bluuebunny/crossref_metadata_2025 huggingface dataset:
Transaortic Aortic Valve Implantation in 100 Patients: Follow-up to 3 Years
Authors: Cocchieri Riccardo , Koh Ezra Y. , Wollersheim Laurens W. , Meregalli Paola G. , Bardai Abdenasser , Bouma Berto J. , De Mol Bas A.
Published: April 2016

Objective

Transaortic aortic valve implantation (TAo-AVI) through the ascending aorta is a novel technique and is used as an alternative in patients with poor femoral access. Although early results have been promising, no midterm data have been published yet. To determine whether this approach is an acceptable treatment option, we analyzed the first 100 cases performed at our institution with a follow-up to 3 years.

Methods

Between July 2011 and January 2015, a total of 100 patients with high-risk or inoperable aortic valve stenosis were treated with TAo-AVI. Preoperative patient data were collected and analyzed retrospectively. All surviving patients were seen for clinical and echocardiographic examination for follow-up.

Results

Median follow-up was 15 months. Device success was accomplished in 94 patients (94%). There were no access site complications. The 30-day mortality rate was 9%. Stroke occurred in a total of six patients (6%). Survival at 1-, 2-, and 3 years was 75%, 62%, and 58%, respectively.

Conclusions

Our results show that TAo-AVI is a promising alternative to transapical implantation for treating severe inoperable aortic valve stenosis.
Laboratory Investigations for Diagnosis of Autoimmune and Inflammatory Periocular Disease: Part II
Authors: Srinivasan Archana , Kleinberg Teri T. , Murchison Ann P. , Bilyk Jurij R.
Published: April 2016

Purpose:

To review the important laboratory serological investigations routinely performed for the diagnosis of autoimmune and inflammatory diseases of the orbit and ocular adnexa.

Methods:

Review of the literature as well as personal clinical experience of the authors. Due to the extensive nature of the topic, the review has been split into 2 parts. Part I covers thyroid eye disease, IgG4-related disease, and myasthenia gravis. In part II of the review, sarcoidosis, vasculitis, Sjögren syndrome, and giant cell arteritis will be discussed.

Results:

Several relatively specific serologic tests are available for the diagnosis of a variety of inflammatory and serologic diseases of the orbit.

Conclusion:

In cases of limited orbital or sino-orbital disease, serologic testing may be negative in a significant number of patients. Specifically, the clinician should be wary of ruling out limited orbital sarcoid or sinoorbital granulomatosis with polyangiitis based on serologic testing alone. Part I of this review has covered serologic testing for thyroid eye disease, IgG4-related disease, and myasthenia gravis. In part II, the authors discuss serologic testing for sarcoidosis, vasculitis, Sjögren syndrome (SS), and giant cell arteritis (GCA).
Blepharophimosis Ptosis Epicanthus Inversus Syndrome With Congenital Hypothyroidism and Brachydactyly in a 7-Year-Old Girl
Authors: Zhou Lu , Wang Tailing , Wang Jiaqi
Published: April 2016

A 7-year-old female presented with blepharophimosis ptosis epicanthus inversus syndrome with congenital hypothyroidism and brachydactyly. She displayed typical manifestations of type II blepharophimosis ptosis epicanthus inversus syndrome (normal uterus position, ovarian volume, and normal serum hormone levels). She takes levothyroxine sodium daily due to her congenital hypothyroidism. Karyotype analysis and genetic analysis of FOXL2 coding sequence was found to be normal. mtDNA A3243G, A8344G, 8993, and 13513 genes were also normal. The absence of mutations excluded mitochondrial encephalomyopathies. To the best of our knowledge, this is the first reported case of blepharophimosis ptosis epicanthus inversus syndrome with congenital hypothyroidism and brachydactyly.
Who Were the Early Adopters of Dabigatran?
Authors: Lo-Ciganic Wei-Hsuan , Gellad Walid F. , Huskamp Haiden A. , Choudhry Niteesh K. , Chang Chung-Chou H. , Zhang Ruoxin , Jones Bobby L. , Guclu Hasan , Richards-Shubik Seth , Donohue Julie M.
Published: April 2016

Background:

Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption.

Objective:

Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant.

Methods:

A retrospective cohort study using prescribing data from IMS Xponent™ on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions.

Outcomes:

Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran.

Results:

We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in ≤3 mo with 45% of prescriptions) and 13.4% were rapid and moderate adopters (≤3 mo with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6–10 mo post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt [odds ratio (OR)=12.2; 95% confidence interval (CI), 9.27–16.1] as were younger prescribers (age 36–45 y: OR=1.49, 95% CI, 1.13–1.95; age 46–55: OR=1.34, 95% CI, 1.07–1.69 vs. >55 y).

