bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic analysis of revenue losses and control costs associated with the spotted wing drosophila, Drosophila suzukii (Matsumura), in the California raspberry industry
Authors: Farnsworth Derek , Hamby Kelly A , Bolda Mark , Goodhue Rachael E , Williams Jeffrey C , Zalom Frank G
Published: December 2016

BACKGROUND

The spotted wing drosophila (SWD), Drosophila suzukii (Matsumura), is an invasive vinegar fly with a preference for infesting commercially viable berries and stone fruits. SWD infestations can reduce yields significantly, necessitating additional management activities. This analysis estimates economic losses in the California raspberry industry that have resulted from the SWD invasion.

RESULTS

California raspberry producers experienced considerable revenue losses and management costs in the first years following SWD's invasion of North America. Conventional producers have since developed effective chemical management programs, virtually eliminating revenue losses due to SWD and reducing the cost of management to that of purchasing and applying insecticides more often. Organic raspberry producers, who do not have access to the same chemical controls, continue to confront substantial SWD‐related revenue losses. These losses can be mitigated only by applying expensive insecticides registered for organic use and by performing labor‐intensive field sanitation.

CONCLUSION

SWD's invasion into North America has caused extensive crop losses to berry and cherry crops in California and elsewhere. Agricultural producers and researchers have responded quickly to this pest by developing management programs that significantly reduce revenue losses. Economic losses are expected to continue to fall as producers learn to manage SWD more efficiently and as new control tactics become available. © 2016 Society of Chemical Industry
Effects of decomposition on carbon and nitrogen stable isotope values of muscle tissue of varying lipid content from three aquatic vertebrate species
Authors: Yurkowski David J. , Hussey Anna J. , Hussey Nigel E. , Fisk Aaron T.
Published: December 2016

Rationale

Stable isotopes are a prominent tool in animal ecology where data is obtained from analyzing animal tissues, which are typically stored prior to analysis. However, the effect of decomposition on the reliability of stable isotope ratios from animal tissue prior to storage has been seldom studied. Here, we examine the long‐term effects of freezing and decomposition of animal tissue on δ13C and δ15N values across three different aquatic species of varying lipid content.

Methods

Ringed seal, lake trout and Greenland shark muscle were divided into different treatment groups and analyzed for their δ13C values, carbon content (%C), δ15N values, and nitrogen content (%N) at specific time intervals. The intervals included days 0, 128 and 700 for the frozen storage treatment and at days 0, 1, 2, 4, 8, 16, 32, 64, 128 and 256 for the tissue decomposition treatment in open and closed vials at room temperature.

Results

The difference in δ13C and δ15N values between the control and days 128 and 700 for the frozen treatment was minimal and not significant for any species. Generally, significant decreases in carbon (%C) and nitrogen (%N) content and significant increases (>0.5‰) in δ13C and δ15N values occurred for muscle of each species left to decompose for 256 days, probably due to the preferential uptake of lighter isotopes during decomposition by microbes. However, the magnitude of change in the δ13C and δ15N values up to 8 days in both treatments was low (generally ≤0.1‰) and not significant across most species.

Conclusions

Freezing for extended time periods (up to 700 days) is a viable storage technique for stable isotope analysis of aquatic animal muscle tissue across a range of lipid contents. Muscle tissue left to decompose at room temperature showed no significant change in δ13C and δ15N values after 8 days, and such tissues would still be reliable for ecological interpretations. However, caution should be used for decomposed tissue for >8 days as the δ13C and δ15N values will probably be artificially high. Copyright © 2016 John Wiley & Sons, Ltd.
Prenatal diagnosis and prognosis of accelerated idioventricular rhythm
Authors: Fouron J.‐C. , McNeal‐Davidson A. , Abadir S. , Fournier A. , Bigras J.‐L. , Boutin C. , Brassard M. , Raboisson M.‐J. , van Doesburg N. , Berger A. , Brisebois S. , Gendron R.
Published: December 2016

Objectives

As postnatal identification of accelerated idioventricular rhythm (AIVR) relies on specific electrocardiographic patterns, prenatal diagnosis of this condition is challenging and its true incidence is unknown. The objectives of this study were to evaluate the performance of prenatal ultrasonography in identifying intrauterine cardiocirculatory events linked to specific electrocardiographic signs of postnatal AIVR, including left or right ventricular origin, and to assess the prenatal prognosis of this arrhythmia.

Methods

We reviewed Doppler tracings from the superior vena cava/ascending aorta (SVC/Ao), ductus venosus (DV), ductus arteriosus (DA) and aortic isthmus (AoI), as well as simultaneous M‐mode recordings of septal and left ventricular wall motions of fetuses diagnosed with AIVR from January 2004 to December 2014.

