bluuebunny/crossref_metadata_2025 huggingface dataset:
Prioritizing landscapes for restoration based on spatial patterns of ecosystem controls and plant–plant interactions
Authors: Barbosa Jomar M. , Asner Gregory P.
Published: December 2016

The widespread degradation of natural ecosystems requires cost‐efficient restoration techniques that minimize risk and consider context‐specific restoration conditions. However, meeting these demands can be difficult because information on ecosystem‐level factors controlling vegetation and continuous spatial data on species interactions are often lacking.

Using airborne light detection and ranging (LiDAR) data from a Hawaiian dry forest, we delineated crowns and assessed the 3D structure of more than 700 000 shrubs and trees. We used Random Forest machine learning to assess the relative importance of resource availability, environmental conditions, and disturbance regimes on canopy density. We then modelled and scaled up plant–plant interactions (i.e. potential nursery effects) to landscape units using a LiDAR‐derived Canopy Coalescence (CC) index. We used the relative importance of ecosystem factors, canopy cover, and CC index to prioritize landscapes for restoration.

Here, we demonstrate a methodological framework that prioritizes landscapes in need of restoration (i.e. planting woody species) using two ecological perspectives: (i) ecosystem‐level controls on remnant woody vegetation, and (ii) potential interactions between established canopies and seedlings (e.g. nursery effect, competition).

Our results highlight the heterogeneous nature of ecosystem‐level drivers affecting forest structure along elevation gradients. Consequently, the degree of potential nursery interactions between established canopies and seedlings at the landscape‐scale was context‐specific.

Synthesis and applications. Our study provides a methodological approach that prioritizes landscapes for restoration by identifying the main controls on tree spatial distribution and by inferring the favourable conditions for seedlings. This approach can guide land managers to define cost‐efficient restoration strategies for large ecological areas.
Sweat bees on hot chillies: provision of pollination services by native bees in traditional slash‐and‐burn agriculture in the Yucatán Peninsula of tropical Mexico
Authors: Landaverde‐González Patricia , Quezada‐Euán José Javier G. , Theodorou Panagiotis , Murray Tomás E. , Husemann Martin , Ayala Ricardo , Moo‐Valle Humberto , Vandame Rémy , Paxton Robert J.
Published: December 2016

Traditional tropical agriculture often entails a form of slash‐and‐burn land management that may adversely affect ecosystem services such as pollination, which are required for successful crop yields. The Yucatán Peninsula of Mexico has a >4000 year history of traditional slash‐and‐burn agriculture, termed ‘milpa’. Hot ‘Habanero’ chilli is a major pollinator‐dependent crop that nowadays is often grown in monoculture within the milpa system.

We studied 37 local farmers’ chilli fields (sites) to evaluate the effects of landscape composition on bee communities. At 11 of these sites, we undertook experimental pollination treatments to quantify the pollination of chilli. We further explored the relationships between landscape composition, bee communities and pollination service provision to chilli.

Bee species richness, particularly species of the family Apidae, was positively related to the amount of forest cover. Species diversity decreased with increasing proportion of crop land surrounding each sampling site. Sweat bees of the genus Lasioglossum were the most abundant bee taxon in chilli fields and, in contrast to other bee species, increased in abundance with the proportion of fallow land, gardens and pastures which are an integral part of the milpa system.

There was an average pollination shortfall of 21% for chilli across all sites; yet the shortfall was unrelated to the proportion of land covered by crops. Rather, chilli pollination was positively related to the abundance of Lasioglossum bees, probably an important pollinator of chilli, as well indirectly to the proportion of fallow land, gardens and pastures that promote Lasioglossum abundance.

Synthesis and applications. Current, low‐intensity traditional slash‐and‐burn (milpa) agriculture provides Lasioglossum spp. pollinators for successful chilli production; fallow land, gardens and pasture therefore need to be valued as important habitats for these and related ground‐nesting bee species. However, the negative impact of agriculture on total bee species diversity highlights how agricultural intensification is likely to reduce pollination services to crops, including chilli. Indeed, natural forest cover is vital in tropical Yucatán to maintain a rich assemblage of bee species and the provision of pollination services for diverse crops and wild flowers.
Ecological and evolutionary effects of selective harvest of non‐lactating female ungulates
Authors: Rughetti Marco , Festa‐Bianchet Marco , Côté Steeve D. , Hamel Sandra
Published: December 2016

Female ungulates are often selectively harvested according to their reproductive status. Because ungulate population growth depends heavily on adult female survival, it is crucial to understand the effects of this selective harvest. Recent studies revealed persistent individual differences in female reproductive potential, with a positive correlation of reproductive success over consecutive years. If current reproduction is correlated with lifetime reproductive success, then selective harvest of non‐lactating females should remove individuals of low reproductive potential, with lower impact on population growth than random harvest. If lifetime reproductive success has a genetic basis, selective harvest may also increase the proportion of successful females.

We used an individual‐based model to understand the short‐term effects of harvest intensity and hunter selectivity on population dynamics, accounting for both heterogeneity in reproductive potential and orphan survival. We also explored the long‐term effect of harvest as a selective pressure on female heterogeneity.