Conclusions:

Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment.
Racial/Ethnic Disparities in Medicare Beneficiaries’ Care Coordination Experiences
Authors: Martino Steven C. , Elliott Marc N. , Hambarsoomian Katrin , Weech-Maldonado Robert , Gaillot Sarah , Haffer Samuel C. , Hays Ron D.
Published: April 2016

Background:

Little is known about racial/ethnic differences in the experience of care coordination. To the extent that they exist, such differences may exacerbate health disparities given the higher prevalence of some chronic conditions among minorities.

Objective:

To investigate the extent to which racial/ethnic disparities exist in the receipt of coordinated care by Medicare beneficiaries.

Subjects:

A total of 260,974 beneficiaries who responded to the 2013 Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey.

Methods:

We fit a series of linear, case-mix adjusted models predicting Medicare CAHPS measures of care coordination from race/ethnicity.

Results:

Hispanic, black, and Asian/Pacific Islander (API) beneficiaries reported that their personal doctor had medical records and other relevant information about their care significantly less often than did non-Hispanic white beneficiaries (−2 points for Hispanics, −1 point for blacks, and −4 points for APIs on a 100-point scale). These 3 groups also reported significantly greater difficulty getting timely follow-up on test results than non-Hispanic white beneficiaries (−9 points for Hispanics, −1 point for blacks, −5 points for APIs). Hispanic and black beneficiaries reported that help was provided in managing their care significantly less often than did non-Hispanic white beneficiaries (−2 points for Hispanics, −3 points for blacks). API beneficiaries reported that their personal doctor discussed their medications and had up-to-date information on care from specialists significantly less often than did non-Hispanic white beneficiaries (−2 and −4 points, respectively).

Discussion:

These results suggest a need for efforts to address racial/ethnic disparities in care coordination to help ensure high-quality care for all patients. Public reporting of plan-level performance data by race/ethnicity may also be helpful to Medicare beneficiaries and their advocates.
‘Waterloo’: when normal blood cells meet leukemia
Authors: Cheng Hui , Cheng Tao
Published: April 2016

Purpose of review

Mortality and morbidity associated with leukemia are largely due to frequently occurring cytopenias or the dysfunction of normal blood cells in patients. Our knowledge of how normal blood cells degenerate in response to leukemic cell infiltration has been quite limited. This review summarizes recent findings and discusses both extrinsic and intrinsic mechanisms underlying the suppression of normal hematopoiesis in leukemia.

Recent findings

Recent studies have shown that leukemic cells are able to remodel the bone marrow niche by secreting specific cytokines or dampening its hematopoietic-supporting functions. In turn, a suitable microenvironment for leukemic cell proliferation but not for normal hematopoietic cell growth is created. Intrinsically, the leukemic condition impairs the normalcy of hematopoietic stem and progenitor cells and alters their signaling networks; consequently, it exhausts hematopoietic progenitor cells and forces stem cells into a more quiescent state, which would allow a reversible suppression of hematopoietic regeneration. The deepened quiescence of hematopoietic stem cells in leukemic marrow was achieved in part via transcription factor Egr3.

These findings provide new insights into the mechanisms underlying hematopoietic suppression in response to leukemic cell outgrowth and offer new strategies to further improve current therapies for leukemias, placing more emphasis on the augmentation of normal hematopoietic regeneration when targeting leukemic cells.
Methylphenidate Overdose Causing Secondary Polydipsia and Severe Hyponatremia in an 8-Year-Old Boy
Authors: Patel Vanisha , Krishna Ashwin Subramani , Lefevre Cassandra , Kaagaza Mildred , Wittkamp Michael
Published: April 2016

Objective

Attention deficit hyperactivity disorder (ADHD) is an increasingly common diagnosis of childhood that manifests with symptoms that affect cognitive, academic, behavioral, emotional, and social functioning. There are a multitude of pharmaceutical therapies to choose from when managing this condition, and though many studies on the safety and efficacy of these medications have been published, adverse effects still occur.