Results

Three cases of AIVR were identified among 27 912 fetuses. SVC/Ao Doppler flow recordings revealed atrioventricular dissociation (ventricular rates within 20% of atrial rates) in all three fetuses and episodes of isorhythmic atrioventricular dissociation in one, while M‐mode confirmed normal left ventricular shortening fraction in all cases. Fusion beats were observed on AoI tracing in one fetus, while simultaneous recordings of AoI and DA revealed signs of right bundle branch block in one case and left bundle branch block in the other two. On DV Doppler recordings, retrograde a‐waves in the presence of simultaneous atrial and ventricular contractions were observed in all three fetuses, leading to an increase in central venous pressure in all and hydrops fetalis in two cases without evidence of ventricular dysfunction.

Conclusions

Echocardiographic criteria required for postnatal diagnosis of AIVR can be documented in utero using specific ultrasonographic approaches. During fetal life, AIVR may not be a benign entity. Hydrops fetalis is frequently associated with AIVR because of increase in central venous pressure related to simultaneous atrioventricular contractions; thus, the ultrasonographic investigation protocol of fetuses with unexplained hydrops fetalis should aim at ruling out AIVR and include Doppler flow recordings in SVC/Ao, DV, AoI, DA and umbilical vein. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Treatment of cervical pregnancy with ultrasound‐guided local methotrexate injection
Authors: Yamaguchi M. , Honda R. , Erdenebaatar C. , Monsur M. , Honda T. , Sakaguchi I. , Okamura Y. , Ohba T. , Katabuchi H.
Published: December 2016

Objectives

Cervical pregnancy (CP) is a rare type of ectopic pregnancy. While methotrexate (MTX) is generally the first‐line method of choice for clinically stable women, there is still no consensus on the most appropriate treatment for this abnormal pregnancy. The aim of this study was to investigate the efficacy of a single local MTX injection under transvaginal ultrasound guidance for the initial treatment of CP and to assess post‐treatment fertility.

Methods

We reviewed retrospectively 15 patients with CP treated with local MTX injection under transvaginal ultrasound guidance. In all patients, the serum human chorionic gonadotropin (hCG) levels were monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging (MRI) was performed as necessary. We evaluated the patients' clinical characteristics and clinical course after treatment, the efficacy of the treatment and the post‐treatment fertility in patients desiring subsequent pregnancy.

Results

The median estimated gestational age at the time of MTX injection was 6 + 2 (range, 5 + 2 to 11 + 0) weeks. All 15 patients were treated successfully, without the need for blood transfusion or surgical procedures; however, three patients required an additional local MTX injection due to a poor decline in serum hCG level following the initial injection, while one patient required uterine artery embolization due to persistent vaginal bleeding and an enlarging gestational sac with blood vessels visible on contrast‐enhanced MRI. The mean time following initial MTX injection for hCG normalization was 43.8 (95% CI, 33.3–54.3) days and for resumption of menses was 68.4 (95% CI, 51.9–84.9) days. Seven of the 10 women desiring subsequent pregnancy following treatment had uneventful pregnancy, one became pregnant but miscarried spontaneously at 8 weeks of gestation, one was treated by laparoscopic surgery after diagnosis of a tubal pregnancy and one did not conceive.

Conclusions

A single, ultrasound‐guided, local MTX injection is apparently effective for the treatment of CP without the need for concomitant procedures or surgical intervention. Furthermore, this conservative technique both preserves fertility and allows for the possibility of subsequent uneventful pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Landscape structure and agricultural intensification are weak predictors of host range and parasitism rate of cereal aphids
Authors: Hawro Violetta , Ceryngier Piotr , Kowalska Anna , Ulrich Werner
Published: December 2016

Proportions of specialist and generalist primary parasitoids have been described by the resource breadth and the trade‐off hypothesis. These alternative hypotheses predict either decreased or increased, respectively, parasitism rate of shared aphid species by specialist parasitoids. We tested both hypotheses and the confounding effects of landscape structure and agricultural intensification (AI) using extensive samplings of aphids and their parasitoids in Polish agricultural landscapes. Abundances, species composition of aphids, primary parasitoids, and parasitism rate of aphids by specialists and generalist parasitoids were analysed. Contrary to our expectations we found equally decreased parasitism rates by both types of primary parasitoids at higher aphid densities and thus proportion of specialists to generalists did not change with increasing host density. In line with the resource breadth hypothesis, specialist parasitoids had always lower abundances and parasitism rates than generalist parasitoids. Landscape diversity and agricultural intensification did not influence the host‐parasitoid population dynamics. We speculate that these contrasting results could be caused by the additional density effects of secondary parasitoids. We conclude that simplistic two‐trophic‐level population models are not able to fully describe the complex dynamics of trophic networks. We also argue that agricultural intensification has lower effects on abundance and effectiveness of parasitoids than predicted by respective predator–prey models and empirical studies performed in controlled and artificial conditions.
Degradation in intrinsic connectivity networks across the Alzheimer's disease spectrum
Authors: Nuttall Rachel , Pasquini Lorenzo , Scherr Martin , Sorg Christian ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2016

Introduction

Changes in intrinsic functional connectivity (iFC) have been reported at various stages of the Alzheimer's disease (AD) spectrum. We aimed to investigate such alterations over a variety of large‐scale intrinsic brain networks (iBNs) across the spectrum of amyloid β positivity and uncover their relation to cognitive impairment.

