bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta‐analysis
Authors: Zhang Jinhua , Tian Lihong , Huang Jinlong , Huang Sihan , Chai Tingting , Shen Jianzhen
Published: September 2016

Aim

To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement.

Methods

A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager version 5.2.3 software was used to analyze the relationship between CYP2C9 polymorphisms and warfarin maintenance doses in pediatric patients. Eight articles with a combined total of 507 pediatric patients were included in the meta‐analysis.

Results

Maintenance warfarin doses in patients with CYP2C9 *1/*2 genotype, CYP2C9 *1/*3 genotype, and CYP2C9 variant carriers which contain at least one variant allele (*2 or *3) were from 15% to 41% lower than doses in patients with the wild‐type allele (CYP2C9 *1/*1): All differences were significant with P‐values <.05. The Fontan procedure as a medical indication for anticoagulation was also associated with a lower warfarin maintenance dose; however, target INR range was not.

Conclusions

We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients.
Physician attitudes and experiences with Maryland's prescription drug monitoring program (PDMP)
Authors: Lin Dora H. , Lucas Eleanor , Murimi Irene B. , Jackson Katherine , Baier Michael , Frattaroli Shannon , Gielen Andrea C. , Moyo Patience , Simoni‐Wastila Linda , Alexander G. Caleb
Published: September 2016

Aims

Physicians’ use of prescription drug monitoring programs (PDMPs) varies by state. Among Maryland physicians, we sought to (1) estimate the PDMP impact on changes in opioid prescribing, (2) approximate the scope of PDMP utility and (3) determine the barriers to PDMP use after its 2013 implementation.

Design

Cross‐sectional postal survey linking responses to state records of PDMP registration and use, randomly sampling physicians within specialty and registration strata.

Setting

Maryland, USA.

Participants

A total of 1000 surveyed primary care, pain and emergency medicine physicians stratified into three subpopulations: PDMP non‐registrants, PDMP registrants who were non‐users and PDMP users; 405 respondents (44%) of 916 eligible physicians were analysed.

Measurements

Primary outcome measure was PDMP use. Key predictors were clinic characteristics, including type of practice and number of patients prescribed opioids.

Findings

No response‐wave bias was identified. Seventy per cent of physicians believed PDMP access decreased their amount and increased their comfort level in prescribing opioids. Three‐fourths (74%) of PDMP users reported the data very useful for informing opioid prescribing, although one‐fifth (20%) reported difficulty accessing the data. Commonly reported barriers to PDMP use were lack of knowledge regarding its existence and registration process. In multivariable analysis after adjusting for key clinic characteristics, practicing at a managed care organization was associated with lower PDMP use [incidence rate ratio (IRR) = 0.19, 95% confidence interval (CI) = 0.05–0.73]. Conversely, physicians who prescribed opioids for more than 50 patients accessed the PDMP three times as often as those prescribing opioids for fewer than 10 patients monthly (IRR = 3.00, 95 % CI = 1.07–8.43).

Conclusions

In this survey of Maryland, USA physicians, most participants reported that prescription drug monitoring programs (PDMPs) improved their opioid prescribing by decreasing prescription amounts and increasing comfort with prescribing opioids. Common barriers to PDMP use included not knowing about the program, registration difficulties and data access difficulties.
Assessment of children's nutritional attitudes before oral food challenges to identify patients at risk of food reintroduction failure: a prospective study
Authors: Polloni L. , Ferruzza E. , Ronconi L. , Toniolo A. , Lazzarotto F. , Bonaguro R. , Celegato N. , Muraro A.
Published: September 2016

Background

Inappropriate dietary eliminations may impair quality of life, affect children's growth and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food‐avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. This study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC.

Methods

A prospective study was conducted involving 81 mothers of children with IgE‐mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State‐Trait Anxiety Inventory on the day of OFC and 6 months later.

Results

In total, 11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants’ characteristics or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC.

Conclusions

Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food.
Population pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in hepatitis C virus genotype 1 infection: analysis of six phase III trials
Authors: Mensing Sven , Eckert Doerthe , Sharma Shringi , Polepally Akshanth R. , Khatri Amit , Podsadecki Thomas J. , Awni Walid M. , Menon Rajeev M. , Dutta Sandeep
Published: September 2016

Aim

The aim of the current study was to characterize the population pharmacokinetics of a triple direct‐acting antiviral (DAA) regimen (3D) (ombitasvir, paritaprevir–ritonavir and dasabuvir) and adjunctive ribavirin, and estimate covariate effects in a broad spectrum of subjects with hepatitis C virus (HCV) genotype 1 infection.

Methods

Pharmacokinetic data from six phase III studies and one phase II study in subjects receiving the currently approved doses of the 3D ± ribavirin regimen for treating HCV genotype 1 infection for 12 weeks or 24 weeks were characterized using separate population pharmacokinetic models, built using each component of the regimen from nonlinear mixed‐effects methodology in NONMEM 7.3. In the models, demographic and clinical covariates were tested. Models were assessed via goodness‐of‐fit plots, visual predictive checks and bootstrap evaluations.

