is capable of activating multiple receptors and could have more than one endogenous receptor. The recent identification of the CGRP‐responsive calcitonin receptor/RAMP1 complex (AMY1 receptor – amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine. This perspective considers some of the issues and implications.
Pediatric pyoderma gangrenosum: a systematic review and update
Authors: Kechichian Elio , Haber Roger , Mourad Nadim , El Khoury Rana , Jabbour Samer , Tomb Roland
Published: February 2017

Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many newly reported associated diseases and drugs. This paper aims to review all recent available data on pediatric PG. A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. A total of 132 articles were included in the review. The most commonly reported underlying diseases in pediatric PG are inflammatory bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of the cases occur with no underlying disease. The most frequently reported clinical presentation is multiple disseminated ulcers. Treatment should be tailored according to the underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as dapsone and cyclosporine, and TNF‐alpha inhibitors such as adalimumab and infliximab. Response to treatment is high with cure rates reaching 90%. A high index of suspicion and a thorough workup are mandatory in the management of pediatric PG.
Feel the Fear: Learning Graphic Design in Affective Places and Online Spaces
Authors: Nottingham Anitra
Published: February 2017

This article explores the idea of pedagogic affect in both onsite and online graphic design learning spaces, and speculates on the role that this affect plays in the formation of the design student. I argue that embodied design knowledge is built by interactions with design professionals, activities that mimic the daily work of designers, and practices of display such as exemplar student work galleries within design schools. Therefore bodies in motion, and the places they move within, take on more importance in the making‐up of a graphic design student than we may expect. This idea has obvious implications for online design learning.

Drawing on concepts from both Actor‐Network Theory (ANT) and Non‐Representational Theory (NRT), this article works three empirical instances of affect. The analysis presented is targeted towards exploring the contribution of affect to teaching in onsite and online learning spaces. As the practices described here carry through time and space to other design schools, the findings put forward have implications for a broad suite of practices in design education. Thinking through how affect plays out in the onsite design school points the way towards the creation of more vibrant online learning spaces.
Outcomes of Catheter Ablation of Idiopathic Outflow Tract Ventricular Arrhythmias With an R Wave Pattern Break in Lead V2: A Distinct Clinical Entity
Authors: HAYASHI TATSUYA , SANTANGELI PASQUALE , PATHAK RAJEEV K. , MUSER DANIELE , LIANG JACKSON J. , CASTRO SIMON A. , GARCIA FERMIN C. , HUTCHINSON MATHEW D. , SUPPLE GREGORY E. , FRANKEL DAVID S. , RILEY MICHAEL P. , LIN DAVID , SCHALLER ROBERT D. , DIXIT SANJAY , CALLANS DAVID J. , ZADO ERICA S. , MARCHLINSKI FRANCIS E.
Published: February 2017

Outflow Tract VT With Pattern Break in Lead V2

Introduction

In outflow tract ventricular arrhythmias (OT‐VAs), an abrupt loss of the R wave in lead V2 compared to V1 and V3 (pattern break in V2–PBV2) suggests an origin close to the anterior interventricular sulcus (anatomically opposite to lead V2) and adjacent to proximal coronaries. We studied the outcome of catheter ablation of OT‐VAs with a PBV2.

Methods and Results

Of 130 consecutive patients with idiopathic left bundle block morphology OT‐VAs and transition ≤V4, 12 (9%) had PBV2. Outcomes in this group were compared to the remaining 118 patients. Patients with PBV2 were more likely to be younger (41 ± 18 vs. 50 ± 14 years, P = 0.0384) and women (11 [92%] vs. 70 [59%], P = 0.0302). The earliest activation was at the RVOT in seven, left coronary cusp (LCC) in one, anterior interventricular vein (AIV) in two and the epicardium in two. In five (42%) cases (earliest activation in the AIV in two, epicardium in two, and RVOT below the valve level in one), ablation was aborted due to proximity to the left anterior descending (LAD) coronary artery. After 36 ± 17 months and 1.3 ± 0.5 procedures, VAs elimination was achieved in 58% of patients with PBV2 compared to 89% of the reference population (P = 0.0125) with effective site in five of seven at the most anterior and leftward RVOT adjacent to the pulmonic valve (PV).

