bluuebunny/crossref_metadata_2025 huggingface dataset:
Missing Data and Technical Variability in Single-Cell RNA-Sequencing Experiments
Authors: Hicks Stephanie C. , Townes F. William , Teng Mingxiang , Irizarry Rafael A.
Published: August 2015

Until recently, high-throughput gene expression technology, such as RNA-Sequencing (RNA-seq) required hundreds of thousands of cells to produce reliable measurements. Recent technical advances permit genome-wide gene expression measurement at the single-cell level. Single-cell RNA-Seq (scRNA-seq) is the most widely used and numerous publications are based on data produced with this technology. However, RNA-Seq and scRNA-seq data are markedly different. In particular, unlike RNA-Seq, the majority of reported expression levels in scRNA-seq are zeros, which could be either biologically-driven, genes not expressing RNA at the time of measurement, or technically-driven, gene expressing RNA, but not at a sufficient level to detected by sequencing technology. Another difference is that the proportion of genes reporting the expression level to be zero varies substantially across single cells compared to RNA-seq samples. However, it remains unclear to what extent this cell-to-cell variation is being driven by technical rather than biological variation. Furthermore, while systematic errors, including batch effects, have been widely reported as a major challenge in high-throughput technologies, these issues have received minimal attention in published studies based on scRNA-seq technology. Here, we use an assessment experiment to examine data from published studies and demonstrate that systematic errors can explain a substantial percentage of observed cell-to-cell expression variability. Specifically, we present evidence that some of these reported zeros are driven by technical variation by demonstrating that scRNA-seq produces more zeros than expected and that this bias is greater for lower expressed genes. In addition, this missing data problem is exacerbated by the fact that this technical variation varies cell-to-cell. Then, we show how this technical cell-to-cell variability can be confused with novel biological results. Finally, we demonstrate and discuss how batch-effects and confounded experiments can intensify the problem.
Fines, fees and funding: makerspaces standing apart
Authors: Crumpton Michael A
Published: August 2015

Purpose

– The purpose of this article is to discuss operational components associated with creating a makerspace unit or department within a library.

Design/methodology/approach

– Several considerations are discussed that should be considered for successful implementation of a makerspace in a library.

Findings

– Makerspaces add a unique and fresh element to libraries and should be provided a sustainable model up front.

Originality/value

– The ideas and concepts expressed are those of the author.
Furthering the librarian’s journey: predicting terrorism?
Authors: Steele Kirstin
Published: August 2015

Purpose

– The purpose of this paper is to compare the traditional librarian positions with intelligence analyst positions.

Design/methodology/approach

– Opinion.

Findings

– Similarities outnumber differences, and borrowing vocabulary and skills could benefit both, especially regarding long-term planning and spending in academic libraries.

Research limitations/implications

– Comparing salaries, management structure and possibilities for advancement would be interesting points of study.

Originality/value

– A literature search for comparing librarians with intelligence analysts revealed, in part, a 2013 lecture at the annual Special Libraries Association conference by Edna Reid, and a 2012 article from the Journal of Education for Library and Information Science on incorporating aspects of intelligence analysis into library school curricula.
Library savings through student labor
Authors: Cottrell Terrance Luther , Bell Brigitte
Published: August 2015

Purpose

– The purpose of this article is to briefly present current research and insight into the subject of student labor as a sharp cost-saving measure in the management of today’s library personnel budgets.

Design/methodology/approach

– Drawing from a recent empirical study on the subject, this article adds commentary from other researchers on the pitfalls and benefits of student library labor versus paraprofessionals and librarians.

Findings

– Although library student workers are commonly not seen as “ideal” employees, their demonstrated performance on many library tasks is compelling enough to consider hiring more of them in place of existing staff.

Originality/value

– This subject can be provocative for managers to simply mention to their staff or professional colleagues. There is little research in this area, and this article helps to broach the subject in a candid manor to spark more discussion among library staff looking to improve their bottom line.
Health risks, social security, and religious choice of rural residents
Authors: Jiang Jinqi , Zheng Fengtian
Published: August 2015

Purpose

– The reform and opening up have triggered a “revival” of religious belief in rural China. The purpose of this paper is to explain why rural residents are increasingly becoming religious, by analysing the inherent relationship between their risks and religious choice, and conducts a preliminary investigation of the common characteristics of rural believers and the determinants of their religious choice.

Design/methodology/approach

– The authors applied a logit model to test the determinants of rural residents’ religious choice. The authors used sample survey data collected in 2008 from the rural area of Songxian County, Henan Province.

Findings

– The results suggest that age, sex, political status, health risks, and social security have a significant effect on rural residents’ religious choice. On this basis, the authors have discussed the inherent logic of “disease-related religious practice”. From these results, the paper points out that lack of basic public services such as medical care due to the government’s withdrawal from these fields has increased the health risks of rural residents, triggering a “revival” of religious belief in rural China.