Methods

Eight iBNs were defined from resting‐state functional magnetic resonance imaging data. In amyloid β–positive healthy subjects, prodromal, and AD patients (N = 70), within‐network iFC (intra‐iFC) and between‐network iFC (inter‐iFC) were correlated with scores of cognitive impairment.

Results

Across all iBNs, a general degradation in intra‐iFC along the scale of cognitive impairment severity was found. Only subtle changes in inter‐iFC were identified.

Discussion

Across the AD spectrum, changes in iFC that are strongly related to cognitive impairment occur within an extensive variety of networks.
Awareness of social studies teacher candidates on refugees in Turkey
Authors: Tarman Bülent , Gürel Davut
Published: December 2016

The aim of this study is to obtain information about the awareness of social studies teacher candidates about the refugee problem in Turkey. In this regard, a group of teacher candidates are asked their opinion on the subject of refugees in Turkey and as to how they perceive the problem. Interview method is used in the study for data collection. The obtained data is subjected to content analysis via Nvivo 8 software package. As a result of the study, it is observed that the participants residing in provinces with high refugee population have a more negative attitude towards refugees, whereas the ones in areas with no refugee population have a more positive attitude towards them. It is also observed that, in general, teacher candidates do not pay any special effort to acquire information about the subject.
Niobian rutile in Cr-V-bearing rocks of the Sludyanka metamorphic complex (Southern Baikal area)
Authors: Reznitsky L.Z. , Sklyarov E.V. , Suvorova L.F. , Kanakin S.V. , Karmanov N.S. , Barash I.G.
Published: December 2016

Cr-V-bearing rocks of the Sludyanka metamorphic complex in the Southern Baikal area contain accessory niobian rutile with Nb contents unusually high for metamorphic rocks (10–12 to 20–25 wt.% Nb2O5, or, occasionally, up to 36–37 wt.%). Incorporation of Nb5+ into the rutile structure is balanced by Cr3+ and V3+, which reach 16 wt.% Cr2O3 and 8 wt.% (or, rarely, up to 20 wt.%) V2O3. The distribution of Nb, Cr, and V in rutile is very uneven, down to the microscale. It does not depend on PT conditions, being rather controlled by crystallization kinetics of minerals competing with rutile in the paragenesis.
Basaltic magmatism and strike-slip tectonics in the Arctic margin of Eurasia: evidence for the early stage of geodynamic evolution of the Amerasia Basin
Authors: Shipilov E.V.
Published: December 2016

Interpretation of geological and geophysical data from several regions in the Arctic continental margin of Eurasia which differ in structure and tectonic settings shed new light on the early history of the Arctic Ocean (Canada Basin) opening. Many issues of regional tectonics and geodynamics become clear due to evidence of Late Mesozoic magmatism within the continental margins of the Barents and East Siberian Seas and strike-slip tectonics in the Chukchi shelf. Interpretation analysis is applied to reconstruct the formation of structures in the Amerasia Basin during the Arctic Ocean initiation.
Physicochemical parameters and age of the Vasil’kovskoe gold deposit (northern Kazakhstan)
Authors: Khomenko M.O. , Gibsher N.A. , Tomilenko A.A. , Bul’bak T.A. , Ryabukha M.A. , Semenova D.V.
Published: December 2016

A superlarge gold-ore stockwork of the Vasil’kovskoe deposit (with gold resources of more than 380 tons) is located at the contact of porphyroblastic granodiorites and diorites in northern Kazakhstan. The specifics of the Vasil’kovskoe deposit is a wide occurrence of gray (so-called ore) gold-bearing quartz, which, together with white quartz, composes quartz–sulfide veins and veinlets in the stockwork. Based on thermobarogeochemical and isotope-geochemical data, we have established that gray quartz and arsenopyrite of the deposit formed with the participation of K–Na–Mg–Cl-containing aqueous CO2–hydrocarbon fluids at 250–550 ºC, 0.1–2.5 kbar, and salinity of 7.0–22.5 wt.% NaCl equiv. (seldom, >30–40 wt.% NaCl equiv.). The cyclic recurrence of parameter fluctuations was accompanied by the deposition of gold, which led to the formation of gold-rich veinlet ores in the stockwork core. White quartz formed at lower temperatures, 120–310 ºC, and 0.2–1.0 kbar, with the participation of Ca–Na–Cl-containing fluids with salinity of 2.0–11.0 wt.% NaCl equiv. In addition to H2O and CO2, hydrocarbons and their derivates (paraffins, olefins, arenes, alcohols, ethers, aldehydes, ketones, and carboxylic acids) as well as nitrogen-containing (C2H3N, C3H9N, C7H5N, and C8H5NO2) and sulfur-containing (CS2, COS, SO2, C2H6S2, etc.) compounds (indicators of reducing conditions) were involved in the ore formation. The sulfur isotope composition of sulfides (δ34S = +5.7 to + 11.8‰) and the carbon isotope composition of CO2 in fluid inclusions in gray (δ13C = –2.1 to –4.6‰) and white (δ13C = –11.0 to –21.4‰) quartz as well as its positive and negative anomalies of Eu point to the crustal source of the fluids. The gray color of quartz is due to abundant CO2–hydrocarbon-containing inclusions, carbon particles, and sulfides. Crystallization of ore-hosting granodiorites happened in the period from 490.0 ± 4.4 to 443.5 ± 4.1 Ma. The age of the areal K-feldspathization of granodiorites, preceding the ore formation, is 375.2 ± 3.7 Ma. Formation of gold-including parageneses took place in the period from 311.7 ± 6.4 to 279.2 ± 2.5 Ma, i.e., lasted no less than 30 Myr.
Oil industry of major historical centers of the Volga–Ural petroleum province: past, current state, and long-run prospects
Authors: Kontorovich A.E. , Eder L.V. , Filimonova I.V. , Mishenin M.V. , Nemov V.Yu
Published: December 2016

