bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of TachoSil (Absorbable Fibrin Sealant Patch) Compared With Current Practice for the Prevention of Cerebrospinal Fluid Leaks in Patients Undergoing Skull Base Surgery: A Randomized Controlled Trial
Authors: George Bernard , Matula Christian , Kihlström Lars , Ferrer Enrique , Tetens Vilhelm
Published: January 2017

BACKGROUND: Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures.

OBJECTIVE: To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure.

METHODS: Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing ± duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment).

RESULTS: A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events.

CONCLUSION: Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.
Cystic Vestibular Schwannomas Respond Best to Radiosurgery
Authors: Bowden Greg , Cavaleri Jonathon , III Edward Monaco , Niranjan Ajay , Flickinger John , Lunsford L. Dade
Published: January 2017

BACKGROUND: Vestibular schwannomas (VS) have a well-documented response to Gamma Knife® (Elekta AB, Stockholm, Sweden) Stereotactic radiosurgery (SRS). However, there are limited data available regarding the volumetric response of cystic tumors.

OBJECTIVE: This report correlates the radiographic appearance of VS before radiosurgery with the delayed volumetric response.

METHODS: This study reviewed our SRS experience with 219 VS patients between 2003 and 2013. Patients were treatment naïve and had a significant extracanalicular tumor volume. Magnetic resonance imaging at the time of SRS identified 42 contrast-enhancing macrocystic tumors, 45 contrast-enhancing microcystic tumors, and 132 homogeneously enhancing tumors with no intratumoral cyst formation. The median follow-up was 49.1 months. The median tumor volume was 2.6 cm3 (0.70-16.1 cm3) and the median dose was 12.5 Gy (11-13 Gy).

RESULTS: The actuarial tumor control rate was 99.4% at 2 years and 96.4% at 5 years. A volumetric reduction of >20% occurred in 85.4% of macrocystic tumors, 76.1% of microcystic tumors, and 62.8% of homogeneously enhancing VS. The median volume decrease per year for macrocystic, microcystic, and homogenous tumors was 17.2%, 7.5%, and 7.9% per year respectively (P < .001). A 2:1 blinded volumetric case match showed a significant size reduction in macrocystic tumors compared to noncystic tumors (P = .007). Serviceable hearing was maintained in 61.5% of patients that had Gardner-Robertson grade I-II hearing before treatment. Surgical resection or repeat radiosurgery was performed in 8 patients (3.6%) who had sustained tumor progression.

CONCLUSION: SRS provided VS tumor control in >95% of patients, regardless of radiographic characteristics. Tumor volume regression was most evident in patients with cystic tumors.
Frontal Sinus Breach During Routine Frontal Craniotomy Significantly Increases Risk of Surgical Site Infection: 10-Year Retrospective Analysis
Authors: Linzey Joseph R. , Wilson Thomas J. , Sullivan Stephen E. , Thompson B. Gregory , Pandey Aditya S.
Published: January 2017

BACKGROUND: Frontotemporal craniotomies are commonly performed for a variety of neurosurgical pathologies. Infections related to craniotomies cause significant morbidity. We hypothesized that the risk of cranial surgical site infections (SSIs) may be increased in patients whose frontal sinuses are breached during craniotomy.

OBJECTIVE: To compare the rate of cranial SSIs in patients undergoing frontotemporal craniotomies with and without frontal sinus breach (FSB).

METHODS: We performed a retrospective analysis of all patients undergoing frontotemporal craniotomies for the management of cerebral aneurysms from 2005 to 2014. This study included 862 patients undergoing 910 craniotomies. Primary outcome of interest was occurrence of a cranial SSI. Standard statistical methods were utilized to explore associations between a variety of variables including FSB, cranial SSI, and infections requiring reoperation.

RESULTS: Of the 910 craniotomies, 141 (15.5%) involved FSB. Of those involving FSB, 22 (15.6%) developed a cranial SSI, compared to only 56 of the 769 without FSB (7.3%; P = .001). Cranial SSI requiring reoperation was much more likely in patients with FSB compared to those without a breach (7.8% vs 1.6%; P < .001). In those presenting with cranial SSIs, epidural abscess formation was more common with FSB compared to no FSB (27.3% vs 5.4%; P = .006). In multivariate analysis, breach of the frontal sinus was significantly associated with cranial SSI (OR 2.16; 95% CI 1.24-3.78; P = .01) and reoperation (OR 4.20; 95% CI 1.66-10.65; P = .003).

CONCLUSION: Patients undergoing frontotemporal craniotomies are at significantly greater risk of serious cranial SSIs if the frontal sinus has been breached.
Geographic and Hospital Variation in Cost of Lumbar Laminectomy and Lumbar Fusion for Degenerative Conditions
Authors: Zygourakis Corinna C. , Liu Caterina Y. , Wakam Glenn , Moriates Christopher , Boscardin Christy , Ames Christopher P. , Mummaneni Praveen V. , Ratliff John , Dudley R. Adams , Gonzales Ralph
Published: January 2017

BACKGROUND: Spinal surgery costs vary significantly across hospitals and regions, but there is insufficient understanding of what drives this variation.