Case

This case discusses a previously healthy 8-year-old boy who had been prescribed 20-mg lisdexamfetamine dimesylate for ADHD however mistakenly took his brother's 36-mg methylphenidate extended-release tablets, resulting in hyperhidrosis, excessive thirst, polydipsia, and combative behavior that began within 3 hours of ingestion. He was evaluated at a community hospital emergency department and given lorazepam due to agitation and combativeness before discharge. However, he returned with hypothermia, hyponatremia, and status epilepticus resulting in intubation. Patient was transferred to our facility where a computer tomography of his head was negative and hyponatremia was corrected with 3% NaCl saline solution. A lumbar puncture was performed due to temperature instability before starting broad-spectrum antibiotics. Cerebrospinal fluid findings were normal, and he was extubated at 18 hours postingestion. Patient was discharged home after 3 days with no residual symptoms.

Discussion/Conclusions

Though both lisdexamfetamine dimesylate and methylphenidate are widely used among pediatricians today for treatment of ADHD, reports of life-threatening water intoxication as a result of overdose is rare. Studies have reported that severe 3,4-methylenedioxymethamphtamine toxicity in adults is associated with syndrome of inappropriate diuretic hormone (SIADH) secretion, hyponatremia, and seizures, along with serotonin-induced transient elevation in antidiuretic hormone. Adult schizophrenics who receive psychostimulants have also been shown to develop polydipsia with hyponatremia. Although the use of psychostimulants in adult schizophrenic patients has been studied, literature on toxicity and effects in the pediatric psychiatric population is scarce. We would suggest that this patient's polydipsia and hyponatremia are most likely a result of his ingestion of a toxic dose of a long-acting agent known to cause secondary psychosis.
Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children
Authors: Bienczak Andrzej , Denti Paolo , Cook Adrian , Wiesner Lubbe , Mulenga Veronica , Kityo Cissy , Kekitiinwa Addy , Gibb Diana M. , Burger David , Walker A. Sarah , McIlleron Helen
Published: April 2016

Background:

Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children.

Methods:

We analyzed data from 128 African children (aged 1.7–13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds.

Results:

The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported.

Conclusions:

Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.
Non–AIDS-Defining Cancer Mortality: Emerging Patterns in the Late HAART Era
Authors: Zucchetto Antonella , Virdone Saverio , Taborelli Martina , Grande Enrico , Camoni Laura , Pappagallo Marilena , Regine Vincenza , Grippo Francesco , Polesel Jerry , Dal Maso Luigino , Suligoi Barbara , Frova Luisa , Serraino Diego
Published: April 2016

Background:

Non–AIDS-defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared with people without AIDS (non-PWA).

Methods:

A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15–74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death data were retrieved up to December 2011. Excess mortality, as compared with non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and the corresponding 95% confidence intervals (CIs).

Results:

Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%), and liver (1.4%), cancers. A 7.3-fold (95% CI: 6.1 to 8.7) excess mortality was observed for all non-ADCs combined. Statistically significant SMRs emerged for specific non-ADCs, ie, anus (5 deaths, SMR = 227.6, 95% CI: 73.9 to 531.0), Hodgkin lymphoma (12 deaths, SMR = 122.0, 95% CI: 63.0 to 213.0), unspecified uterus (4 deaths, SMR = 52.5, 95% CI: 14.3 to 134.5), liver (17 deaths, SMR = 13.2, 95% CI: 7.7 to 21.1), skin melanoma (4 deaths, SMR = 10.9, 95% CI: 3.0 to 27.8), lung (38 deaths, SMR = 8.0, 95% CI: 5.7 to 11.0), head and neck (9 deaths, SMR = 7.8, 95% CI: 3.6 to 14.9), leukemia (5 deaths, SMR = 7.6, 95% CI: 2.4 to 17.7), and colon-rectum (10 deaths, SMR = 5.4, 95% CI: 2.6 to 10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use.

Conclusion:

This population-based study documented extremely elevated risks of death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non–virus-related cancers among HIV-infected individuals.
Revisiting the Potential of Alternating Repetition Time Balanced Steady-State Free Precession Imaging of the Abdomen at 3 T
Authors: Gurney-Champion Oliver J. , Nederveen Aart J. , Klaassen Remy , Engelbrecht Marc R. , Bel Arjan , van Laarhoven Hanneke W.M. , Stoker Jaap , Goncalves Sonia I.
Published: April 2016

Objective

The aim was to investigate the value of optimized 3-dimensional alternating repetition time balanced steady-state free precession (ATR-SSFP), as an alternative to conventional segmented balanced steady-state free precession (bSSFP) with fat suppression prepulse (FS-bSSFP), in single breath-hold abdominal magnetic resonance imaging at 3 T.

