bluuebunny/crossref_metadata_2025 huggingface dataset:
A conceptual Lean Six Sigma framework for quality excellence in higher education institutions
Authors: Sunder M. Vijaya , Antony Jiju
Published: February 2018

Purpose

The purpose of this paper is to present the potent application of Lean Six Sigma (LSS) in higher education services and to suggest a conceptual framework of deploying LSS in the higher education institutions (HEIs).

Design/methodology/approach

This paper aims to outline the importance of the quality excellence criterion in general through different constructs from the literature including TQM, Lean, Six Sigma and LSS. The paper further expands on the applicability of LSS in the HEI setting, with an understanding of HEI as comparatively different from the manufacturing sector from where LSS originated. The published literature on LSS and authors’ experience in the field of LSS (as practitioners) were used as sources for devising a conceptual framework for LSS deployment in HEIs.

Findings

The key finding from the study is the confirmation of LSS applicability in HEIs. The study also confirms that LSS is not anyone’s job but a key part of leadership agenda. The six-staged conceptual framework prescribed for the HEIs as part of the paper is the key contribution of this study. The model describes that LSS readiness is the foremost step in the LSS deployment journey in HEIs. The strategic perspectives of aligning the organisational vision for quality excellence need to be achieved by establishing a need for LSS through leadership. Then, developing an LSS deployment strategy becomes the next step. Educating the appropriate stakeholders (students) and team formation becomes the next important steps in the LSS deployment. Once the above steps are implemented in right way, identifying and implementing LSS projects becomes critical. The execution and closure of the LSS projects leads to quality excellence in HEIs.

Research limitations/implications

Since the framework prescribed here is a conceptual framework, it deserved a testing in the real-life context. This leaves an opportunity for future researchers to test and expand on the implications of the model. Though the LSS framework is customised for HEIs, the fundamental factors essential for any change management initiative holds correct for LSS as well, and hence these are not elaborated as part of this paper.

Originality/value

This paper would serve as an excellent resource for both academicians and LSS practitioners in HEIs, for deployment. The framework presented here is the original work contributed by the authors, as the first of its kind in the academic literature relevant to LSS in HEIs.
Quantifying the relationship between latent variables after successful implementation of QM practices in MSMEs
Authors: Kharub Manjeet , Sharma Rajiv Kumar
Published: February 2018

Purpose

The purpose of this paper is to explore the relationship between latent variables, i.e. human resource management (HRM) effectiveness, quality cost (QC), and firm performance (FP) for the successful implementation of quality management (QM) practices in micro, small and medium enterprises.

Design/methodology/approach

The data analysis is accomplished in three steps: in the first step, factor analysis was conducted to extract the latent variables representing key QM practices. In the second step, a descriptive analysis (cross-tabulation) was performed to examine the current situation and association between key QM variables and firm size. In the third step, to test the research hypotheses based on latent constructs, structural equation modelling (SEM) has been used.

Findings

The percent point score shows that there are substantial improvements in all organisational aspects after successful implementation of QM practices. The χ2-test revealed that only three domains namely employee participation, recruitment and retaining and supplier relationship are having a significant variation with respect to the firm size. The SEM results show that HRM effectiveness has a direct and positive relationship with FP, whereas QC has a negative association with HRM effectiveness and FP.

Originality/value

Managers will know which aspect they must consider seeing as an indicator of QM practice in their company(s). Out of the three identified latent constructs first will help to create an efficient human capital, whereas the second will help for addressing extra cost due to poor quality. Finally, the third latent variable will show the effectiveness of these two and will assist in evaluating firm’s performance.
Impact of knowledge enabling factors on organizational effectiveness in construction companies
Authors: Dang Chau Ngoc , Le-Hoai Long , Kim Soo-Yong
Published: February 2018

Purpose

This study aims to identify key knowledge enabling factors (KEFs) which can enable construction companies to improve various organizational effectiveness outcomes (OEOs).

Design/methodology/approach

Using a questionnaire, data are collected from construction companies in Vietnam. Mean score method is used to calculate the mean values of KEFs. In addition, regression analysis is used to identify KEFs which significantly affect OEOs.

Findings

A list of 32 KEFs, whose ranking orders of importance are provided according to different types of construction companies, is presented. In addition, different lists of specific KEFs which could significantly affect different OEOs are identified. Furthermore, seven key KEFs which could have a significant impact on many OEOs are highlighted.