OBJECTIVE: To examine the factors underlying the cost variation for lumbar laminectomy/discectomy and lumbar fusions.

METHODS: We obtained patient information (age, gender, race, severity of illness, risk of mortality, population of county of residence, median zipcode income, insurance status, elective vs nonelective admission, length of stay) and hospital data (region, hospital type, bed size, wage index) for all patients who underwent lumbar laminectomy/discectomy (n = 181 267) or lumbar fusions (n = 433 364) for degenerative conditions in the 2001 to 2013 National Inpatient Sample database. We performed unadjusted and adjusted analyses to determine which factors affect cost.

RESULTS: Mean costs for lumbar laminectomy/discectomy and lumbar fusion increased from $8316 and $21 473 in 2001 (in inflation-adjusted 2013 dollars), to $11 405 and $29 438, respectively, in 2013. There was significant regional variation in cost, with the West being the most expensive region across all years and showing the steepest increase in cost over time. After adjusting for patient and hospital factors, the West was 23% more expensive than the Northeast for lumbar laminectomy/discectomy, and 25% more expensive than the Northeast for lumbar fusion (P < .01). Higher wage index, smaller hospital bed size, and rural/urban nonteaching hospital type were also associated with higher cost for lumbar laminectomy/discectomy and fusion (P < .01).

CONCLUSION: After adjusting for patient factors and wage index, the Western region, hospitals with smaller bed sizes, and rural/urban nonteaching hospitals were associated with higher costs for lumbar laminectomy/discectomy and lumbar fusion.
The Nationwide Burden of Neurological Conditions Requiring Emergency Neurosurgery
Authors: De la Garza Ramos Rafael , Goodwin C. Rory , Nakhla Jonathan , Nasser Rani , Yassari Reza , Flamm Eugene S. , Bydon Ali , Colby Geoffrey , Sciubba Daniel M.
Published: January 2017

BACKGROUND: Neurosurgical emergencies are an important cause of disability and mortality.

OBJECTIVE: To examine the nationwide burden of neurological conditions requiring emergency neurosurgery.

METHODS: The Nationwide Inpatient Sample database (2002-2011) was queried to identify adult patients with a primary discharge diagnosis of a neurosurgical condition who were admitted urgently/emergently or through a trauma center and underwent surgical intervention within 2 days of admission. Diagnostic groups were ranked based on their inpatient complication and mortality burden, and their contribution to total complications, deaths, hospital charges, and length of stay (LOS) was assessed. All analyses were weighted to produce national estimates.

RESULTS: After application of discharge weights, 810 404 patients who underwent emergency neurosurgery were identified. The average complication rate for the entire sample was 8.8%, the mortality rate was 11.2%, average charges were $106 802, and average LOS was 9.0 days. The top 4 diagnostic groups ranked by complication/mortality burden accounted for 76% of all complications, 96% of all deaths, 81% of all charges, and 82% of all days in the hospital for the entire study sample. This was equal to 62 648 complications, 86 683 deaths, $69 billion in charges, and 5962 932 days. These 4 diagnostic groups included (1) acute cerebrovascular disease, (2) intracranial injury, (3) spinal cord injury, and (4) occlusion or stenosis of precerebral arteries.

CONCLUSION: Acute cerebrovascular disease, intracranial injury, spinal cord injury, and occlusion/stenosis of precerebral arteries requiring emergency neurosurgery carry an important nationwide burden in terms of complications, deaths, charges, and LOS. Efforts in prevention and/or treatment of these conditions should continue.
Great strides of China's space programmes
Authors: Qiu Jane ,   writes for NSR from Beijing.
Published: January 2017

While China's almost flawless space endeavours—such as its space lab Tiangong-2, launched last year, and the 2012 mission that sent a rover to the surface of the Moon—have long impressed the world, space-science missions were not among its priorities until recently. The situation improved in 2011 when the Chinese Academy of Sciences won government support for a 10-year Strategic Pioneering Programme on Space Science—with a total budget of nearly 1 billion dollars. Since then, China has launched satellites to probe dark matter, detect black holes and conduct quantum experiments from space. This year will see the launch of an astronomy satellite and a highly anticipated mission to bring back rocks from the Moon.

In a forum chaired by National Science Review's Executive Associate Editor Mu-ming Poo, space scientists discussed different types of Chinese space programmes, the science missions already launched or in development, the importance and challenges of international collaboration, and the uncertain future of the country's space-science development.