Originality/value

– This paper has improved on previous research in two ways. First, it analyses the relationship between health risk and religious choice, shedding light on the underlying causes of the religious revival in rural China. Second, the methodology involves an analysis of household survey data, thus filling the gap created by less-rigorous quantitative analysis in rural China-based religious research.
Unpacking the perceived opportunity to misbehave
Authors: Daunt (née Reynolds) Kate L. , Greer Dominique A.
Published: August 2015

Purpose

– This study aims to use opportunity as a theoretical lens to investigate how the spatio-temporal and social dimensions of the consumption environment create perceived opportunities for consumers to misbehave.

Design/methodology/approach

– Drawing on routine activity theory and social impact theory, the authors use two experiments to demonstrate that spatio-temporal and social dimensions can explain consumer theft in retail settings.

Findings

– Study 1 reveals mixed empirical support for the basic dimensions of routine activity theory, which posits that the opportunity to thieve is optimised when a motivated offender, suitable target and the absence of a capable formal guardian transpire in time and space. Extending the notion of guardianship, Study 2 tests social impact theory and shows that informal guardianship impacts the likelihood of theft under optimal routine activity conditions.

Originality/value

– The study findings highlight important implications for academicians and retail managers: rather than focusing on the uncontrollable characteristics of thieving offenders, more controllable spatio-temporal and social factors of the retail environment can be actively monitored and manipulated to reduce perceived opportunities for consumer misbehaviour.
Strategic management of salespeople when promoting new products
Authors: Chen Annie , Peng Norman , Hung Kuang-peng
Published: August 2015

Purpose

– The purpose of this paper is to examine the performance of salespeople when selling new products (namely, electronic goods) in a business-to-business context by incorporating the organizations’ perceived psychological climate into goal orientation theory.

Design/methodology/approach

– The current study uses the goal orientation theory to examine the performance of 158 salespeople based on new electronic product sales. Organizational psychological climate perceptions (i.e. customer orientation, sales supportiveness and sales innovativeness) are included as variables that can moderate salespeople’s performance. This study used partial least squares to examine its proposed model.

Findings

– This study found that the learning goal orientation and the performance-prove goal orientation positively affect salespeople’s self-efficacy to sell new products, whereas a performance-avoid goal orientation negatively affects efficacy. In addition, new product selling self-efficacy itself has a positive influence on new product sales performance. As for the moderator, sales supportiveness and customer orientation have the ability to moderate the relationship between self-efficacy and performance.

Practical implications

– This study has implications for sales managers or product managers who are responsible for promoting new products. First, this study’s findings suggest that managers should consider employing performance-prove goal-oriented staff and learning goal oriented staff to sell new products. Second, management can attempt to develop a more supportive climate for the sales team, such as assisting the team in obtaining needed resources from other departments. Finally, management needs to let salespeople know that they are doing their best to understand what new products existing and potential customers will need in the near future.

Originality/value

– This current research is one of the first to examine how the perceived psychological climates of organizations (i.e. sales supportiveness, sales innovativeness and customer orientation) may moderate salespeople’s performance when selling new products. Second, this research examines how different types of goal orientation affect salespeople’s self-efficacy when selling new products. Previous results have not always been consistent regarding the influence of a performance-prove goal orientation. Last but not least, this study tests how new product selling self-efficacy mediates the relationships between goal orientations and new product sales performance as scholars have suggested that more research into the mediating role of self-efficacy is needed.
Two- or one-dimensional view of arousal?
Authors: Fan Xiaomeng , Chang En-Chung , Wegener Duane Theodore
Published: August 2015

Purpose

– The purpose of this paper is to test whether separate tense and energetic forms of arousal impact consumer attitudes and provide a more complete understanding of the role of arousal in product evaluations. Past consumer research has treated arousal as a single dimension and found mixed results of the relation of arousal to consumer attitudes.

Design/methodology/approach

– Study 1 was an online survey of consumers’ experiences with interactive products. The study tested whether the two hypothesized types of arousal were associated with different product features and related to attitudes in different (opposite) patterns. Study 2 was an experiment in which the type of arousal used to describe a vacation location was manipulated. The study tested the role of the two types of arousal in determining the effectiveness of the advertisements for people with different arousal-related orientations.

Findings

– In Study 1, tense arousal mediated effects on the ergonomic qualities of the product on attitudes, whereas energetic arousal mediated effects on the hedonic qualities on attitudes. In Study 2, effects of advertisements were primarily driven by the tense arousal dimension for more telic-oriented (i.e. planning ahead) people and by the energetic arousal dimension for more paratelic-oriented (i.e. spontaneous) people. In both studies, treating arousal as a single dimension would have led to misleading conclusions.

