bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating invasive species policies across ornamental horticulture supply chains to prevent plant invasions
Authors: Hulme Philip E. , Brundu Giuseppe , Carboni Marta , Dehnen‐Schmutz Katharina , Dullinger Stefan , Early Regan , Essl Franz , González‐Moreno Pablo , Groom Quentin J. , Kueffer Christoph , Kühn Ingolf , Maurel Noëlie , Novoa Ana , Pergl Jan , Pyšek Petr , Seebens Hanno , Tanner Rob , Touza Julia M. , van Kleunen Mark , Verbrugge Laura N.H.
Published: June 2017

Ornamental horticulture is the primary pathway for invasive alien plant introductions. We critically appraise published evidence on the effectiveness of four policy instruments that tackle invasions along the horticulture supply chain: pre‐border import restrictions, post‐border bans, industry codes of conduct and consumer education.

Effective pre‐border interventions rely on rigorous risk assessment and high industry compliance. Post‐border sales bans become progressively less effective when alien species become widespread in a region.

A lack of independent performance evaluation and of public disclosure, limits the uptake and effectiveness of voluntary codes of conduct and discourages shifts in consumer preference away from invasive alien species.

Policy implications. Closing the plant invasion pathway associated with ornamental horticulture requires government‐industry agreements to fund effective pre‐ and post‐border weed risk assessments that can be subsequently supported by widely adopted, as well as verifiable, industry codes of conduct. This will ensure producers and consumers make informed choices in the face of better targeted public education addressing plant invasions.
Generalized spatial mark–resight models with an application to grizzly bears
Authors: Whittington Jesse , Hebblewhite Mark , Chandler Richard B.
Published: June 2017

The high cost associated with capture–recapture studies presents a major challenge when monitoring and managing wildlife populations. Recently developed spatial mark–resight (SMR) models were proposed as a cost‐effective alternative because they only require a single marking event. However, existingSMRmodels ignore the marking process and make the tenuous assumption that marked and unmarked populations have the same encounter probabilities. This assumption will be violated in most situations because the marking process results in different spatial distributions of marked and unmarked animals.

We developed a generalizedSMRmodel that includes sub‐models for the marking and resighting processes, thereby relaxing the assumption that marked and unmarked populations have the same spatial distributions and encounter probabilities.

Our simulation study demonstrated that conventionalSMRmodels produce biased density estimates with low credible interval coverage (CIC) when marked and unmarked animals had differing spatial distributions. In contrast, generalizedSMRmodels produced unbiased density estimates with correct CIC in all scenarios.

We applied ourSMRmodel to grizzly bear (Ursus arctos) data where the marking process occurred along a transportation route through Banff and Yoho National Parks, Canada. Twenty‐two grizzly bears were trapped, fitted with radiocollars and then detected along with unmarked bears on 214 remote cameras. Closed population density estimates (posterior median ± 1SD) averaged from 2012 to 2014 were much lower for conventionalSMRmodels (7.4 ± 1.0 bears per 1,000 km2) than for generalizedSMRmodels (12.4 ± 1.5). When compared to previousDNA‐based estimates, conventionalSMRestimates erroneously suggested a 51% decline in density. Conversely, generalizedSMRestimates were similar to previous estimates, indicating that the grizzly bear population was relatively stable.

Synthesis and applications. Mark–resight studies often cost less than capture–recapture studies, but require that marked and unmarked animals have equal encounter rates. Generalized spatial mark–resight models relax this assumption by including sub‐models for both the marking and resighting processes. They produce unbiased density estimates even when marked and unmarked animals have differing spatial distributions and encounter rates. They thus provide a cost‐effective and widely applicable approach for estimating the density of wildlife populations.
Herbivores safeguard plant diversity by reducing variability in dominance
Authors: Mortensen Brent , Danielson Brent , Harpole W. Stanley , Alberti Juan , Arnillas Carlos Alberto , Biederman Lori , Borer Elizabeth T. , Cadotte Marc W. , Dwyer John M. , Hagenah Nicole , Hautier Yann , Peri Pablo Luis , Seabloom Eric W.
Published: June 2017

Reductions in community evenness can lead to local extinctions as dominant species exclude subordinate species; however, herbivores can prevent competitive exclusion by consuming otherwise dominant plant species, thus increasing evenness. While these predictions logically result from chronic, gradual reductions in evenness, rapid, temporary pulses of dominance may also reduce species richness. Short pulses of dominance can occur as biotic or abiotic conditions temporarily favour one or a few species, manifested as increased temporal variability (the inverse of temporal stability) in community evenness. Here, we tested whether consumers help maintain plant diversity by reducing the temporal variability in community evenness.

We tested our hypothesis by reducing herbivore abundance in a detailed study of a developing, tallgrass prairie restoration. To assess the broader implications of the importance of herbivory on community evenness as well as potential mechanisms, we paired this study with a global herbivore reduction experiment.