Chunlai Li Deputy Director, National Astronomical Observatories, Chinese Academy of Sciences, Beijing Ji Wu Director, National Centre of Space Science, Chinese Academy of Sciences, Beijing Jianyu Wang Deputy Director, Chinese Academy of Sciences Shanghai Branch Shuangnan Zhang Institute of High-Energy Physics, Chinese Academy of Sciences, Beijing Yifang Wang Director, Institute of High-Energy Physics, Chinese Academy of Sciences, Beijing Mu-ming Poo (Chair) Director, Institute of Neuroscience, Institute of High-Energy Physics, Chinese Academy of Sciences, Shanghai
Perinatal Biochemical Confirmation of Smoking Status by Trimester
Authors: Ashford Kristin , Wiggins Amanda , Rayens Emily , Assef Sara , Fallin Amanda , Rayens Mary Kay
Published: January 2017

Introduction:

Tobacco use during pregnancy is the most modifiable risk factor associated with poor pregnancy outcomes. Self-reported tobacco use has been demonstrated to have high misclassification rates. The aims were to examine misclassification rates of perinatal tobacco use during each trimester of pregnancy and 8 weeks postpartum, and to evaluate characteristics associated with misclassification of tobacco use status.

Methods:

This is secondary analysis of a prospective, multicenter trial of pregnant women, and it includes participants who were biochemically identified as tobacco users during their first trimester (N = 103). Each trimester and once postpartum, tobacco use was assessed via self-report and validated using a cutoff of 100 ng/mL for urine cotinine via NicAlert test strips to indicate current use. Those who self-reported as nonusers but were identified as users via urine cotinine were considered misclassified; misclassification rates were determined for each time period. Logistic regression assessed maternal factors associated with misclassification status.

Results:

Misclassification rates declined from 35.0% at first trimester to 31.9% and 26.6% at the second and third; the postpartum rate was 30.4%. These rates did not differ significantly from each other at the 0.05 level. Race/ethnicity was associated with misclassification status; white/non-Hispanic women were 87% less likely to be misclassified (p < .001).

Conclusion:

Misclassification of prenatal smoking status decreases as pregnancy progresses, though the observed rate change was not significant. Minority women may be at particular risk for non-disclosure of tobacco use. Biochemical validation should be considered when assessing perinatal tobacco use via self-report, given high misclassification rates throughout the perinatal period.

Implications:

These results demonstrate that regardless of trimester, more than one-quarter of tobacco-using pregnant women may not disclose tobacco use throughout pregnancy and early postpartum. Although the rate of misclassification decreased from first to third trimester and then increased in the immediate postpartum, these changes in misclassification rates were not significant. Minority groups may be at particular risk of misclassification compared with white/non-Hispanic women. Biochemical validation is warranted throughout pregnancy to encourage cessation as tobacco use is one of the most easily-modified risk factors for poor birth outcomes.
Leveraging Lotteries for School Value-Added: Testing and Estimation*
Authors: Angrist Joshua D. , Hull Peter D. , Pathak Parag A. , Walters Christopher R.
Published: January 2017

Conventional value-added models (VAMs) compare average test scores across schools after regression-adjusting for students’ demographic characteristics and previous scores. This article tests for VAM bias using a procedure that asks whether VAM estimates accurately predict the achievement consequences of random assignment to specific schools. Test results from admissions lotteries in Boston suggest conventional VAM estimates are biased, a finding that motivates the development of a hierarchical model describing the joint distribution of school value-added, bias, and lottery compliance. We use this model to assess the substantive importance of bias in conventional VAM estimates and to construct hybrid value-added estimates that optimally combine ordinary least squares and lottery-based estimates of VAM parameters. The hybrid estimation strategy provides a general recipe for combining nonexperimental and quasi-experimental estimates. While still biased, hybrid school value-added estimates have lower mean squared error than conventional VAM estimates. Simulations calibrated to the Boston data show that, bias notwithstanding, policy decisions based on conventional VAMs that control for lagged achievement are likely to generate substantial achievement gains. Hybrid estimates that incorporate lotteries yield further gains.
Labor Markets and Poverty in Village Economies*
Authors: Bandiera Oriana , Burgess Robin , Das Narayan , Gulesci Selim , Rasul Imran , Sulaiman Munshi
Published: January 2017

We study how women's choices over labor activities in village economies correlate with poverty and whether enabling the poorest women to take on the activities of their richer counterparts can set them on a sustainable trajectory out of poverty. To do this we conduct a large-scale randomized control trial, covering over 21,000 households in 1,309 villages surveyed four times over a seven-year period, to evaluate a nationwide program in Bangladesh that transfers livestock assets and skills to the poorest women. At baseline, the poorest women mostly engage in low return and seasonal casual wage labor while wealthier women solely engage in livestock rearing. The program enables poor women to start engaging in livestock rearing, increasing their aggregate labor supply and earnings. This leads to asset accumulation (livestock, land, and business assets) and poverty reduction, both sustained after four and seven years. These gains do not crowd out the livestock businesses of noneligible households while the wages these receive for casual jobs increase as the poor reduce their labor supply. Our results show that (i) the poor are able to take on the work activities of the nonpoor but face barriers to doing so, and, (ii) one-off interventions that remove these barriers lead to sustainable poverty reduction.
Salt acclimation process: a comparison between a sensitive and a tolerant Olea europaea cultivar
Authors: Pandolfi Camilla , Bazihizina Nadia , Giordano Cristiana , Mancuso Stefano , Azzarello Elisa
Published: January 2017