Methods

Bloch simulations were performed to determine the optimal flip angle (FA = 1–90 degrees) and τ (1–3) with respect to signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between abdominal organs for ATR-SSFP. These were corroborated by phantom measurements for different T1/T2 values (5–47) as well as in a healthy volunteer. In addition, fat suppression efficiency was studied using phantom and volunteer measurements. The effect of resolution on image quality was studied in a healthy volunteer. Using the optimal settings, ATR-SSFP images as well as FS-bSSFP images were obtained in 15 pancreatic cancer patients. For 10 structures of interest, the signal ratio with respect to the pancreas was computed and compared between both sequences. Finally, 10 items on image quality (fat suppression, artifacts, and sharpness) and tissue conspicuity (ducts, vessels, and duodenum) were scored by 2 abdominal radiologists for both image sequences.

Results

The results of simulations, phantom measurements, and volunteer measurements showed that, considering scan time, fat suppression, and clinical relevance, the ideal settings for ATR-SSFP were as follows: τ = 3; TR1 = 3.46 milliseconds; radiofrequency phase cycling 0, 180, 180, 0 degrees; and FA = 13–16 degrees (highest SNR) and 24–26 degrees (highest CNR). The optimized feasible additional settings implemented for patient scans were FA = 18 degrees and resolution = 1.4 × 1.4 × 1.4 mm3. In patients, the signal ratios of both ATR-SSFP and FS-bSSFP were comparable and had a T2-like contrast behavior, although more accentuated in ATR-SSFP. The ATR-SSFP scored significantly higher than FS-bSSFP for 9 of 10 items scored.

Conclusions

For single breath-hold abdominal imaging at 3 T, ATR-SSFP performs best with τ = 3 and an FA between 13 degrees (highest SNR) and 26 degrees (highest CNR). The scoring of both abdominal radiologists indicated that, at τ = 3, FA = 18 degrees, and 1.4 × 1.4 × 1.4 mm3 resolution, ATR-SSFP was preferred over conventional FS-bSSFP with similar settings.
Adverse Reactions to Gadoterate Meglumine
Authors: de Kerviler Eric , Maravilla Kenneth , Meder Jean-François , Naggara Olivier , Dubourdieu Corinne , Jullien Vincent , Desché Pierre
Published: April 2016

Objective

The aim of this study was to evaluate the safety profile of gadoterate meglumine from clinical trials, postmarketing observational studies, and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years of clinical use and over 50 million administered doses.

Materials and Methods

Assessment of the safety of gadoterate meglumine through processing and review of all safety data was collected after magnetic resonance imaging procedures. All ADRs originated from 3 major sources: (1) a clinical study database including 50 phase I to IV studies involving 2822 patients, (2) a safety database including 8 postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a pharmacovigilance database compiling safety experience following over 50 million doses administered between March 1989 and September 2015.

Results

Among the 2822 patients receiving gadoterate meglumine in the clinical trials, 241 (8.5%) experienced 405 postinjection adverse events (AEs), considered related to the contrast agent for 113 patients (4.0%). Serious AEs were reported for 27 patients (1.0%) and assessed as related to gadoterate meglumine for 2 patients (0.07%). None of the PMS studies showed evidence of unexpected safety issues, with a very low rate of AEs (<1%). Postmarketing safety experience with over 50 million doses of gadoterate meglumine prescribed for 25 years of approved use worldwide compiled spontaneous reports for 3797 patients who experienced 8397 ADRs, yielding a very low reported incidence of ADRs of 0.007% of patients. There was no single-agent case of confirmed nephrogenic systemic fibrosis with gadoterate meglumine either from clinical development programs or from postmarketing experience.

Conclusions

Based on clinical trials, postmarketing observational studies and pharmacovigilance data, a very low incidence of ADRs was reported with gadoterate meglumine, which has no impact on its favourable benefit-risk ratio.
Biodiversity and ecosystem functioning in dynamic landscapes
Authors: Brose Ulrich , Hillebrand Helmut
Published: April 2016