We found that herbivores maintained plant richness in a tallgrass prairie restoration by limiting temporary pulses in dominance by a single species. Dominance by an annual species in a single year was negatively associated with species richness, suggesting that short pulses of dominance may be sufficient to exclude subordinate species.

The generality of this site‐level relationship was supported by the global experiment in which inter‐annual variability in evenness declined in the presence of vertebrate herbivores over timeframes ranging in length from 2 to 5 years, preventing declines in species richness. Furthermore, inter‐annual variability of community evenness was also negatively associated with pre‐treatment species richness.

Synthesis. A loss or reduction of herbivores can destabilize plant communities by allowing brief periods of dominance by one or a few species, potentially triggering a feedback cycle of dominance and extinction. Such cycles may not occur immediately following the loss of herbivores, being delayed until conditions allow temporary periods of dominance by a subset of plant species.
Reframing sociologies of ethnicity and migration in encounters with Chinese London
Authors: Knowles Caroline
Published: June 2017

In this paper I argue that the intersecting sociologies of ethnicity and migration work from a series of interconnected blind spots hindering effective analysis of the current UK situation. Both operate analytically within the limitations of an ‘immigrant problem’ framework; are overinvested in state agendas; privilege a nation state analysis; are narrowly focused on distributions of migrant bodies, and on receiving, at the expense of sending, contexts. Exploring these limitations with data derived from a modest small‐scale qualitative study of young Chinese migrants in London, I argue for a reframing along four dimensions. Firstly, in an era of elite migration, sociology could reach beyond its immigrant problem framework and open up to a broader range of UK migrant ethnicities and circumstances. Secondly, a stronger focus on cities as the scale on which lives are lived, and through which diverse streams of translocal activity are routed, would open new avenues of sociological exploration. Thirdly, including translocal activities connected with distributions of ethnic migrant bodies, such as capital transfers, would broaden its focus, taking migration and ethnicity more centrally into the analysis of globalization as one of its constituting practices. Finally, paying attention to sending, as well as arrival cities, reveals migrants’ thinking and shapes the ways in which they live, as my data shows. The Chinese are both one of the UK's neglected minorities, and one of its fastest growing populations. They are a good example of new UK migrants and they bring globalization's realignment with the rising significance of China to the UK.
Simultaneous detection and identification of pathogenic Cronobacter species by high‐resolution melting analysis in powdered infant formulas
Authors: Hu Shuangfang , Yu Yigang , Wu Xinwei , Xia Xingzhou , Xiao Xinglong , Wu Hui
Published: June 2017

A combination method of real‐time PCR and high‐resolution melting (HRM) analysis for the rapid detection and specific classification of six pathogenic Cronobacter species based on gene cgcA was developed. HRM profiles with distinct Tm (melting temperature) peaks were consistently obtained with each species, represented by a single peak ranging from 86.02 to 86.80 °C. The detection limit ranged from 0.1 to 1 pg per reaction. Desiccated Cronobacter sakazakii and Cronobacter muytjensii of 2 cfu/25 g were successfully detected after 4‐week storage at room temperature. The newly developed method provided a molecular tool for direct detection and simultaneous identification of pathogenic Cronobacter species in powdered infant formulae.
Food Insecurity and Health Care Expenditures in the United States, 2011–2013
Authors: Berkowitz Seth A. , Basu Sanjay , Meigs James B. , Seligman Hilary K.
Published: June 2017

Objective

To determine whether food insecurity, limited or uncertain food access owing to cost, is associated with greater health care expenditures.

Data Source/Study Setting

Nationally representative sample of the civilian noninstitutionalized population of the United States (2011 National Health Interview Survey [NHIS] linked to 2012–2013 Medication Expenditure Panel Survey [MEPS]).

Study Design

Longitudinal retrospective cohort.

Data Collection/Extraction Methods

A total of 16,663 individuals underwent assessment of food insecurity, using the 10‐item adult 30‐day food security module, in the 2011 NHIS. Their total health care expenditures in 2012 and 2013 were recorded in MEPS. Expenditure data were analyzed using zero‐inflated negative binomial regression and adjusted for age, gender, race/ethnicity, education, income, insurance, and residence area.

Principal Findings

Fourteen percent of individuals reported food insecurity, representing 41,616,255 Americans. Mean annualized total expenditures were $4,113 (standard error $115); 9.2 percent of all individuals had no health care expenditures. In multivariable analyses, those with food insecurity had significantly greater estimated mean annualized health care expenditures ($6,072 vs. $4,208,p < .0001), an extra $1,863 in health care expenditure per year, or $77.5 billion in additional health care expenditure annually.