Results

The population pharmacokinetic models for each component of the 3D ± ribavirin regimen (DAAs and ritonavir, n = 2348) and ribavirin (n = 1841) adequately described their respective plasma concentration–time data. Model parameter estimates were precise and robust, and all models showed good predictive ability. Significant covariate effects associated with apparent clearance and volume of distribution included age, body weight, gender, cirrhosis, HCV subtype, opioid or antidiabetic agent use, and creatinine clearance.

Conclusion

The population pharmacokinetics of the 3D ± ribavirin regimen components in HCV‐infected patients were characterized using phase II and III HCV clinical trial data. Although several statistically significant covariates were identified, their effects were modest and not clinically meaningful to necessitate dose adjustments for any component of the 3D regimen.
The Australian laparoscopic non robotic radical prostatectomy experience – analysis of 2943 cases (USANZ supplement)
Authors: Louie‐Johnsun Mark William , Handmer Marcus M. , Calopedos Ross John Spero , Chabert Charles , Cohen Ronald J. , Gianduzzo Troy R. J. , Kearns Paul A. , Moon Daniel A. , Ooi Jason , Shannon Tom , Sofield David , Tan Andrew H. H.
Published: September 2016

Objectives

To analyse the Australian experience of high‐volume Fellowship‐trained Laparoscopic Radical Prostatectomy (LRP) surgeons.

Materials and Methods

2943 LRP cases were performed by nine Australian surgeons. The inclusion criteria were a prospectively collected database with a minimum of 100 consecutive LRP cases. The surgeons’ LRP experience commenced at various times from July 2003 to September 2009. Data were analysed for demographic, peri‐operative, oncological and functional outcomes.

Results

The mean age of patients were 61.5 years and mean preoperative PSA 7.4 ng/ml. Mean operating time was 168 minutes with conversion to open surgery in 0.5% and a blood transfusion rate of 1.1%. Overall mean length of stay was 2.5 days. 73.6% of pathological specimens were pT2 and 86.3% had Gleason Score >7. Overall positive surgical margins (PSM) occurred in 15.9% with pT2 PSM 9.8%, pT3a PSM 30.8% and pT3b PSM 39.2%. Mean urinary continence at 12 months was 91.4% (data available from five surgeons). Mean 12 months potency after bilateral nerve spare was 47.2% (data available from four surgeons). Biochemical recurrence occurred in 10.6% (mean follow up 17 months).

Conclusion

The Australian experience of Fellowship trained surgeons performing LRP demonstrates favourable peri‐operative, oncological and functional outcomes in comparison to published data for open, laparoscopic and robotic assisted radical prostatectomy. In our Australian centres, LRP remains an acceptable minimally invasive surgical treatment for prostate cancer despite the increasing use of robotic assisted surgery.
The use of 68 Ga‐PSMA PET CT in men with biochemical recurrence after definitive treatment of acinar prostate cancer
Authors: Meredith Greta , Wong David , Yaxley John , Coughlin Geoff , Thompson Les , Kua Boon , Gianduzzo Troy
Published: September 2016

Introduction

Early localisation of disease recurrence after definitive treatment of prostate cancer is vital to determine suitability for salvage treatment. Our aim was to further investigate the relationship between prostate specific antigen (PSA) level and detection of suspected cancer recurrence using 68 Ga‐PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy (RP) or radiotherapy, particularly at low PSA levels.

Methods

This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga‐PSMA PET/CT scans for investigation of post RP and post radiotherapy PSA recurrence following primary treatment of prostate cancer. We included men with suspected recurrent prostate cancer based on an elevated post treatment PSA level. The data collected analyzed the relationship of the pre‐scan PSA level to the probability of a positive scan finding for recurrent prostate cancer.

Results

Of the cohort of 532 men, 425 had a previous RP and 107 had prior radiotherapy. The median PSA of the RP group was 0.59 ng/mL and 5.8 ng/mL in the radiotherapy group. In the post RP cohort, the detection rate of 68 Ga‐PSMA PET/CT was 11.3% for PSA 0.01 to <0.2 ng/mL, 26.6% for PSA 0.2 to <0.5 ng/mL, 53.3% for PSA 0.5 to <1 ng/mL, 79.1% for PSA 1 to <2 ng/mL and 95.5% for PSA ≥2. Lymph node metastasis post RP was identified in 68% of men with suspected disease recurrence. In the post radiotherapy cohort the detection rate was 33.3% for PSA 0.01 to <0.5 ng/mL, 71.4% for PSA 0.5 to <1 ng/mL, 93.3% for PSA 1 to <2 ng/mL and 100% for PSA ≥2. Local recurrence after radiotherapy was suspected in 71% of the cohort and 40% had suspected lymph node metastasis.