We analyze the history of oil discoveries of different sizes in two centers of the Volga–Ural petroleum province, the Republics of Bashkortostan and Tatarstan, and demonstrate the important role played by Academicians I.M. Gubkin and A.A. Trofimuk in these discoveries. Special focus is placed on the analysis of small and smallest oil fields and the sequence of their discovery. It was shown that all discoveries in Tatarstan and Bashkortostan were the result of the exploration filter. It was also shown that the establishment and support of small oil businesses in Bashkortostan and Tatarstan can be an importance means of the facilitating development of small and smallest fields. The study discusses the role of small independent oil companies in the regional oil production, considers priority areas of state and regional and legal support of small and medium oil enterprises, and presents oil production forecast for Bashkortostan and Tatarstan.
Reading Raindrops: Microphysics in Typhoon Matmo
Authors: Crane Leah
Published: December 2016

Quantitative predictions about tropical storms require an understanding of even their smallest physical processes. A new study observes unusual microphysics in 2014's Typhoon Matmo.
Moving Forward at Fall Meeting Against Harassment
Authors: Davidson Eric
Published: December 2016

With buttons, signage, nine planned events, and a Thunderclap campaign, Fall Meeting will combat harassment and support a safe and welcoming scientific community.
Obama Science Adviser Warns Against Retreats on Climate, Science
Authors: Showstack Randy
Published: December 2016

Holdren sees pitfalls for U.S. global leadership in withdrawing from climate accord and says that moving Earth observations out of NASA "is a terrible idea."
Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems
Authors: Eklund Lauri , Kangas Jaakko , Saharinen Pipsa
Published: December 2016

Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases.
Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance
Authors: Luo Yong , Li Ling , Xu Xiaohui , Wu Tong , Yang Mengliu , Zhang Cheng , Mou Huaming , Zhou Tingting , Jia Yanjun , Cai Chenrongrong , Liu Hua , Yang Gangyi , Zhang Xianxiang
Published: December 2016

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose. Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.
Resting Tremor after Mild Head Injury: Case Report
Authors: Magalhães Marcelo , Martins Ana , Freire Anna , Dias Jamile , Ribeiro Ludmila , de Oliveira Mariana , Mendes Mateus , de Carvalho Monique , Versiani Theresa
Published: December 2016

Over the past few decades, it has been recognized that traumatic brain injury (TBI) may result in various movement disorders. However, moderate or mild TBI only rarely causes persistent post-traumatic movement disorders. In the present report, we describe a case of secondary tremor due to a mild head injury with a transitory loss of consciousness. A 26-year-old man developed an isolated rest tremor of the hands and legs without other neurologic signs. The interval between the head trauma and the onset of the symptoms was 4 months. Neuroimaging studies reveled gliosis in the lentiform nucleus. Haloperidol administration resulted in tremor reduction. A rest tremor, similar to essential tremor, can be a rare complication of head trauma. Haloperidol may be an effective and safe treatment modality for post-traumatic tremor. Further studies are needed to clarify the optimal drug for the treatment of post-traumatic tremor.
Roles of density-dependent growth and life history evolution in accounting for fisheries-induced trait changes
Authors: Eikeset Anne Maria , Dunlop Erin S. , Heino Mikko , Storvik Geir , Stenseth Nils C. , Dieckmann Ulf
Published: December 2016

Significance

Rapid anthropogenic trait changes in fish stocks is a highly publicized ocean conservation issue, yet the relative contributions of evolutionary and ecological dynamics are unknown. We present an integrative empirically based simulation model to determine the role of these contributions in the world’s largest cod stock. We quantitatively evaluate predictions with different density-dependent growth models using historical stock-specific data. The amount of evolution required for explaining observed maturation trends is small, yet with weakly density-dependent growth, critical for preventing stock collapse. The role of evolution in explaining trends is diminished when density-dependent growth is present. Our study reveals how interactions among evolution, ecology, and fisheries influence stock dynamics and harvest sustainability, emphasizing the need for integrated approaches to fisheries management.
Kinetic isotope effects reveal early transition state of protein lysine methyltransferase SET8
Authors: Linscott Joshua A. , Kapilashrami Kanishk , Wang Zhen , Senevirathne Chamara , Bothwell Ian R. , Blum Gil , Luo Minkui
Published: December 2016