Conclusions

Food insecurity was associated with greater subsequent health care expenditures. Future studies should determine whether food insecurity interventions can improve health and reduce health care costs.
Real Assets, Collateral and the Limits of Debt Capacity
Authors: Giambona Erasmo , Mello Antonio S. , Riddiough Timothy J.
Published: June 2017

We develop a model in which better quality firms separate themselves by issuing unsecured debt and committing to maintain a strong balance sheet, something lower‐quality firms find too costly to do. Lower‐quality firms, in contrast, pledge real assets in secured debt transactions. However, during turbulent financial periods, pooling occurs in the secured debt market, which raises the average quality of firms in that market. We use the 1998 Russian crisis together with the role played by Fannie Mae and Freddie Mac for apartment REITs to highlight the relation between financing outcomes and firm type.
Optimization of Bleaching Parameters in Refining Process of Kenaf Seed Oil with a Central Composite Design Model
Authors: Chew Sook Chin , Tan Chin Ping , Nyam Kar Lin
Published: June 2017

Kenaf seed oil has been suggested to be used as nutritious edible oil due to its unique fatty acid composition and nutritional value. The objective of this study was to optimize the bleaching parameters of the chemical refining process for kenaf seed oil, namely concentration of bleaching earth (0.5 to 2.5% w/w), temperature (30 to 110 °C) and time (5 to 65 min) based on the responses of total oxidation value (TOTOX) and color reduction using response surface methodology. The results indicated that the corresponding response surface models were highly statistical significant (P < 0.0001) and sufficient to describe and predict TOTOX value and color reduction with R2 of 0.9713 and 0.9388, respectively. The optimal parameters in the bleaching stage of kenaf seed oil were: 1.5% w/w of the concentration of bleaching earth, temperature of 70 °C, and time of 40 min. These optimum parameters produced bleached kenaf seed oil with TOTOX value of 8.09 and color reduction of 32.95%. There were no significant differences (P > 0.05) between experimental and predicted values, indicating the adequacy of the fitted models.
Extraction and Isolation of β‐Glucan from Grain Sources—A Review
Authors: Maheshwari Gunjan , Sowrirajan Sumathi , Joseph Baby
Published: June 2017

A collective report on the extraction and isolation of β‐glucan from grain sources, namely, oat, barley, and wheat is presented. An analysis on the effect of medium, pH, and temperature on the purity and yield of the β‐glucan derived under acidic/alkaline/aqueous/enzymatic conditions is also made. Water extraction and alkali extraction processes are preferred as the yield and recovery of extracted β‐glucan were good. Cost‐effective development of the process for deriving high molecular weight β‐glucan is the current requirement for its wide applications in food and pharmaceutical industries.
Salicornia Extract Ameliorates Salt‐Induced Aggravation of Nonalcoholic Fatty Liver Disease in Obese Mice Fed a High‐Fat Diet
Authors: Kim Jae Hwan , Suk Sujin , Jang Woo Jung , Lee Chang Hyung , Kim Jong‐Eun , Park Jin‐Kyu , Kweon Mee‐Hyang , Kim Jong Hun , Lee Ki Won
Published: June 2017

High‐fat and high‐salt intakes are among the major risks of chronic diseases including obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Salicornia is a halophytic plant known to exert antioxidant, antidiabetic, and hypolipidemic effects, and Salicornia‐extracted salt (SS) has been used as a salt substitute. In this study, the effects of SS and purified salt (PS) on the aggravation of NAFLD/NASH were compared. C57BL/6J male mice (8‐wk‐old) were fed a high‐fat diet (HFD) for 6 mo and divided into 3 dietary groups, which were additionally fed HFD, HFD + SS, and HFD + PS for 13 wk. PS induced aggravation of NAFLD/NASH in HFD‐fed mice. Although the actual salt intake was same between the PS and SS groups as 1% of the diet (extrapolated from the World Health Organization [WHO] guideline), SS induced less liver injury and hepatic steatosis compared to PS. The hepatic mRNA expressions of inflammatory cytokines and fibrosis marker were significantly lower in the SS group than the PS group. Oxidative stress is one of the major causes of inflammation in NAFLD/NASH. Results of the component analysis showed that the major polyphenols that exhibited antioxidant activity in the Salicornia water extract were ferulic acid, caffeic acid, and isorhamnetin. These results suggest that even the level of salt intake recommended by WHO can accelerate the progression of liver disease in obese individuals consuming HFD. It is proposed that SS can be a salt substitute for obese individuals who consume HFD.
Relationships of sex hormone levels with leukocyte telomere length in Black, Hispanic, and Asian/Pacific Islander postmenopausal women
Authors: Song Yan , Cho Michele , Brennan Kathleen M. , Chen Brian H. , Song Yiqing , Manson JoAnn E. , Hevener Andrea L. , You Nai‐Chieh Y. , Butch Anthony W. , Liu Simin
Published: June 2017

Background

Sex hormones may play important roles in sex‐specific biological aging. In the study, we specifically examined associations between circulating sex hormone concentrations and leukocyte telomere length (TL).