Saline soils are highly heterogeneous in time and space, and this is a critical factor influencing plant physiology and productivity. Temporal changes in soil salinity can alter plant responses to salinity, and pre-treating plants with low NaCl concentrations has been found to substantially increase salt tolerance in different species in a process called acclimation. However, it still remains unclear whether this process is common to all plants or is only expressed in certain genotypes. We addressed this question by assessing the physiological changes to 100 mM NaCl in two contrasting olive cultivars (the salt-sensitive Leccino and the salt-tolerant Frantoio), following a 1-month acclimation period with 5 or 25 mM NaCl. The acclimation improved salt tolerance in both cultivars, but activated substantially different physiological adjustments in the tolerant and the sensitive cultivars. In the tolerant Frantoio the acclimation with 5 mM NaCl was more effective in increasing plant salt tolerance, with a 47% increase in total plant dry mass compared with non-acclimated saline plants. This enhanced biomass accumulation was associated with a 50% increase in K+ retention ability in roots. On the other hand, in the sensitive Leccino, although the acclimation process did not improve performance in terms of plant growth, pre-treatment with 5 and 25 mM NaCl substantially decreased salt-induced leaf cell ultrastructural changes, with leaf cell relatively similar to those of control plants. Taken together these results suggest that in the tolerant cultivar the acclimation took place primarily in the root tissues, while in the sensitive they occurred mainly at the shoot level.
Evolution of a wild-plant tobamovirus passaged through an exotic host: Fixation of mutations and increased replication
Authors: Koh Shu Hui , Li Hua , Sivasithamparam Krishnapillai , Admiraal Ryan , Jones Michael G.K. , Wylie Stephen J.
Published: January 2017

Tobamovirus is a group of viruses that have become serious pathogens of crop plants. As part of a study informing risk of wild plant virus spill over to crops, we investigated the capacity of a solanaceous-infecting tobamovirus from an isolated indigenous flora to adapt to new exotic hosts. Yellow tailflower mild mottle virus (YTMMV) (genus Tobamovirus, family Virgaviridae) was isolated from a wild plant of yellow tailflower (Anthocercis littoria, family Solanaceae) and initially passaged through a plant of Nicotiana benthamiana, then one of Nicotiana glutinosa where a single local lesion was used to inoculate a N. benthamiana plant. Sap from this plant was used as starting material for nine serial passages through three plant species. The virus titre was recorded periodically, and 85% of the virus genome was sequenced at each passage for each host. Six polymorphic sites were found in the YTMMV genome across all hosts and passages. At five of these, the alternate alleles became fixed in the viral genome until the end of the experiment. Of these five alleles, one was a non-synonymous mutation (U1499C) that occurred only when the virus replicated in tomato. The mutant isolate harbouring U1499C, designated YTMMV-δ, increased its titre over passages in tomato and outcompeted the wild-type isolate when both were co-inoculated to tomato. That YTMMV-δ had greater reproductive fitness in an exotic host than did the wild type isolate suggests YTMMV evolution is influenced by host changes.
Cash Transfers and Health: Evidence from Tanzania
Authors: Evans David K , Holtemeyer Brian , Kosec Katrina
Published: January 2017

How do cash transfers conditioned on health clinic visits and school attendance impact health-related outcomes? Examining the 2010 randomized introduction of a program in Tanzania, this paper finds nuanced impacts. An initial surge in clinic visits after 1.5 years—due to more visits by those already complying with program health conditions and by non-compliers—disappeared after 2.5 years, largely due to compliers reducing above-minimal visits. The study finds significant increases in take-up of health insurance and the likelihood of seeking treatment when ill. Health improvements were concentrated among children ages 0–5 years rather than the elderly, and took time to materialize; the study finds no improvements after 1.5 years, but 0.76 fewer sick days per month after 2.5 years, suggesting the importance of looking beyond short-term impacts. Reductions in sick days were largest in villages with more baseline health workers per capita, consistent with improvements being sensitive to capacity constraints. These results are robust to adjustments for multiple hypothesis testing.
Gender-Neutral Inheritance Laws, Family Structure, and Women’s Status in India
Authors: Mookerjee Sulagna
Published: January 2017