Conclusions

To our knowledge, this is largest cohort study of detection rates of 68 Ga‐PSMA PET/CT in patients with biochemical recurrence after definitive treatment of prostate cancer, including patients with PSA <0.5 and in a post radiotherapy cohort. Detection of suspected recurrent disease outside the pelvis at low PSA levels will influence the decision for salvage treatment options.
Mucosal and lacrimal flaps for endonasal dacryocystorhinostomy: a systematic review
Authors: Green R. , Gohil R. , Ross P.
Published: September 2016

Background

Historically dacryocystorhinostomy (DCR) has been performed externally with very good outcomes. Current literature shows comparable success rates between endonasal and external approaches. A common reason for the failure of a DCR is the reclosure of the nasolacrimal stoma by granulation tissue and synechiae.

Objective of review

A systematic review and critical evaluation of the evidence relating to the preservation of nasal mucosal flaps in DCR surgery.

Type of review and evaluation method

A systematic review using the consort guidance for review of randomised control trials.

Search strategy

A search of the following evidence‐based medicine databases was performed: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, Ovid, Medline, EMBASE and PubMed. The search was limited to English language articles, and the following key words were used: Endonasal, Endoscopic, Dacryocystorhinostomy, DCR, Mucosal Flaps, between years 1970 and 2015.

Results

The best available evidence was level 1B, comprising two randomised control trials and three comparative studies included in the review. The main outcome measures used were lacrimal irrigation and absence of epiphora. Two of the studies demonstrated a statistically significant benefit of mucosal sparing either with nasal mucosal flaps or with lacrimal flaps. More debridement was needed, and granulation tissue was also seen in the groups without mucosal preservation. There was no difference in surgical complications between a mucosal and non‐mucosal‐sparing technique.

Conclusions

The overall quality of current evidence is poor, and there does however appear to be a trend towards improved outcomes and reduced granulation in groups where nasal mucosal and lacrimal flaps were preserved, but this is not clear‐cut. There was no evidence of increased complication rates with mucosal‐sparing techniques. We recommend that until further good quality research is available we should be performing a mucosal‐sparing technique when performing DCR routinely.
Iatrogenic facial nerve injuries during chronic otitis media surgery: a multicentre retrospective study
Authors: Linder T. , Mulazimoglu S. , El Hadi T. , Darrouzet V. , Ayache D. , Somers T. , Schmerber S. , Vincent C. , Mondain M. , Lescanne E. , Bonnard D.
Published: September 2016

Objectives

To give an insight into why, when and where iatrogenic facial nerve (FN) injuries may occur and to explain how to deal with them in an emergency setting.

Design and setting

Multicentre retrospective study in eight tertiary referral hospitals over 17 years.

Participants

Twenty patients with partial or total FN injury during surgery for chronic otitis media (COM) were revised.

Main outcome measures

Indication and type of surgery, experience of the surgeon, intra‐ and postoperative findings, value of CT scanning, patient management and final FN outcome were recorded.

Results

In 12 cases, the nerve was completely transected, but the surgeon was unaware in 11 cases. A minority of cases occurred in academic teaching hospitals. Tympanic segment, second genu and proximal mastoid segments were the sites involved during injury. The FN was not deliberately identified in 18 patients at the time of injury, and nerve monitoring was only applied in one patient. Before revision surgery, CT scanning correctly identified the lesion site in 11 of 12 cases and depicted additional lesions such as damage to the lateral semicircular canal.

A greater auricular nerve graft was interposed in 10 cases of total transection and in one partially lesioned nerve: seven of them resulted in an HB III functional outcome. In two of the transected nerves, rerouting and direct end‐to‐end anastomosis was applied. A simple FN decompression was used in four cases of superficially traumatised nerves.

Conclusions

We suggest checklists for preoperative, intraoperative and postoperative management to prevent and treat iatrogenic FN injury during COM surgery.
Sharks, ice cream, and neonatal seizures
Authors: Kirkpatrick Martin , Jollands Alice
Published: September 2016

This commentary is on the original article by Kharoshankaya et al. on pages 1242–1248 of this issue.
Individual and combined effects of the generalist Forficula auricularia and the specialist Episyrphus balteatus on Dysaphis plantaginea – are two predators better than one?
Authors: Dib Hazem , Jamont Marie , Sauphanor Benoît , Capowiez Yvan
Published: September 2016

