bluuebunny/crossref_metadata_2025 huggingface dataset:
Home range establishment and utilization by reintroduced lions (Panthera leo) in a small South African wildlife reserve
Authors: YIU Sze‐Wing , PARRINI Francesca , KARCZMARSKI Leszek , KEITH Mark
Published: October 2016

Understanding of animal spatial behavior is essential for informed management decisions. In southern Africa, reintroduction of lions (Panthera leo) to small reserves (<1000 km2) has increased since the early 2000s, however studies on their ranging behavior in these enclosed systems remain lacking. We applied Time Local Convex Hull (T‐LoCoH) methods to study the home range establishment and utilization of 11 lions reintroduced to Dinokeng Game Reserve, South Africa, during 2011 through 2014. Lions established home ranges close to their release sites and during the following 3 years their home range sizes continued to increase, but in each individual case the size remained smaller than half of the reserve area (<70 km2). Space use strategies differed between the core and the entire home range, with higher frequency of visits found in core areas. Exceptionally high rates (>60 separate visits) around the largest dam and along rivers suggest the importance of water and its surrounding vegetation in the lions' space utilization pattern. The home range size did not differ with season or sex of the individuals, whereas shifts in locations of home ranges revealed differences in the response of the 2 sexes to territorial conflicts and management interventions. Our study shows a dynamic home range utilization pattern and highlights the importance of both fine‐scale space use patterns (frequency and duration of visits) and broad‐scale home range changes in understanding the ranging behavior of reintroduced animals.
The Earls of Derby and the Opposition to their Estate Bills in Parliament, 1660–92: Some New Manuscript Sources
Authors: Littleton Charles
Published: October 2016

The bills introduced in 1660–2 by Charles Stanley, 8th earl of Derby, to reclaim property legally conveyed during the interregnum are well known to students of the Restoration, as their ultimate defeat is seen as evidence of the government's wish to enforce ‘indemnity and oblivion’ after the civil war. The leading members of the house of lords opposed to the bill of 1661–2 can be gauged by the protest against its passage on 6 February 1662, which has been readily available to students to consult since the 18th‐century publication of the Lords journals. A number of manuscript lists of the protesters against the bill's passage reveal that the opposition to the bill was even more extensive and politically varied than the protest in the journal suggests, which raises questions of why the printed protest is so incomplete. A voting forecast drawn up by William Stanley, 9th earl of Derby, in 1691, further reminds us of the often‐neglected point that the Stanleys continued to submit bills for the resumption of their hereditary lands well after the disappointment of 1662. Derby's manuscript calculations, though ultimately highly inaccurate, reveal much about how this particular peer envisaged the forces ranged for and against the claims of an old civil war royalist family, a good 40 years after the loss of their land.
The Irish Parliamentary Diary (1776–89) of Sir Henry Cavendish
Authors: Thomas P.D.G.
Published: October 2016

This article clarifies the history of the ‘parliamentary diary’ compiled by Sir Henry Cavendish while a member of the Irish parliament between 1776 and 1789, correcting misapprehensions in previous accounts, in particular the assertion by A.P.W. Malcomson and D.J. Jackson that Cavendish paid less attention to recording debates in the 1780s.
Evaluation of the Penetration of Multiple Classes of Pesticides in Fresh Produce Using Surface‐Enhanced Raman Scattering Mapping
Authors: Yang Tianxi , Zhao Bin , Hou Ruyan , Zhang Zhiyun , Kinchla Amanda J. , Clark John M. , He Lili
Published: October 2016

Understanding pesticide penetration is important for effectively applying pesticides and in reducing pesticide exposures from food. This study aims to evaluate multiclass systemic and nonsystemic pesticide penetration in 3 representative fresh produce (apples, grapes, and spinach leaves). Surface‐enhanced Raman scattering mapping was applied for in situ and real‐time tracking of pesticide penetration over time. The results show that 100 mg/L of systemic pesticides, thiabendazole and acetamiprid, penetrated more rapidly and deeply with maximum depth around 220 μm after 48‐h exposure into the tested fresh produce than 100 mg/L of nonsystemic pesticides, ferbam and phosmet, with maximum depth about 80 μm. The fact that 2 nonsystemic pesticides were also able to penetrate over time into all 3 fresh produce tested may raise additional food safety concerns. Comparatively, grapes were generally more resistant for pesticide penetration with all pesticides penetration depth below 80 μm compared to apples and spinach leaves. The information obtained here could provide technical support and guidance for accurate, effective, and safe application of pesticides and for the reduction of pesticide exposure from fresh produce.
Diagnostic reference levels for digital mammography in New South Wales
Authors: Suleiman Moayyad E , McEntee Mark F , Cartwright Lucy , Diffey Jennifer , Brennan Patrick C
Published: October 2016

Introduction

This work aims to explore radiation doses delivered in screening mammography in Australia, with a focus on whether compressed breast thickness should be used as a guide when determining patient derived diagnostic reference levels (DRLs).

Methods

Anonymized mammograms (52,405) were retrieved from a central database, and DICOM headers were extracted using third party software. Women with breast implants, breast thicknesses outside 20–110 mm and images with incomplete exposure or quality assurance (QA) data were excluded. Exposure and QA information were utilized to calculate the mean glandular dose (MGD) for 45,054 mammograms from 61 units representing four manufacturers using previously well‐established methods. The 75th and 95th percentiles were calculated across median image MGDs obtained for all included data and according to specific compressed breast thickness ranges.