Practical implications

The findings of this study could help construction companies to know the controllable KEFs, on which they should focus more. Hence, they could perform these KEFs properly to improve various aspects of organizational effectiveness.

Originality/value

This study identifies 32 KEFs and 10 OEOs specifically for knowledge management in construction companies. This study also provides construction companies with a better understanding of the impact of KEFs on various aspects of organizational effectiveness. Hence, they could develop effective KEFs-based management strategies to enhance various aspects of organizational effectiveness.
The contribution of spatial dependency to office building price indexes
Authors: Liang Jerry , Reed Richard , Crabb Tony
Published: February 2018

Purpose

The purpose of this paper is to investigate the role of spatial dependency in the construction of a price index for the transactions of whole office buildings. It examines transactions of office buildings over a 15-year period and addresses an under-researched area in investment property analysis.

Design/methodology/approach

The study examines data relating to transactions of all office buildings in the Melbourne (Australia) central business district between 2000 and 2015. The methodology uses a spatial weights matrix to construct a hedonic model, spatial error model, spatial lagged model and an office building transactional price index.

Findings

The findings confirm the existence of spatial dependency for the transactions of office buildings. In addition, incorporating the effect of spatial dependency by constructing spatial error and spatial lagged model improved the accuracy of the estimated transactional price index for office buildings.

Research limitations/implications

These findings make an important contribution to the literature by highlighting the importance of the issue of spatial autocorrelation in the estimation of valuation models and price indexes for office buildings. Until now the focus has predominantly been on individual office units rather than whole office buildings, where the barrier has traditionally been access to comprehensive data. The analysis did not consider leasing details as this information is not accessible in the Australian market.

Practical implications

The research will assist stakeholders including valuers, investors and market regulators to improve their understanding of movements in the office property transactional market. The findings provide an insight into trends associated with the transfer of office buildings. It will assist future decisions about the location of a new office building developments in order to optimise their proximity to transport and other buildings.

Social implications

The study will assist planners to ensure the location of office buildings are optimised from a social sustainability perspective. This equates to buildings located in close proximity to transport facilities and also supporting the development of office buildings in locations, which are associated with lower future risk.

Originality/value

The construction of an accurate and reliable property index is critically important for practitioners to understand the movement in both the property market and also in the broader economy. A substantial increase in whole office building acquisitions has been observed in recent years, especially after the 2007 Global Financial Crisis (Lizieri and Pain, 2014) although there has remained limited research undertaken in this area.
Resolving the data debacle in commercial property
Authors: Olapade Daramola Thompson , Olaleye Abel
Published: February 2018

Purpose

With a focus on Lagos, Nigeria property market, the purpose of this paper is to examine the willingness of property practitioners towards property data sharing and assemblage with a view to improving accessibility to commercial property data in Nigerian property market.

Design/methodology/approach

Primary data were sourced through the use of questionnaire administered on property practitioners (referred as estate surveying and valuation (ESV) firms) in Lagos property market. In total, 190 ESV firms were selected using stratified random sampling based on their geographical location, frequency distribution, percentage, and cross-tabulation were employed for data analysis.

Findings

The results showed that majority of the practitioners (68.1 per cent) were willing to share property data among themselves while 52.6 per cent of the practitioners were in support of data assemblage. The result also revealed the higher the experience of the practitioners, the more they are averse to data sharing. It was also revealed that the bigger firm are more averse to data assemblage than the smaller firms. Meanwhile, majority of the practitioners (93.3 per cent) were in support of creation of a central database.

Practical implications

The study concluded that without the willingness of practitioners to support data assemblage, the data debacle in property market might not be resolved.

Originality/value

The paper is an attempt towards the possibility of creating database of concluded transactions, which will improve accessibility to property data in opaque property market.
Measurement of shock effect following change of one-child policy based on grey forecasting approach
Authors: Xie Naiming , Wang Ruizhi , Chen Nanlei
Published: February 2018

Purpose

This paper aims to analyze general development trend of China’s population and to forecast China’s total population under the change of China’s family planning policy so as to measure shock disturbance effects on China’s population development.