Selective harvest of non‐lactating females reduced survival to primiparity compared to random harvest, because of high harvest rates of pre‐reproductive females. After primiparity, however, females of higher reproductive potential had higher survival under selective than random harvest. Therefore, the overall effect on population dynamics depends on a trade‐off between a high harvest of pre‐reproductive females and a reduced harvest of reproductive females with high reproductive potential.

Female heterogeneity and the length of the pre‐reproductive period affected this trade‐off. Over the short term, high heterogeneity in reproductive potential of pre‐reproductive females made selective harvest the most effective strategy to maintain a high population growth rate. With low heterogeneity and little effects of orphaning on juvenile mortality, however, random harvest had a lower impact on population growth than selective harvest. Over the long term, selective female harvest may increase the proportion of successful reproducers in the population.

Synthesis and applications. Selective harvests of non‐lactating females appear justified only if female heterogeneity in reproductive potential and/or orphan mortality are very high. Because pre‐reproductive females will be subject to intense harvest, selective harvest may reduce population growth rate compared to random harvest in species with late primiparity, especially if most pre‐reproductive female normally survive to primiparity. When heterogeneity in reproductive potential and orphan mortality are low, random female harvest appears preferable to selective harvest.
General allometric scaling of net primary production agrees with plant adaptive strategy theory and has tipping points
Authors: Jenkins David G. , Pierce Simon
Published: December 2016

Allometric scaling of net primary production (NPP) with plant biomass (B) is important to ecological carbon dynamics and energetics. Metabolic theory predicts a nonlinear power law forNPPscaling, based on fractal vascular systems, resulting in a linear model when using logNPP/log B axes that are standard in allometry. Alternatively, two other hypotheses predict nonlinear models for log‐transformed data, with potential tipping points. Size‐based competition may cause a quadratic curve as larger plants limitNPPby smaller plants. More inclusively, the plant adaptive strategies hypothesis predicts a sigmoidal curve to represent those same competitive effects, plus stress and ruderal adaptations that maintain relatively lowNPPin habitats that are abiotically limiting or disturbed.

We evaluated all three hypotheses for terrestrial vascular plants, using information theoretic model selection based on the Akaike Information Criterion (AICc). Published data (N = 709) were organised in subsets according to reported organisational level and plant growth form. Alternative curves were compared for a general model (using all data) and per subset. Potential tipping points were estimated using segmented regression.

The plant adaptive strategies hypothesis was supported in general (AICc weight = 1·00) and via internal consistency for five of six subsets (86% of data). Competition was supported as affectingNPPat greater B, where quadratic and sigmoidal models often coincided. Only non‐woody assemblages most plausibly fit a power law model, perhaps related to sparse data at lowest B.

Synthesis. Adaptive strategies and corresponding environmental conditions appear to constrain terrestrial net primary production scaling relative to metabolic theory's ideal. Moreover, tipping points in general nonlinear net primary production scaling (at c. 38 and 360 g m−2B) indicate thresholds for rapid changes in net primary production given changing B that occurs via changing climate, human appropriation and land use.
Species interactions increase the temporal stability of community productivity in Pinus sylvestris–Fagus sylvatica mixtures across Europe
Authors: del Río Miren , Pretzsch Hans , Ruíz‐Peinado Ricardo , Ampoorter Evy , Annighöfer Peter , Barbeito Ignacio , Bielak Kamil , Brazaitis Gediminas , Coll Lluís , Drössler Lars , Fabrika Marek , Forrester David I. , Heym Michael , Hurt Václav , Kurylyak Viktor , Löf Magnus , Lombardi Fabio , Madrickiene Ekaterina , Matović Bratislav , Mohren Frits , Motta Renzo , den Ouden Jan , Pach Maciej , Ponette Quentin , Schütze Gerhard , Skrzyszewski Jerzy , Sramek Vit , Sterba Hubert , Stojanović Dejan , Svoboda Miroslav , Zlatanov Tzvetan M. , Bravo‐Oviedo Andrés
Published: December 2016

There is increasing evidence that species diversity enhances the temporal stability (TS) of community productivity in different ecosystems, although its effect at the population and tree levels seems to be negative or neutral. Asynchrony in species responses to environmental conditions was found to be one of the main drivers of this stabilizing process. However, the effect of species mixing on the stability of productivity, and the relative importance of the associated mechanisms, remain poorly understood in forest communities.

We investigated the way mixing species influenced the TS of productivity in Pinus sylvestris L. and Fagus sylvatica L. forests, and attempted to determine the main drivers among overyielding, asynchrony between species annual growth responses to environmental conditions, and temporal shifts in species interactions. We used a network of 93 experimental plots distributed across Europe to compare the TS of basal area growth over a 15‐year period (1999–2013) in mixed and monospecific forest stands at different organizational levels, namely the community, population and individual tree levels.

Mixed stands showed a higher TS of basal area growth than monospecific stands at the community level, but not at the population or individual tree levels. The TS at the community level was related to asynchrony between species growth in mixtures, but not to overyielding nor to asynchrony between species growth in monospecific stands. Temporal shifts in species interactions were also related to asynchrony and to the mixing effect on the TS.