This paper examines whether economic empowerment of women improves their autonomy within their marital household, and investigates the mechanism, by exploiting variation from a legal reform aimed at improving women’s inheritance rights in India. Results suggest that the reform increased women’s participation in decision-making but at the expense of the older generation of household members and not at the expense of their husbands. Two channels are proposed to explain this phenomenon. First, this can be driven by a shift in the family structure from traditional joint families to nuclear households. Such a change is consistent both with the increase in women’s decision-making authority, which they can exert to move out of the joint household, as well as with men’s incentives, since men have weaker financial links with their parents post-reform. Second, even within joint families, the amendments empowered young couples at the expense of the older generation of household members.
Effect of Wheat Bran on Dough Rheology and Final Quality of Chinese Steamed Bread
Authors: Liu Wenjun , Brennan Margaret , Serventi Luca , Brennan Charles
Published: January 2017

Wheat bran is a low‐cost by‐product abundantly produced by the wheat flour industry. As a staple food of China, Chinese steamed bread (CSB) represents about 40% of China's wheat consumption. This study investigated the effects of incorporating wheat bran into the CSB at different levels (5, 10, and 15%). The dough behavior was measured by analyzing rheological properties. Quality of CSB was analyzed from two perspectives: physical properties and nutritional quality. For physical properties, specific volume, loaf height, moisture, and texture were measured by AACC International Approved Methods. The predicted glycemic response of the bread was analyzed by using an in vitro digestion method. The results illustrated that the incorporation of wheat bran into wheat flour reduced the extensibility of the dough, decreased specific volume, and increased bread hardness, gumminess, and chewiness. However, this study also showed that addition of wheat bran can decrease the predicted glycemic response of steamed bread by up to 39%.
Adaptation to Partial Resistance to Powdery Mildew in the Hop Cultivar Cascade by Podosphaera macularis
Authors: Gent David H. , Massie Stephen T. , Twomey Megan C. , Wolfenbarger Sierra N.
Published: January 2017

The hop cultivar Cascade has been grown in the Pacific Northwestern U.S. and elsewhere with minimal input for management of powdery mildew (Podosphaera macularis) for nearly 15 years due to the putatively quantitative resistance in this cultivar. While partial resistance is generally thought to be more durable than qualitative resistance, in 2012, powdery mildew was reported on Cascade in Washington State. Field surveys conducted during 2013 to 2016 indicated increasing prevalence of powdery mildew on Cascade, as well as an increasing number of fungicide applications applied to this cultivar in Washington State. Nearly all isolates of P. macularis tested were able to infect Cascade in laboratory inoculations. However, the greatest number of colonies, most conidia produced, and the shortest latent period was only observed with isolates derived originally from Cascade, as compared with other isolates derived from other cultivars. Further, the enhanced aggressiveness of these isolates was only manifested on Cascade and not six other susceptible cultivars, further indicating a specific adaptation to Cascade by the isolates. There was no evidence of a known major R-gene in Cascade, as seven isolates of P. macularis with contrasting virulence all infected Cascade. Among 158 isolates obtained from hop yards planted to Cascade, only two (1.3%) were able to infect the cultivar Nugget, which possesses the resistance factor termed R6, indicating that isolates of P. macularis virulent on Nugget are largely distinct from those adapted to Cascade. Further, race characterization indicated Cascade-adapted isolates of P. macularis were able to overcome R-genes Rb, R3, and R5, but not other known R-genes. Therefore, multiple R-genes and other sources of partial resistance are expected to provide resistance to Cascade-adapted strains of the fungus. Given the plasticity of the powdery mildew fungus, breeding strategies for powdery mildew need to consider the potential for adaptation to both qualitative and partial resistance in the host.
Arabidopsis JASMONATE-INDUCED OXYGENASES down-regulate plant immunity by hydroxylation and inactivation of the hormone jasmonic acid
Authors: Caarls Lotte , Elberse Joyce , Awwanah Mo , Ludwig Nora R. , de Vries Michel , Zeilmaker Tieme , Van Wees Saskia C.M. , Schuurink Robert C. , Van den Ackerveken Guido
Published: January 2017

The phytohormone jasmonic acid (JA) is vital in plant defense and development. Although biosynthesis of JA and activation of JA-responsive gene expression by the bioactive form JA-isoleucine (JA-Ile) have been well-studied, knowledge on JA metabolism is incomplete. In particular, the enzyme that hydroxylates JA to 12-OH-JA, an inactive form of JA that accumulates after wounding and pathogen attack, is unknown. Here, we report the identification of four paralogous 2-oxoglutarate/Fe(II)-dependent oxygenases inArabidopsis thalianaas JA hydroxylases and show that they down-regulate JA-dependent responses. As they are induced by JA we named themJASMONATE-INDUCED OXYGENASEs(JOXs). Concurrent mutation of the four genes in a quadruple Arabidopsis mutant resulted in increased defense gene expression and increased resistance to the necrotrophic fungusBotrytis cinereaand the caterpillarMamestra brassicae. In addition, root and shoot growth of the plants was inhibited. Metabolite analysis of leaves showed that loss of function of the four JOX enzymes resulted in over-accumulation of JA and in reduced turnover of JA into 12-OH-JA. Transformation of the quadruple mutant with eachJOXgene strongly reduced JA levels, demonstrating that all four JOXs inactivate JA in plants. Thein vitrocatalysis of 12-OH-JA from JA by recombinant enzyme could be confirmed for three JOXs. The identification of the enzymes responsible for hydroxylation of JA reveals a missing step in JA metabolism, which is important for the inactivation of the hormone and subsequent down-regulation of JA-dependent defenses.