Methods

A cross‐sectional study was conducted among 1124 Black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Estradiol and testosterone concentrations were measured using electrochemiluminescence immunoassays; TL was measured using quantitative polymerase chain reaction.

Results

Women in the study were aged 50–79 years. Estradiol concentrations were not significantly associated with TL in this sample. The associations between total and free testosterone and TL differed by race/ethnicity (Pinteraction = 0.03 and 0.05 for total and free testosterone, respectively). Total and free testosterone concentrations were not associated with TL in Black and Hispanic women, whereas in Asian/Pacific Islander women their concentrations were inversely associated with TL (Ptrend = 0.003 for both). These associations appeared robust in multiple subgroup analyses and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islander women, a doubling of serum free and total testosterone concentrations was associated with a 202‐bp shorter TL (95% confidence interval [CI] 51–353 bp) and 203‐bp shorter TL (95% CI 50–355 bp), respectively.

Conclusions

Serum estradiol concentrations were not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone concentrations were inversely associated with TL in Asian/Pacific Islander women, but not in Black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity‐specific relationships.
Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan
Authors: Krag M. , Perner A. , Wetterslev J. , Lange T. , Wise M. P. , Borthwick M. , Bendel S. , Pelosi P. , Keus F. , Guttormsen A. B. , Schefold J. C. , Meyhoff T. S. , Marker S. , Møller M. H.
Published: June 2017

Background

In this statistical analysis plan, we aim to provide details of the pre‐defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP‐ICU) trial. The aim of the SUP‐ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU).

Methods

The SUP‐ICU trial is an investigator‐initiated, international, multicentre, randomised, blinded, parallel‐group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90‐day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1‐year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre‐defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention‐to‐treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention‐to‐treat population.

Conclusion

Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high‐quality randomised placebo‐controlled trials. The SUP‐ICU trial will provide important high‐quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.
Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure
Authors: Suttie Michael , Wetherill Leah , Jacobson Sandra W. , Jacobson Joseph L. , Hoyme H. Eugene , Sowell Elizabeth R. , Coles Claire , Wozniak Jeffrey R. , Riley Edward P. , Jones Kenneth L. , Foroud Tatiana , Hammond Peter ,   the CIFASD
Published: June 2017

Background

Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer‐based tools for screening facial form.

Methods

All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature‐based delineations of facial form were introduced.

Results

(i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC‐FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC‐FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control‐FAS philtrum difference, greater homogeneity in Caucasians; for control‐FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control‐like and FAS‐like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control‐like facial dysmorphism shows orbital hypertelorism.

Conclusions

Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control‐FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long‐standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.
Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure
Authors: Kitaya Kotaro , Matsubayashi Hidehiko , Takaya Yukiko , Nishiyama Rie , Yamaguchi Kohei , Takeuchi Takumi , Ishikawa Tomomoto
Published: June 2017

Problem

The aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in infertile women with a history of repeated implantation failure (RIF) and to determine whether oral antibiotic treatment improves their live birth rate in the following embryo transfer (ET) cycles.

Method of study

Endometrial biopsy samples obtained from infertile women with RIF were subjected to immunohistochemistrical/histopathologic diagnosis of CE. Following antibiotic administration to the RIF/CE group, their histopathologic cure rate, microbial detection rate, and reproductive outcome in the subsequent ET cycles were prospectively studied.

Results

33.7% of infertile women with RIF were diagnosed with CE. Following the first‐line doxycycline treatment, the histopathologic cure rate in the subsequent endometrial biopsy was 92.3%. Following the second‐line metronidazole/ciprofloxacin treatment, the overall cure rate was 99.1%. The live birth rate in the first ET cycle (P=.031, RR 1.48, 95% CI 1.03‐2.12) and cumulative three ET cycles (P=.037, RR 1.39, 95% CI 1.02‐1.90) following antibiotic treatment in the cured RIF/CE group (32.8% and 38.8%, respectively) was significantly higher than in the RIF/non‐CE group (22.1% and 27.9%, respectively).

Conclusion

Chronic endometritis was found in one‐third of infertile women with RIF. The oral antibiotic treatment against CE might be a promising therapeutic option for infertile women with RIF.
Toll‐like receptor4 as a modulator of fertilization and subsequent pre‐implantation development following in vitro maturation in mice
Authors: Hosseini Sara , Dehghani‐Mohammadabadi Maryam , Ghafarri Novin Marefat , Haji Molla Hoseini Mostafa , Arefian Ehsan , Mohammadi Yeganeh Samira , Salehi Mohammad
Published: June 2017

Problem

The use of in vitro maturation (IVM) as an alternative approach to the conventional assisted reproductive technique in clinical practice is limited due to low fertilization rate. The expression of Toll‐like receptors (TLRs) as members of an innate immune system in cumulus cells are thought to affect fertilization. This study was aimed to evaluate the effect of IVM on TLR4 gene expression and fertilization rate in oocytes derived from IVM in comparison with in vivo matured one.