Originality/value

– This research demonstrates that separating arousal into a two- rather than one-dimensional construct can provide greater insights to the affective mechanisms underlying consumer attitudes.
Exploring front-line employee contributions to service innovation
Authors: Karlsson Jenny , Skålén Per
Published: August 2015

Purpose

– This paper aims to study front-line employees’ contribution to service innovation, when they contribute and how they are involved in service innovation.

Design/methodology/approach

– The paper draws on a multiple-case study on service innovation in four organizations with extensive front-line employee involvement. The main data collection methods are interviews and observations.

Findings

– The paper suggests that front-line employees contribute customer knowledge, product knowledge and practice knowledge during five phases of the service innovation process – project formation, idea generation, service design, testing and implementation – and that front-line employee involvement ranges from active to passive.

Research limitations/implications

– Statistical generalization of the results is needed.

Practical implications

– The paper reveals that early and active front-line employee involvement in the service innovation process creates conditions for a positive contribution to service innovation.

Originality/value

– The paper suggests that early and active knowledge contributions by front-line employees to the service innovation process are associated with the creation of attractive value propositions.
Effectuation and foreign market entry of entrepreneurial firms
Authors: Chetty Sylvie , Ojala Arto , Leppäaho Tanja
Published: August 2015

Purpose

– The purpose of this study is to examine the decision-making process for entrepreneurial firms when entering foreign markets and how and why they entered those markets.

Design/methodology/approach

– A nascent theory in entrepreneurship called effectuation is combined with internationalization process theory as the conceptual framework to study decision-making under uncertainty. The central concept in both these theories is relationships and how they can be used to gain knowledge and thus reduce uncertainty and in the case of effectuation to co-create opportunities to enter foreign markets. The research design involves a multiple case study of software firms from Finland and New Zealand.

Findings

– It was found that entrepreneurs differentiate between foreign market selection and foreign market entry during their internationalization process, potentially using different decision-making processes in them. They tend to interweave effectuation and causation logics as substitutes in their decision-making. Uncertainty during foreign market entry is not always a barrier because it can provide opportunities depending on the logic used. In addition, there is evidence that entrepreneurs who have existing relationships in foreign markets tend to use effectuation to select and enter foreign markets.

Originality/value

– This paper transposes effectuation from its original field of entrepreneurship research to the context of internationalizing entrepreneurial firms. Consequently, it contributes toward understanding the decision-making process for selecting and entering foreign markets.
A Strategy Tripod Perspective on Knowledge Creation Capability
Authors: Su Zhongfeng , Peng Mike W. , Xie En
Published: August 2015

Drawing on the strategy tripod perspective, in this study we examine how the performance effect of knowledge creation capability is contingent on key industrial and institutional variables. We find that technological turbulence, competitive intensity and government support all positively moderate the relationship between knowledge creation capability and firm performance, while dysfunctional competition has a negative moderating impact. This study provides a more fine‐grained analysis on the performance implications of knowledge creation capability. Moreover, it represents one of the first attempts to empirically test the interactive effects of the three legs of the strategy tripod (the industry‐based, resource‐based and institution‐based views) in one study and supports the importance of integrating the three legs to better understand the complex phenomenon.
Chlamydia screening for pregnant women aged 16–25 years attending an antenatal service: a cost‐effectiveness study
Authors: Ong JJ , Chen M , Hocking J , Fairley CK , Carter R , Bulfone L , Hsueh A
Published: August 2015

Objective

Determine the cost‐effectiveness of screening all pregnant women aged 16–25 years for chlamydia compared with selective screening or no screening.

Design

Cost effectiveness based on a decision model.

Setting

Antenatal clinics in Australia.

Sample

Pregnant women, aged 16–25 years.

Methods

Using clinical data from a previous study, and outcomes data from the literature, we modelled the short‐term perinatal (12‐month time horizon) incremental direct costs and outcomes from a government (as the primary third‐party funder) perspective for chlamydia screening. Costs were derived from the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, and average cost‐weights reported for hospitalisations classified according to the Australian refined diagnosis‐related groups.

Main outcome measures

Direct costs of screening and managing chlamydia complications, number of chlamydia cases detected and treated, and the incremental cost‐effectiveness ratios were estimated and subjected to sensitivity analyses.

Results

Assuming a chlamydia prevalence rate of 3%, screening all antenatal women aged 16–25 years at their first antenatal visit compared with no screening was $34,931 per quality‐adjusted life‐years gained. Screening all women could result in cost savings when chlamydia prevalence was higher than 11%. The incremental cost‐effectiveness ratios were most sensitive to the assumed prevalence of chlamydia, the probability of pelvic inflammatory disease, the utility weight of a positive chlamydia test and the cost of the chlamydia test and doctor's appointment.