Significance

We developed an MS-based method to determine kinetic isotope effects and binding isotope effects on protein lysine methyltransferase SET8-catalyzed monomethylation. These parameters, coupled with steady-state kinetics and molecular modeling, outlined the reaction path of SET8-catalyzed methylation. Upon the formation of the
S
-adenosyl-
l
-methionine–SET8–histone 4 lysine 20 intermediate complex followed by lysine deprotonation, the reaction goes through an early, asymmetrical transition state (TS) with the small engagement of the C-N bond and the partial dissociation of the C-S bond. This TS structure is distinct from the known TS structures of other protein lysine methyltransferases (PKMTs) and thus presents the feasibility to design selective TS analog inhibitors against PKMTs. The developed techniques can also be generally applicable to examining other protein methylation and posttranslational modifications.
Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide
Authors: Barde Swapnali , Rüegg Joelle , Prud’homme Josée , Ekström Tomas J. , Palkovits Miklos , Turecki Gustavo , Bagdy Gyorgy , Ihnatko Robert , Theodorsson Elvar , Juhasz Gabriella , Diaz-Heijtz Rochellys , Mechawar Naguib , Hökfelt Tomas G. M.
Published: December 2016

Significance

Depression is a seriously disabling disorder, twice as common in women as in men. Lack of efficacy of existing pharmacotherapies in subsets of patients has led to an intensive search for new targets for antidepressant development, including receptors for neuropeptides such as galanin (GAL). In this study, we explore GAL and its three receptors, GAL1–3, comparing postmortem brain regions from depressed suicide patients and controls. Using quantitative PCR and bisulfite pyrosequencing, we report significant changes in the transcript and DNA methylation levels ofGALand galanin receptor 3 (GALR3) in the locus coeruleus and dorsal raphe nucleus, two regions important for mood regulation. Our findings suggest GAL3involvement in depressive disorder, making it a possible drug target for this disease.
To act or not to act: responses to electronic health record prompts by family medicine clinicians
Authors: Zazove Philip , McKee Michael , Schleicher Lauren , Green Lee , Kileny Paul , Rapai Mary , Mulhem Elie
Published: December 2016

Objective: A major focus of health care today is a strong emphasis on improving the health and quality of care for entire patient populations. One common approach utilizes electronic clinical alerts to prompt clinicians when certain interventions are due for individual patients being seen. However, these alerts have not been consistently effective, particularly for less visible (though important) conditions such as hearing loss (HL) screening.

Materials and Methods: We conducted hour-long cognitive task analysis interviews to explore how family medicine clinicians view, perceive, and use electronic clinical alerts, and to utilize this information to design a more effective alert using HL identification and referral as a model diagnosis.

Results: Four key direct barriers were identified that impeded alert use: poor standardization and formatting, time pressures in primary care, clinic workflow variations, and mental models of the condition being prompted (in this case, HL). One indirect barrier was identified: electronic health record and institution/government regulations. We identified that clinicians’ mental model of the condition being prompted was probably the major barrier, though this was often expressed as time pressure. We discuss solutions to each of the 5 identified barriers, such as addressing physicians’ mental models, by focusing on physicians’ expertise rather than knowledge to improve their comfort when caring for patients with the conditions being prompted.

Conclusions: To unleash the potential of electronic clinical alerts, electronic health record and health care institutions need to address some key barriers. We outline these barriers and propose solutions.
Mechanobiological implications of articular cartilage crystals
Authors: Carlson Alyssa K. , McCutchen Carley N. , June Ronald K.
Published: December 2016

Purpose of review

Calcium crystals exist in both pathological and normal articular cartilage. The prevalence of these crystals dramatically increases with age, and crystals are typically found in osteoarthritic cartilage and synovial fluid. Relatively few studies have examined the effects of crystals on cartilage biomechanics or chondrocyte mechanotransduction. The purpose of this review is to describe how crystals could influence cartilage biomechanics and mechanotransduction in osteoarthritis.

Recent findings

Crystals are found in both loaded and unloaded regions of articular cartilage. Exogenous crystals, in combination with joint motion, result in substantial joint inflammation. Articular cartilage vesicles promote crystal formation, and these vesicles are found near the periphery of chondrocytes. Crystallographic studies report monoclinic symmetry for synthetic crystals, suggesting that crystals will have a large stiffness compared with the cartilage extracellular matrix, the pericellular matrix, or the chondrocyte. This stiffness imbalance may cause crystal-induced dysregulation of chondrocyte mechanotransduction promoting both aging and osteoarthritis chondrocyte phenotypes.