SIGNIFICANCE STATEMENT

In plants, the hormone jasmonic acid (JA) is synthesized in response to attack by pathogens and herbivores, leading to activation of defense responses. Rapidly following JA accumulation, the hormone is metabolized, presumably to prevent inhibitive effects of high JA levels on growth and development. The enzymes that directly inactivate JA were so far unknown. Here, we identify four jasmonate-induced oxygenases (JOXs) in Arabidopsis that hydroxylate jasmonic acid to form inactive 12-OH-JA. A mutant that no longer produces the four enzymes hyperaccumulates JA, exhibits reduced growth, and is highly resistant to attackers that are sensitive to JA-dependent defense. The JOX enzymes thus play an important role in determining the amplitude and duration of JA responses to balance the growth-defense tradeoff.
Transcriptional response to West Nile virus infection in the zebra finch (Taeniopygia guttata), a songbird model for immune function
Authors: Newhouse Daniel J , Hofmeister Erik K , Balakrishnan Christopher N
Published: January 2017

West Nile Virus (WNV) is the one of most widespread arboviruses worldwide. WNV exists in a bird-mosquito transmission cycle where passerine birds act as the primary reservoir host. As a public health concern, the mammalian immune response to WNV has been studied in detail. Little, however, is known about the avian immune response to WNV. Avian taxa show variable susceptibility to WNV and what drives this variation is unknown. Thus, to study the immune response to WNV in birds, we experimentally infected captive zebra finches (Taeniopygia guttata). Zebra finches provide a useful model, as like many natural avian hosts they are moderately susceptible to WNV and thus provide sufficient viremia to infect mosquitoes. We performed splenic RNAseq during peak viremia to provide an overview of the transcriptional response. In general, we find strong parallels with the mammalian immune response to WNV, including up-regulation of five genes in the Rig-I-like receptor signaling pathway, and offer insights into avian specific responses. Together with complementary immunological assays, we provide a model of the avian immune response to WNV and set the stage for future comparative studies among variably susceptible populations and species.
Semiparametric methods for estimation of a non-linear exposure–outcome relationship using instrumental variables with application to Mendelian randomization
Authors: Staley James R , Burgess Stephen
Published: January 2017

Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure-outcome relationship) is linear. However, in practice this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure-outcome relationship: a fractional polynomial method and a piecewise linear method. We divide the population into strata using the exposure distribution, and estimate a causal effect, referred to as a localized average causal effect (LACE), in each stratum of population. The fractional polynomial method performs meta-regression on these LACE estimates. The piecewise linear method estimates a continuous piecewise linear function, the gradient of which is the LACE estimate in each stratum. Both methods were demonstrated in a simulation study to estimate the true exposure-outcome relationship well, particularly when the relationship was a fractional polynomial (for the fractional polynomial method) or was piecewise linear (for the piecewise linear method). The methods were used to investigate the shape of relationship of body mass index with systolic blood pressure and diastolic blood pressure.

Availability and implementation:https://github.com/jrs95/nlmr
Clustering huge protein sequence sets in linear time
Authors: Steinegger Martin , Söding Johannes
Published: January 2017

Metagenomic datasets contain billions of protein sequences that could greatly enhance large-scale functional annotation and structure prediction. Utilizing this enormous resource would require reducing its redundancy by similarity clustering. However, clustering hundreds of million of sequences is impractical using current algorithms because their runtimes scale as the input set sizeNtimes the number of clustersK, which is typically of similar order asN, resulting in runtimes that increase almost quadratically withN. We developed Linclust, the first clustering algorithm whose runtime scales asN, independent ofK. It can also cluster datasets several times larger than the available main memory. We cluster 1.6 billion metagenomic sequence fragments in 10 hours on a single server to 50% sequence identity,>1000 times faster than has been possible before. Linclust will help to unlock the great wealth contained in metagenomic and genomic sequence databases. (Open-source software and Metaclust database:https://mmseqs.org/).
Outlier detection for improved differential splicing quantification from RNA-Seq experiments with replicates
Authors: Norton Scott , Vaquero-Garcia Jorge , Barash Yoseph
Published: January 2017

Motivation

A key component in many RNA-Seq based studies is contrasting multiple replicates from different experimental conditions. In this setup replicates play a key role as they allow to capture underlying biological variability inherent to the compared conditions, as well as experimental variability. However, what constitutes a “bad” replicate is not necessarily well defined. Consequently, researchers might discard valuable data or downstream analysis may be hampered by failed experiments.