Synthesis. Our findings confirm that species mixing can stabilize productivity at the community level, whereas there is a neutral or negative effect on stability at the population and individual tree levels. The contrasting findings regarding the relationships between the temporal stability and asynchrony in species growth in mixed and monospecific stands suggest that the main driver in the stabilizing process may be the temporal niche complementarity between species rather than differences in species’ intrinsic responses to environmental conditions.
Neither ‘foolish’ nor ‘finished’: identity control among older adults with HIV in rural Malawi
Authors: Freeman Emily
Published: December 2016

Prevalence of HIV after age 50 is considerable, especially in southern Africa. Negative social constructions of HIV in older age, and the health consequences of ageing with the virus, mean that having HIV presents a challenge for many people's roles and social memberships, threatening to disrupt their sense of self. Using constructivist grounded theory and qualitative data from rural Malawi, this paper describes how older men and women deal with these identity challenges. Drawing on a symbolic interactionist framework, it uses identity control theory to explore how the study's participants presented their post‐diagnosis behaviours in ways that maintained their most significant pre‐diagnosis identities as ‘adults’, a label they gave to the core identity of being a person who belongs in the social world. Considering the processes through which older people with HIV navigated challenges to their identities in light of the intersectional influences of HIV and age‐related stigma and illness, provides insight into how older people might experience HIV, as well as informing theoretical understandings of identity formation and maintenance in light of chronic and/or stigmatising illness more broadly.
How simple is reading in Arabic? A cross‐sectional investigation of reading comprehension from first to sixth grade
Authors: Asadi Ibrahim A. , Khateb Asaid , Shany Michal
Published: December 2016

This study aimed to examine, from a cross‐sectional perspective, the extent to which the simple view of reading (SVR) model can be adapted to the Arabic language. This was carried out by verifying, in both beginning and more skilled readers, whether the unique orthographical and morphological characteristics of Arabic contribute to reading comprehension beyond decoding and listening comprehension abilities. Reading comprehension was evaluated in a large sample of first to sixth‐grade Arabic‐speaking children. The participants' decoding and listening comprehension abilities were investigated together with their orthographic and morphological knowledge. Path analysis indicated that reading comprehension was moderately explained by the SVR (56–38%). Orthographic and morphological knowledge explained an additional 10–22% of the variance beyond that explained by the basic SVR components. These findings demonstrate that certain linguistic aspects of Arabic impact reading processes differently when compared with other languages. The psycholinguistic implications of these findings are discussed in the light of previous findings in the literature.

What is already known about this topic?

The ‘simple view of reading’ model explains reading comprehension as the product of decoding and listening comprehension.

This model explains between 70% and 83% of the variance in reading comprehension in English, in which the contribution of decoding and listening comprehension varies as a function of the level of the readers.

Orthographic transparency and other unique characteristics of the languages studied might influence reading comprehension in these languages

What does this paper add?

Arabic is a diglossic language that is characterised by relatively unique orthographic and morphological features for which the validity of the simple view of reading (SVR) has not been tested.

The basic components of the SVR (decoding and listening comprehension) have explained between 56% and 38% of the variance in reading comprehension in children from the first to the sixth grade.

Decoding, as one of the basic components of the SVR, failed to contribute to reading comprehension when orthography and morphology were considered.

Implications for practice and/or policy

This large‐scale cross‐sectional study is the first of its type to assess reading comprehension in Arabic.

The study justifies the necessity to assess the suitability of the SVR in languages with very specific linguistic characteristics such as Arabic.

The results emphasise the necessity of considering the complex orthography and the rich morphology of Arabic for improving teaching, assessment and intervention.
Reviews, reviews, reviews
Authors: Chien Patrick
Published: December 2016

Deputy Editor‐in‐Chief, Dr Patrick Chien, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/january-editors-choice-2017
BJOG Editor's Choice: Demystifying pelvic pain and haemostatic methods for myomectomy
Authors: Tu Frank
Published: December 2016

Guest Editor, Dr Frank Tu, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/benign-gynae-editors-choice-2017.
Is the Pictorial Blood Loss Assessment Chart (PBAC) score associated with treatment outcome after endometrial ablation for heavy menstrual bleeding? A cohort study
Authors: Herman MC , Mak N , Geomini PM , Winkens B , Mol BW , Bongers MY ,   the International Heavy Menstrual Bleeding IPD Meta‐analysis Collaborative Group
Published: December 2016

Objective

The Pictorial Blood Loss Assessment Chart (PBAC) is a validated tool that is used to diagnose heavy menstrual bleeding (HMB). Knowledge of the effect of its score and its relationship with outcome could have implications for using the PBAC as an outcome measurement in future HMB studies, and as a tool to evaluate the treatment effect in research and clinical practice. Our aim was to relate PBAC scores to other measures of success after endometrial ablation for HMB.

Design

Analysis of individual patient data (IPD) of randomised controlled trials studying women with HMB.

Setting

Women with HMB consulting their gynecologists.

Population or sample

Individual patient data (IPD) of randomised controlled trials studying women with HMB.