Results

The overall median image MGD, minimum, maximum were: 1.39, 0.19 and 10.00 mGy, respectively, the 75th and 95th percentiles across all units’ median image MGD for 60 ± 5 mm compressed breast thickness were 2.06 and 2.69 mGy respectively. Median MGDs, minimum, maximum, 75th and 95th percentiles were presented for nine compressed breast thickness ranges, DRLs for NSW are suggested for the compressed breast thickness range of 60 ± 5 mm for the whole study and three detector technologies CR, DR, and photon counting to be 2.06, 2.22, 2.04 and 0.79 mGy respectively.

Conclusion

MGD is dependent upon compressed breast thickness and it is recommended that DRL values should be specific to compressed breast thickness and image detector technology.
Intraspecific genetic variation in complex assemblages from mitochondrial metagenomics: comparison with DNA barcodes
Authors: Gómez‐Rodríguez Carola , Timmermans Martijn J. T. N. , Crampton‐Platt Alex , Vogler Alfried P.
Published: October 2016

Metagenomic shotgun sequencing, using Illumina technology, and de novo genome assembly of mixed field‐collected samples of invertebrates readily produce mitochondrial genome sequences, allowing rapid identification and quantification of species diversity. However, intraspecific genetic variability present in the specimen pools is lost during mitogenome assembly, which limits the utility of ‘mitochondrial metagenomics’ for studies of population diversity.

Using 10 natural communities (>2600 individuals) of leaf beetles (Chrysomelidae), DNA variation in the mitochondrial cox1‐5′ ‘barcode’ was compared for Sanger‐sequenced individuals and Illumina shotgun‐sequenced specimen pools.

Generally, only a single mitochondrial contig was assembled per species, even in the presence of intraspecific variation. Ignoring ambiguity from the use of two different assemblers, the cox1 barcode regions from these assemblies were exact nucleotide matches of a Sanger‐sequenced barcode in 90·7% of cases, which dropped to 76% in assemblies from samples with large intra‐ and interspecific variability. Nucleotide differences between barcodes from both data types were almost exclusively in synonymous 3rd codon positions, although the number of affected sites was very low, and the greatest discrepancies were correlated with poor quality of Sanger sequences.

Unassembled shotgun reads were also used to score single nucleotide polymorphisms and to calculate intraspecific nucleotide diversity (pi) for all available populations at each site. These values correlated with Sanger‐sequenced cox1 variation but were significantly higher.

Overall, the assemblage‐focused shotgun sequencing of pooled samples produced nucleotide variation data comparable to the well‐established specimen‐focused Sanger approach. The findings thus extend the application of mitochondrial metagenomics of complex biodiversity samples to the estimation of diversity below the species level.
Internal and contextual drivers of dairy restructuring: evidence from French mountainous areas and post‐quota prospects
Authors: Dervillé Marie , Allaire Gilles , Maigné Élise , Cahuzac Éric
Published: October 2016

The end of the milk quota system in Europe has resulted in substantial structural changes to the dairy industry, calling its future into question, especially in mountainous areas. This study analyzes the internal and contextual factors that influence dairy restructuring in French mountainous areas. Three complementary logit models are used to specify farmer decisions (e.g., dairy production exit, stability, and growth). Original and exhaustive geo‐located administrative datasets are combined to create a farm longitudinal dataset and characterize farm‐restructuring patterns on a fine geographical scale. Farm size, corporate legal status, and specialization are positively associated with farm growth. Viable diversification strategies through either farm processing or agro‐environmental scheme contracting are also highlighted. Farm sustainability is supported by the economic success of the local industry and the propensity to adopt extensive practices. With respect to public policy, dairy policy appears to have the strongest impact. Thus, the liberalization of dairy policy threatens the future of dairy farming, particularly in areas with low milk density and no production under labels. This work calls for a policy that promotes the collective dimension of dairy farm performance. The current rural development policy alone may be insufficient to support farms’ long‐term sustainability.
Assessing guideline adherence and patient outcomes in cervical cancer
Authors: Chiew Kim‐Lin , Chong Shanley , Duggan Kirsten J , Kaadan Nasreen , Vinod Shalini K
Published: October 2016

Aim

To investigate adherence to clinical practice guidelines (CPGs) in cervical cancer and the correlation with clinical outcomes.

Methods

A retrospective analysis was conducted using patient information from a population‐based cancer registry (2005–2011, n = 208). Compliance to 10 widely accepted CPGs was assessed. Univariate and multivariate analyses were performed to assess sociodemographic factors associated with CPG adherence. Multivariate Cox regression was performed to assess the relationship between CPG adherence and 5‐year survival.

Results

Adherence to individual CPGs ranged from 47% to 100%. Compliance to all applicable CPGs was seen in 54% (n = 72) of patients, 62% of stage I and II patients and 22% of stage III and IV patients. Poorest adherence was seen with those with locally advanced disease receiving chemoradiotherapy. Patients who lived within 5 km of the treatment facility were more likely to be compliant. No difference was found for either age, country of birth or socioeconomic status group. Five‐year survival was greater for stage I and II patients who received guideline adherent care (93.7% vs 69.7%, P = 0.002), and they had a significant lower risk of death on multivariate analysis (HR = 0.22, P = 0.015). There was no significant difference for those with stage III or IV disease.