Conclusion

From an Australian government perspective, chlamydia screening of all women aged 16–25 years old during one antenatal visit was likely to be cost‐effective compared with no screening or selective screening, especially with increasing chlamydia prevalence.

Tweetable abstract

Chlamydia screening for all pregnant women aged 16–25 years during an antenatal visit is cost effective.
Focused parathyroidectomy through an open‐lateral approach for treating solitary parathyroid adenoma
Authors: Yang Zhili , Guo Minggao , Wu Bo , Zheng Qi , Fan Youben
Published: August 2015

Aim

Most cases of primary hyperparathyroidism are caused by a solitary parathyroid adenoma. Many patients are now being treated with focused approaches in parathyroidectomy. The aim of the present study was to investigate the safety and efficacy of focused parathyroidectomy that is performed through an open‐lateral approach under the effect of regional anaesthesia.

Patients and Methods

We carried out a retrospective analysis of 210 patients with solitary parathyroid adenoma. Ninety‐five patients underwent conventional middle‐access exploration, while the remaining 115 patients underwent focused parathyroidectomy through an open‐lateral approach. We recorded biochemical parameters of these patients at the preoperative and postoperative stages and during the follow‐up period. We compared the operative times, hospital stays and morbidity rates of these patients.

Results

There was one case of relapse in each group during the follow‐up period. These two cases were treated with focused parathyroidectomy through an open‐lateral approach under the effect of cervical plexus block anaesthesia. All the other patients were cured by the primary operation. Regional anaesthesia was administered to all patients who were treated with focused parathyroidectomy. However, owing to an ectopical parathyroid gland, one patient required general anaesthesia. There was no significant difference in temporary hypocalcaemia of these patients postoperatively (P > 0.05). Compared to conventional parathyroidectomy, the focused approach was more advantageous, with shorter operative times, smaller scar lengths and shorter hospital stays (P < 0.05).

Conclusions

When focused parathyroidectomy is performed through an open‐lateral approach, it is safe and effective, even under the effect of regional anaesthesia, provided an accurate localization is conducted.
Evaluating environmental DNA‐based quantification of ranavirus infection in wood frog populations
Authors: Hall Emily M. , Crespi Erica J. , Goldberg Caren S. , Brunner Jesse L.
Published: August 2015

A variety of challenges arise when monitoring wildlife populations for disease. Sampling tissues can be invasive to hosts, and obtaining sufficient sample sizes can be expensive and time‐consuming, particularly for rare species and when pathogen prevalence is low. Environmental DNA (eDNA)‐based detection of pathogens is an alternative approach to surveillance for aquatic communities that circumvents many of these issues. Ranaviruses are emerging pathogens of ectothermic vertebrates linked to die‐offs of amphibian populations. Detecting ranavirus infections is critical, but nonlethal methods have the above issues and are prone to false negatives. We report on the feasibility and effectiveness of eDNA‐based ranavirus detection in the field. We compared ranavirus titres in eDNA samples collected from pond water to titres in wood frog (Lithobates sylvaticus; n = 5) tadpoles in sites dominated by this one species (n = 20 pond visits). We examined whether ranavirus DNA can be detected in eDNA from pond water when infections are present in the pond and if viral titres detected in eDNA samples correlate with the prevalence or intensity of ranavirus infections in tadpoles. With three 250 mL water samples, we were able to detect the virus in all visits with infected larvae (0.92 diagnostic sensitivity). Also, we found a strong relationship between the viral eDNA titres and titres in larval tissues. eDNA titres increased prior to observed die‐offs and declined afterwards, and were two orders of magnitude higher in ponds with a die‐off. Our results suggest that eDNA is useful for detecting ranavirus infections in wildlife and aquaculture.
Nonparametric upscaling of stochastic simulation models using transition matrices
Authors: Cipriotti Pablo A. , Wiegand Thorsten , Pütz Sandro , Bartoloni Norberto J. , Paruelo José M.
Published: August 2015

The problem of scaling up from tractable, small‐scale observations and experiments to prediction of large‐scale patterns is at the core of ecological theory and application, and one of the central problems in ecology.

We present and test a general nonparametric framework to upscale spatially explicit and stochastic simulation models. The idea is to design a state space, defined by the important state variables of the small‐scale model, and to divide it into a finite number of discrete states. Transition probabilities are then tallied by monitoring extensive simulation runs of the small‐scale model, covering the entire range of initial conditions, states and external drivers that may occur for the desired application. We exemplify our approach by upscaling an individual‐based model that simulates the spatiotemporal dynamics of Festuca pallescens steppes under sheep grazing in Western Patagonia, Argentina, with a spatial resolution of 0·3 m × 0·3 m and a 0·15‐ha extent. The upscaled model simulates a 2500‐ha paddock with 0·15‐ha resolution and is enriched with additional rules that describe heterogeneity in the local stocking rate at the paddock scale.