Design/methodology/approach

China has been the most populous country for hundreds of years. And this state will be sustained in the forthcoming decade. Obviously, China is confronted with greater pressure on controlling total scale of population than any other country. Meanwhile, controlling population will be beneficial for not only China but also the whole world. This paper first analyzes general development trend of China’s population total amount, sex ratio and aging ratio. The mechanism for measurement of the impact effect of a policy shock disturbance is proposed. Linear regression model, exponential curve model and grey Verhulst model are adopted to test accuracy of simulation of China’s total population. Then considering the policy shock disturbance on population, discrete grey model, DGM (1, 1), and grey Verhulst model were adopted to measure how China’s one-child policy affected its total population between 1978 and 2015. And similarly, the grey Verhulst model and scenario analysis of economic developing level were further used to forecast the effect of adjustment from China’s one-child policy to two-child policy.

Findings

Results show that China has made an outstanding contribution toward controlling population; it was estimated that China prevented nearly 470 million births since the late 1970s to 2015. However, according to the forecast, with the adjustment of the one-child policy, the birth rate will be a little higher, China’s total population was estimated to reach 1,485.59 million in 2025. Although the scale of population will keep increasing, but it is tolerable for China and sex ratio and trend of aging will be relieved obviously.

Practical implications

The approach constructed in the paper can be used to measure the effect of population change under the policy shock disturbance. It can be used for other policy effect measurement problems under shock events’ disturbance.

Originality/value

The paper succeeded in studying the mechanism for the measurement of the post-impact effect of a policy and the effect of changes in China’s population following the revision of the one-child policy. The mechanism is useful for solving system forecasting problems and can contribute toward improving the grey decision-making models.
The impact of asymmetry on performance in different collaboration and integration environments in supply chain management
Authors: Michalski Marek , Montes-Botella Jose-Luis , Narasimhan Ram
Published: February 2018

Purpose

This paper aims to examine the non-linear aspects of the relationship between asymmetry and performance in supply chains (SCs), under varying intensities of collaboration and integration.

Design/methodology/approach

The paper offers a useful new approach to designing strategic elements of supply chain management (SCM) relationships. Using the partial least squares method, an empirical study of 66 companies in Spain has been conducted to clarify contemporary relationships, suggest new directions and ultimately contribute toward developing SCM theory.

Findings

The influences of asymmetry on performance in varying collaboration and integration contexts are shown to be unstable and have non-linear paths. It is inappropriate for all firms to collaborate or integrate continually, even for a prescribed period. Furthermore, due to asymmetry, SCM processes are more complex.

Research limitations/implications

The results’ validity may be limited to contexts specific to Spanish SCs. It would be valuable to investigate the impact of asymmetry on firms’ performance and relationships in other markets.

Practical implications

Collaborations and integration between partners in a SC might change the role of asymmetry from restraining to improving performance. The best way to improve performance in asymmetric relationships is to collaborate. Certain dimensions of integration and full integration are not necessarily required to improve firms’ performance under asymmetry conditions.

Originality/value

The study adds a new viewpoint on SCM by suggesting that not all collaboration and integration developments lead directly to improved performance.
N‐acetylcysteine for major mental disorders: a systematic review and meta‐analysis of randomized controlled trials
Authors: Zheng W. , Zhang Q.‐E. , Cai D.‐B. , Yang X.‐H. , Qiu Y. , Ungvari G. S. , Ng C. H. , Berk M. , Ning Y.‐P. , Xiang Y.‐T.
Published: February 2018

Objective

This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N‐acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia.

Methods

The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed.

Results

Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = −0.74, 95% CI: −1.43, −0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders.

Conclusions

Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
Male infertility is associated with altered treatment course of men with cancer
Authors: Eminaga O. , Li S. , Baker L. C. , Brooks J. D. , Eisenberg M. L.
Published: February 2018

This study aims to evaluate whether cancer treatments differ in infertile men compared to men who have undergone vasectomy and age‐matched controls. We analyzed subjects from the Truven Health MarketScan Claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups included vasectomized men and an age‐matched cohort who were not infertile and had not undergone vasectomy. We considered cancer types previously associated with infertility that were diagnosed after the diagnosis of infertility. The treatment regimens were determined based on the presence of claims with CPT codes for chemotherapy (CTX), radiation (RTX) or surgical treatment (ST) for each entity in all study groups. Cases with multimodal treatments were also identified. As a result, CTX was similarly distributed among the infertile, vasectomized, and control groups. In contrast, RTX treatment length was shorter in infertile men. The frequency of multimodal treatment (i.e., radiation and chemotherapy) was twofold lower in men with infertility compared to other men. By focusing on treatment patterns for each cancer type among these groups, the duration of RTX and CTX was shorter in infertile men diagnosed with NHL compared to controls. We conclude that Infertile men diagnosed with cancer and specific cancer types experience different treatment courses, with shorter RTX and less combined RTX/CTX compared to fertile and vasectomized men. These differences could reflect differences in stage at presentation, biological behavior, or treatment responses in infertile men.
Modeling suicide in bipolar disorders
Authors: Malhi Gin S , Outhred Tim , Das Pritha , Morris Grace , Hamilton Amber , Mannie Zola
Published: February 2018

Introduction

Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20–30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence.