Method of study

Cumulus cells are collected from oocytes derived IVM and in vivo. The expression level of Tlr4 in cumulus cells of both groups was assessed by quantitative real‐time PCR. To examine the protein expression level of TLR4, immunocytochemistry and Western blotting techniques were carried out. TLR4 receptor functions were also confirmed by blockade assay and TLR4 receptor activation with lipopolysaccharide.

Result

There was a substantial decrease in fertilization and blastulation rate in the IVM group in comparison with the in vivo one. The mRNA expression and protein levels of TLR4 declined in cumulus cells following IVM. Anti‐TLR4 blocking antibody dramatically decreased the rate of fertilization and blastocyst formation compared to the in vivo group. In contrast, the fertilization rate was enhanced significantly in the presence of LPS as a TLR4 ligand compared to the control group.

Conclusion

Low expression level of Tlr4 following IVM and higher fertilization rate through TLR4 receptor activation with LPS proposed that alteration in TLR4 expression and subsequent cytokine section could be a possible cause of low fertilization rate in IVM‐derived oocytes.
Brugada syndrome, Brugada phenocopy or none?
Authors: Kocabas Umut , Hasdemir Can , Kaya Esra , Turkoglu Cuneyt , Baranchuk Adrian
Published: June 2017

Brugada syndrome is a form of inherited arrhythmia syndrome characterized by a distinct ST‐segment elevation in the right precordial leads. Brugada phenocopies are clinical entities that present with an electrocardiographic pattern identical to Brugada syndrome and may obey to various clinical conditions. We present a case of a suicidal attempt using a high dose of propafenone causing a Brugada‐type electrocardiographic pattern. Is this a Brugada syndrome case, a Brugada phenocopy or something else?
Voriconazole Concentrations in Plasma and Epithelial Lining Fluid after Inhalation and Oral Treatment
Authors: Andersen Charlotte U. , Sønderskov Lene Dahl , Bendstrup Elisabeth , Voldby Nina , Cass Lindsey , Ayrton John , Hilberg Ole
Published: June 2017

Adverse effects can compromise oral voriconazole treatment of pulmonary aspergillosis. Inhaled low‐dose voriconazole may be an alternative treatment. In this study, six patients inhaled 40 mg voriconazole b.i.d. for 2 days, and six patients ingested 400 and 200 mg orally b.i.d. on day one and two, respectively. Blood samples were collected after the first inhalation, and bronchial alveolar lavage fluids and blood samples were collected for measurements of voriconazole 12 hr after the last administration. The concentration of voriconazole in epithelial lining fluid (ELF) was calculated by the urea dilution method. Voriconazole concentrations were detectable in plasma 15 min. after inhalation and declined at 30 and 60 min. Twelve hours after the last dose, median (95% CI) plasma voriconazole concentration was 8 (4–26) ng/mL in the inhalation group and 1224 (535–2341) ng/mL in the oral group (p < 0.0001). In ELF, median concentration was 190 (55–318) ng/mL and 8827 (4369–35172) ng/mL, respectively (p < 0.0001). Median ELF/plasma concentration ratio was 21 (6–63) in the inhalation group and 8 (3–20) in the oral group (p = 0.2). In conclusion, voriconazole is rapidly absorbed into the systemic circulation after inhalation. There was a non‐significant trend towards a higher ELF/plasma concentration ratio in the inhalation group compared to the oral group.
The experiences of pregnant women in an interventional clinical trial: Research In Pregnancy Ethics (RIPE) study
Authors: Ballantyne Angela , Pullon Susan , Macdonald Lindsay , Barthow Christine , Wickens Kristen , Crane Julian
Published: June 2017

There is increasing global pressure to ensure that pregnant women are responsibly and safely included in clinical research in order to improve the evidence base that underpins healthcare delivery during pregnancy. One supposed barrier to inclusion is the assumption that pregnant women will be reluctant to participate in research. There is however very little empirical research investigating the views of pregnant women. Their perspective on the benefits, burdens and risks of research is a crucial component to ensuring effective recruitment. The Research In Pregnancy Ethics (RIPE) study set out to ascertain the views of pregnant women about research participation using an inductive thematic analysis. We conducted semi‐structured interviews with 20 women who had participated in a double‐blind randomised placebo controlled trial in Wellington (New Zealand) while pregnant. Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes. Key motivations for participating were altruism, playing a valuable civic role and the importance of research. The main perceived burdens related to inconvenience and time commitment. For some women, possible randomization to the placebo arm was regarded as a burden or disadvantage.
Who Fared Better? The Fortunes of Performance Pay and Fixed Pay Workers through Recession
Authors: Stokes Lucy , Bryson Alex , Forth John , Weale Martin
Published: June 2017