The interactions between specialist and generalist natural enemies could affect the success of biological pest control, especially in augmentation programmes. The aim of this laboratory study was to quantitate the individual and combined effects of the generalist predator Forficula auricularia L. (Dermaptera: Forficulidae) and the specialist Episyrphus balteatus De Geer (Diptera: Syrphidae) on the population growth of the rosy apple aphid (RAA), Dysaphis plantaginea Passerini (Hemiptera: Aphididae). The experiment was carried out using apple seedlings with five levels of initial RAA infestation. In most cases, both predator species (alone and in combination) were able to reduce RAA densities or to keep them at their initial level. This suppression effect was greater when RAA densities were low and resulted in near‐complete mortality of the RAA colony after 4–6 days. Without predators, RAA population size almost doubled within 10 days, whereas with predators, RAA population size was reduced by about 20 (alone) and 50% (in combination). Although RAA numbers in the two‐predators treatment were ca. 81% of RAA numbers in the one‐predator treatment for pooled numbers across dates and densities, the difference between the two treatments was not significant. Some predator mortality occurred with first and second instars of the syrphid larvae and only at the two lowest initial RAA infestation levels. This mortality may be explained by inadequate food supply, intraguild predation (IGP) (in 13.3% of the possible cases), or both. However, the incidence of IGP under natural conditions could be even less frequent, as both predators were never observed on the same leaf.
Effect of fertilized, unfertilized, and UV‐irradiated hosts on parasitism and suitability for Trichogramma parasitoids
Authors: Xu Jing , Yang Xiangbing , Lin Ying , Zang Lian‐Sheng , Tian Chun‐Yu , Ruan Chang‐Chun
Published: September 2016

Trichogramma spp. (Hymenoptera: Trichogrammatidae) parasitoids have been commonly used as biological control agents in insect pest management. Host quality is believed to influence parasitism, host preference, and suitability for parasitoids. To date, limited studies have compared the parasitism of Trichogramma parasitoids on fertilized, unfertilized, and sterilized host eggs. Hence, we studied the performance of three Trichogramma egg parasitoids, Trichogramma japonicum Ashmead, Trichogramma chilonis Ishii, and Trichogramma leucaniae Pang & Chen, on fertilized, unfertilized, and ultraviolet (UV)‐irradiated fertilized (UVF) eggs of rice moth, Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae). In a no‐choice test, T. japonicum and T. leucaniae parasitized significantly more fertilized or UVF than unfertilized hosts, and T. chilonis parasitized significantly more UVF than either fertilized or unfertilized hosts. In a choice test, all three Trichogramma parasitoids parasitized UVF hosts the most, and unfertilized hosts the least. There were similar percentages of adult emergence and female progeny among fertilized, unfertilized, and UVF hosts for all three Trichogramma parasitoids, except that T. japonicum had significantly lower adult emergence on fertilized hosts. We also found that all three Trichogramma parasitoids developed slower on unfertilized hosts. Regardless of host treatments, T. leucaniae had the longest developmental time and T. chilonis had the shortest. We conclude that Trichogramma parasitoids prefer parasitizing UVF eggs of C. cephalonica without negative effects on their emergence and sex allocation.
A dirty job: manure removal by dung beetles in both a cattle ranch and laboratory setting
Authors: Ortega‐Martínez I.J. , Moreno C.E. , Escobar F.
Published: September 2016

Dung beetles (Coleoptera: Scarabaeidae, Scarabaeinae) play a crucial role in natural ecosystems and grazing areas because they are actively involved in dung removal and other ecosystem processes such as nutrient cycling. We assess the manure removal process performed by dung beetles on a cattle ranch with temperate forest remnants in the Mexican Transition Zone of central Mexico. Despite having similar species richness, the amount of dung removed by the beetle community on pastures was higher than in forest remnants, but there were no significant differences between dung types (cow and sheep). Using field mesocosms, we found differences in the amount of dung removed by eight of the most abundant species in the study area. As in the field, in the laboratory large species (Deltochilum scabriusculum Bates, Dichotomius colonicus Say, and Phanaeus adonis Harold) removed larger amounts of dung during the first days of the process. We found positive and significant relationships between species biomass and the amount of dung removed, both in mesocosms and in the laboratory. Our results suggest that in spite of habitat type, dung beetle biomass is one of the main factors driving the process of dung removal. A better understanding of the dynamics of ecosystem processes where dung beetles participate will improve the design of management plans to promote sustainability and ecosystems integrity in livestock areas.
Potential vectors of Xylella fastidiosa: a study of leafhoppers and treehoppers in citrus agroecosystems affected by Citrus Variegated Chlorosis
Authors: Dellapé G. , Paradell S. , Semorile L. , Delfederico L.
Published: September 2016