Conclusions

OT‐VAs with PBV2 demonstrate a unique ECG pattern and challenging catheter ablation. Proximity to LAD precludes ablation in about half. Long‐term VA suppression could be achieved in only 58% of cases most commonly when the earliest site is at the anterior and leftward RVOT just under the PV.
Histology and ultrastructure of the thymus during development in tilapia, Oreochromis niloticus
Authors: Cao Jianmeng , Chen Qiong , Lu Maixin , Hu Xinxin , Wang Miao
Published: February 2017

The thymus in teleost fishes plays an important role in producing functionally competent T‐lymphocytes. However, the thymus in tilapia is not well known, which greatly hampers investigations into the immune responses of tilapia infected by aquatic pathogens. The histological structure and ultrastructure of the thymus in Oreochromis niloticus, including embryos and larvae at different developmental stages, juveniles, and adult fish, were systematically investigated using whole mount in situ hybridization (WISH), and light and transmission electron microscopy (TEM). The position of the thymus primordium was first labeled in the embryo at 2 days post‐fertilization (dpf) with the thymus marker gene recombination activating gene 1 (Rag1), when the water temperature was 27 °C. Obvious structures of the thymus were easily observed in 4‐dpf embryos. At this stage, the thymus was filled with stem cells. At 6 dpf, the thymus differentiated into the cortex and medulla. The shape of the thymus was ‘broad bean’‐like during the early stages from 4 to 10 dpf, and became wedge‐shaped in fish larvae at 20 dpf. At 6 months post‐fertilization (mpf), the thymus differentiated into the peripheral zone, central zone, and inner zone. During this stage, myoid cells and adipocytes appeared in the inner zone following thymus degeneration. Then, the thymus displayed more advanced degeneration by 1 year post‐fertilization (ypf), and the separation of cortex and medulla was not observed at this stage. The thymic trabecula and lobule were absent during the entire course of development. However, the typical Hassall's corpuscle was present and underwent degeneration. Additionally, TEM showed that the thymic tissues contained a wide variety of cell types, namely lymphocytes, macrophages, epithelial cells, fibroblasts, and mastocytes.
Compassion fatigue in nurses: A metasynthesis
Authors: Nolte Anna GW , Downing Charlene , Temane Annie , Hastings‐Tolsma Marie
Published: February 2017

Aims and objectives

To interpret the body of qualitative work focusing on compassion fatigue to distil a common understanding that could then be applied to nursing care.

Background

Complex demands place extraordinary stress on nurses struggling to work in overburdened healthcare systems. The result can be the inability to care well for others, leading to compassion fatigue, burnout and increased numbers leaving the profession. Metasynthesis offers a means of more fully illuminating compassion fatigue and further understanding of practices which might reduce its negative consequences.

Design

Metasynthesis.

Method

As a method designed to facilitate knowledge development, metasynthesis allowed for integration of qualitative study findings conducted between 1992–2016 using defined search terms. Six databases were searched for articles published in English. Nine papers met the criteria for review and metasynthesis was conducted using the meta‐ethnographic approach detailed by Noblit and Hare.

Results

Four themes related to compassion fatigue were found by consensus discussion. The themes included: physical (“just plain worn out”) and emotional symptoms (“walking on a tightrope”), triggering factors (“an unbearable weight on shoulders” and “alone in a crowded room”), and measures to overcome/prevent (“who has my back?”).

Conclusions

Compassion fatigue is a concept of documented relevance to those in nursing and represents a basic inability to nurture others and engenders a temporal component. Synthesis of studies provides evidence of the veracity of the concept for application to clinical practice and research related to nursing care.