Methods

A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords “suicide”, “suicide in bipolar disorders”, “suicide process”, “suicide risk”, “neurobiology of suicide” and “suicide models”. Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance.

Results

Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis‐stress model, the bipolar model of suicide and the ideation‐to‐action models, the interpersonal theory of suicide, the integrated motivational‐volitional model, and the three‐step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action.

Conclusion

Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only for research purposes, but also for future real‐world clinical practice.
Infants' Understanding of Distributive Fairness as a Test Case for Identifying the Extents and Limits of Infants' Sociomoral Cognition and Behavior
Authors: Sommerville Jessica A.
Published: February 2018

In this article, I use infants' sensitivity to distributive fairness as a test case to identify the extents and limits of infants' sociomoral cognition and behavior. Infants' sensitivity to distributive fairness is in some ways commensurate with this understanding in older children and adults; infants expect fair distributions of resources and evaluate others based on their adherence to or violation of fairness norms. Yet these sensitivities also differ in important ways, including that infants do not spontaneously punish unfair individuals. I address questions about the role of experience in infants' development of sociomoral cognition and behavior, and whether infants' moral cognition and behavior are differentiated appropriately (from their social knowledge and behavior) and integrated (across subaspects of morality). I suggest two approaches to move the field forward: investigating processes that contribute to developing sociomoral cognition and behavior, and considering infants' successes and failures in this domain.
Does Microfinance Reduce Poverty among the Poorest? A Macro Quantile Regression Approach
Authors: Lacalle‐Calderon Maricruz , Perez‐Trujillo Manuel , Neira Isabel
Published: February 2018

The goal of this paper is to provide empirical evidence to determine whether microfinance, measured through a country's gross loan portfolio per capita, has a heterogeneous effect on poverty reduction among countries with different levels of poverty. We have used a panel‐data quantile regression with a data set for 57 countries for the years 2005, 2008, and 2011 to estimate the distributional impacts of microcredits on two poverty indices. Results reveal not only that microfinance significantly reduces the incidence and depth of poverty, but also that this effect differs across the different poverty levels (quantiles). The effect of microcredit on poverty reduction is slightly larger among countries where the incidence and depth of poverty are the highest, suggesting that microcredit reaches and benefits even the poorest individuals.
Rethinking the origins of transnational humanitarian organizations: the curious case of the International Shipwreck Society
Authors: DAVIES THOMAS
Published: February 2018

This exploration of the evolution of the International Shipwreck Society (ISS) – a previously neglected transnational humanitarian organization that by the late 1830s had branches in every continent – casts new light on three key aspects of the development of global humanitarianism. First, that there was a secular humanitarian association with a global organizational structure in the 1830s challenges widespread assumptions about the timing of internationally organized humanitarian action. Second, the influence of Chinese precedents on the ISS points to the importance of long forgotten Eastern origins of transnational humanitarianism. And third, the evaluation of the role of individuals in the development of the ISS reveals that early transnational humanitarian organizations faced leadership problems that scholars had previously neglected. In each of these respects, this article provides a new perspective on the origins of global networks.
Subjective sleep quality, blood pressure, and hypertension: a meta‐analysis
Authors: Lo Kenneth , Woo Brigitte , Wong Martin , Tam Wilson
Published: February 2018

Sleep quality is an important aspect of sleep, but no meta‐analysis has elucidated its relationship with blood pressure (BP) and hypertension. A meta‐analysis was conducted in October 2016 using multiple databases, including Embase and Medline. Studies that assessed subjective sleep quality and BP or hypertension were included. Upon full‐text evaluation, 29 articles from 45 041 patients were selected, of which 22 articles were included in the meta‐analysis and seven were presented narratively. Poor sleep quality was significantly associated with a greater likelihood of hypertension (odds ratio, 1.48; P value = .01). Poor sleepers had higher average systolic BP (mean difference = 4.37, P value = .09) and diastolic BP (mean difference = 1.25, P value = .32) than normal sleepers without statistical significance. Patients with hypertension had significantly worse sleep quality scores (mean difference = 1.51, P value < .01), while BP dippers had significantly better scores (mean difference = −1.67, P value < .01). The findings highlight the relationship between sleep quality and hypertension.
When Protection Puts You in Jeopardy — How Removing Small‐Business Clauses Affects Employment Duration
Authors: Luecke Christine
Published: February 2018