The relationship between biodiversity and ecosystem functioning (BEF) and its consequence for ecosystem services has predominantly been studied by controlled, short-term and small-scale experiments under standardized environmental conditions and constant community compositions. However, changes in biodiversity occur in real-world ecosystems with varying environments and a dynamic community composition. In this theme issue, we present novel research on BEF in such dynamic communities. The contributions are organized in three sections on BEF relationships in (i) multi-trophic diversity, (ii) non-equilibrium biodiversity under disturbance and varying environmental conditions, and (iii) large spatial and long temporal scales. The first section shows that multi-trophic BEF relationships often appear idiosyncratic, while accounting for species traits enables a predictive understanding. Future BEF research on complex communities needs to include ecological theory that is based on first principles of species-averaged body masses, stoichiometry and effects of environmental conditions such as temperature. The second section illustrates that disturbance and varying environments have direct as well as indirect (via changes in species richness, community composition and species' traits) effects on BEF relationships. Fluctuations in biodiversity (species richness, community composition and also trait dominance within species) can severely modify BEF relationships. The third section demonstrates that BEF at larger spatial scales is driven by different variables. While species richness
per se
and community biomass are most important, species identity effects and community composition are less important than at small scales. Across long temporal scales, mass extinctions represent severe changes in biodiversity with mixed effects on ecosystem functions. Together, the contributions of this theme issue identify new research frontiers and answer some open questions on BEF relationships in dynamic communities of real-world landscapes.
Climate modifies response of non-native and native species richness to nutrient enrichment
Authors: Flores-Moreno Habacuc , Reich Peter B. , Lind Eric M. , Sullivan Lauren L. , Seabloom Eric W. , Yahdjian Laura , MacDougall Andrew S. , Reichmann Lara G. , Alberti Juan , Báez Selene , Bakker Jonathan D. , Cadotte Marc W. , Caldeira Maria C. , Chaneton Enrique J. , D'Antonio Carla M. , Fay Philip A. , Firn Jennifer , Hagenah Nicole , Harpole W. Stanley , Iribarne Oscar , Kirkman Kevin P. , Knops Johannes M. H. , La Pierre Kimberly J. , Laungani Ramesh , Leakey Andrew D. B. , McCulley Rebecca L. , Moore Joslin L. , Pascual Jesus , Borer Elizabeth T.
Published: April 2016

Ecosystem eutrophication often increases domination by non-natives and causes displacement of native taxa. However, variation in environmental conditions may affect the outcome of interactions between native and non-native taxa in environments where nutrient supply is elevated. We examined the interactive effects of eutrophication, climate variability and climate average conditions on the success of native and non-native plant species using experimental nutrient manipulations replicated at 32 grassland sites on four continents. We hypothesized that effects of nutrient addition would be greatest where climate was stable and benign, owing to reduced niche partitioning. We found that the abundance of non-native species increased with nutrient addition independent of climate; however, nutrient addition increased non-native species richness and decreased native species richness, with these effects dampened in warmer or wetter sites. Eutrophication also altered the time scale in which grassland invasion responded to climate, decreasing the importance of long-term climate and increasing that of annual climate. Thus, climatic conditions mediate the responses of native and non-native flora to nutrient enrichment. Our results suggest that the negative effect of nutrient addition on native abundance is decoupled from its effect on richness, and reduces the time scale of the links between climate and compositional change.
The effects of climatic fluctuations and extreme events on running water ecosystems
Authors: Woodward Guy , Bonada Núria , Brown Lee E. , Death Russell G. , Durance Isabelle , Gray Clare , Hladyz Sally , Ledger Mark E. , Milner Alexander M. , Ormerod Steve J. , Thompson Ross M. , Pawar Samraat
Published: April 2016

Most research on the effects of environmental change in freshwaters has focused on incremental changes in average conditions, rather than fluctuations or extreme events such as heatwaves, cold snaps, droughts, floods or wildfires, which may have even more profound consequences. Such events are commonly predicted to increase in frequency, intensity and duration with global climate change, with many systems being exposed to conditions with no recent historical precedent. We propose a mechanistic framework for predicting potential impacts of environmental fluctuations on running-water ecosystems by scaling up effects of fluctuations from individuals to entire ecosystems. This framework requires integration of four key components: effects of the environment on individual metabolism, metabolic and biomechanical constraints on fluctuating species interactions, assembly dynamics of local food webs, and mapping the dynamics of the meta-community onto ecosystem function. We illustrate the framework by developing a mathematical model of environmental fluctuations on dynamically assembling food webs. We highlight (currently limited) empirical evidence for emerging insights and theoretical predictions. For example, widely supported predictions about the effects of environmental fluctuations are: high vulnerability of species with highper capitametabolic demands such as large-bodied ones at the top of food webs; simplification of food web network structure and impaired energetic transfer efficiency; and reduced resilience and top-down relative to bottom-up regulation of food web and ecosystem processes. We conclude by identifying key questions and challenges that need to be addressed to develop more accurate and predictive bio-assessments of the effects of fluctuations, and implications of fluctuations for management practices in an increasingly uncertain world.
Ecological and socio-economic functions across tropical land use systems after rainforest conversion
Authors: Drescher Jochen , Rembold Katja , Allen Kara , Beckschäfer Philip , Buchori Damayanti , Clough Yann , Faust Heiko , Fauzi Anas M. , Gunawan Dodo , Hertel Dietrich , Irawan Bambang , Jaya I. Nengah S. , Klarner Bernhard , Kleinn Christoph , Knohl Alexander , Kotowska Martyna M. , Krashevska Valentyna , Krishna Vijesh , Leuschner Christoph , Lorenz Wolfram , Meijide Ana , Melati Dian , Nomura Miki , Pérez-Cruzado César , Qaim Matin , Siregar Iskandar Z. , Steinebach Stefanie , Tjoa Aiyen , Tscharntke Teja , Wick Barbara , Wiegand Kerstin , Kreft Holger , Scheu Stefan
Published: April 2016