Using the Annual Survey of Hours and Earnings, we explore whether the fortunes of employees paid for performance differ from those of fixed pay workers during recession. Only in the bottom quintile of the wage distribution were performance pay employees more likely to experience greater falls in real wages than fixed pay employees. Accounting for fixed unobserved worker characteristics suggests that this was not due to the wage‐setting mechanism itself, but that other factors are likely to be at play. While across most of the earnings distribution there was little evidence of greater wage flexibility among performance pay employees, they did have longer job tenure than fixed pay employees over the recession.
Mild external heating and reduction in spontaneous contractions of the bladder
Authors: Kitney Darryl G. , Jabr Rita I. , Vahabi Bahareh , Fry Christopher H.
Published: June 2017

Objectives

To measure the effect of external heating on bladder wall contractile function, histological structure and expression of proteins related to tissue protection and apoptosis.

Material and Methods

In vitro preparations of bladder wall and ex vivo perfused pig bladders were heated from 37 to 42°C, 46 and 50°C for 15 min. Isolated preparations were heated by radiant energy and perfused bladders were heated by altering perfusate temperature. Spontaneous contractions or pressure variations were recorded, as well as responses to the muscarinic agonist carbachol or motor nerve excitation in vitro during heating. Tissue histology in control and after heating was analysed using haematoxylin and eosin staining and 4′‐6‐diamidino‐2‐phenylindole (DAPI) nuclear labelling. The effects of heating on protein expression levels of (i) heat shock proteins HSP27‐pSer82 and inducible‐HSP70 and (ii) caspase‐3 and its downstream DNA‐repair substrate poly‐[ADP‐ribose] polymerase (PARP) were measured.

Results

Heating to 42°C reduced spontaneous contractions or pressure variations by ~70%; effects were fully reversible. There were no effects on carbachol or nerve‐mediated responses. Tissue histology was unaffected by heating, and expression of heat shock proteins as well as caspase‐3 and PARP were also unaltered. A TRPV1 antagonist had no effect on the reduction of spontaneous activity. Heating to 46°C had a similar effect on spontaneous activity and also reduced the carbachol contracture. Urothelial structure was damaged, caspase‐3 levels were increased and inducible‐HSP70 levels declined. At 50°C evoked contractions were abolished, the urothelium was absent and heat shock proteins and PARP expression was reduced with raised caspase‐3 expression.

Conclusions

Heating to 42°C caused a profound, reversible and reproducible attenuation of spontaneous activity, with no tissue damage and no initiation of apoptosis pathways. Higher temperatures caused tissue damage and activation of apoptotic mechanisms. Mild heating offers a novel approach to reducing bladder spontaneous activity.
Recent advances in the development of T‐type calcium channel blockers for pain intervention
Authors: Snutch Terrance P , Zamponi Gerald W
Published: June 2017

Cav3.2 T‐type calcium channels are important regulators of pain signals in the afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore, it is reasonable to predict that inhibiting T‐type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T‐type channel blockers, such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 channels. In the past 5 years, considerable effort has been applied towards identifying novel classes of T‐type calcium channel blockers. Here, we review recent developments in the discovery of novel classes of T‐type calcium channel blockers, and their analgesic effects in animal models of pain and in clinical trials.

Linked Articles

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
A novel individual‐cell‐based mathematical model based on multicellular tumour spheroids for evaluating doxorubicin‐related delivery in avascular regions
Authors: Liu Jiali , Yan Fangrong , Chen Hongzhu , Wang Wenjie , Liu Wenyue , Hao Kun , Wang Guangji , Zhou Fang , Zhang Jingwei
Published: June 2017

Background and Purpose

Effective drug delivery in the avascular regions of tumours, which is crucial for the promising antitumour activity of doxorubicin‐related therapy, is governed by two inseparable processes: intercellular diffusion and intracellular retention. To accurately evaluate doxorubicin‐related delivery in the avascular regions, these two processes should be assessed together. Here we describe a new approach to such an assessment.

Experimental Approach

An individual‐cell‐based mathematical model based on multicellular tumour spheroids was developed that describes the different intercellular diffusion and intracellular retention kinetics of doxorubicin in each cell layer. The different effects of a P‐glycoprotein inhibitor (LY335979) and a hypoxia inhibitor (YC‐1) were quantitatively evaluated and compared, in vitro (tumour spheroids) and in vivo (HepG2 tumours in mice). This approach was further tested by evaluating in these models, an experimental doxorubicin derivative, INNO 206, which is in Phase II clinical trials.