Because of their high stiffness compared with cartilage matrix, crystals likely alter chondrocyte mechanotransduction, and high concentrations of crystals within cartilage may alter macroscale biomechanics. Future studies should focus on understanding the mechanical properties of joint crystals and developing methods to understand how crystals affect chondrocyte mechanotransduction.
Modification of the alignment between the tibial tubercle and the trochlear groove induced by temporary hemiepiphysiodesis for lower extremity angular deformities: a trigonometric analysis
Authors: Ceroni Dimitri , Dhouib Amira , Merlini Laura , Kampouroglou Georgios
Published: December 2016

This study aimed to predict the modification of the alignment between the tibial tubercle (TT) and the trochlear groove (TG) that occurs during femoral or tibial hemiepiphysiodesis. MRI scans of 541 knees were retrospectively reviewed to determine the distances between the cranial insertion of the patellar tendon on the TT and the femoral physis (FP)/tibial physis (TP). Thereafter, we developed a trigonometric formula to calculate the predicted change of the TT–TG distance that occurs during hemiepiphysiodesis around the knee using both the planned angular correction as well as the length between the physis (both distal femoral and proximal tibial) and the insertion of the patellar tendon of the TT. This study showed that TT–FP and TT–TP distances vary very little with sex and age during growth and the mean values of FP–TT and TP–TT distances (55 and 7 mm, respectively) can thus be used in clinical settings for calculating a rough estimate of the translation of the TT position that will occur during ‘guided growth’. On this subject, one can expect a 1 mm simultaneous lateral or medial transfer of the TT for every 1° of angular correction during distal femoral hemiepiphysiodesis. For proximal tibial hemiepiphysiodesis, an angular correction of 8° should roughly translate into a simultaneous 1 mm transfer of the TT. This study puts forward the hypothesis that a simultaneous modification of the TT–TG distance has to be expected following hemiepiphysiodesis, whether femoral or tibial. Level of evidence: III.
Hallux valgus deformity correction without fusion in children with cerebral palsy
Authors: Bayhan Ilhan A. , Kadhim Muayad , Sees Julieanne P. , Nishnianidze Tristan , Rogers Kenneth J. , Er Mehmet S. , Miller Freeman
Published: December 2016

This study aimed to evaluate the outcomes of nonarthrodesis surgical treatment of hallux valgus (HV) deformity in children with cerebral palsy using radiographic and gait analysis parameters. There were 25 patients who had hallux valgus correction in 39 feet. The mean age at surgery was 15±2.8 years and the mean follow-up duration was 14.6 months. The first metatarsal osteotomy was performed in nine feet, bunionectomy in 25 feet, and Aiken osteotomy in 32 feet. None had metatarsophalangeal joint fusion. We observed a significant correlation between HV correction and other foot and ankle gait parameters. Our study showed correction of HV deformity at short-term follow-up without fusion of the metatarsophalangeal joint. Level of evidence: Level IV Therapeutic Studies.
Short article: Capsule endoscopy in graft-versus-host disease
Authors: Pérez-Cuadrado-Robles Enrique , Castilla-Llorente Cristina , Quénéhervé Lucille , López-Higueras Antonio , Pérez-Cuadrado-Martínez Enrique
Published: December 2016

Introduction

The gold standard in the diagnosis of gastrointestinal graft-versus-host disease (GVHD) after allogenic hematopoietic stem cell transplantation is conventional endoscopy with histopathological assessment. The role of capsule endoscopy (CE) is uncertain. The aim of the present study was to investigate the accuracy of CE in this setting, comparing the clinical, endoscopic and histological data.

Methods

This was a retrospective single-centre study that included 57 (mean age: 47.18±15.05 years, 57.89% men) patients presenting with GVHD who underwent a valid CE and histopathological analysis by conventional endoscopy between January 2004 and July 2016. The endoscopic scored findings, clinical data and histopathological diagnosis were compared using duodenal histology as the gold standard.

Results

CE detected mild (n=4, 7.02%), moderate (n=6, 10.53%) and severe (n=21, 36.84%) grades, with a higher diagnostic yield than conventional endoscopy (54.39 vs. 28.07%, P<0.001). A positive CE predicted positive histology (80.64 vs. 15.38%, P<0.001) with a sensitivity, specificity, negative predictive value and accuracy of 86.21, 78.57, 84.62 and 82.46%. This procedure detected more mild-to-moderate histological lesions than conventional endoscopy (8.77 vs. 3.51%, P=0.25). In addition, 16% of patients with a previous normal endoscopy with biopsies had a pathological CE and there were eight (25.81%) patients with positive CE images unreachable by conventional endoscopy.