This study investigated the predominant leafhopper and treehopper (Hemiptera, Auchenorrhyncha) species in Citrus Variegated Chlorosis (CVC)‐affected citrus agroecosystems in Argentina, their seasonal fluctuation, and their potential role as vectors of Xylella fastidiosa Wells et al., using molecular methods for detection. More than 6 000 Auchenorrhyncha were collected from three citrus agroecosystems over a period of 3 years using yellow sticky traps and entomological nets. Cicadellidae and Membracidae were the most abundant families. Of the 43 species identified, five were predominant in citrus orchards, and three were predominant in weeds surrounding citrus plants. All predominant species and another four non‐predominant species tested positive for X. fastidiosa in PCR and real‐time PCR assays. In a transmission assay, Dechacona missionum (Berg), Tapajosa rubromarginata (Signoret), and Cyphonia clavigera (Fabricius) transmitted X. fastidiosa successfully. Scaphytopius bolivianus Oman and Frequenamia spiniventris (Linnavuori) populations increased once (during the summer), possibly due to favorable weather conditions, and Bucephalogonia xanthophis (Berg), Molomea lineiceps Young, and T. rubromarginata populations increased twice a year: once in summer and once in winter, coinciding with the increase in early citrus shoots (flush). Among the X. fastidiosa‐positive species, those with the higher population densities during the sprouting period, where trees are highly susceptible to infection, must be considered as most relevant vectors of CVC in the citrus‐growing areas in Argentina.
Financial Flexibility and Investment Ability Across the Euro Area and the UK
Authors: Ferrando Annalisa , Marchica Maria‐Teresa , Mura Roberto
Published: September 2016

We use a very large sample of European private and public firms to show that financial flexibility attained through a conservative leverage policy is more important for private, small‐medium‐sized, and young firms and for firms in countries with less access to credit and weaker investor protection. Further, using the 2007 financial crisis as a natural experiment, we show that a higher degree of financial flexibility allows firms to reduce the negative impact of liquidity shocks on investment. Our findings support the hypothesis that financial flexibility improves companies' ability to undertake future investment, despite market frictions hampering possible growth opportunities.
Ectomycorrhizal fungal response to warming is linked to poor host performance at the boreal‐temperate ecotone
Authors: Fernandez Christopher W. , Nguyen Nhu H. , Stefanski Artur , Han Ying , Hobbie Sarah E. , Montgomery Rebecca A. , Reich Peter B. , Kennedy Peter G.
Published: September 2016

Rising temperatures associated with climate change have been shown to negatively affect the photosynthetic rates of boreal forest tree saplings at their southern range limits. To quantify the responses of ectomycorrhizal (EM) fungal communities associated with poorly performing hosts, we sampled the roots of Betula papyrifera and Abies balsamea saplings growing in the B4Warmed (Boreal Forest Warming at an Ecotone in Danger) experiment. EM fungi on the root systems of both hosts were compared from ambient and +3.4 °C air and soil warmed plots at two sites in northern Minnesota. EM fungal communities were assessed with high‐throughput sequencing along with measures of plant photosynthesis, soil temperature, moisture, and nitrogen. Warming selectively altered EM fungal community composition at both the phylum and genus levels, but had no significant effect on EM fungal operational taxonomic unit (OTU) diversity. Notably, warming strongly favored EM Ascomycetes and EM fungi with short‐contact hyphal exploration types. Declining host photosynthetic rates were also significantly inversely correlated with EM Ascomycete and EM short‐contact exploration type abundance, which may reflect a shift to less carbon demanding fungi due to lower photosynthetic capacity. Given the variation in EM host responses to warming, both within and between ecosystems, better understanding the link between host performance and EM fungal community structure will to clarify how climate change effects cascade belowground.
Development of mouse models of malignant phyllodes tumors by transplantation of syngeneic mammary gland cells expressing mutant H‐Ras
Authors: Takamoto Yayoi , Arima Yoshimi , Saya Hideyuki
Published: September 2016

Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast with epithelial and stromal components, and surgical resection is the standard and only available treatment for malignant PTs. To provide a better understanding of these tumors, we developed mouse models that recapitulate the pathological and clinical properties of human malignant PTs. Mouse undifferentiated mammary gland cells were infected with a retrovirus encoding the human oncoprotein H‐RasG12V, and the infected cells were transplanted orthotopically into the mammary fat pads of syngeneic mice. The transplanted cells showed a high tumorigenic activity, with the resulting tumors manifesting pathological characteristics including stromal overgrowth similar to those of human malignant PTs. The tumors also showed high rates of both local recurrence and lung metastasis. Our models may prove useful for studies of the pathophysiology of malignant PTs as well as facilitate the development of new treatments.
Highly multiplexed CRISPR‐Cas9‐nuclease and Cas9‐nickase vectors for inactivation of hepatitis B virus
Authors: Sakuma Tetsushi , Masaki Keiichi , Abe‐Chayama Hiromi , Mochida Keiji , Yamamoto Takashi , Chayama Kazuaki
Published: September 2016