Conclusions

In this study, CPG adherence is variable between treatment modalities and only half complied to all applicable CPGs. There was better adherence in those with early‐stage disease and this was associated with improved patient outcomes. CPG adherence may be a useful surrogate for quality of care.
Assessing the validity and response distribution of the simplified psoriasis index in patients receiving phototherapy
Authors: Meah Nekma , Alsharqi Ali , Azurdia Richard M , Owens Lynne‐Catherine , Parslew Richard , Chularojanamontri Leena
Published: October 2016

Background/Objectives

The simplified psoriasis index (SPI) is a three‐part multidimensional tool incorporating disease severity, psychosocial impact and historical course completed by the health‐care professional (professional SPI, [proSPI]) or the patient (self‐assessment SPI, [saSPI]). We aimed to assess the validity and response distribution of proSPI and saSPI in patients with psoriasis undergoing phototherapy.

Methods

The validity and response distribution of SPI was assessed by recording saSPI and proSPI in patients with psoriasis before and after a course of phototherapy. Recruitment ended once 100 complete data sets were available for analysis.

Results

Altogether 52 of the 100 patients evaluated were male and most (93) underwent narrowband UVB phototherapy. There was a close correlation between the proSPI‐current severity score (proSPI‐s) with the psoriasis area and severity index (PASI) score (r = 0.76, r = 0.86) before and after treatment, respectively. Although pretreatment correlation between the saSPI‐current severity score (saSPI‐s) and PASI was weak (r = 0.39), a more close correlation was noted at the end of treatment (r = 0.50). A moderate correlation was observed between the SPI‐psychosocial impact score (SPI‐p) and the dermatology life quality index (DLQI), both before and after phototherapy (r = 0.64, r = 0.73). The SPI had wide response distributions in all three domains.

Conclusions

Both versions of SPI demonstrated wide response distributions and the proSPI‐s in particular was shown to have good validity with PASI.
A randomised controlled trial comparing two popliteal nerve catheter tip positions for postoperative analgesia after day‐case hallux valgus repair
Authors: Ambrosoli A. L. , Guzzetti L. , Chiaranda M. , Cuffari S. , Gemma M. , Cappelleri G.
Published: October 2016

We compared the effect of two different positions of a sciatic nerve catheter within the popliteal fossa on local anaesthetic consumption and postoperative analgesia in patients undergoing day‐case hallux valgus repair. Eighty‐four patients were randomly allocated to receive a sciatic nerve catheter either between the tibial and peroneal components (sciatic group) or medial to the tibial nerve (tibial group). The primary endpoint was postoperative local anaesthetic consumption, while secondary endpoints were pain scores, number of occasions where sleep was disturbed by pain and incidence of insensate limb and foot drop at 24 h and 48 h postoperatively. Postoperative median (IQR [range]) local anaesthetic consumption was 126 (106–146 [98–180]) ml in the sciatic group versus 125 (114–158 [98–200]) ml in the tibial group (p = 0.103). Insensate limb occurred in 14 patients in the sciatic group versus one patient in the tibial group (p < 0.001), while foot drop was reported by six patients in the sciatic group and none in the tibial group (p = 0.012). Sciatic nerve catheter placement medial to the tibial nerve may be a superior analgesic technique for day‐case foot surgery.
Submucosal dissection has advantages over full‐thickness transanal endoscopic microsurgery in selected rectal lesions
Authors: Yap Kiryu , Mills Sarah , Thomas Michelle , Moore James
Published: October 2016

Background

To establish the incidence of unsuspected malignancy in lesions excised through transanal endoscopic microsurgery (TEM) and examine the justification for full‐thickness excision of all lesions thought to be benign pre‐operatively.

Methods

Demographic, operative and pathology data of all patients undergoing TEM at a single institution were collected in a prospectively maintained database. Follow‐up data were collected with a focus on polyp recurrence rates and outcome in patients found to harbour malignancy. For lesions thought to be benign pre‐operatively, a submucosal excision was routinely performed.

Results

TEM was attempted in 156 cases between June 1999 and April 2013. Mean (standard deviation) patient age was 66.8 (2.1) years, with 111 males. Mean tumour size was 4.1 (1.6) cm, and mean height from anal verge was 10.4 (2.1) cm. In nine cases, the procedure was unable to be completed and in eight cases a deliberate full‐thickness excision was performed. In 139 patients with a presumed benign lesion, mean operating time was 53.4 min. A total of 17 (12.2%) were found to harbour an unsuspected malignancy. Recurrent polyp was seen in 14 (11.7%) of 122 cases of benign pathology (mean follow‐up 24.5 months) and was managed by endoscopic means in 10 patients. Mean length of stay was 1.2 days and complications occurred in 7% of cases. No patient with an unsuspected malignancy has developed recurrent disease (mean follow‐up 43 months).