Dismissal protection has undergone many statutory changes in Germany. In a 2004 reform, small firms were exempted from dismissal protection. This paper estimates the effects of dismissal protection on the risk of leaving the establishment, taking advantage of the fact that workers employed before the amendment maintained their previous dismissal protection. Workers become eligible for dismissal protection after 6 months of tenure. These 6 months might work as an entry barrier to consequent employment. Utilizing administrative linked employer–employee data, the results hint at a higher risk during the first 6 months in a job and a lower risk thereafter, if dismissal protection is provided. The estimated survivor curves suggest that even after 5 years the protecting effect of dismissal protection did not compensate the initially adverse effect during the first 6 months of tenure. No evidence is found of a positive link between dismissal protection and matching quality.
Factors associated with nutritional status and dietary practices of Bangladeshi adolescents in early pregnancy
Authors: Mridha Malay K. , Matias Susana L. , Arnold Charles D. , Dewey Kathryn G.
Published: February 2018

Bangladesh has a high prevalence of adolescent pregnancy, but little is known about the nutritional status and dietary practices of Bangladeshi adolescents in early pregnancy or associated factors. We used the baseline data of 1552 pregnant adolescents from a longitudinal, cluster‐randomized effectiveness trial conducted in northwest Bangladesh. Forty‐four percent of the adolescents were short for their age, 36% had low body mass index, 28% were anemic, 10% had iron deficiency, and 32% had vitamin A deficiency. The mean consumption of animal‐source foods was 10.3 times/week. In multivariate analysis, socioeconomic status, education, and food security were generally positively associated with anthropometric indicators and dietary practices but not with iron or vitamin A status. Our findings confirm that there is a high burden of undernutrition among these Bangladeshi adolescents in early pregnancy. Understanding factors related to undernutrition can help to identify adolescent pregnant women at higher risk and provide appropriate counseling and care.
Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease
Authors: Goletti Delia , Lee Meng‐Rui , Wang Jann‐Yuan , Walter Nicholas , Ottenhoff Tom H.M.
Published: February 2018

Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB‐BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB‐BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB‐BM currently studied are host‐derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations (‘signatures’). In particular, vaccine‐inducible CoP are expected to be transformative in developing new TB vaccines as they will de‐risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals.

Of key importance is that TB‐BM are tested and validated in different well‐characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non‐tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations.

In this study, we review the most recent advances in research into TB‐BM for the diagnosis of active TB, risk of TB development and treatment‐induced TB cure.
Modular radical cross-coupling with sulfones enables access to sp
3
-rich (fluoro)alkylated scaffolds
Authors: Merchant Rohan R. , Edwards Jacob T. , Qin Tian , Kruszyk Monika M. , Bi Cheng , Che Guanda , Bao Deng-Hui , Qiao Wenhua , Sun Lijie , Collins Michael R. , Fadeyi Olugbeminiyi O. , Gallego Gary M. , Mousseau James J. , Nuhant Philippe , Baran Phil S.
Published: February 2018

A sulfur matchmaker for fluorous coupling

Fluorination is a burgeoning technique for fine-tuning the properties of pharmaceutical compounds. Unfortunately, the cross-coupling reactions widely used to make carbon-carbon bonds in drug research can be tripped up by fluorine substituents. Merchant
et al.
report a class of easily prepared, solid sulfone compounds that engage in nickel-catalyzed coupling of their fluoroalkyl groups with aryl zinc reagents. These sulfones considerably simplify the synthetic routes to fluorinated analogs that would previously have required multistep strategies focused strictly on the fluorination protocol.