CRISPR‐Cas9‐mediated genome‐editing technology contributes not only to basic genomic studies but also to clinical studies such as genetic correction and virus inactivation. Hepatitis B virus (HBV) is a major target for potential application of CRISPR‐Cas9 in eliminating viral DNA from human cells. However, the high stability of covalently closed circular DNA (cccDNA) makes it difficult to completely clear HBV infection. Here, we report highly multiplexed CRISPR‐Cas9‐nuclease and Cas9‐nickase vector systems that simultaneously target three critical domains of the HBV genome. Co‐transfection of an HBV‐expressing plasmid and all‐in‐one CRISPR‐Cas9 vectors resulted in significant reduction in viral replicative intermediates and extracellular hepatitis B surface and envelope antigens. In addition, successful fragmentation of the HBV genome was confirmed by DNA sequencing. Despite its high efficacy in suppressing HBV, no apparent off‐target mutations were detected by genomic cleavage detection assay and the small number of observed mutations was extremely rare and could only be detected by deep sequencing analysis. Thus, our all‐in‐one CRISPR‐Cas9‐nuclease and Cas9‐nickase vectors present a model for simultaneous targeting of multiple HBV domains, potentially contributing to a well‐designed therapeutic approach for curing HBV patients.
Dendritic transport element of human arc mRNA confers RNA degradation activity in a translation‐dependent manner
Authors: Ninomiya Kensuke , Ohno Mutsuhito , Kataoka Naoyuki
Published: September 2016

Localization of mRNA in neuronal cells is a critical process for spatiotemporal regulation of gene expression. Cytoplasmic localization of mRNA is often conferred by transport elements in 3′ untranslated region (UTR). Activity‐regulated cytoskeleton‐associated protein (arc) mRNA is one of the localizing mRNAs in neuronal cells, and its localization is mediated by dendritic targeting element (DTE). As arc mRNA has introns in its 3′ UTR, it was thought that arc mRNA is a natural target of nonsense‐mediated mRNA decay (NMD). Here, we show that DTE in human arc 3′ UTR has destabilizing activity of RNA independent of NMD pathway. DTE alone was able to cause instability of the reporter mRNA and this degradation was dependent on translation. Our results indicate that DTE has dual activity in mRNA transport and degradation, which suggests the novel spatiotemporal regulation mechanism of activity‐dependent degradation of the mRNA.
TIC y crecimiento de la productividad del trabajo en el África Subsahariana
Authors: WAMBOYE Evelyn , ADEKOLA Abel , SERGI Bruno
Published: September 2016

Se investigan los efectos de las TIC en la productividad del trabajo en 43 países subsaharianos. Se observa que el desarrollo de la telefonía fija y móvil celular estimula el crecimiento de la productividad en forma de retornos crecientes, lo cual confirma la presencia de efectos de red: cuando se duplica la tasa de penetración de la telefonía fija y de la móvil, el crecimiento de la productividad del trabajo aumenta en alrededor de 0,12–0,15 por ciento y 0,05 por ciento, respectivamente. La inclusión financiera aparece como uno de los posibles vectores de los efectos de la telefonía móvil en la productividad en los países estudiados.
Actitudes de los empleadores hacia los inmigrantes refugiados según una encuesta sueca
Authors: LUNDBORG Per , SKEDINGER Per
Published: September 2016

Sobre la base de una encuesta a gran escala de empresas suecas, los autores identifican una heterogeneidad significativa en las actitudes de los empleadores hacia los refugiados, su contratación, la fijación de sus salarios y la discriminación, aunque la experiencia de tener refugiados en plantilla reduce las actitudes negativas. Las razones de las empresas para dejar de contratar refugiados no tienen que ver con la discriminación por parte del personal nativo o los clientes, sino con su rendimiento. Si bien la mayoría de las empresas no considera el salario mínimo estipulado por convenio como un obstáculo importante a la contratación de refugiados, las empresas con un gran porcentaje de refugiados en plantilla declaran que reducirlo mejoraría sustancialmente el empleo.
Social Reproduction of Religiosity in the Immigrant Context: The Role of Family Transmission and Family Formation — Evidence from France
Authors: Soehl Thomas
Published: September 2016

This paper compares two aspects of the social reproduction of religion: parent-to-child transmission, and religious homogamy. Analysis of a survey of immigrants in France shows that for parent-to-child transmission, immigrant status/generation is not the central variable — rather, variation is across religions with Muslim families showing high continuity. Immigrant status/generation does directly matter for partner choice. In Christian and Muslim families alike, religious in-partnering significantly declines in the second generation. In turn, the offspring of religiously non-homogamous families is less religious. For Muslim immigrants this points to the possibility of a non-trivial decline in religiosity in the third generation.
Disaster nursing experiences of Chinese nurses responding to the Sichuan Ya'an earthquake
Authors: Li Y.H. , Li S.J. , Chen S.H. , Xie X.P. , Song Y.Q. , Jin Z.H. , Zheng X.Y.
Published: September 2016

Aim

The aim of this study was to investigate the disaster experiences of nurses called to assist survivors one month after the 2013 Ya'an earthquake.

Background

China has experienced an increasing number of earthquake disasters in the past four decades. Although a health and disaster management system was initiated after the 2008 Wenchuan earthquake, nurses' roles and experiences in a disaster have been overlooked.

Methods

The researchers used qualitative descriptive design that included 16 participants. Data were collected using semi‐structured interviews and observation notes, after which a qualitative content analysis was conducted.