Methods

We included studies if they had studied second‐generation endometrial ablation techniques and had collected PBAC scores for both baseline and follow‐up. The effectiveness of treatment was scored as satisfaction or re‐intervention (yes/no) 12 months after treatment. We related these outcomes to the PBAC score at 12 months after treatment, and to PBAC decrease between baseline and 12 months of follow‐up.

Results

We studied data for 900 patients included in nine studies. The median PBAC score at 12 months was 7 (0–2500). The overall satisfaction rate was 89% and the overall re‐intervention rate was 7.2%. A clear association was found between absolute PBAC score at the 12‐month follow‐up and satisfaction (odds ratio, OR 0.16; 95% confidence interval, 95% CI 0.11–0.24) and surgical re‐intervention (OR 2.3, 95% CI 1.8–2.8). A change in PBAC score was also associated with satisfaction (OR 2.0, 95% CI 1.7–2.3) and surgical re‐intervention (OR 0.69, 95% CI 0.63–0.75). Both the absolute PBAC scores and the changes in score show high accuracy for both treatment outcomes.

Conclusions

PBAC scores at 12 months after treatment are significantly associated with satisfaction and re‐intervention rates. We propose to use the PBAC in research as a primary end point in studies on HMB, and in clinical practice as a measure to assess the effectiveness of treatment.

Tweetable abstract

PBAC scores 12 months after treatment are significantly associated with satisfaction and reintervention rates.
Timing of insertion of levonorgestrel‐releasing intrauterine system: a randomised controlled trial
Authors: van der Heijden PAHH , Geomini PMAJ , Herman MC , Veersema S , Bongers MY
Published: December 2016

Objective

The objective was to assess whether patient‐perceived pain during the insertion of the levonorgestrel‐releasing intrauterine system (LNG‐IUS) depends on the timing during the menstrual cycle.

Design

A stratified two‐armed non‐inferiority randomised controlled trial.

Setting

Large teaching hospital in Veldhoven, the Netherlands.

Sample

From October 2013 to May 2014, 60 nulliparous and 60 multiparous women were randomised. Eight women withdrew after randomisation and before insertion took place: therefore, data from 112 women were collected and analysed.

Methods

Women were randomised to the groups ‘during menstruation’ (i.e. days 1–7 of menstruation) or ‘outside menstruation’ (i.e. any day of the cycle after menstruation without the presence of vaginal blood loss) in a ratio of 1 : 1.

Main outcome measures

The primary outcome was pain during insertion, measured by the visual analogue scale (VAS, 0–100 mm). Second, we analysed ease of insertion, bleeding pattern, satisfaction, pregnancy, and expulsion rate. The follow‐up time was 3 months.

Results

The mean VAS score for nulliparous women was 74 mm (95% confidence interval, 95% CI 67–81) in the ‘during menstruation’ group, compared with 66 mm (95% CI 59–74) in the ‘outside menstruation’ group (P = 0.14). The mean VAS score for multiparous women was 30 mm (95% CI 20–40) in the ‘during menstruation group’, compared with 43 mm (95% CI 32–53) in the ‘outside menstruation’ group (P = 0.08). There was no difference between the stratified ‘during menstruation’ group and the ‘outside menstruation’ group with regards to ease of insertion, satisfaction, bleeding pattern, and median spotting and bleeding days for the use of the LNG‐IUS 3 months after insertion.

Conclusions

As we did not find that the level of pain perceived during insertion was higher during menstruation, compared with outside menstruation, we conclude that the LNG‐IUS can be inserted at any time during the menstrual cycle, especially in the case of nulliparous women.

Tweetable abstract

We conducted an RCT on time of insertion of LNG‐IUS. We conclude that the LNG‐IUS can be inserted at any time.
Enhancing Loan Quality Through Transparency: Evidence from the European Central Bank Loan Level Reporting Initiative
Authors: ERTAN AYTEKIN , LOUMIOTI MARIA , WITTENBERG‐MOERMAN REGINA
Published: December 2016

We explore whether transparency in banks’ securitization activities enhances loan quality. We take advantage of a novel disclosure initiative introduced by the European Central Bank, which requires, as of January 2013, banks that use their asset‐backed securities as collateral for repo financing to report securitized loan characteristics and performance in a standardized format. We find that securitized loans originated under the transparency regime are of better quality with a lower default probability, a lower delinquent amount, fewer days in delinquency, and lower losses upon default. Additionally, banks with more intensive loan level information collection and those operating under stronger market discipline experience greater improvement in their loan quality under the new reporting standards. Overall, we demonstrate that greater transparency has real effects by incentivizing banks to improve their credit practices.
Household susceptibility to hydrological change in the Lower Mekong Basin
Authors: Grantham Ruby W. , Rudd Murray A.
Published: December 2016