Tropical lowland rainforests are increasingly threatened by the expansion of agriculture and the extraction of natural resources. In Jambi Province, Indonesia, the interdisciplinary EFForTS project focuses on the ecological and socio-economic dimensions of rainforest conversion to jungle rubber agroforests and monoculture plantations of rubber and oil palm. Our data confirm that rainforest transformation and land use intensification lead to substantial losses in biodiversity and related ecosystem functions, such as decreased above- and below-ground carbon stocks. Owing to rapid step-wise transformation from forests to agroforests to monoculture plantations and renewal of each plantation type every few decades, the converted land use systems are continuously dynamic, thus hampering the adaptation of animal and plant communities. On the other hand, agricultural rainforest transformation systems provide increased income and access to education, especially for migrant smallholders. Jungle rubber and rubber monocultures are associated with higher financial land productivity but lower financial labour productivity compared to oil palm, which influences crop choice: smallholders that are labour-scarce would prefer oil palm while land-scarce smallholders would prefer rubber. Collecting long-term data in an interdisciplinary context enables us to provide decision-makers and stakeholders with scientific insights to facilitate the reconciliation between economic interests and ecological sustainability in tropical agricultural landscapes.
Plant species richness and functional traits affect community stability after a flood event
Authors: Fischer Felícia M. , Wright Alexandra J. , Eisenhauer Nico , Ebeling Anne , Roscher Christiane , Wagg Cameron , Weigelt Alexandra , Weisser Wolfgang W. , Pillar Valério D.
Published: April 2016

Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance.
Plant diversity effects on grassland productivity are robust to both nutrient enrichment and drought
Authors: Craven Dylan , Isbell Forest , Manning Pete , Connolly John , Bruelheide Helge , Ebeling Anne , Roscher Christiane , van Ruijven Jasper , Weigelt Alexandra , Wilsey Brian , Beierkuhnlein Carl , de Luca Enrica , Griffin John N. , Hautier Yann , Hector Andy , Jentsch Anke , Kreyling Jürgen , Lanta Vojtech , Loreau Michel , Meyer Sebastian T. , Mori Akira S. , Naeem Shahid , Palmborg Cecilia , Polley H. Wayne , Reich Peter B. , Schmid Bernhard , Siebenkäs Alrun , Seabloom Eric , Thakur Madhav P. , Tilman David , Vogel Anja , Eisenhauer Nico
Published: April 2016

Global change drivers are rapidly altering resource availability and biodiversity. While there is consensus that greater biodiversity increases the functioning of ecosystems, the extent to which biodiversity buffers ecosystem productivity in response to changes in resource availability remains unclear. We use data from 16 grassland experiments across North America and Europe that manipulated plant species richness and one of two essential resources—soil nutrients or water—to assess the direction and strength of the interaction between plant diversity and resource alteration on above-ground productivity and net biodiversity, complementarity, and selection effects. Despite strong increases in productivity with nutrient addition and decreases in productivity with drought, we found that resource alterations did not alter biodiversity–ecosystem functioning relationships. Our results suggest that these relationships are largely determined by increases in complementarity effects along plant species richness gradients. Although nutrient addition reduced complementarity effects at high diversity, this appears to be due to high biomass in monocultures under nutrient enrichment. Our results indicate that diversity and the complementarity of species are important regulators of grassland ecosystem productivity, regardless of changes in other drivers of ecosystem function.
How does the functional diversity of frugivorous birds shape the spatial pattern of seed dispersal? A case study in a relict plant species
Authors: Lavabre Jessica E. , Gilarranz Luis J. , Fortuna Miguel A. , Bascompte Jordi
Published: April 2016