Findings

Three major themes emerged: the process of being dispatched from hospitals to the disaster zone, the effort involved in getting to and working in the affected site and reflecting on the challenges they encountered.

Discussion

About half of the participants had received disaster nursing training before deploying to the disaster site, but they consistently expressed a lack of physical and psychological preparedness regarding the process of being dispatched from their hospitals to the disaster zone.

Limitations

This was a single‐incident experience. Caution should be taken when trying to extend the findings to other parts of China.

Conclusion

These findings highlighted the need for disaster in‐service training as well as for having disaster plans in place.

Implications for nursing and health policy

Hospital and nursing leaders should provide disaster training opportunities that included topics such as compiling resource inventories, formulating disaster drills and simulations, managing emergencies, and using emergency communication methods. Health policy‐makers should be required to prioritize capacity‐building training for front‐line nurses as well as to develop and implement disaster management plans to better prepare nurses for future disasters.
Dermal fillers: pathophysiology, prevention and treatment of complications
Authors: Chiang Y.Z. , Pierone G. , Al‐Niaimi F.
Published: September 2016

Dermal fillers are increasingly used for soft tissue augmentation of the face and hands. The widespread use of dermal fillers for rejuvenation has led to a rise in reports of associated complications. Although the majority of complications are mild and transient, serious and long‐lasting complications have been observed. This article discusses the key complications including pigmentary changes, hypersensitivity reactions, infections, nodule formation, granulomatous reactions, vascular occlusion and migration of filler material. A thorough literature review was performed in addition to the combined extensive authors’ (GP and FA) experience. Complications from fillers are increasingly being recognized and highlighted in the literature partly reflecting the growth in the market. This article provides a comprehensive overview of the filler complications with mechanisms of prevention and treatment per complication. A thorough understanding of the preventative and management strategies for the associated dermal filler complications will help the physician to prepare the patient well, and deal with complications that may arise effectively.
Nail involvement as a negative prognostic factor in biological therapy for psoriasis: a retrospective study
Authors: Bardazzi F. , Lambertini M. , Chessa M.A. , Magnano M. , Patrizi A. , Piraccini B.M.
Published: September 2016

Background

Psoriasis (Pso) has a strong impact on quality of life and a positive association has been reported between nail psoriasis (NP) and more severe disease, together with a longer duration of skin lesions. The treatment of NP represents a challenge and biological therapy can be recommended for severe disease.

Objective

The first end point of this retrospective study was to evaluate the time to achieve Psoriasis Area Severity Index (PASI) 75 in patients with and without NP treated with biological therapy. The second end point was to evaluate the efficacy of biological therapy to improve NP.

Methods

A total of 127 patients (88 men and 39 women) with moderate to severe Pso referring to our Service between 2007 and 2014 were included. Inclusion criteria were age ≥18 years and a 24 week treatment. The outcome variable was achievement of PASI 75 at 24 weeks with and without NP. All patients were treated with topical therapy and one of four different biological treatments: adalimumab (44.09%), etanercept (18.11%), infliximab (13.39%) and ustekinumab (24.41%). Physical examinations were performed every 4 weeks, and at each visit, the clinician assessed the PASI and Nail Psoriasis Severity Index (NAPSI).

Results

At multivariate Cox regression analysis, a smaller proportion of patients with NP achieved PASI 75 at 24 weeks than patients without NP when adjusted for the epidemiological, clinical features and biological treatment received. With all biological drugs, the NAPSI score began to improve already after 8 weeks (from 18.53 at week 0–2.83 at week 24).

Conclusion

Patients with NP reach PASI 75 more slowly than patients without NP. Clinicians should therefore consider that treatment with a biological agent may require a longer period before reaching a satisfying therapeutical goal. Nevertheless, adalimumab, infliximab, ustekinumab and etanercept demonstrated their equal effectiveness in reducing the NAPSI score.
The peri‐esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging
Authors: Weijs T. J. , Goense L. , van Rossum P. S. N. , Meijer G. J. , van Lier A. L. H. M. W. , Wessels F. J. , Braat M. N. G. , Lips I. M. , Ruurda J. P. , Cuesta M. A. , van Hillegersberg R. , Bleys R. L. A. W.
Published: September 2016

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri‐esophageal fascias have not been described and it is unclear whether this layer can be visualized by non‐invasive imaging. This study aimed to provide a comprehensive description of the peri‐esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2‐weightedMRIscanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri‐esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion‐triggeredMRIscans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualizedex vivoin the cadaver onMRimages, macroscopic tissue sections, and after histologic staining, as well as onin vivoMRimages. The layer connecting esophagus and aorta was named ‘aorto‐esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto‐pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri‐esophageal compartment’ and the posterior compartment ‘para‐aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long‐standing paradigm that no such structure exists. A comprehensive, detailed description of the peri‐esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualizedin vivobyMRI.
Does Exclusive Dealing Matter? Evidence from Distribution Contract Changes in The U.S. Beer Industry
Authors: Chen Chia‐Wen , Shieh Shiou
Published: September 2016