Conclusion

CE is a useful device in GVHD, achieving high accuracy values and diagnostic yield. However, its results may be interpreted in conjunction with clinical and histological features, particularly in mild-to-moderate stages.
MultiCellDS: a standard and a community for sharing multicellular data
Authors: Friedman Samuel H. , Anderson Alexander R. A. , Bortz David M. , Fletcher Alexander G. , Frieboes Hermann B. , Ghaffarizadeh Ahmadreza , Grimes David Robert , Hawkins-Daarud Andrea , Hoehme Stefan , Juarez Edwin F. , Kesselman Carl , Merks Roeland M.H. , Mumenthaler Shannon M. , Newton Paul K. , Norton Kerri-Ann , Rawat Rishi , Rockne Russell C. , Ruderman Daniel , Scott Jacob , Sindi Suzanne S. , Sparks Jessica L. , Swanson Kristin , Agus David B. , Macklin Paul
Published: December 2016

Cell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated “public data libraries”, and tools to combine and analyze shared data. To address these needs, our multidisciplinary community created MultiCellDS (MultiCellular Data Standard): an extensible standard, a library of digital cell lines and tissue snapshots, and support software. With the help of experimentalists, clinicians, modelers, and data and library scientists, we can grow this seed into a community-owned ecosystem of shared data and tools, to the benefit of basic science, engineering, and human health.
Practical Use of Methods for Imputation of HLA Alleles from SNP Genotype Data
Authors: Motyer Allan , Vukcevic Damjan , Dilthey Alexander , Donnelly Peter , McVean Gil , Leslie Stephen
Published: December 2016

The human leukocyte antigen (HLA) genes play an essential role in immune function. Typing of HLA alleles is critical for transplantation and is informative for many disease associations. The high cost of accurate lab-based HLA typing has precluded its use in large-scale disease-association studies. The development of statistical methods to type alleles using linkage disequilibrium with nearby SNPs, called HLA imputation, has allowed large cohorts of individuals to be typed accurately, so that massive numbers of affected individuals and controls may be studied. This has resulted in many important findings. Several HLA imputation methods have been widely used, however their relative performance has not been adequately addressed. We have conducted a comprehensive study to evaluate the most widely used HLA imputation methods. We assembled a multi-ethnic panel of 10,561 individuals with SNP genotype data and lab-based typing of alleles at 11 HLA genes at two-field resolution, and used it to train and validate each method. Use of this panel leads to imputation accuracy far superior to what is currently publicly available. We present a highly-accurate new imputation method, HLA*IMP:03. We address the question of optimal use of HLA imputations in tests of genetic association, showing that it is usually not necessary to apply a probability threshold to achieve maximal power. We also investigated the effect on accuracy of SNP density and population stratification at the continental level and show that neither of these are a significant concern.
Direct and context-dependent effects of light, temperature, and phytoplankton shape bacterial community composition
Authors: Paver Sara F. , Kent Angela D.
Published: December 2016

Species interactions, environmental conditions, and stochastic processes work in concert to bring about changes in community structure. However, the relative importance of specific factors and how their combined influence affects community composition remain largely unclear. We conducted a multi-factorial experiment to 1) disentangle the direct and interaction-mediated effects of environmental conditions and 2) augment our understanding of how environmental context modulates species interactions. We focus on a planktonic system where interactions with phytoplankton effect changes in the composition of bacterial communities, and light and temperature conditions can influence bacteria directly as well as through their interactions with phytoplankton. Epilimnetic bacteria from two humic lakes were combined with phytoplankton assemblages from each lake (“home” or “away”) or a no-phytoplankton control and incubated for 5 days under all combinations of light (surface, ∼25% surface irradiance) and temperature (5 levels from 10°C to 25°C). Observed light effects were primarily direct while phytoplankton and temperature effects on bacterial community composition were highly interdependent. The influence of temperature on aquatic bacteria was consistently mediated by phytoplankton and most pronounced for bacteria incubated with “away” phytoplankton treatments, likely due to the availability of novel phytoplankton-derived resources. The effects of phytoplankton on bacterial community composition were generally increased at higher temperatures. Incorporating mechanisms underlying the observed interdependent effects of species interactions and environmental conditions into modeling frameworks may improve our ability to forecast ecological responses to environmental change.
Yorkie is required to restrict the injury responses in planarians
Authors: Lin Alexander Y.T. , Pearson Bret J.
Published: December 2016

Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding cues remains relatively unknown. The freshwater planarian,Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade,yorkie, during planarian regeneration and its role in restricting early injury responses. Inyki(RNAi)regenerating animals, wound responses are hyper-activated; the bimodal proliferation kinetics are heighted and prolonged, while the transcriptional injury responses are similarly augmented with dysregulated temporal patterns. We also uncovered novel wound-induced genes by RNAseq that are primarily associated with tissue patterning. Indeed, a high proportion of non-wound- and wound-induced patterning molecules are mis-expressed inyki(RNAi), which we demonstrate is in part due to an expanded muscle cell population. These altered injury responses have consequential effects on regenerative outcomes, specifically sensing the size of a given injury and appropriately scaling organ and tissue sizes. Taken together, our results suggest thatykifunctions as a key node to integrate the injury responses of proliferation, apoptosis, injury-induced transcription, and patterning to coordinate regeneration.
NextSV: a meta-caller for structural variants from low-coverage long-read sequencing data
Authors: Fang Li , Hu Jiang , Wang Depeng , Wang Kai
Published: December 2016

Background

Structural variants (SVs) in human genomes are implicated in a variety of human diseases. Long-read sequencing delivers much longer read lengths than short-read sequencing and may greatly improve SV detection. However, due to the relatively high cost of long-read sequencing, it is unclear what coverage is needed and how to optimally use the aligners and SV callers.