We obtained 24 transition matrices that governed the upscaled model for different combinations of stocking rates and annual precipitation. The upscaled model produced excellent predictions for the long‐term dynamics, but as expected, it did not fully capture the interannual dynamics of the original model. Rules for heterogeneity in the local stocking rate allowed for emergence of realistic vegetation patterns as commonly observed for water points in arid rangelands.

Our general nonparametric upscaling approach can be applied to a wide range of stochastic simulation models in which the dynamics can be approximated by a set of states, transitions and external drivers. Because estimation of the transition probabilities can be done parallel, our approach can be applied to a wide range of models of intermediate complexity. Our approach closes a gap in our ability to scale up from small scales, where the biological knowledge is available, to larger scales that are relevant for management.
Systemic review: the pathogenesis and pharmacological treatment of hiccups
Authors: Steger M. , Schneemann M. , Fox M.
Published: August 2015

Background

Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat.

Aim

To review the management of hiccups, including a systematic review of reported efficacy and safety of pharmacological treatments.

Methods

Available articles were identified using three electronic databases in addition to hand searching of published articles. Inclusion criteria were any reports of pharmaceutical therapy of ‘hiccup(s)’, ‘hiccough(s)’ or ‘singultus’ in English or German.

Results

Treatment of 341 patients with persistent or intractable hiccups was reported in 15 published studies. Management was most effective when directed at the underlying condition. An empirical trial of anti‐reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well‐designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo‐controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long‐term therapy.

Conclusions

This systematic review revealed no high quality data on which to base treatment recommendations. Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve.
Open for Entrepreneurship: How Open Innovation Can Foster New Venture Creation
Authors: Eftekhari Nazanin , Bogers Marcel
Published: August 2015

This paper explores how an open approach to new venture creation – purposefully managing knowledge flows across the venture's organizational boundary – can be beneficial for start‐up entrepreneurs. Our inductive case study, of both failure and success, identifies the key attributes of this open approach and how they affect start‐ups' short‐term survival. We find that ecosystem collaboration, user involvement and an open environment directly influence new venture survival, and that their effects were moderated by the entrepreneurs' open mindset. These findings carry a number of implications for entrepreneurship and innovation research and practice, providing some attention points for researchers, entrepreneurs, investors and policy makers interested in developing successful new ventures.
Considerations of Protein Subpockets in Fragment‐Based Drug Design
Authors: Bartolowits Matthew , Davisson V. Jo
Published: August 2015

While the fragment‐based drug design approach continues to gain importance, gaps in the tools and methods available in the identification and accurate utilization of protein subpockets have limited the scope. The importance of these features of small molecule–protein recognition is highlighted with several examples. A generalized solution for the identification of subpockets and corresponding chemical fragments remains elusive, but there are numerous advancements in methods that can be used in combination to address subpockets. Finally, additional examples of approaches that consider the relative importance of small‐molecule co‐dependence of protein conformations are highlighted to emphasize an increased significance of subpockets, especially at protein interfaces.
Prenatal Caloric Intake and the Development of Academic Achievement Among U.S. Children From Ages 5 to 14
Authors: Connolly Eric J. , Beaver Kevin M.
Published: August 2015

Few studies have examined the relation between maternal caloric intake during pregnancy and growth in child academic achievement while controlling for important confounding influences. Using data from the National Longitudinal Survey of Youth, the current study examined the effects of reduced prenatal caloric intake on growth in scores on the Peabody Individual Achievement Test from ages 5 to 14. While models controlling for within‐family covariates showed that prenatal caloric intake was associated with lower reading and mathematical achievement at age 5, models controlling for between‐family covariates (such as maternalIQ) and unobserved familial confounders revealed only a statistically significant association between siblings differentially exposed to prenatal caloric intake and mathematical achievement at age 5.
Does Helping Keep Teens Protected? Longitudinal Bidirectional Relations Between Prosocial Behavior and Problem Behavior
Authors: Padilla‐Walker Laura M. , Carlo Gustavo , Nielson Matthew G.
Published: August 2015

The current study examined bidirectional, longitudinal links between prosocial and problem behavior. Participants (N = 500) were recruited from a Northwestern city in the United States and assessed for 3 consecutive years from 2009 to 2011 (Mage of youth at Time 1 = 13.32, SD = 1.05; 52% girls; 67% European American, 33% single‐parent families). Results suggested that effects of earlier prosocial behavior toward family and strangers were predictive of fewer problem behaviors 2 years later, while results for prosocial behavior toward friends were more mixed. Results also suggested depression predicted lower prosocial behavior toward family members and anxiety predicted higher prosocial behavior toward friends. Findings show a complex pattern of relations that demonstrate the need to consider targets of helping.
Anti-CD20 monoclonal antibody-dependent phagocytosis of chronic lymphocytic leukaemia cells by autologous macrophages
Authors: Church A K , VanDerMeid K R , Baig N A , Baran A M , Witzig T E , Nowakowski G S , Zent C S
Published: August 2015