Science
, this issue p.
75
Pharmacokinetics of Penicillin G in Preterm and Term Neonates
Authors: Padari Helgi , Metsvaht Tuuli , Germovsek Eva , Barker Charlotte I. , Kipper Karin , Herodes Koit , Standing Joseph F. , Oselin Kersti , Tasa Tõnis , Soeorg Hiie , Lutsar Irja
Published: February 2018

Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but have been poorly described for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We describe the PK of penicillin G in neonates with a gestational age (GA) of ≥32 weeks and a postnatal age of <72 h. Penicillin G was administered intravenously at a dose of 25,000 or 50,000 IU/kg of body weight every 12 h (q12h). At steady state, PK blood samples were collected prior to and at 5 min, 1 h, 3 h, 8 h, and 12 h after injection. Noncompartmental PK analysis was performed with WinNonlin software. With those data in combination with data from neonates with a GA of ≤28 weeks, we developed a population PK model using NONMEM software and performed probability of target attainment (PTA) simulations. In total, 16 neonates with a GA of ≥32 weeks were included in noncompartmental analysis. The median volume of distribution (
V
) was 0.50 liters/kg (interquartile range, 0.42 to 0.57 liters/kg), the median clearance (CL) was 0.21 liters/h (interquartile range, 0.16 to 0.29 liters/kg), and the median half-life was 3.6 h (interquartile range, 3.2 to 4.3 h). In the population PK analysis that included 35 neonates, a two-compartment model best described the data. The final parameter estimates were 10.3 liters/70 kg and 29.8 liters/70 kg for
V
of the central and peripheral compartments, respectively, and 13.2 liters/h/70 kg for CL. Considering the fraction of unbound penicillin G to be 40%, the PTA of an unbound drug concentration that exceeds the MIC for 40% of the dosing interval was >90% for MICs of ≤2 mg/liter with doses of 25,000 IU/kg q12h. In neonates, regardless of GA, the PK parameters of penicillin G were similar. The dose of 25,000 IU/kg q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 h of life. (This study was registered with the EU Clinical Trials Register under EudraCT number 2012-002836-97.)
Mesoscopic Energy Minimization Drives Pseudomonas aeruginosa Biofilm Morphologies and Consequent Stratification of Antibiotic Activity Based on Cell Metabolism
Authors: Sheraton M. V. , Yam J. K. H. , Tan C. H. , Oh H. S. , Mancini E. , Yang L. , Rice S. A. , Sloot P. M. A.
Published: February 2018

Segregation of bacteria based on their metabolic activities in biofilms plays an important role in the development of antibiotic resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explored the development of metabolically heterogeneous
Pseudomonas aeruginosa
biofilms using numerical models and laboratory knockout experiments on wild-type and chemotaxis-deficient mutants. We show that chemotactic processes dominate the transformation of slender and hemispherical structures into mushroom structures with a signature cap. Cellular Potts model simulation and experimental data provide evidence that accelerated movement of bacteria along the periphery of the biofilm, due to nutrient cues, results in the formation of mushroom structures and bacterial segregation. Multidrug resistance of bacteria is one of the most threatening dangers to public health. Understanding the mechanisms of the development of mushroom-shaped biofilms helps to identify the multidrug-resistant regions. We decoded the dynamics of the structural evolution of bacterial biofilms and the physics behind the formation of biofilm structures as well as the biological triggers that produce them. Combining
in vitro
gene knockout experiments with
in silico
models showed that chemotactic motility is one of the main driving forces for the formation of stalks and caps. Our results provide physicists and biologists with a new perspective on biofilm removal and eradication strategies.
High Microbial Diversity Promotes Soil Ecosystem Functioning
Authors: Maron Pierre-Alain , Sarr Amadou , Kaisermann Aurore , Lévêque Jean , Mathieu Olivier , Guigue Julien , Karimi Battle , Bernard Laetitia , Dequiedt Samuel , Terrat Sébastien , Chabbi Abad , Ranjard Lionel
Published: February 2018

In soil, the link between microbial diversity and carbon transformations is challenged by the concept of functional redundancy. Here, we hypothesized that functional redundancy may decrease with increasing carbon source recalcitrance and that coupling of diversity with C cycling may change accordingly. We manipulated microbial diversity to examine how diversity decrease affects the decomposition of easily degradable (i.e., allochthonous plant residues) versus recalcitrant (i.e., autochthonous organic matter) C sources. We found that a decrease in microbial diversity (i) affected the decomposition of both autochthonous and allochthonous carbon sources, thereby reducing global CO
2
emission by up to 40%, and (ii) shaped the source of CO
2
emission toward preferential decomposition of most degradable C sources. Our results also revealed that the significance of the diversity effect increases with nutrient availability. Altogether, these findings show that C cycling in soil may be more vulnerable to microbial diversity changes than expected from previous studies, particularly in ecosystems exposed to nutrient inputs. Thus, concern about the preservation of microbial diversity may be highly relevant in the current global-change context assumed to impact soil biodiversity and the pulse inputs of plant residues and rhizodeposits into the soil.