Relevance to clinical practice

Findings provide insight into the clinical milieu needed to prevent compassion fatigue. A theoretical model is presented which can be used to guide future research, as well as the creation of clinical practice policies which might mitigate the development of compassion fatigue and its potential consequences.
The patients’ perspective of international normalized ratio self‐testing, remote communication of test results and confidence to move to self‐management
Authors: Grogan Anne , Coughlan Michael , Prizeman Geraldine , O'Connell Niamh , O'Mahony Nora , Quinn Katherine , McKee Gabrielle
Published: February 2017

Aims and objectives

To elicit the perceptions of patients, who self‐tested their international normalized ratio and communicated their results via a text or phone messaging system, to determine their satisfaction with the education and support that they received and to establish their confidence to move to self‐management.

Background

Self‐testing of international normalized ratio has been shown to be reliable and is fast becoming common practice. As innovations are introduced to point of care testing, more research is needed to elicit patients’ perceptions of the self‐testing process.

Design

This three site study used a cross‐sectional prospective descriptive survey.

Methods

Three hundred and thirty patients who were prescribed warfarin and using international normalized ratio self‐testing were invited to take part in the study. The anonymous survey examined patient profile, patients’ usage, issues, perceptions, confidence and satisfaction with using the self‐testing system and their preparedness for self‐management of warfarin dosage.

Results

The response rate was 57% (n = 178). Patients’ confidence in self‐testing was high (90%). Patients expressed a high level of satisfaction with the support received, but expressed the need for more information on support groups, side effects of warfarin, dietary information and how to dispose of needles. When asked if they felt confident to adjust their own warfarin levels 73% agreed. Chi‐squared tests for independence revealed that none of the patient profile factors examined influenced this confidence. The patients cited the greatest advantages of the service were reduced burden, more autonomy, convenience and ease of use. The main disadvantages cited were cost and communication issues.

Conclusion

Patients were satisfied with self‐testing. The majority felt they were ready to move to self‐management.

Relevance to clinical practice

The introduction of innovations to remote point of care testing, such as warfarin self‐testing, needs to have support at least equal to that provided in a hospital setting.
Barriers to regaining control within a constructivist grounded theory of family resilience in ICU: Living with uncertainty
Authors: Wong Pauline , Liamputtong Pranee , Koch Susan , Rawson Helen
Published: February 2017

Aims and objectives

To discuss families’ experiences of their interactions when a relative is admitted unexpectedly to an Australian intensive care unit.

Background

The overwhelming emotions associated with the unexpected admission of a relative to an intensive care unit are often due to the uncertainty surrounding the condition of their critically ill relative. There is limited in‐depth understanding of the nature of uncertainty experienced by families in intensive care, and interventions perceived by families to minimise their uncertainty are not well documented. Furthermore, the interrelationships between factors, such as staff–family interactions and the intensive care unit environment, and its influence on families’ uncertainty particularly in the context of the Australian healthcare system, are not well delineated.

Design

A grounded theory methodology was adopted for the study.

Methods

Data were collected between 2009–2013, using in‐depth interviews with 25 family members of 21 critically ill patients admitted to a metropolitan, tertiary‐level intensive care unit in Australia.

Results

This paper describes the families experiences of heightened emotional vulnerability and uncertainty when a relative is admitted unexpectedly to the intensive care unit. Families uncertainty is directly influenced by their emotional state, the foreign environment and perceptions of being 'kept in the dark', as well as the interrelationships between these factors.

Conclusion

Staff are offered an improved understanding of the barriers to families’ ability to regain control, guided by a grounded theory of family resilience in the intensive care unit.

Relevance to clinical practice

The findings reveal in‐depth understanding of families’ uncertainty in intensive care. It suggests that intensive care unit staff need to focus clinical interventions on reducing factors that heighten their uncertainty, while optimising strategies that help alleviate it. Families are facilitated to move beyond feelings of helplessness and loss of control, and cope better with their situation.