Unconjugated monoclonal antibodies (mAbs) are an important component of effective combination therapies for chronic lymphocytic leukaemia (CLL). Antibody-dependent phagocytosis (ADP) is a major mediator of mAb cytotoxicity, but there is limited knowledge of the determinants of ADP efficacy. We used macrophages derived in vitro from autologous circulating monocytes to test the effects of mAb structure and concentration, target : effector cell ratio, duration of co-incubation and CLL cell CD20 expression on ADP. Next-generation anti-CD20 mAbs (ofatumumab, ublituximab, obinutuzumab, ocaratuzumab) were significantly more effective at inducing ADP compared to rituximab, but none were as effective as the anti-CD52 mAb alemtuzumab. Ofatumumab (10 μg/ml) used as a representative next-generation anti-CD20 mAb achieved an ADP plateau at 3 h co-incubation with a target : effector ratio of 10 : 1 (mean = 2·1 CLL cells/macrophage, range = 1·5–3·5). At 0·156 μg/ml (the lowest concentration tested) ofatumumab ADP was significantly higher than alemtuzumab. However, ofatumumab-induced ADP did not increase significantly at higher mAb concentrations. We show that anti-CD20 mAb ADP efficacy is determined by the mAb characteristics, target : effector ratio and incubation time. We suggest that preclinical evaluation of anti-CD20 mAbs to understand the determinants of ADP could be useful in designing future combination therapies for CLL.
Exploring Temporal Progression of Events Using Eye Tracking
Authors: Welke Tinka , Raisig Susanne , Hagendorf Herbert , van der Meer Elke
Published: August 2015

This study investigates the representation of the temporal progression of events by means of the causal change in a patient. Subjects were asked to verify the relationship between adjectives denoting a source and resulting feature of a patient. The features were presented either chronologically or inversely to a primed event context given by a verb (to cut: long–short vs. short–long). Effects on response time and on eye movement data show that the relationship between features presented chronologically is verified more easily than that between features presented inversely. Post hoc, however, we found that the effects of temporal order occurred only when subjects read the features more than once. Then, the relationship between the features is matched with the causal change implied by the event context (contextual strategy). When subjects read the features only once, subjects respond to the relationship between the features without taking into account the event context.
Dissemination of an Electronic Manual to Build Capacity for Implementing Farmers’ Markets with Community Health Centers
Authors: Guest M. Aaron , Freedman Darcy , Alia Kassandra A. , Brandt Heather M. , Friedman Daniela B.
Published: August 2015

Community–university partnerships can lend themselves to the development of tools that encourage and promote future community health development. The electronic manual, “Building Farmacies,” describes an approach for developing capacity and sustaining a community health center–based farmers’ market that emerged through a community–university partnership. Manual development was guided by the Knowledge to Action Framework and experiences developing a multivendor, produce‐only farmers’ market at a community health center in rural South Carolina. The manual was created to illustrate an innovative solution for community health development. The manual was disseminated electronically through 25 listservs and interested individuals voluntarily completed a Web‐based survey to access the free manual. During the 6‐month dissemination period, 271 individuals downloaded the manual. Findings highlighted the value of translating community‐based participatory research into user‐friendly manuals to guide future intervention development and dissemination approaches, and demonstrate the need to include capacity building opportunities to support translation and adoption of interventions.
Infants’ unprovoked acts of force toward others
Authors: Dahl Audun
Published: August 2015

Infants harm others at higher rates than older children and adults. A common explanation is that infants fail to regulate their frustration, becoming aggressive when they do not get what they want. The present research investigated whether infants also use force against others without provocation, for instance because they seek to explore the consequences of hitting or try to pet someone using too much force. Two studies with infants aged 11 to 24 months investigated infants’ use of force against others in everyday life using maternal report (Study 1) and direct observation (Study 2). In both studies, a large proportion of infants’ acts of force were unprovoked and occurred without signs of infant distress. Unlike provoked acts, unprovoked acts showed a decrease late in the second year and were positively associated with reports of infant pleasure‐proneness. The presence of unprovoked acts of harm may reflect that infants’ actions are not reliably guided by an aversion for harming others and may provide unique opportunities for early moral development.
Improving prognostication in childhood stroke
Authors: Ganesan Vijeya
Published: August 2015