Results

Here we develop a probability model to weigh a given RNA-Seq sample as a representative of an experimental condition when performing alternative splicing analysis. We demonstrate that this model detects outlier samples which are consistently and significantly different compared to other samples from the same condition. Moreover, we show that instead of discarding such samples the proposed weighting scheme can be used to downweight samples and specific splicing variations suspected as outliers, gaining statistical power. These weights can then be used for differential splicing (DS) analysis, where the resulting algorithm offers a generalization of the MAJIQ algorithm. Using both synthetic and real-life data we perform an extensive evaluation of the improved MAJIQ algorithm in different scenarios involving perturbed samples, mislabeled samples, no-signal groups, and different levels of coverage, showing it compares favorably to other tools. Overall, this work offers an outlier detection algorithm that can be combined with any splicing pipeline, a generalized and improved version of MAJIQ for differential splicing detection, and an evaluation pipeline researchers can use to evaluate which algorithm may work best for their needs.

Availability

Program is accessible viahttp://majiq.biociphers.org/norton_et_al_2017/

Contact

http://yosephb@upenn.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Improving the performance of minimizers and winnowing schemes
Authors: Marçais Guillaume , Pellow David , Bork Daniel , Orenstein Yaron , Shamir Ron , Kingsford Carl
Published: January 2017

The minimizers scheme is a method for selectingk-mers from sequences. It is used in many bioinformatics software tools to bin comparable sequences or to sample a sequence in a deterministic fashion at approximately regular intervals, in order to reduce memory consumption and processing time. Although very useful, the minimizers selection procedure has undesirable behaviors (e.g., too manyk-mers are selected when processing certain sequences). Some of these problems were already known to the authors of the minimizers technique, and the natural lexicographic ordering ofk-mers used by minimizers was recognized as their origin. Many software tools using minimizers employ ad hoc variations of the lexicographic order to alleviate those issues.

We provide an in-depth analysis of the effect ofk-mer ordering on the performance of the minimizers technique. By using small universal hitting sets (a recently defined concept), we show how to significantly improve the performance of minimizers and avoid some of its worse behaviors. Based on these results, we encourage bioinformatics software developers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering, rather than the lexicographic order. This analysis also settles negatively a conjecture (by Schleimeret al.) on the expected density of minimizers in a random sequence.

The software used for this analysis is available on GitHub:https://github.com/gmarcais/minimizers.git.

Contact:gmarcais@cs.cmu.edu
THiCweed: fast, sensitive detection of sequence features by clustering big data sets
Authors: Agrawal Ankit , Sambare Snehal V. , Narlikar Leelavati , Siddharthan Rahul
Published: January 2017

We present THiCweed, a new approach to analyzing transcription factor binding data from high-throughput chromatin-immunoprecipitation-sequencing (ChIP-seq) experiments. THiCweed clusters bound regions based on sequence similarity using a divisive hierarchical clustering approach based on sequence similarity within sliding windows, while exploring both strands. ThiCweed is specially geared towards data containing mixtures of motifs, which present a challenge to traditional motif-finders. Our implementation is significantly faster than standard motif-finding programs, able to process 30,000 peaks in 1-2 hours, on a single CPU core of a desktop computer. On synthetic data containing mixtures of motifs it is as accurate or more accurate than all other tested programs.

THiCweed performs best with large “window” sizes (≥ 50bp), much longer than typical binding sites (7-15 base pairs). On real data it successfully recovers literature motifs, but also uncovers complex sequence characteristics in flanking DNA, variant motifs, and secondary motifs even when they occur in < 5% of the input, all of which appear biologically relevant. We also find recurring sequence patterns across diverse ChIP-seq data sets, possibly related to chromatin architecture and looping. THiCweed thus goes beyond traditional motif-finding to give new insights into genomic TF binding complexity.
Asymmetry in serial femtosecond crystallography data
Authors: Sharma Amit , Johansson Linda , Dunevall Elin , Wahlgren Weixiao Y. , Neutze Richard , Katona Gergely
Published: January 2017