The hydrological conditions of the Lower Mekong Basin support a multitude of ecosystem services. Processes that influence water flow in the Mekong River will thus have implications for the tens of millions of people whose livelihoods depend on these services. This study presents an assessment of livelihood susceptibility to hydrological change in the Lower Mekong Basin. Using an index‐based approach, susceptibility scores were calculated for 2,703 households. Using those scores, we compared average household susceptibility across the basin, among countries and among eco‐zones. Due to their greater livelihood dependency on water‐related activities, mean household susceptibility was higher in Vietnam than in Cambodia, Laos, or Thailand. Households in Northern Laos also had high susceptibility, which was attributed to their low adaptive capacity. The findings suggest that policies aimed at reducing vulnerability to hydrological change in the Lower Mekong Basin should account for geographic context. Further, they highlight how policies may be able to strategically target the most susceptible households, but that poorly designed policies have the potential to exacerbate vulnerability. In the face of high uncertainty surrounding hydrological change in the Lower Mekong Basin, our assessment of susceptibility should help inform precautionary water management policies and provide baseline information needed for more comprehensive vulnerability assessments.
Feeling the HEAT: Using Hourly Emergency Activity Tracking to demonstrate a novel method of describing activity and patient flow
Authors: Bein Kendall J , Berendsen Russell Saartje , Muscatello David , Chalkley Dane , Ivers Rebecca , Dinh Michael M
Published: December 2016

Objective

The objective of the present study is to demonstrate a novel method of mapping ED activity to analyse patterns presentations, occupancy and performance trends.

Methods

This was a retrospective, descriptive analysis of de‐identified and linked ED presentations across NSW, Australia, over five calendar years, 2010–2014. It was undertaken as part of the Demand for Emergency Services Trend in Years 2010–2014 (DESTINY) study. The DESTINY project analysed 10.8 million presentations during 2010–2014. Hourly Emergency Activity Tracking (HEAT) maps were generated to visually represent and analyse the number of emergency arrivals to ED occupancy and proportion of patients leaving the ED within 4 h per hour of day across consecutive months of the year.

Results

HEAT maps provided a means of visually representing ED activity to demonstrate hour‐to‐hour trends in presentations, occupancy and performance between 2010 and 2014. This analysis has shown that the most marked increase in presentations per hour has occurred during the 10.00–14.00 hour period, associated with an improvement in ED performance during the same period.

Conclusion

HEAT maps may be used to facilitate further analyses of ED demand, patterns of patient presentations and patient flow and future health system redesign.
Tuberculosis screening using IGRA and chest computed tomography in patients with inflammatory bowel disease: A retrospective study
Authors: Song Dong Juan , Tong Jin Lu , Peng Jiang Chen , Cai Chen Wen , Xu Xi Tao , Zhu Ming Ming , Ran Zhi Hua , Zheng Qing
Published: December 2016

Objectives

To assess the prevalence and potential risk factors of latent tuberculosis infection (LTBI) in Chinese patients with inflammatory bowel disease (IBD) and to evaluate the role of chest computed tomography (CT) in the screening of LTBI.

Methods

A single‐center retrospective study was conducted and all IBD patients who had been screened for LTBI by T‐SPOT.TB between December 2011 and January 2016 were enrolled in the study. Both inpatient and outpatient records were collected and comprehensively reviewed.

Results

Altogether 534 IBD patients were included. The positivity rate of T‐SPOT.TB was 18.0% overall, 31.9% in IBD unclassified, 22.5% in ulcerative colitis and 13.0% in Crohn's disease patients, respectively. Age, history of TB and the administration of immunosuppressants were significantly associated with T‐SPOT.TB positivity. Among 123 patients who underwent serial testing, the conversion and reversion rate of T‐SPOT.TB was 10.2% and 42.9%, respectively. Furthermore, 102 of 447 (22.8%) patients who underwent chest computed tomography (CT) were found with abnormal CT findings suggestive of LTBI. The concordance rate was 75% between the T‐SPOT.TB and chest CT with a kappa value of 0.25 (95% CI 0.15–0.35).

Conclusions

The prevalence of LTBI in IBD patients is high in China. Chest CT is recommended as an alternative to IGRA for screening LTBI of IBD patients before commencing immunosuppressive therapy in high‐prevalence regions.
In vitro spontaneous contractile activity of colonic smooth muscle in naive Lewis rats: Acute effect of gonadal hormones
Authors: Baumgartner Christine , Hubacher Thomas , Krayer Magali , Gschossmann Juergen
Published: December 2016

Objective

Functional gastrointestinal disorders affect females more often. Changes in colonic motility may be etiological co‐factors for the clinical symptoms. The aim of the present study was to analyze the influence of gonadal hormones on colonic contractile activity.

Methods

In vitro measurements of colonic contractile activity in longitudinal smooth muscle strips of female and male Lewis rats were performed in an organ chamber experiment. After the administration of a gonadal hormone estradiol [EST], progesterone [PROG] and testosterone [TEST]) or ethanol solution as control, stimulation with acetylcholine (ACh) or inhibition with norepinephrine (NE) was performed.

Results

Compared to the smooth muscle strips of male rats, significantly higher spontaneous colonic contractile activity (SCCA) was observed in female animals. Increasing doses of ACh showed the progressive stimulation of SCCA whereas rising doses of NE resulted in a stepwise inhibition of SCCA, respectively. EST superfusion displayed an inhibitory effect on SCCA in both sexes and inhibited the ACh effect in female rats. Similarly, acute superfusion with high‐dose PROG inhibited SCCA in females. Acute TEST superfusion inhibited SCCA in males and led to significant higher colonic contractile activity in males following subsequent stimulation with ACh. In female rats, the inhibitory effect of NE was reduced by prior exposure to TEST.