This commentary is on the original article by Ghotra et al. on pages 1027–1034 of this issue.
Use of the Hammersmith Infant Neurological Examination in infants with cerebral palsy: a critical review of the literature
Authors: Romeo Domenico M , Ricci Daniela , Brogna Claudia , Mercuri Eugenio
Published: August 2015

The Hammersmith Infant Neurological Examination (HINE) has been proposed as one of the early neurological examination tools for the diagnosis of cerebral palsy (CP). The aim of the present study was to critically review the existing literature and our experience with the use of the HINE in infants at risk of CP. The published papers confirm that the HINE can play an important role in the diagnosis and prognosis of infants at risk of developing CP, and provide information on aspects of neurological findings impaired in different forms of CP and brain lesions.
Language and literacy in children with benign epilepsy with centrotemporal spikes
Authors: Datta Alexandre N
Published: August 2015

This commentary is on the systematic review by Smith et al. on pages 1019–1026 of this issue.
In vitro models for peripheral nerve regeneration
Authors: Geuna S. , Raimondo S. , Fregnan F. , Haastert‐Talini K. , Grothe C.
Published: August 2015

The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre‐clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three‐step stair model based on their increasing ethical impact: (i) cell line‐based models, which raise no ethical concern; (ii) primary cell‐based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo‐based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the ‘Three Rs’ (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research.
Ixodes tick saliva suppresses the keratinocyte cytokine response to TLR2/TLR3 ligands during early exposure to Lyme borreliosis
Authors: Bernard Quentin , Gallo Richard L. , Jaulhac Benoît , Nakatsuji Teruaki , Luft Benjamin , Yang Xiahoua , Boulanger Nathalie
Published: August 2015

Ixodes hard tick induces skin injury by its sophisticated biting process. Its saliva plays a key role to enable an efficient blood meal that lasts for several days. We hypothesized that this feeding process may also be exploited by pathogens to facilitate their transmission, especially in the context of arthropod‐borne diseases. To test this, we used Lyme borreliosis as a model. This bacterial infection is caused by Borrelia burgdorferi sensu lato transmitted by Ixodes. We co‐incubated Borrelia with human keratinocytes in the presence of poly (I: C), a dsRNA TLR3 agonist generated by skin injury. This induced a strong cytokine response from human primary keratinocytes that was much greater than that induced by Borrelia alone. OspC, a TLR2/1 agonist and a major surface lipoprotein of Borrelia also amplified the process. Interestingly, tick saliva inhibited cytokine responses by keratinocytes to these TLR agonists. We propose that Borrelia uses the immunoprivileged site produced by tick saliva to facilitate its transmission.
Silence and Memories of War: An Autoethnographic Exploration of Family Secrecy
Authors: Rober Peter , Rosenblatt Paul C.
Published: August 2015

A personal journey and a scientific challenge, this is an autoethnographic study about my own family's secrecy. I knew my grandfather had been a German prisoner of war during World War II. We all knew. But nobody talked about it. Then one day I decided I wanted to do systematic research on the issue of family secrecy around my grandfather's war experiences. Researching one's own family can be called autoethnography. It could be said that autoethnography is an approach to research that aims to describe and systemically analyze (graphy) personal experience (auto) to understand social and cultural phenomena (ethno). This scientific approach is quite new in the field of family therapy. This study has been an important personal quest, but it also led to important reflections on silences in families, on my own professional development, and on methodological issues concerning autoethnographical research. For one thing, it highlights some of the positive aspects of family secrecy and silences, and invites us—when confronted with family secrecy in clinical practice—to carefully consider the potential destructive and life‐giving aspects of the silence.
O‐glycosylation effects on family 1 carbohydrate‐binding module solution structures
Authors: Happs Renee M. , Guan Xiaoyang , Resch Michael G. , Davis Mark F. , Beckham Gregg T. , Tan Zhongping , Crowley Michael F.
Published: August 2015

Family 1 carbohydrate‐binding modules (CBMs) are ubiquitous components of multimodular fungal enzymes that degrade plant cell wall polysaccharides and bind specifically to cellulose. Native glycosylation of family 1 CBMs has been shown to substantially impact multiple physical properties, including thermal and proteolytic stability and cellulose binding affinity. To gain molecular insights into the changes in CBM properties upon glycosylation, solution structures of two glycoforms of a Trichoderma reesei family 1 CBM were studied by NMR spectroscopy: a glycosylated family 1 CBM with a mannose group attached to both Thr1 and Ser3 and a second family 1 CBM with single mannose groups attached to Thr1, Ser3 and Ser14. The structures clearly reveal that monosaccharides at both Ser3 and Ser14 on family 1 CBMs present additional cellulose binding platforms, similar to well‐characterized aromatic residues at the binding interface, which align to the cellulose surface. These results are in agreement with previous experimental work demonstrating that glycans at Ser3 and Ser14 impart significant improvements in binding affinity. Additionally, detailed analysis of the NMR structures and molecular simulations indicates that the protein backbone of the CBM is not significantly altered by attachment of monosaccharides, and that the mannose attached to Ser14 may be more flexible than the mannose at Ser3. Overall, the present study reveals how family 1 CBM structures are affected by covalent attachment of monosaccharides, which are likely important post‐translational modifications of these common subdomains of fungal plant cell wall degrading enzymes.