IMPORTANCE
With hundreds of thousands of taxa per gram of soil, microbial diversity dominates soil biodiversity. While numerous studies have established that microbial communities respond rapidly to environmental changes, the relationship between microbial diversity and soil functioning remains controversial. Using a well-controlled laboratory approach, we provide empirical evidence that microbial diversity may be of high significance for organic matter decomposition, a major process on which rely many of the ecosystem services provided by the soil ecosystem. These new findings should be taken into account in future studies aimed at understanding and predicting the functional consequences of changes in microbial diversity on soil ecosystem services and carbon storage in soil.
Efficient and Scalable Precision Genome Editing in
Staphylococcus aureus
through Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection
Authors: Penewit Kelsi , Holmes Elizabeth A. , McLean Kathryn , Ren Mingxin , Waalkes Adam , Salipante Stephen J.
Published: February 2018

Staphylococcus aureus
is an important human pathogen, but studies of the organism have suffered from the lack of a robust tool set for its genetic and genomic manipulation. Here we report the development of a system for the facile and high-throughput genomic engineering of
S. aureus
using single-stranded DNA (ssDNA) oligonucleotide recombineering coupled with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated counterselection. We identify recombinase
EF2132
, derived from
Enterococcus faecalis
, as being capable of integrating single-stranded DNA oligonucleotides into the
S. aureus
genome. We found that
EF2132
can readily mediate recombineering across multiple characterized strains (3 of 3 tested) and primary clinical isolates (6 of 6 tested), typically yielding thousands of recombinants per transformation. Surprisingly, we also found that some
S. aureus
strains are naturally recombinogenic at measurable frequencies when oligonucleotides are introduced by electroporation, even without exogenous recombinase expression. We construct a temperature-sensitive, two-vector system which enables conditional recombineering and CRISPR/Cas9-mediated counterselection in
S. aureus
without permanently introducing exogenous genetic material or unintended genetic lesions. We demonstrate the ability of this system to efficiently and precisely engineer point mutations and large single-gene deletions in the
S. aureus
genome and to yield highly enriched populations of engineered recombinants even in the absence of an externally selectable phenotype. By virtue of utilizing inexpensive, commercially synthesized synthetic DNA oligonucleotides as substrates for recombineering and counterselection, this system provides a scalable, versatile, precise, inexpensive, and generally useful tool for producing isogenic strains in
S. aureus
which will enable the high-throughput functional assessment of genome variation and gene function across multiple strain backgrounds.

IMPORTANCE
Engineering genetic changes in bacteria is critical to understanding the function of particular genes or mutations but is currently a laborious and technically challenging process to perform for the important human pathogen
Staphylococcus aureus
. In an effort to develop methods which are rapid, easy, scalable, versatile, and inexpensive, here we describe a system for incorporating synthetic, mutagenic DNA molecules into the
S. aureus
genome and for eliminating cells that lack the engineered mutation. This method allows efficient, precise, and high-throughput genetic engineering of
S. aureus
strains and will facilitate studies seeking to address a variety of issues about the function of particular genes and specific mutations.
De Novo
Assembly and Phasing of Dikaryotic Genomes from Two Isolates of
Puccinia coronata
f. sp.
avenae
, the Causal Agent of Oat Crown Rust
Authors: Miller Marisa E. , Zhang Ying , Omidvar Vahid , Sperschneider Jana , Schwessinger Benjamin , Raley Castle , Palmer Jonathan M. , Garnica Diana , Upadhyaya Narayana , Rathjen John , Taylor Jennifer M. , Park Robert F. , Dodds Peter N. , Hirsch Cory D. , Kianian Shahryar F. , Figueroa Melania
Published: February 2018