Conclusion

In our in vitro study the acute exposure of colonic smooth muscle tissue to gonadal hormones led to sex‐dependent changes in SCCA and translated in a modified response of smooth muscle strips to both pro‐contractile and anti‐contractile neurotransmitters.
HSP90 inhibition suppresses inflammatory response and reduces carotid atherosclerotic plaque formation in ApoE mice
Authors: Mu Hongmei , Wang Liyong , Zhao Lei
Published: December 2016

Aim

Emerging evidences indicate that heat‐shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In this study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature.

Methods

Heat‐shock protein90‐overexpression lentivirus (Lenti‐HSP90) was used to transfect apoE−/− mice after constrictive collars were planted at the right common carotid arteries.

Results

As a result, HSP90 gene overexpression led to reduction in en face plaque area and increase in unstable plaque with heavier accumulation of lipids. Concomitantly, more macrophages, less smooth muscle cells, and collagen were generated, suggesting aggravated inflammation. However, inhibition of HSP90 with 17‐AAG, a HSP90‐inhibitor, induced opposing effects. Moreover, HSP90 upregulated plaque MMP‐8, which might be the underlying mechanism of the change in plaque vulnerability index. Further, the translocation of NF‐κB was promoted by HSP90, while inhibition of NF‐κB significantly reduced MMP‐8 production, which is upregulated by HSP90.

Conclusions

These findings suggested that HSP90 governs plaque development and vulnerability, as well as inflammation, at least in part via MMP‐8 and NF‐κB signaling pathways.
Do more robust prescription drug monitoring programs reduce prescription opioid overdose?
Authors: Pardo Bryce
Published: December 2016

Background and Aims

In the United States, overdose deaths attributed to opioid pain relievers (OPR) have quadrupled since 1999, prompting many states to adopt Prescription Drug Monitoring Programs (PMP). This study aimed to: (1) estimate the relationship of PMP strength with OPR overdose deaths across states and over time; (2) measure what threshold in PMP strength is associated with the greatest reduction in OPR overdose; and (3) assess the relationship of medical marijuana dispensaries with OPR overdose deaths.

Design

Panel data from the Centers for Disease Control and Prevention's (CDC's) Wide‐ranging Online Data for Epidemiologic Research database (WONDER) were analyzed using fixed effects to regress state–year death rates on an index variable compiled from the Prescription Drug Abuse Policy System (PDAPS) while controlling for PMP administration, demographic factors and laws that might affect OPR overdose.

Setting and Participants

Age‐adjusted opioid overdose death rates for all 50 states and the District of Columbia between 1999 and 2014 for a total of 816 observations.

Measurements

PMP strength was calculated using legal data compiled by the Prescription Drug Abuse Policy System (PDAPS). In addition to demographic controls, other covariates included laws that regulate pain clinics, access to naloxone, use of emergency services (Good Samaritan Laws) and medical marijuana.

Findings

PMP strength was associated negatively with OPR overdose deaths. Every 1‐point increase in PMP strength was associated with a 1% [95% confidence interval (CI) = 0.2–2%] reduction in overdose deaths. When collapsed into quartiles, PMPs in the third quartile were associated with an approximately 18% (95% CI = 1.6–29%) reduction in OPR overdose death rates compared with states without a PMP. States with medical marijuana dispensaries reported a 16% (95% CI = 1–30%) reduction in OPR overdoses.

Conclusions

US states that have more robust prescription drug monitoring programs have fewer prescription opioid overdose deaths than states with weaker PMPs. States with medical marijuana dispensaries also report fewer opioid overdose deaths than states without these.
Adolescents at risk for drug abuse: a 3‐year dual‐process analysis
Authors: Ames Susan L. , Xie Bin , Shono Yusuke , Stacy Alan W.
Published: December 2016

Aims

To test longitudinal additive and synergistic dual‐process models in youth at documented risk for drug use. The specific dual‐process approach examined suggests that engaging in drug use behaviors results from a dynamic interplay between automatically activated associative memory processes and executive reflective/control processes.

Design

This 3‐year, three‐wave population‐based prospective study used mobile computer‐based assessments.

Setting

Self‐directed computer assessments were completed in school settings in the Los Angeles metropolitan area, California, USA.

Participants

Seven hundred and twenty‐five at‐risk adolescents (44% female) in continuation high schools were recruited during 9th grade (age at recruitment, 14–16).

Measurements

Key outcome measures included past year alcohol, marijuana and cigarette use at each assessment. Predictors included working memory capacity (WMC), associative memory, the interaction term WMC by associative memory, sex, age, ethnicity and acculturation.

Findings

A significant cross‐sectional interaction revealed tobacco‐relevant associations were weaker predictors of cigarette use among males with higher WMC than among those with lower WMC (P < 0.004). Alternatively, drug‐relevant associations were stronger predictors of past year alcohol (P < 0.001) and marijuana use (P = 0.02) among females with higher WMC than among those with lower WMC. Longitudinal analyses revealed no significant interactions after adjusting for predictive effects of previous drug use. With respect to WMC, females with higher WMC were less likely to use marijuana at 2‐year follow‐up (P = 0.03). First‐order effects of drug‐related associations predicted greater alcohol and marijuana use prospectively in males at 1‐ and 2‐year follow up (P ≤ 0.03), and greater past year alcohol and marijuana use in females at 1‐year follow up (P ≤ 0.03).