Conclusion

Submucosal TEM can result in low complication rates, short duration of surgery, short hospital stay and satisfactory recurrence rates when performed for presumed benign rectal tumours.
A comprehensive renal vascular access clinic results in improved patient outcomes and reduced costs
Authors: Thomas Shannon D. , Ip Eugenia C. , Katib Nedal , Pugh Debbie , Lennox Andrew , Endre Zoltan , Tan Elaine , Ellery Chris , Varcoe Ramon L.
Published: October 2016

Background

Management of vascular access for haemodialysis is a leading cause of morbidity and hospitalization in patients with end‐stage renal disease. We sought to evaluate the change in admission and procedural outcomes before and after the establishment of a vascular surgeon‐led comprehensive renal vascular access clinic (RVAC).

Method

A retrospective clinical study was conducted after an RVAC was established in January 2013, with retrospective database created for the 24‐month period prior to and after.

Results

The number of inpatient encounters for haemodialysis vascular access care fell over identical time periods before (n = 193) and after (n = 164) the RVAC was established. This reduction was associated with a significant decrease in length of stay (from 10.71 to 3.14 days; P = 0.0056) and thrombosed access procedures (from 32 to 16; P = 0.048). The proportion of emergency procedures fell (from 54.5 to 25.4%; P = 0.002) with a trend towards less arteriovenous fistula formations in the latter group (from 75 to 49; P = 0.099). There was also a trend towards fewer procedures in the latter group (from 195 to 151; P = 0.22). A case‐mix costing analysis showed an estimated reduction in mean admission cost from $25 883.15 to $9332.81 for those 2‐year periods, equating to a saving of $3.46 million associated with the introduction of the clinic.

Conclusion

The establishment of an RVAC has led to a variety of objective performance outcome improvements, including a decrease in hospital admission, length of stay, revision and emergency surgeries, with associated cost saving. It reflects positive outcomes observed in other surgical specialties’ clinics.
Detection of fetal abnormalities by second‐trimester ultrasound screening in a non‐selected population
Authors: Rydberg Catharina , Tunón Katarina
Published: October 2016

Introduction

This study assessed the sensitivity of routine ultrasound examination for the detection of abnormal chromosomes and structural malformations in fetuses in the second trimester in a non‐selected population.

Material and methods

Prenatal diagnoses of fetal abnormalities in 10 414 fetuses and newborns were reviewed and compared with all postnatal diagnoses of congenital abnormalities between 2006 and 2013.

Results

Overall, 243 fetuses and newborns had confirmed congenital abnormalities, with a prevalence of 2.3%. Of these fetuses and newborns, 23% (56/243) had chromosomal abnormalities (overall prevalence 0.5%), and 77% (187/243) had normal chromosomes with either major (44%; 82/187) or minor (56%; 105/187) structural malformations (overall prevalence 1.8%). One hundred and seven abnormalities were detected prenatally, yielding a total sensitivity for prenatal detection of fetal abnormalities of 44.0% (107/243; 95% CI 37.8–50.2), with specificity of 99.9%, a positive predictive value of 94.7%, and a negative predictive value of 98.7%. The sensitivity for prenatal detection before 22 weeks of gestation was 40.3% (98/243; 95% CI 34.1–46.5). The prenatal detection rate of chromosomal abnormalities was 60.7% (34/56) and, for structural malformations, was 39.0% (73/187).

Conclusions

In a routine clinical setting at a county hospital with a non‐selected population, half of the major structural malformations in chromosomally normal fetuses are detected by routine ultrasound examination in the second trimester. Chromosomal abnormalities have the highest probability for prenatal detection; the majority are diagnosed by amniocentesis before the routine ultrasound examination in high‐risk women.
Both high expression of nucleophosmin/B23 and CRM1 predicts poorer prognosis in human gastric cancer
Authors: Zhou Fang , Chen Ercheng , You Dong , Song Yipeng , Sun Zhenni , Yue Lu
Published: October 2016

Nucleophosmin/B23 and CRM1 are molecular markers which play an important role in tumorigenesis and tumor progression in gastric cancer (GC). However, the association between the two remains unclear. This study evaluated the expression and the correlation of B23 and CRM1 in GC. B23 and CRM1 expression in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 131 GC patients was measured by immunohistochemistry. Positive expression rates of B23 and CRM1 were significantly higher in GC tissues than in ANCT. The high expression rates of B23 and CRM1 were significantly higher in patients with more advanced tumor stages and distant metastasis (all p < 0.05). Only high expression of CRM1was correlated with positive Her2 status (p = 0.01). B23 expression was positively correlated with CRM1expression in GC tissues (p = 0.038). Univariate analysis showed that TNM stage (p = 0.0001), metastasis (p = 0.027), B23 (p = 0.0111), and CRM1 expression (p = 0.0019) were significant risk factors affecting overall survival. Both high expression of B23 and CRM1 in GC patients suggests poor prognosis, co‐expression of the two (p = 0.043) even worse. Cox multivariate analysis showed that positive B23 (p = 0.0231) and CRM1 (p = 0.0048) expression were both independent prognostic factors that negatively correlated with survival. We revealed the co‐expression of B23 or CRM1 in GC. The expression levels of B23 or CRM1 were closely related to poor prognosis in GC, and both B23 or CRM1 were independent risk factor.
Traditional Chinese medicine for schizophrenia: A survey of randomized trials
Authors: Deng Hongyong , Adams Clive E.
Published: October 2016

Objective

To survey the reports of randomized trials of traditional Chinese medicine (TCM) interventions for schizophrenia and produce a broad overview of this type of research activity in this area.