Key Results

Inhomogeneous, hypoxia‐induced, P‐glycoprotein expression compromised active transport of doxorubicin in the central area, that is, far from the vasculature. LY335979 inhibited efflux due to P‐glycoprotein but limited levels of doxorubicin outside the inner cells, whereas YC‐1 co‐administration specifically increased doxorubicin accumulation in the inner cells without affecting the extracellular levels. INNO 206 exhibited a more effective distribution profile than doxorubicin.

Conclusions and Implications

The individual‐cell‐based mathematical model accurately evaluated and predicted doxorubicin‐related delivery and regulation in the avascular regions of tumours. The described framework provides a mechanistic basis for the proper development of doxorubicin‐related drug co‐administration profiles and nanoparticle development and could avoid unnecessary clinical trials.
Sensitivity to Shared Information in Social Learning
Authors: Whalen Andrew , Griffiths Thomas L. , Buchsbaum Daphna
Published: June 2017

Social learning has been shown to be an evolutionarily adaptive strategy, but it can be implemented via many different cognitive mechanisms. The adaptive advantage of social learning depends crucially on the ability of each learner to obtain relevant and accurate information from informants. The source of informants’ knowledge is a particularly important cue for evaluating advice from multiple informants; if the informants share the source of their information or have obtained their information from each other, then their testimony is statistically dependent and may be less reliable than testimony from informants who do not share information. In this study, we use a Bayesian model to determine how rational learners should incorporate the effects of shared information when learning from other people, conducting three experiments that examine whether human learners behave similarly. We find that people are sensitive to a number of different patterns of dependency, supporting the use of a sophisticated strategy for social learning that goes beyond copying the majority, and broadening the situations in which social learning is likely to be an adaptive strategy.
Long‐term safety and efficacy of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes
Authors: Kadowaki Takashi , Inagaki Nobuya , Kondo Kazuoki , Nishimura Kenichi , Kaneko Genki , Maruyama Nobuko , Nakanishi Nobuhiro , Watanabe Yumi , Gouda Maki , Iijima Hiroaki
Published: June 2017

Aim

To evaluate the long‐term safety and efficacy of canagliflozin as add‐on therapy in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control with teneligliptin monotherapy.

Methods

This open‐label 52‐week study was conducted in Japan. Patients received canagliflozin 100 mg added to teneligliptin 20 mg orally once daily for 52 weeks. The safety endpoint was the incidence of adverse events (AEs). The efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight from baseline to week 52 (with last observation carried forward).

Results

Overall, 153 patients entered the treatment period and 142 completed the study. The overall incidence rates of AEs and drug‐related AEs were 69.9% and 22.9%, respectively. Most AEs and drug‐related AEs were mild or moderate in severity. There were no previously undescribed safety signals. The mean changes in HbA1c, FPG and body weight were −0.99% (95% confidence interval [CI] −1.12 to −0.85), −38.6 mg/dL (95% CI −43.4 to −33.9) and −3.92% (95% CI −4.53 to −3.31), respectively. These effects were maintained for 52 weeks without attenuation. HbA1c and body weight were both decreased in 82.24% of patients at the end of the treatment period. Reductions in postprandial glucose were observed at weeks 24 and 52.

Conclusions

No new safety risks with this combination were identified, and sustained improvements in HbA1c, FPG and body weight were observed. The findings suggest that long‐term co‐administration of canagliflozin with teneligliptin is well tolerated and effective in Japanese patients with T2DM who have inadequate glycaemic control on teneligliptin alone.
The challenge of modeling niches and distributions for data‐poor species: a comprehensive approach to model complexity
Authors: Galante Peter J. , Alade Babatunde , Muscarella Robert , Jansa Sharon A. , Goodman Steven M. , Anderson Robert P.
Published: June 2017

Models of species ecological niches and geographic distributions now represent a widely used tool in ecology, evolution, and biogeography. However, the very common situation of species with few available occurrence localities presents major challenges for such modeling techniques, in particular regarding model complexity and evaluation. Here, we summarize the state of the field regarding these issues and provide a worked example using the technique Maxent for a small mammal endemic to Madagascar (the nesomyine rodent Eliurus majori). Two relevant model‐selection approaches exist in the literature (information criteria, specifically AICc; and performance predicting withheld data, via a jackknife), but AICc is not strictly applicable to machine‐learning algorithms like Maxent. We compare models chosen under each selection approach with those corresponding to Maxent default settings, both with and without spatial filtering of occurrence records to reduce the effects of sampling bias. Both selection approaches chose simpler models than those made using default settings. Furthermore, the approaches converged on a similar answer when sampling bias was taken into account, but differed markedly with the unfiltered occurrence data. Specifically, for that dataset, the models selected by AICc had substantially fewer parameters than those identified by performance on withheld data. Based on our knowledge of the study species, models chosen under both AICc and withheld‐data‐selection showed higher ecological plausibility when combined with spatial filtering. The results for this species intimate that AICc may consistently select models with fewer parameters and be more robust to sampling bias. To test these hypotheses and reach general conclusions, comprehensive research should be undertaken with a wide variety of real and simulated species. Meanwhile, we recommend that researchers assess the critical yet underappreciated issue of model complexity both via information criteria and performance on withheld data, comparing the results between the two approaches and taking into account ecological plausibility.
Used‐habitat calibration plots: a new procedure for validating species distribution, resource selection, and step‐selection models
Authors: Fieberg John R. , Forester James D. , Street Garrett M. , Johnson Douglas H. , ArchMiller Althea A. , Matthiopoulos Jason
Published: June 2017