Oat crown rust, caused by the fungus
Pucinnia coronata
f. sp.
avenae
, is a devastating disease that impacts worldwide oat production. For much of its life cycle,
P. coronata
f. sp.
avenae
is dikaryotic, with two separate haploid nuclei that may vary in virulence genotype, highlighting the importance of understanding haplotype diversity in this species. We generated highly contiguous
de novo
genome assemblies of two
P. coronata
f. sp.
avenae
isolates, 12SD80 and 12NC29, from long-read sequences. In total, we assembled 603 primary contigs for 12SD80, for a total assembly length of 99.16 Mbp, and 777 primary contigs for 12NC29, for a total length of 105.25 Mbp; approximately 52% of each genome was assembled into alternate haplotypes. This revealed structural variation between haplotypes in each isolate equivalent to more than 2% of the genome size, in addition to about 260,000 and 380,000 heterozygous single-nucleotide polymorphisms in 12SD80 and 12NC29, respectively. Transcript-based annotation identified 26,796 and 28,801 coding sequences for isolates 12SD80 and 12NC29, respectively, including about 7,000 allele pairs in haplotype-phased regions. Furthermore, expression profiling revealed clusters of coexpressed secreted effector candidates, and the majority of orthologous effectors between isolates showed conservation of expression patterns. However, a small subset of orthologs showed divergence in expression, which may contribute to differences in virulence between 12SD80 and 12NC29. This study provides the first haplotype-phased reference genome for a dikaryotic rust fungus as a foundation for future studies into virulence mechanisms in
P. coronata
f. sp.
avenae
.

IMPORTANCE
Disease management strategies for oat crown rust are challenged by the rapid evolution of
Puccinia coronata
f. sp.
avenae
, which renders resistance genes in oat varieties ineffective. Despite the economic importance of understanding
P. coronata
f. sp.
avenae
, resources to study the molecular mechanisms underpinning pathogenicity and the emergence of new virulence traits are lacking. Such limitations are partly due to the obligate biotrophic lifestyle of
P. coronata
f. sp.
avenae
as well as the dikaryotic nature of the genome, features that are also shared with other important rust pathogens. This study reports the first release of a haplotype-phased genome assembly for a dikaryotic fungal species and demonstrates the amenability of using emerging technologies to investigate genetic diversity in populations of
P. coronata
f. sp.
avenae
.
14-year case series of eyelid sebaceous gland carcinoma in Chinese patients and review of management
Authors: Lam Stacey C , Li Emmy Y M , Yuen Hunter K L
Published: February 2018

Aims

Sebaceous gland carcinoma (SGC) of the eyelid is a rare but potentially deadly cancer. The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) 7th Edition T category for SGC correlated with metastasis and survival in the Chinese population.

Methods

This was a retrospective, single-centre cohort study. Patients with surgically resected eyelid SGC between January 2001 and May 2015 at the Hong Kong Eye Hospital were reviewed. Tumours were staged using the AJCC criteria. The main outcome measures included local recurrence, metastasis and death. Disease-free survival (DFS) was measured from the completion of treatment; overall survival was measured from the date of initial diagnosis.

Results

The study included 22 Chinese patients with a mean age of 65.4 years. The majority presented as a nodular lesion (91%) with 12 eyes (54.5%) initially misdiagnosed and a mean presentation time of 1 year. It was found that those with AJCC stage T2b or higher were significantly associated with lymph node metastasis (P=0.002) when compared with those with stage T2a. Older age at diagnosis (P=0.035) and no misdiagnosis (P=0.025) were associated with shorter DFS. Those with stage 3a or higher were associated with shorter DFS (P=0.007) and overall survival (P=0.024).

Conclusion

Similar to previous reports, in this Chinese cohort, AJCC staging for SGC correlated with lymph node metastasis, DFS and overall survival. Those with stage 2b or higher on presentation will need closer surveillance for lymph node metastasis and may benefit from sentinel lymph node biopsy.
Gender differences in the use of anti-infective medications before and after widowhood: a register-based study
Authors: Santacroce Adriana , Wastesson Jonas W , Höhn Andreas , Christensen Kaare , Oksuzyan Anna
Published: February 2018

Background

Recent findings suggest that bereavement due to spousal loss is associated with a decline in general immune functions, and thus to increased susceptibility to infections among widowed individuals. The present study aims to investigate whether spousal loss weakens immune defences more among men than among women using a 5% random sample of the total Danish population, and anti-infective medication use as a proxy for immune response.

Methods

We followed 6076 Danish individuals (67% women) aged ≥50 from 5 years before and up to 5 years after widowhood to examine changes in prescriptions of anti-infectives for systemic use.

Results

Women used more anti-infective drugs both before and after spousal loss (women: OR= 1.31; 95% CI 1.21 to 1.42). The age-related changes in the use of anti-infective medications in the period before widowhood were similar to that in the period after widowhood among both men and women. Also, age-related changes in the use of anti-infective medications were similar in both genders.

Conclusions

The present study shows that individuals are more likely to use anti-infective medication after being widowed than before being widowed, but this change is likely to be related to increasing age and it is similar in both genders.