Method

We searched the Cochrane Schizophrenia Group's comprehensive Trials Register (January 2016), selected all relevant randomized trials, and extracted the data within each study. Finally, we sought relevant reviews on the Cochrane Library.

Results

We initially screened 423 articles from which we identified 378 relevant studies randomizing 35 341 participants (average study size 94, SD 60). There were 7 herbs used as single medicine, 4 compositions or extractions, more than 144 herbal mixes, and 7 TCM principles reported for schizophrenia. Nonpharmacological interventions of TCM included acupuncture and exercise. The most commonly evaluated treatments are Ginkgo biloba, acupuncture, Wendan decoction, and Shugan Jieyu Capsule. There are 3 directly relevant Cochrane reviews.

Conclusions

Most treatment approaches—and some in common use—have only one or two relevant small trials. Some coordination of effort would help ensure that further well‐designed appropriately sized randomized trials are conducted. Systematic reviews should be performed in this field but with titles that take into account the complexity of TCM.
The politics of water democracy: insights from grassroot struggles in the Ecuadorian Highlands
Authors: Hoogesteger Jaime
Published: October 2016

In the past two decades spaces for user participation have been opened within water governance structures at many scales. In this contribution, based on a case study of the Provincial Water Users Federation Interjuntas‐Chimborazo in the Ecuadorian Highlands, I explore how and why formal participation of water users in itself is problematic in terms of democracy. The case shows that for organised peasant water users to work on more democratic water governance, the creation of upscaled federations, alliances, networks and sometimes street protests is crucial to open up spaces in which their interests are represented. This suggests that democracy is not merely about participation, but more importantly, it is about the politics of how democracy is made through conflicts, protests, negotiations and the creation of strategic alliances that challenge the structures and processes through which decisions are taken.
Land‐use legacies and the role of persistence traits in species recovery
Authors: Fraterrigo Jennifer M.
Published: October 2016

Modern‐day plant communities often retain imprints of intensive past land use. Do low‐intensity land‐use practices also produce legacies? In this issue, Jonason et al. (Applied Vegetation Science) demonstrate that, 80 yrs after grassland abandonment, meadow species can recover if habitat improves. I interpret these findings in the context of the spatiotemporal processes that shape regional‐scale population dynamics.
Characterization of human cytochrome P450 mediated bioactivation of amodiaquine and its major metabolite N‐desethylamodiaquine
Authors: Zhang Yongjie , Vermeulen Nico P. E. , Commandeur Jan N. M.
Published: October 2016

Aims

Oxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a reactive quinoneimine is considered as an important mechanism underlying its idiosyncratic hepatotoxicity. However, because internal exposure to its major metabolite N‐desethylamodiaquine (DEAQ) is up to 240‐fold higher than AQ, bioactivation of DEAQ might significantly contribute to covalent binding. The aim of the present study was to compare the kinetics of bioactivation of AQ and DEAQ by human liver microsomes (HLM) and to characterize the CYPs involved in bioactivation of AQ and DEAQ.

Methods

Glutathione was used to trap reactive metabolites formed in incubations of AQ and DEAQ with HLM and recombinant human cytochrome P450s (hCYPs). Kinetics of bioactivation of AQ and DEAQ in HLM and involvement of hCYPs were characterized by measuring corresponding glutathione conjugates (AQ‐SG and DEAQ‐SG) using a high‐performance liquid chromatography method.

Results

Bioactivation of AQ and DEAQ in HLM both exhibited Michaelis–Menten kinetics. For AQ bioactivation, enzyme kinetical parameters were Km, 11.5 ± 2.0 μmol l–1, Vmax, 59.2 ± 3.2 pmol min−1 mg−1 and CLint, 5.15 μl min−1 mg−1. For DEAQ, parameters for bioactivation were Km, 6.1 ± 1.3 μmol l–1, Vmax, 5.5 ± 0.4 pmol min−1 mg−1 and CLint 0.90 μl min−1 mg−1. Recombinant hCYPs and inhibition studies with HLM showed involvement of CYP3A4, CYP2C8, CYP2C9 and CYP2D6 in bioactivation.

Conclusions

The major metabolite DEAQ is likely to be quantitatively more important than AQ with respect to hepatic exposure to reactive metabolites in vivo. High expression of CYP3A4, CYP2C8, CYP2C9, and CYP2D6 may be risk factors for hepatotoxicity caused by AQ‐therapy.
Effects of policy interventions on the introduction of novel oral anticoagulants in Stockholm: an interrupted time series analysis
Authors: Komen Joris , Forslund Tomas , Hjemdahl Paul , Andersen Morten , Wettermark Björn
Published: October 2016

Aims

The aim of the present study was to assess the effect of policy interventions – i.e. reimbursement decisions, guidelines and regional recommendations – on the prescribing of oral anticoagulant treatment in patients with atrial fibrillation (AF).

Methods

Interrupted time series analyses were carried out using monthly data on all patients with a recorded diagnosis of AF newly initiated (switchers and anticoagulant‐naïve patients alike) on warfarin, dabigatran, rivaroxaban or apixaban in the Stockholm region from April 2011 until February 2016.