Database

Structural data have been deposited in the RCSB Protein Data Bank (PDB codes: 2MWJ and 2MWK) and the BioMagRes Bank (BMRB codes: 25331 and 25332) for CBM_M2 and CBM_M3, respectively.
Improved experimental protocols to evaluate cold tolerance thresholds in Miscanthus and switchgrass rhizomes
Authors: Peixoto Murilo de Melo , Sage Rowan F.
Published: August 2015

This study investigates protocols to evaluate cold tolerance thresholds for overwintering rhizomes of perennial bioenergy grasses. Protocols examined include the temperature at which ice formation occurs, cooling rate, incubation time at the treatment temperature, and the electrolyte leakage (EL) method to assess mortality thresholds. Using these protocols, we assessed low temperature injury in two genotypes of Miscanthus and two genotypes of lowland switchgrass (Panicum virgatum). Ice formed near −1 C in the rhizomes cooled at 1 C h−1, but at variable temperatures at cooling rates of 3  and 5 C h−1. Rhizome temperature followed chamber temperature at a cooling rate of 1 C h−1, whereas at faster cooling rates, there was a lag in rhizome temperature that affected treatment exposure time. A 1 C h−1 cooling rate is thus suitable. In rhizomes incubated for <4 h at the treatment temperature, EL values were variable, while there was no change in EL when samples were incubated 4–20 h. A continuous, steady rate of cooling at 1 C h−1 demonstrated the Miscanthus and lowland switchgrass varieties exhibited lethal levels of electrolyte leakage below −6 C. Continuous cooling does not allow for subzero acclimation and reflects thermal tolerances of sampled tissue in situ. To allow for maximum acclimation at subzero temperatures, a prolonged, staged‐cooling procedure was adopted. This procedure showed diploid Miscanthus rhizomes could acclimate and adjust their tolerance limit to −12 C, while a triploid Illinois line showed little acclimation and was still killed below −6 C.
Pyrophyllite formation in the thermal aureole of a hydrothermal system in the Lower Saxony Basin, Germany
Authors: Will P. , Lüders V. , Wemmer K. , Gilg H. A.
Published: August 2015

A combined clay mineralogical, fluid inclusion, and K‐Ar study of Upper Jurassic metasediments at the Gehn (Lower Saxony Basin, Germany) provides evidence for a transient hydrothermal event during Upper Cretaceous basin inversion centered on a prominent gravimetric anomaly. Kaolinite and smectite in Oxfordian pelitic parent rocks that cap a deltaic sandstone unit were locally transformed into pyrophyllite, 2M1 illite, R3 illite–smectite, chlorite, and berthierine at the Ueffeln quarry. The pyrophyllite‐bearing metapelites lack bedding‐parallel preferred orientation of sheet silicates and experienced peak temperatures of about 260–270°C consistent with microthermometric data on quartz veins in the underlying silicified sandstones. The presence of expandable layers in illite–smectite and high Kübler Index values indicate that the thermal event was rather short‐lived. K‐Ar dating of the <0.2 μm fraction of the pyrophyllite‐bearing Ueffeln metapelite yields a maximum illitization age of 117 ± 2 Ma. Lower trapping temperatures of aqueous fluid inclusions in quartz veins and the absence of pyrophyllite in metapelites of the Frettberg quarry in a distance of about 2.5 km from the Ueffeln quarry infer maximum paleotemperatures of only 220°C. The highly localized thermal anomaly at Ueffeln suggests fault‐controlled fluid migration and heat transfer that provided a thermal aureole for pyrophyllite formation in the metapelites rather than metamorphism due to deep burial. A pH neutral hydrothermal fluid that formed by devolatilization reactions or less likely by mixing of meteoric and marine waters that interacted at depth with shales is indicated by the low salinity (3–5 wt. % NaCl equiv.) of aqueous inclusions, their coexistence with methane–carbon dioxide‐dominated gas inclusions as well as carbon, hydrogen, and oxygen isotope data. The upwelling zone of hydrothermal fluids and the thermal maximum is centered on a gravimetric anomaly interpreted as an igneous intrusion (‘Bramsche Massif’) providing the heat source for the intrabasinal hydrothermal system.