Genetic markers used in combination with network analysis can characterize the fine spatial pattern of seed dispersal and assess the differential contribution of dispersers. As a case study, we focus on the seed dispersal service provided by a small guild of frugivorous birds to the common yew,Taxus baccataL., in southern Spain. We build the spatial networks of seed dispersal events between trees and seed-plots within the studied population—local network—and the spatial network that includes all dispersal events—regional network. Such networks are structured in well-defined modules, i.e. groups of tightly connected mother trees and seed-plots. Neither geographical distance, nor microhabitat type explained this modular structure, but when long-distance dispersal events are incorporated in the network it shows a relative increase in overall modularity. Independent field observations suggested the co-occurrence of two complementary groups, short- and long-distance dispersers, mostly contributing to the local and regional seed rain, respectively. The main long-distance disperser at our site,Turdus viscivorus, preferentially visits the most productive trees, thus shaping the seed rain at the landscape scale and affecting the local modular organization. We end by discussing how DNA barcoding could serve to better quantify the role of functional diversity.
The influence of balanced and imbalanced resource supply on biodiversity–functioning relationship across ecosystems
Authors: Lewandowska Aleksandra M. , Biermann Antje , Borer Elizabeth T. , Cebrián-Piqueras Miguel A. , Declerck Steven A. J. , De Meester Luc , Van Donk Ellen , Gamfeldt Lars , Gruner Daniel S. , Hagenah Nicole , Harpole W. Stanley , Kirkman Kevin P. , Klausmeier Christopher A. , Kleyer Michael , Knops Johannes M. H. , Lemmens Pieter , Lind Eric M. , Litchman Elena , Mantilla-Contreras Jasmin , Martens Koen , Meier Sandra , Minden Vanessa , Moore Joslin L. , Venterink Harry Olde , Seabloom Eric W. , Sommer Ulrich , Striebel Maren , Trenkamp Anastasia , Trinogga Juliane , Urabe Jotaro , Vyverman Wim , Van de Waal Dedmer B. , Widdicombe Claire E. , Hillebrand Helmut
Published: April 2016

Numerous studies show that increasing species richness leads to higher ecosystem productivity. This effect is often attributed to more efficient portioning of multiple resources in communities with higher numbers of competing species, indicating the role of resource supply and stoichiometry for biodiversity–ecosystem functioning relationships. Here, we merged theory on ecological stoichiometry with a framework of biodiversity–ecosystem functioning to understand how resource use transfers into primary production. We applied a structural equation model to define patterns of diversity–productivity relationships with respect to available resources. Meta-analysis was used to summarize the findings across ecosystem types ranging from aquatic ecosystems to grasslands and forests. As hypothesized, resource supply increased realized productivity and richness, but we found significant differences between ecosystems and study types. Increased richness was associated with increased productivity, although this effect was not seen in experiments. More even communities had lower productivity, indicating that biomass production is often maintained by a few dominant species, and reduced dominance generally reduced ecosystem productivity. This synthesis, which integrates observational and experimental studies in a variety of ecosystems and geographical regions, exposes common patterns and differences in biodiversity–functioning relationships, and increases the mechanistic understanding of changes in ecosystems productivity.
Consistent drivers of plant biodiversity across managed ecosystems
Authors: Minden Vanessa , Scherber Christoph , Cebrián Piqueras Miguel A. , Trinogga Juliane , Trenkamp Anastasia , Mantilla-Contreras Jasmin , Lienin Patrick , Kleyer Michael
Published: April 2016

Ecosystems managed for production of biomass are often characterized by low biodiversity because management aims to optimize single ecosystem functions (i.e. yield) involving deliberate selection of species or cultivars. In consequence, considerable differences in observed plant species richness and productivity remain across systems, and the drivers of these differences have remained poorly resolved so far. In addition, it has remained unclear if species richness feeds back on ecosystem functions such as yield in real-world systems. Here, we establish
N
= 360 experimental plots across a broad range of managed ecosystems in several European countries, and use structural equation models to unravel potential drivers of plant species richness. We hypothesize that the relationships between productivity, total biomass and observed species richness are affected by management intensity, and that these effects differ between habitat types (dry grasslands, grasslands, and wetlands). We found that local management was an important driver of species richness across systems. Management caused system disturbance, resulting in reduced productivity yet enhanced total biomass. Plant species richness was directly and positively driven by management, with consistently negative effects of total biomass. Productivity effects on richness were positive, negative or neutral. Our study shows that management and total biomass drive plant species richness across real-world managed systems.
Annotation Regression for Genome-Wide Association Studies with an Application to Psychiatric Genomic Consortium Data
Authors: Shin Sunyoung , Keleş Sündüz
Published: April 2016