Results

A total of 34 165 initiations in 27 942 patients were included. The publication of the European Guidelines was associated with an increase in novel oral anticoagulant (NOAC) initiations of 12.5% [95% confidence interval (CI) 7.3, 17.7] after 5 months. The choice between the different NOACs was mainly associated with changes in the regional recommendations, with apixaban initiations increasing by 19.5% (95% CI 16.3, 22.7) 5 months after the drug was recommended as a first‐line alternative to warfarin. Dabigatran received a second‐line recommendation but initiations decreased by −9.5% (95% CI −12.6, –6.4), and initiations of rivaroxaban, which had no specific recommendation, decreased by −9.2% (95% CI −12.7, –5.7). A steady decrease in warfarin and increase in NOAC initiations was seen throughout the study period and from November 2015, AF patients were more likely to receive apixaban than any other anticoagulant, while less than 20% of the initiations were with warfarin.

Conclusions

After reimbursement and inclusion in the European guidelines, the NOACs started gaining in popularity, while changes in regional recommendations were associated with the biggest change in prescribers’ choice between the different NOACs.
Long‐term Use of Z‐Hypnotics and Co‐medication with Benzodiazepines and Opioids
Authors: Sakshaug Solveig , Handal Marte , Hjellvik Vidar , Berg Christian , Ripel Åse , Gustavsen Ingebjørg , Mørland Jørg , Skurtveit Svetlana
Published: October 2016

Benzodiazepine‐like drugs (z‐hypnotics) are the most commonly used drugs for treatment of insomnia in Norway. Z‐hypnotics are recommended for short‐term treatment not exceeding 4 weeks. We aimed to study the use of z‐hypnotics in the adult population in Norway with focus on recurrent use in new users, treatment intensity and co‐medication with benzodiazepines and opioids in long‐term users. Data were obtained from the Norwegian Prescription Database. New users in 2009 were followed through 2013. Recurrent z‐hypnotic use was defined as new fillings at least once in each of the four 365‐day follow‐up periods. Age groups of 18–39, 40–64 and 65+ years were analysed separately for men and women. In 2013, 354,571 (8.9%) of the population filled at least one prescription of z‐hypnotics and the prevalence was relatively stable over time. Among the 92,911 new users of z‐hypnotics in 2009, 13,996 (16.8%) received z‐hypnotics all four 365‐day periods of follow‐up. In these long‐term recurrent users, the treatment intensity was high already the second year, with mean annual amounts of 199 and 169 DDDs per patient in men and women, respectively. The interquartile differences were greatest in the youngest age group. 27.9% of the long‐term recurrent users of z‐hypnotics used benzodiazepines the fourth year and 33.9% used opioids. The proportions with co‐medication increased with level of z‐hypnotic treatment intensity. Overall, many z‐hypnotic users had medicines dispensed for longer periods than recommended, and co‐medications with drugs that may reinforce the central depressing and intoxicating effects were common.
Predictors of anticoagulation quality in 15 834 patients performing patient self‐management of oral anticoagulation with vitamin K antagonists in real‐life practice: a survey of the International Self‐Monitoring Association of Orally Anticoagulated Patients
Authors: Schaefer Christian , Wuillemin Walter A. , Kessels Alfons , Jacobson Alan , Nagler Michael
Published: October 2016

Although patient self‐management (PSM) of oral anticoagulation with vitamin K antagonists is recommended for patients requiring long‐term anticoagulation, important aspects are still unclear. Using data from a large international survey (n = 15 834; median age 72 years; 30·1% female), we studied predictors of poor anticoagulation control (percentage of International Normalized Ratio values within therapeutic range below 75%) and developed a simple prediction model. The following variables were identified as risk factors for poor anticoagulation control and included in the final model: higher intensity of therapeutic range (odds ratio [OR] on every level 1·9; 95% confidence interval [CI] 1·8–2·0), long intervals between measurements (>14 d; 1·5; 95% CI 1·3–1·7), female sex (OR 1·3; 95% CI 1·2–1·4), and management other than PSM (OR 1·4; 95% CI 1·2–1·6). At a threshold of 0·2 (at least one variable present), the model predicted poor anticoagulation control with a sensitivity of 85·3% (95% CI: 84·0, 86·4) and a specificity of 28·5% (27·6, 29·5). The area under the receiver operated characteristic curve was 0·65. Using the proposed prediction model, physicians will be able to identify patients with a low chance of performing well, considering additional training, regular follow‐up, or adjustment of therapeutic ranges.
Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from unmanipulated, haploidentical donors compared with that from matched sibling donors for patients with haematological malignancies
Authors: Li Hong‐Hua , Li Fei , Gao Chun‐Ji , Huang Wen‐Rong , Bo Jian , Dou Li‐Ping , Wang Li‐Li , Jing Yu , Wang Lu , Li Wen‐Jun , Yu Li , Liu Dai‐Hong
Published: October 2016