Conclusions

Drug‐relevant memory associations play a key role in drug use behavior in at‐risk youth.
Racial Inequality in Democratic Accountability: Evidence from Retrospective Voting in Local Elections
Authors: Flavin Patrick , Hartney Michael T.
Published: December 2016

One important and, to date, overlooked component of democratic accountability is the extent to which it might exacerbate existing societal inequalities if the outcomes for some groups of citizens are prioritized over others when voters evaluate governmental performance. We analyze a decade of California school board elections and find evidence that voters reward or punish incumbent board members based on the achievement of white students in their district, whereas outcomes for African American and Hispanic students receive comparatively little attention. We then examine public opinion data on the racial education achievement gap and report results from an original list experiment of California school board members that finds approximately 40% of incumbents detect no electoral pressure to address poor academic outcomes among racial minority students. We conclude by discussing the implications of these findings for several scholarly literatures, including retrospective voting, racial inequality in political influence, intergovernmental policymaking, and education politics.
Medicine information exchange networks among healthcare professionals and prescribing in geriatric medicine wards
Authors: Chan Bosco , Reeve Emily , Matthews Slade , Carroll Peter R. , Long Janet C. , Held Fabian , Latt Mark , Naganathan Vasi , Caplan Gideon A. , Hilmer Sarah N.
Published: December 2016

Aims

Effective transfer of information is vital for rational drug therapy. This is particularly important for older patients, who have a high prevalence of polypharmacy and are managed by multidisciplinary teams. We aimed to assess medicine information exchange (MIE) networks in geriatric medicine wards and whether they are associated with prescribing patterns.

Methods

We conducted network analysis in acute geriatric medicine wards from four hospitals to characterize MIE networks among multidisciplinary team members. Corresponding patient data were collected to analyze high‐risk prescribing in conjunction with network characteristics.

Results

We found that junior doctors, senior nurses and pharmacists were central to MIE across all four hospitals. Doctors were more likely than other professions to receive medicines information in three hospitals. Reciprocity and the tendency to communicate within one's own profession also influenced network formation. No difference was observed in prescribing practice between hospitals.

Conclusions

Understanding MIE networks can identify gaps in multidisciplinary communication that can be addressed. Networks may identify targets for dissemination of interventions to improve prescribing.
Population pharmacokinetics and exposure‐response of osimertinib in patients with non‐small cell lung cancer
Authors: Brown Kathryn , Comisar Craig , Witjes Han , Maringwa John , de Greef Rik , Vishwanathan Karthick , Cantarini Mireille , Cox Eugène
Published: December 2016

Aims

To develop a population (pop) pharmacokinetic (PK) model for osimertinib (AZD9291) and its metabolite (AZ5104) and investigate the exposure–response relationships for selected efficacy and safety parameters.

Methods

PK, safety and efficacy data were collected from two non‐small cell lung cancer (NSCLC) patient studies (n = 748) and one healthy volunteer study (n = 32), after single or multiple once‐daily dosing of 20–240 mg osimertinib. Nonlinear mixed effects modelling was used to characterise the popPK. Individual exposure values were used to investigate the relationship with response evaluation criteria in solid tumours (RECIST 1.1) efficacy parameters and key safety parameters (rash, diarrhoea, QTcF).

Results

A popPK model that adequately described osimertinib and its metabolite AZ5104 in a joint manner was developed. Body weight, serum albumin and ethnicity were identified as significant covariates on PK in the analysis, but were not found to have a clinically relevant impact on osimertinib exposure. No relationship was identified between exposure and efficacy over the dose range studied. A linear relationship was observed between exposure and the occurrence of rash or diarrhoea, and between concentration and QTcF, with a predicted mean (upper 90% confidence interval) increase of 14.2 (15.8) ms at the maximum concentration for an 80 mg once‐daily dose at steady state.

Conclusions

PopPK and exposure–response models were developed for osimertinib and AZ5104. There was no relationship between exposure and efficacy but a linear relationship between exposure and safety endpoints (rash, diarrhoea and QTcF) was observed.
Direct Estimation for Adaptive Treatment Length Policies: Methods and Application to Evaluating the Effect of Delayed PEG Insertion
Authors: Lu Xin , Johnson Brent A.
Published: December 2016

Dysphagia is a primary cause of death among patients diagnosed with amyotrophic lateral sclerosis (ALS), and percutaneous endoscopic gastrostomy (PEG) is a procedure to insert a tube into the stomach to assist or replace oral feeding. It is believed that PEG is beneficial and, generally, earlier insertion is preferable to later. However, gathering clinical evidence to support these beliefs on the use and timing of PEG is challenging because controlled clinical trials are not feasible and clinical endpoints are confounded with PEG in observational data. Moreover, the confounders are time-varying and time to PEG insertion may be only partially observed. We show how one can view this problem as an adaptive treatment length policy and propose a new estimator via g-computation. We show that our estimator is consistent and asymptotically normal for the causal estimand and explore its finite sample properties in simulation studies. Finally, using more than 10 years of data from Emory ALS clinic registry, we found no evidence to suggest that earlier PEG reduced 4-year mortality; thus, our results do not support the hypothesis and belief that initiating palliative care earlier extends life, on average. At the same, we cannot be certain that all important confounding variables are collected and observed to ensure our modeling assumptions are correct, so more work is needed to address these important end-of-life questions for ALS patients.
Inflammasomes as therapeutic targets for Alzheimer's disease
Authors: White Claire S. , Lawrence Catherine B. , Brough David , Rivers‐Auty Jack
Published: December 2016