We examine whether restricting a beer distributor's external trading opportunities increases the market shares of brands carried by the distributor. We use distribution status changes from the Anheuser‐Busch‐InBev distribution agreement, along with a panel scanner data set from a grocery chain in California, to implement a ‘difference‐in‐differences’ empirical strategy. We find that InBev's market share increased by 6% once InBev was carried by Anheuser‐Busch's exclusive distributors, while InBev's retail price had no significant change. The effect on InBev's market share is stronger for smaller stores that carry more brands. These results are consistent with the efficiency‐based theory of exclusive dealing.
Diagnosing Foreclosure due to Exclusive Dealing
Authors: Asker John
Published: September 2016

Exclusive dealing arrangements, in which a distributor agrees to work exclusively with a single manufacturer, can be efficiency enhancing or can be an anticompetitive means to foreclose markets. This paper evaluates the effect of exclusive distribution arrangements on competition in the Chicago beer market in 1994. A diagnostic test is provided to judge whether exclusive arrangements lead to foreclosure. To implement this test a model of consumer demand and firm behavior is estimated that incorporates industry details and allows for distribution through exclusive and shared channels. The test indicates that foreclosure effects are not present in this market.
Fixed Costs and the Product Market Treatment of Preference Minorities
Authors: Berry Steven , Eizenberg Alon , Waldfogel Joel
Published: September 2016

We clarify the sense in which the market outcome may be biased against preference minorities, and estimate the degree of bias using an empirical model of entry into American radio broadcasting markets. Listening model estimates are used to infer fixed costs, and these estimates are then used to compute optimal station configurations as well as the welfare weights on different groups that rationalize the observed configuration. Welfare weights are 2 to 3 times higher for whites than for blacks, and 1.5 to 2 times higher for non‐Hispanic than for Hispanic, listeners. We explore the role of ‘importing’ and ‘exporting’ patterns in generating these findings.
A call for more diverse sources of data: Variationist approaches in non‐English contexts
Authors: Stanford James N.
Published: September 2016

Over the past 50 years, variationist sociolinguists have taken the influential ideas and pioneering methods of Labov () to many locations around the world. But the majority of variationist research still focuses on English and other European languages, rather than lesser‐studied language communities. Like other subfields of linguistics, the variationist paradigm needs to continually explore new data from a range of languages. The present article examines how the principles and methods of Labov () have been applied to non‐English language communities, testing the impact and relevance of those half‐century‐old notions in new and sociolinguistically diverse settings, and calling for more research in new field sites.
‘Oral versions of personal experience’: Labovian narrative analysis and its uptake
Authors: Johnstone Barbara
Published: September 2016

William Labov is known across the human and social sciences for his work on oral narratives about personal experience. This article provides an overview of that research and discusses its uptake and influence in linguistics and in other fields. Subsequent scholarship on narrative has critiqued Labov's model on the grounds that it privileges a certain genre of personal‐experience narrative and underplays the role of interlocutors and other contextual features in shaping oral narratives, but such scholarship inevitably borrows Labov's insight that the form of narrative is linked to its interactional functions. Narrative research in psychology and other fields often cites Labov without actually making much use of Labov's model, but Labovian narrative analysis has nonetheless had an enormous influence in making possible and legitimizing the study of everyday, vernacular narration.
Child cyclists: A study of factors affecting their safety
Authors: Bromell Rebecca J , Geddis David C
Published: September 2016

Aim

To study various factors that contribute to a child cyclist's risk of having, or being injured in the event of, an accident.

Methods

All children aged 8–12 years, attending four primary schools, who had access to a bicycle were invited to participate. The study consisted of: a questionnaire; a helmet and bicycle check (by professional cycle shop staff) and a practical assessment.

Results

Two hundred and ninety‐three children participated in one or more parts of the study. Of the 214 helmets checked, 41% were deemed ‘unsafe’. Forty‐one percent of 205 bicycles checked were not considered roadworthy. Of the 127 children who usually ride their bicycle to school, 59% had either a bicycle that was not considered roadworthy or a helmet that was judged ‘unsafe’. Of the 200 children, 91% knew the correct hand signals for a right and left turn. Eleven‐ and 12‐year‐olds were significantly better at performing the practical assessment than 8‐ to 10‐year‐olds (P < 0.0001).

Conclusions

Parents cannot assume that simply providing a cycle helmet and ensuring it is worn means a child will have maximum protection in the event of an accident. Calculations that base the safety benefits of cycle helmets on observation studies are likely to be underestimates. Regular checking of the roadworthiness of a child's bicycle is advised as simple things such as underinflated tyres or worn brake pads can adversely affect handling. There is no specific age at which it can be said a young child is ‘safe’ to ride unaccompanied on public roads.