Serial crystallography is an increasingly important approach to protein crystallography that exploits both X-ray free-electron laser (XFEL) and synchrotron radiation. Serial crystallography recovers complete X-ray diffraction data by processing and merging diffraction images from thousands of randomly oriented non-uniform microcrystals, of which all observations are partial Bragg reflections. Random fluctuations in the XFEL pulse energy spectrum, variations in the size and shape of microcrystals, integrating over millions of weak partial observations and instabilities in the XFEL beam position lead to new types of experimental errors. The quality of Bragg intensity estimates deriving from serial crystallography is therefore contingent upon assumptions made while modeling these data. Here it is observed that serial femtosecond crystallography (SFX) Bragg reflections do not follow a unimodal Gaussian distribution and it is recommended that an idealized assumption of single Gaussian peak profiles be relaxed to incorporate apparent asymmetries when processing SFX data. The phenomenon is illustrated by re-analyzing data collected from microcrystals of the Blastochloris viridis photosynthetic reaction center and comparing these intensity observations with conventional synchrotron data. The results show that skewness in the SFX observations captures the essence of the Wilson plot and an empirical treatment is suggested that can help to separate the diffraction Bragg intensity from the background.
Effects of frontline employee role overload on customer responses and sales performance
Authors: Jha Subhash , Balaji M.S. , Yavas Ugur , Babakus Emin
Published: January 2017

Purpose

Using the basic framework of the service profit chain, this study aims to develop an integrated model that explains the relationships among role overload (RO), customer orientation (CO), service interaction quality (IQ), customer satisfaction (CS) and sales performance.

Design/methodology/approach

A large-scale survey of 872 customers and 530 frontline employees across 50 branches of a major retail bank in New Zealand serves as the study setting.

Findings

The results indicate that RO has a significant negative effect on IQ. Nevertheless, CO mitigates the negative outcome of RO on IQ. IQ fully mediates the relationship between RO and CS. Additionally, the effect of IQ on branch sales is fully mediated by CS.

Research limitations/implications

The cross-sectional nature of the current survey does not permit causal inferences. Thus, future studies should adopt longitudinal designs. Also, future studies should explore the roles of other variables (e.g. job crafting, work-related self-efficacy) as possible moderators.

Practical implications

Results suggest that service managers should create a balance between the role requirements and organizational resources to mitigate the adverse effects of employee RO. To enhance IQ and CS, bank managers should coach employees about work overload and train them in CO while prioritizing the tasks.

Originality/value

Empirical research pertaining to employee–customer interaction through a nested framework accommodating data from customers, employees and firm performance is scarce. This study fills in the void.
The impact of country-of-origin cues on consumer investment behavior
Authors: Carlsson Hauff Jeanette , Nilsson Jonas
Published: January 2017

Purpose

Choosing how to invest one’s assets is one of the more important decisions consumers are faced with. However, determining the objective financial quality of complex investment products such as mutual funds is not an easy task for consumers. Against this background, this study aims to clarify the potential impact of one, not necessarily rational, cue on consumer perceptions of financial quality in the investment context: the country-of-origin (COO) of the mutual fund or stock.

Design/methodology/approach

Two Web-based experiments are used to test the study’s hypotheses.

Findings

COO is found to impact investors’ evaluation of the financial metrics of mutual funds, both in terms of perceived risk and potential return. Moreover, the results of Experiment 2 show that although a strong financial brand can partially overcome the COO effect, the extent of this effect is moderated by whether the fund utilizes an active or passive management style.

Research limitations/implications

Although mutual fund providers with a strong financial country image (CI) may leverage that image and build on their home country’s brand, providers from countries with a poor financial CI may do well focusing on passive management to minimize negative COO influence.

Originality/value

The results highlight that COO can be an important source of sub-optimal investment decisions. These insights are of high importance for efforts to improve consumer decision-making and for individual service providers.
Inter-study and intra-study replications in leading marketing journals: a longitudinal analysis
Authors: Kwon Eun Sook , Shan Yan , Lee Joong Suk , Reid Leonard N.
Published: January 2017

Purpose

The authors aimed to examine the presence and character of inter- and intra-approaches to replication studies published in five leading marketing journals (Journal of Marketing,Journal of Marketing Research,Journal of Public Policy & Marketing,Marketing Science,Journal of the Academy of Marketing Science) across four decade intervals (i.e. 1980s, 1990s, 2000s and 2010/2011). The research sought answers to three research questions.

Design/methodology/approach

Content analysis of a randomly selected sample of 2,717 articles found 128 replicative studies in the journal issues. Comparisons of the replication approaches of the studies address two issues: the criticism that intra-study replication is not true replication as it is inconsistent with the criterion of researcher independence and the reported outcomes of the replicative studies relative to those of the original studies.

Findings

Overall, the presence of replications increased over time; however, the increase was attributable primarily to the number of intra-study replications published in two decades, the 2000s and 2010/2011 intervals. Conflicting findings infrequently appeared in the replication studies regardless of approach, indicating the possible existence of confirmation bias in the marketing literature.

Originality/value

Replication in marketing is either improving or stagnant depending on the accepted definition of replication. Of special importance, given the questioning of the intra-study approach as true replicative research, more replicated findings produced by independent researchers are needed to establish theoretical validity of marketing knowledge for use by both marketing academicians and decision makers.