Results

In this study, we developed NextSV, a meta-caller to perform SV calling from low coverage long-read sequencing data. NextSV integrates three aligners and three SV callers and generates two integrated call sets (sensitive/stringent) for different analysis purposes. We evaluated SV calling performance of NextSV under different PacBio coverages on two personal genomes, NA12878 and HX1. Our results showed that, compared with running any single SV caller, NextSV stringent call set had higher precision and balanced accuracy (F1 score) while NextSV sensitive call set had a higher recall. At 10X coverage, the recall of NextSV sensitive call set was 93.5% to 94.1% for deletions and 87.9% to 93.2% for insertions, indicating that ~10X coverage might be an optimal coverage to use in practice, considering the balance between the sequencing costs and the recall rates. We further evaluated the Mendelian errors on an Ashkenazi Jewish trio dataset.

Conclusions

Our results provide useful guidelines for SV detection from low coverage whole-genome PacBio data and we expect that NextSV will facilitate the analysis of SVs on long-read sequencing data.
Cas13b is a Type VI-B CRISPR-associated RNA-Guided RNase differentially regulated by accessory proteins Csx27 and Csx28
Authors: Smargon Aaron , Cox David B.T. , Pyzocha Neena , Zheng Kaijie , Slaymaker Ian M. , Gootenberg Jonathan S. , Abudayyeh Omar A. , Essletzbichler Patrick , Shmakov Sergey , Makarova Kira S. , Koonin Eugene V. , Zhang Feng
Published: December 2016

CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two Class 2 CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 and encompass a single large effector protein, Cas13b, along with one of two previously uncharacterized associated proteins, Csx27 or Csx28. We establish that these CRISPR-Cas systems can achieve RNA interference when heterologously expressed. Through a combination of biochemical and genetic experiments, we show that Cas13b processes its own CRISPR array with short and long direct repeats, cleaves target RNA, and exhibits collateral RNase activity. Using anE. coliessential gene screen, we demonstrate that Cas13b has a double-sided protospacer-flanking sequence and elucidate RNA secondary structure requirements for targeting. We also find that Csx27 represses, whereas Csx28 enhances, Cas13b-mediated RNA interference. Characterization of these CRISPR systems creates opportunities to develop tools to manipulate and monitor cellular transcripts.
Evolutionary rescue through partly heritable phenotypic variability
Authors: Carja Oana , Plotkin Joshua B.
Published: December 2016

Environmental variation is commonplace, but unpredictable. Populations that encounter a deleterious environment can sometimes avoid extinction by rapid evolutionary adaptation. Phenotypic variability, whereby a single genotype can express multiple different phenotypes, might play an important role in rescuing such populations from extinction. This type of evolutionary bet-hedging need not confer a direct benefit to a single individual, but it may increase the chance of long-term survival of a lineage. Here we develop a population-genetic model to explore how partly heritable phenotypic variability influences the probability of evolutionary rescue and the mean duration of population persistence in changing environments. We find that the probability of population persistence depends non-monotonically on the degree of phenotypic heritability between generations: some heritability can help avert extinction, but too much heritability removes any benefit of phenotypic variability. We discuss the implications of these results in the context of therapies designed to eradicate populations of pathogens or aberrant cellular lineages.
LOCALIZER: subcellular localization prediction of both plant and effector proteins in the plant cell
Authors: Sperschneider Jana , Catanzariti Ann-Maree , DeBoer Kathleen , Petre Benjamin , Gardiner Donald M. , Singh Karam B , Dodds Peter N. , Taylor Jennifer M.
Published: December 2016

Pathogens are able to deliver effector proteins into plant cells to enable infection. Some effectors have been found to enter subcellular compartments by mimicking host targeting sequences. Although many computational methods exist to predict plant protein subcellular localization, they perform poorly for effectors. We introduce LOCALIZER for predicting plant and effector protein localization to chloroplasts, mitochondria, and nuclei. LOCALIZER shows greater prediction accuracy for chloroplast and mitochondrial targeting compared to other methods for 652 plant proteins. For 108 eukaryotic effectors, LOCALIZER outperforms other methods and predicts a previously unrecognized chloroplast transit peptide for the ToxA effector, which we show translocates into tobacco chloroplasts. Secretome-wide predictions and confocal microscopy reveal that rust fungi might have evolved multiple effectors that target chloroplasts or nuclei. LOCALIZER is the first method for predicting effector localisation in plants and is a valuable tool for prioritizing effector candidates for functional investigations. LOCALIZER is available athttp://localizer.csiro.au/.