Alzheimer's disease is the most common form of progressive dementia, typified initially by short term memory deficits which develop into a dramatic global cognitive decline. The classical hall marks of Alzheimer's disease include the accumulation of amyloid oligomers and fibrils, and the intracellular formation of neurofibrillary tangles of hyperphosphorylated tau. It is now clear that inflammation also plays a central role in the pathogenesis of the disease through a number of neurotoxic mechanisms. Microglia are the key immune regulators of the CNS which detect amyloidopathy through cell surface and cytosolic pattern recognition receptors (PRRs) and respond by initiating inflammation through the secretion of cytokines such as interleukin‐1β (IL‐1β). Inflammasomes, which regulate IL‐1β release, are formed following activation of cytosolic PRRs, and using genetic and pharmacological approaches, NLRP3 and NLRP1 inflammasomes have been found to be integral in pathogenic neuroinflammation in animal models of Alzheimer's disease. Therefore, the inflammasomes are very promising novel pharmacological targets which merit further research in the continued endeavor for efficacious therapeutics for Alzheimer's disease.
Anti‐CD22 and anti‐CD79b antibody‐drug conjugates preferentially target proliferating B cells
Authors: Fuh Franklin K , Looney Caroline , Li Dongwei , Poon Kirsten A , Dere Randall C , Danilenko Dimitry M , McBride Jacqueline , Reed Chae , Chung Shan , Zheng Bing , Mathews William Rodney , Polson Andrew , Prabhu Saileta , Williams Marna
Published: December 2016

Background and Purpose

CD22 and CD79b are cell‐surface receptors expressed on B‐cell‐derived malignancies such as non‐Hodgkin's lymphoma (NHL). An anti‐mitotic agent, monomethyl auristatin E, was conjugated to anti‐CD22 and anti‐CD79b antibodies to develop target‐specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody‐drug conjugates (ADCs) were investigated in cynomolgus monkeys.

Experimental Approach

Animals were administered anti‐CD22 or anti‐CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) of the ADCs were evaluated in vitro.

Key Results

Depletion of B cells was observed after administration of either ADC or the respective unconjugated antibodies. An extended duration of depletion was observed in animals administered ADCs. Similarly, preferential depletion of proliferating B cells in blood and germinal centre B cells in spleen were only observed in animals administered ADCs. Serum PK profiles of ADCs and respective unconjugated antibodies were comparable. In vitro, anti‐human CD22 and anti‐human CD79b antibodies showed no or only moderate ADCC activity, respectively; neither antibody had CDC activity.

Conclusions and Implications

The findings support the proposed MOA: initial depletion of total B cells by antibody‐mediated opsonization, followed by preferential, sustained depletion of proliferating B cells by the auristatin conjugate due to its anti‐mitotic action. Delivering potent anti‐mitotic agents to B cells via the specificity of monoclonal antibodies provides a means to eliminate pathogenic B cells in NHL with improved risk–benefit profiles over traditional chemotherapeutics.
Sunk costs and the measurement of commercial property depreciation
Authors: Diewert W. Erwin , Fox Kevin J.
Published: December 2016

Developments in property markets greatly influence economic growth, monetary policy, productivity measurement, inflation measurement and hence welfare payments to the disadvantaged. Property price bubbles often lead to financial crises; those experienced during the 20th century were often triggered by commercial property price movements. Yet property poses significant challenges for national accountants in producing key economic variables used in informing policy assessment and formulation. To address these challenges, this paper formalizes a framework for measuring prices and quantities of capital inputs for a commercial property. In particular, it addresses problems associated with obtaining separate estimates for the land and structure components of a property, a decomposition of property value that is important for the national accounts, productivity measurement and taxation. A key contribution is to address the problem of estimating structure depreciation taking into account the fixity of the structure. We find that structure depreciation is determined primarily by the cash flows that the property generates rather than physical deterioration of the building. Finally, we provide a framework for the determination of the optimal length of life for a structure.
Has Canadian house price growth been excessive?
Authors: Head Allen , Lloyd‐Ellis Huw
Published: December 2016

The dramatic rise in the ratio of Canada's average house price to average rent has led to speculation that there is a bubble in the Canadian housing market. Others have argued, however, that the currently high level of house prices may be rationalized by the low cost of financing, given the decline in interest rates over the last two decades. In this article, we assess these arguments through the lens of a simple asset pricing model applied to city‐level data. We quantify the extent to which excess growth in Canadian house prices depends on the nature of the current regime governing real interest rates, expectations of rent growth in different cities and variations in property taxes.