‘Species distribution modeling’ was recently ranked as one of the top five ‘research fronts’ in ecology and the environmental sciences by ISI's Essential Science Indicators, reflecting the importance of predicting how species distributions will respond to anthropogenic change. Unfortunately, species distribution models (SDMs) often perform poorly when applied to novel environments. Compounding on this problem is the shortage of methods for evaluating SDMs (hence, we may be getting our predictions wrong and not even know it). Traditional methods for validating SDMs quantify a model's ability to classify locations as used or unused. Instead, we propose to focus on how well SDMs can predict the characteristics of used locations. This subtle shift in viewpoint leads to a more natural and informative evaluation and validation of models across the entire spectrum of SDMs. Through a series of examples, we show how simple graphical methods can help with three fundamental challenges of habitat modeling: identifying missing covariates, non‐linearity, and multicollinearity. Identifying habitat characteristics that are not well‐predicted by the model can provide insights into variables affecting the distribution of species, suggest appropriate model modifications, and ultimately improve the reliability and generality of conservation and management recommendations.
Cascading effects of herbivore protective symbionts on hyperparasitoids
Authors: MCLEAN AILSA H. C. , HRČEK JAN , PARKER BENJAMIN J. , GODFRAY H. CHARLES J.
Published: June 2017

1. Microbial symbionts can play an important role in defending their insect hosts against natural enemies. However, researchers have little idea how the presence of such protective symbionts impacts food web interactions and species diversity.

2. This study investigated the effects of a protective symbiont (Hamiltonella defensa) in pea aphids (Acyrthosiphon pisum) on hyperparasitoids, which are a trophic level above the natural enemy target of the symbiont (primary parasitoids).

3. Pea aphids, with and without their natural infections of H. defensa, were exposed first to a primary parasitoid against which the symbiont provides partial protection (either Aphidius ervi or Aphelinus abdominalis), and second to a hyperparasitoid known to attack the primary parasitoid species.

4. It was found that hyperparasitoid hatch rate was substantially affected by the presence of the symbiont. This effect appears to be entirely due to the removal of potential hosts by the action of the symbiont: there was no additional benefit or cost experienced by the hyperparasitoids in response to symbiont presence. The results were similar across the two different aphid–parasitoid–hyperparasitoid interactions we studied.

5. It is concluded that protective symbionts can have an important cascading effect on multiple trophic levels by altering the success of natural enemies, but that there is no evidence for more complex interactions. These findings demonstrate that the potential influence of protective symbionts on the wider community should be considered in future food web studies.
Pupal colour dimorphism in a desert swallowtail (Lepidoptera: Papilionidae) is driven by changes in food availability, not photoperiod
Authors: PIÑONES‐TAPIA DANIEL , RIOS RODRIGO S. , GIANOLI ERNESTO
Published: June 2017

1. The swallowtail butterfly Battus polydamas archidamas Boisduval, 1936, exhibits polyphenism for pupal coloration (green and brown). It is distributed across arid regions with winter rains and is monophagous on Aristolochia plants, which emerge after the winter rains and dry out the during summer. Thus, day length does not covary positively with host plant productivity. It was hypothesised that pupal colour was driven by food availability, not photoperiod. The benefits of pupal coloration matching the colour of pupation sites in terms of field survival were also investigated to evaluate the adaptive value of pupa colour.

2. Larvae were reared under a factorial array of two photoperiods (LD 10:14 h and LD 14:10 h) and two food availability regimes (leaves ad libitum and available every other day) to assess the frequency of green and brown pupae. Field survival of green and brown pupae was quantified in three commonly used habitats that differ in background coloration (cacti, rocks and shrubs).

3. Food availability determined pupal colour. Larvae in the ad libitum regime resulted mostly in green pupae, while those with restricted food were mostly brown. In contrast, photoperiod did not influence pupal colour. Survival probability of pupae placed on cacti was higher than those placed on rocks and shrubs, and the lowest predation risk across habitats was for green pupae on cacti.

4. Food availability plays a major role in the seasonal polyphenism for pupal colour of specialist butterflies inhabiting arid environments with winter rains.