Although genome-wide association studies (GWAS) have been successful at finding thousands of disease-associated genetic variants (GVs), identifying causal variants and elucidating the mechanisms by which genotypes influence phenotypes are critical open questions. A key challenge is that a large percentage of disease-associated GVs are potential regulatory variants located in noncoding regions, making them difficult to interpret. Recent research efforts focus on going beyond annotating GVs by integrating functional annotation data with GWAS to prioritize GVs. However, applicability of these approaches is challenged by high dimensionality and heterogeneity of functional annotation data. Furthermore, existing methods often assume global associations of GVs with annotation data. This strong assumption is susceptible to violations for GVs involved in many complex diseases. To address these issues, we develop a general regression framework, named Annotation Regression for GWAS (ARoG). ARoG is based on finite mixture of linear regression models where GWAS association measures are viewed as responses and functional annotations as predictors. This mixture framework addresses heterogeneity of effects of GVs by grouping them into clusters and high dimensionality of the functional annotations by enabling annotation selection within each cluster. ARoG further employs permutation testing to evaluate the significance of selected annotations. Computational experiments indicate that ARoG can discover distinct associations between disease risk and functional annotations. Application of ARoG to autism and schizophrenia data from Psychiatric Genomics Consortium led to identification of GVs that significantly affect interactions of several transcription factors with DNA as potential mechanisms contributing to these disorders.
Chromatin structure shapes the search process of transcription factors
Authors: Avcu Neslihan , Molina Nacho
Published: April 2016

The diffusion of regulatory proteins within the nucleus plays a crucial role in the dynamics of transcriptional regulation. The standard model assumes a 3D plus ID diffusion process: regulatory proteins either move freely in solution or slide on DNA. This model however does not considered the 3D structure of chromatin. Here we proposed a multi-scale stochastic model that integrates, for the first time, high-resolution information on chromatin structure as well as DNA-protein interactions. The dynamics of transcription factors was modeled as a slide plus jump diffusion process on a chromatin network based on pair-wise contact maps obtained from high-resolution Hi-C experiments. Our model allowed us to uncover the effects of chromatin structure on transcription factor occupancy profiles and target search times. Finally, we showed that binding sites clustered on few topological associated domains leading to a higher local concentration of transcription factors which could reflect an optimal strategy to efficiently use limited transcriptional resources.
The rate and potential relevance of new mutations in a colonizing plant lineage
Authors: Exposito-Alonso Moises , Becker Claude , Schuenemann Verena J. , Reiter Ella , Setzer Claudia , Slovak Radka , Brachi Benjamin , Hagmann Jörg , Grimm Dominik G. , Chen Jiahui , Busch Wolfgang , Bergelson Joy , Ness Rob W. , Krause Johannes , Burbano Hernán A. , Weigel Detlef
Published: April 2016

By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence ofde novomutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by “natural evolution experiments” that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plantArabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions – the subset of mutations that survived natural selection and drift –, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17thcentury, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.
A Land Plant-Specific Transcription Factor Directly Enhances Transcription of a Pathogenic Noncoding RNA Template by DNA-Dependent RNA Polymerase II
Authors: Wang Ying , Qu Jie , Ji Shaoyi , Wallace Andrew J. , Wu Jian , Li Yi , Gopalan Venkat , Ding Biao
Published: April 2016

Some DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato (Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP. PSTVd replication in the nucleoplasm generates (−)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (−)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA-9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.
Crystal structures of three 3,4,5-trimethoxybenzamide-based derivatives
Authors: Gomes Ligia R. , Low John Nicolson , Oliveira Catarina , Cagide Fernando , Borges Fernanda
Published: April 2016

The crystal structures of three benzamide derivatives,viz. N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide, C16H25NO5, (1),N-(6-anilinohexyl)-3,4,5-trimethoxybenzamide, C22H30N2O4, (2), andN-(6,6-diethoxyhexyl)-3,4,5-trimethoxybenzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the molecules. In each molecule, them-methoxy substituents are virtually coplanar with the benzyl ring, while thep-methoxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer istransrelated with the amidic H atom. In each structure, the benzamide N—H donor group and O acceptor atoms link the molecules intoC(4) chains. In1, a terminal –OH group links the molecules into aC(3) chain and the combined effect of theC(4) andC(3) chains is a ribbon made up of screw relatedR22(17) rings in which the ...O—H... chain lies in the centre of the ribbon and the trimethoxybenzyl groups forms the edges. In2, the combination of the benzamideC(4) chain and the hydrogen bond formed by the terminal N—H group to an O atom of the 4-methoxy group link the molecules into a chain ofR22(17) rings. In3, the molecules are linked only byC(4) chains.