The features of graft‐versus‐host disease (GVHD) were compared between patients who underwent myeloablative conditioning and received a peripheral blood stem cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched sibling donor (MSD) during the same period of time. The HID group included more patients with advanced disease. Both groups received the same GVHD prophylaxis with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative incidences (CI) of acute GVHD grade 2–4 (35·1% vs. 13·9%, P = 0·003), similar CI of grade 3–4 (14·5% vs. 9·8%, P = 0·595), less 3‐year CI of extensive chronic GVHD (17·1% vs. 41·5%, P = 0·017) and less severe chronic GVHD (5·8% vs. 21·2%, P = 0·049) occurred in the HID group compared with the MSD group. There was no difference in the sites of the involved organs between these two groups. Higher 3‐year CI of non‐relapse mortality (24·0% vs. 10·2%, P = 0·014), relapse (39·0% vs. 22·6%, P = 0·032) and inferior disease‐free survival (45·7% vs. 78·9%, P = 0·000) were recorded in the HID cohort compared with the MSD group. More HID patients had Karnofsky scores above 90 than those in MSD group (P = 0·016). In conclusion, ATG plays a key role in the unmanipulated HID PBSCT protocol, producing better quality of life in survivors.
Histamine H4 receptor agonist‐induced relief from painful peripheral neuropathy is mediated by inhibition of spinal neuroinflammation and oxidative stress
Authors: Sanna Maria Domenica , Lucarini Laura , Durante Mariaconcetta , Ghelardini Carla , Masini Emanuela , Galeotti Nicoletta
Published: October 2016

Background and Purpose

Neuropathic pain is under‐treated, with a detrimental effect on quality of life, partly because of low treatment efficacy, but also because pathophysiological mechanisms are not fully elucidated. To clarify the pathobiology of neuropathic pain, we studied the contribution of neuroinflammation and oxidative stress in a model of peripheral neuropathy. We also assessed an innovative treatment for neuropathic pain by investigating the effects of histamine H4 receptor ligands in this model.

Experimental Approach

A peripheral mononeuropathy was induced in mice, by spared nerve injury (SNI). Neuroinflammation and oxidative stress parameters were evaluated by spectrophotometry. The mechanical (von Frey test) and thermal (plantar test) nociceptive thresholds were evaluated.

Key Results

SNI mice showed increased expression of the pro‐inflammatory cytokines IL‐1ß and TNF‐α, decreased antioxidant enzyme Mn‐containing SOD (MnSOD), increased levels of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), an indicator of oxidative DNA damage, and of PARP, nuclear enzyme activated upon DNA damage. Intrathecal administration of VUF 8430 (H4 receptor agonist) reversed the mechanical and thermal allodynia and was associated with decreased expression of IL‐1ß, TNF‐α, 8‐OHdG and PARP and with restoration of MnSOD activity in the spinal cord and sciatic nerve. These effects were prevented by JNJ 10191584 (H4 receptor antagonist).

Conclusion and Implications

In the SNI mouse model of neuropathic pain, neuronal H4 receptor stimulation counteracts hyperalgesia and reduces neuroinflammation and oxidative stress in the spinal cord and sciatic nerve. Targeting both oxidative stress and pro‐neuroinflammatory pathways through H4 receptor‐mediated mechanisms could have promising therapeutic potential for neuropathic pain management.
Role of oxidative stress in oxaliplatin‐induced enteric neuropathy and colonic dysmotility in mice
Authors: McQuade Rachel M , Carbone Simona E , Stojanovska Vanesa , Rahman Ahmed , Gwynne Rachel M , Robinson Ainsley M , Goodman Craig A , Bornstein Joel C , Nurgali Kulmira
Published: October 2016

Background and Purpose

Oxaliplatin is a platinum‐based chemotherapeutic drug used as a first‐line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side‐effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility.

Experimental Approach

Oxaliplatin (3 mg·kg−1 per day) was administered in vivo to Balb/c mice intraperitoneally three times a week. The distal colon was collected at day 14 of treatment. Immunohistochemistry was performed in wholemount preparations of submucosal and myenteric ganglia. Neuromuscular transmission was studied by intracellular electrophysiology. Circular muscle tone was studied by force transducers. Colon propulsive activity studied in organ bath experiments and faeces were collected to measure water content.

Key Results

Chronic in vivo oxaliplatin treatment resulted in increased formation of reactive oxygen species (O2ˉ), nitration of proteins, mitochondrial membrane depolarisation resulting in the release of cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment enhanced NO‐mediated inhibitory junction potentials and altered the response of circular muscles to the NO donor, sodium nitroprusside. It also reduced the frequency of colonic migrating motor complexes and decreased circular muscle tone, effects reversed by the NO synthase inhibitor, Nω‐Nitro‐L‐arginine.

Conclusion and Implications

Our study is the first to provide evidence that oxidative stress is a key player in enteric neuropathy and colonic dysmotility leading to symptoms of chronic constipation observed in oxaliplatin‐treated mice.
Why did heterospory evolve?
Authors: Petersen Kurt B. , Burd Martin
Published: October 2016

The primitive land plant life cycle featured the production of spores of unimodal size, a condition called homospory. The evolution of bimodal size distributions with small male spores and large female spores, known as heterospory, was an innovation that occurred repeatedly in the history of land plants. The importance of desiccation‐resistant spores for colonization of the land is well known, but the adaptive value of heterospory has never been well established. It was an addition to a sexual life cycle that already involved male and female gametes. Its role as a precursor to the evolution of seeds has received much attention, but this is an evolutionary consequence of heterospory that cannot explain the transition from homospory to heterospory (and the lack of evolutionary reversal from heterospory to homospory). Enforced outcrossing of gametophytes has often been mentioned in connection to heterospory, but we review the shortcomings of this argument as an explanation of the selective advantage of heterospory. Few alternative arguments concerning the selective forces favouring heterospory have been proposed, a paucity of attention that is surprising given the importance of this innovation in land plant evolution. In this review we highlight two ideas that may lead us to a better understanding of why heterospory evolved. First, models of optimal resource allocation – an approach that has been used for decades in evolutionary ecology to help understand parental investment and other life‐history patterns – suggest that an evolutionary increase in spore size could reach a threshold at which small spores yielding small, sperm‐producing gametophytes would return greater fitness per unit of resource investment than would large spores and bisexual gametophytes. With the advent of such microspores, megaspores would evolve under frequency‐dependent selection. This argument can account for the appearance of heterospory in the Devonian, when increasingly tall and complex vegetative communities presented competitive conditions that made large spore size advantageous. Second, heterospory is analogous in many ways to anisogamy. Indeed, heterospory is a kind of re‐invention of anisogamy within the context of a sporophyte‐dominant land plant life cycle. The evolution of anisogamy has been the subject of important theoretical and empirical investigation. Recent work in this area suggests that mate‐encounter dynamics set up selective forces that can drive the evolution of anisogamy. We suggest that similar dispersal and mating dynamics could have underlain spore size differentiation. The two approaches offer predictions that are consistent with currently available data but could be tested far more thoroughly. We hope to re‐establish attention on this neglected aspect of plant evolutionary biology and suggest some paths for empirical investigation.
How lichens impact on terrestrial community and ecosystem properties
Authors: Asplund Johan , Wardle David A.
Published: October 2016

Lichens occur in most terrestrial ecosystems; they are often present as minor contributors, but in some forests, drylands and tundras they can make up most of the ground layer biomass. As such, lichens dominate approximately 8% of theEarth's land surface. Despite their potential importance in driving ecosystem biogeochemistry, the influence of lichens on community processes and ecosystem functioning have attracted relatively little attention. Here, we review the role of lichens in terrestrial ecosystems and draw attention to the important, but often overlooked role of lichens as determinants of ecological processes. We start by assessing characteristics that vary among lichens and that may be important in determining their ecological role; these include their growth form, the types of photobionts that they contain, their key functional traits, their water‐holding capacity, their colour, and the levels of secondary compounds in their thalli. We then assess how these differences among lichens influence their impacts on ecosystem and community processes. As such, we consider the consequences of these differences for determining the impacts of lichens on ecosystem nutrient inputs and fluxes, on the loss of mass and nutrients during lichen thallus decomposition, and on the role of lichenivorous invertebrates in moderating decomposition. We then consider how differences among lichens impact on their interactions with consumer organisms that utilize lichen thalli, and that range in size from microfauna (for which the primary role of lichens is habitat provision) to large mammals (for which lichens are primarily a food source). We then address how differences among lichens impact on plants, through for example increasing nutrient inputs and availability during primary succession, and serving as a filter for plant seedling establishment. Finally we identify areas in need of further work for better understanding the role of lichens in terrestrial ecosystems. These include understanding how the high intraspecific trait variation that characterizes many lichens impacts on community assembly processes and ecosystem functioning, how multiple species mixtures of lichens affect the key community‐ and ecosystem‐level processes that they drive, the extent to which lichens in early succession influence vascular plant succession and ecosystem development in the longer term, and how global change drivers may impact on ecosystem functioning through altering the functional composition of lichen communities.
The odd couple: Richard Hartshorne and William Bunge
Authors: Barnes Trevor J.
Published: October 2016

Key Messages

Drawing on personal correspondence can enhance histories of geography.

Adding “backstage” histories of geography to conventional “frontstage” versions demonstrates the effect that private relationships can have on public scholarship.
Different Styles for Different Needs – The Effect of Cognitive Styles on Idea Generation
Authors: Lomberg Carina , Kollmann Tobias , Stöckmann Christoph
Published: October 2016

Researchers are engaged in finding the precursors for innovation. Drawing on Kirton's Adaption‐Innovation (KAI) Inventory, we explicitly test Kirton's central premise that cognitive styles differentiate between preferences for producing ideas in a certain way. We argue that the generation of either a magnitude or original ideas is governed by different underlying cognitive styles. In a study with 191 individuals, we find that the cognitive style originality associates with ideational fluency whereas the rule governance style associates with the generation of original ideas. By providing a cognitive explanation for how ideas are generated, we deepen the understanding of the idea generation process. This is particularly important for the future use of the KAI and for organizations that strive to be innovative.
A Lattice Model of the Development of Reading Comprehension
Authors: Connor Carol McDonald
Published: October 2016

In this article, I present a developmental model of how children learn to comprehend what they read, which builds on current models of reading comprehension and integrates findings from instructional research and evidence‐based models of development in early and middle childhood. The lattice model holds that children's developing reading comprehension is a function of the interacting, reciprocal, and bootstrapping effects of developing text‐specific, linguistic, and social‐cognitive processes, which interact with instruction as Child Characteristic × Instruction (C × I) interaction effects. The processes develop over time and in the context of classroom, home, peer, community, and other influences to affect children's development of proficient reading comprehension. First, I describe models of reading comprehension; then, I review the basic processes in the model, the role of instruction, and C × I interactions in the context of the lattice model. Finally, I discuss implications for instruction and research.