bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver Transplantation From Donors With a History of Malignancy: A Single-Center Experience
Authors: Benkö Tamas , Hoyer Dieter P. , Saner Fuat H. , Treckmann Jürgen W. , Paul Andreas , Radunz Sonia
Published: October 2017

Background

The demand for transplantable organs exceeds donor organ supply. Transplantation of organs from donors with a history of malignancy remains controversial and the transmission of cancer in liver transplant recipients has not been sufficiently examined.

Methods

From 2002 until 2017, 83 livers from donors with a history of malignancy were transplanted at the University Hospital Essen, Germany. Donor and recipient data, type of malignancy, tumor-free interval at organ procurement, and follow-up data were analyzed.

Results

Nine different tumor sites (central nervous system [n = 27], genitourinary [n = 24], breast [n = 10], skin [n = 8], colorectal [n = 5], lung [n = 3], hemato-oncological [n = 3], thyroid [n = 2], and larynx [n = 1]) were detected in 83 donors. The majority (58%) of donors had tumor-free intervals of less than 5 years versus 19% of 6 to 10 years versus 23% over 10 years. The risk of tumor transmission from donors was assessed as low in 44 (53%), intermediate in 28 (34%), and high in 11 (13%) cases. During median follow-up of 19.9 (0-155) months, none of the recipients developed donor-transmitted malignancy.

Conclusions

Liver transplantation with organs from donors with a medical history of malignancy is feasible, and the risk of donor-transmitted malignancy appears to be low in this single-center analysis. A careful selection of donors remains mandatory and can expand the donor pool.
Pitfalls in the Assessment of Brain-Machine Interfaces Using Information Transfer Rate
Authors: Lebedev Mikhail A. , Tseng Po-He , Ifft Peter J. , Ochei Dennis , Nicolelis Miguel A.L.
Published: October 2017

Information transfer rate (ITR), measured in bits/s, can be applied to evaluate motor performance, including the capacity of brain-machine interfaces (BMIs) to control external actuators. In a 2013 article entitled “Transfer of information by BMI” and published in Neuroscience, Tehovnik and his colleagues utilized ITR to assess the performance of several BMIs reported in the literature. We examined these analyses closely and found several fundamental flaws in their evaluation of ITR. Here we discuss the pitfalls in Tehovnik’s measurements of ITR, as well as several other issues raised in “Transfer of information by BMI”, including the claim that BMIs cannot be a reasonable option for paralyzed patients.

Highlights

Information transfer rate is discussed for BMI experiments, where subjects reach to targets.

Task settings, not just the number of possible targets, are important to calculate information correctly.

Active tactile exploration can be quantified as information transfer, but the number of targets is insufficient for such quantification.

Information transfer rate increases with the number of neural recording channels.

For practical applications, improvement in quality of life is essential, not information transfer rate per se.
ZmCOL3, a CCT-domain containing gene affects maize adaptation as a repressor and upstream of ZmCCT
Authors: Jin Minliang , Liu Xiangguo , Jia Wei , Liu Haijun , Li Wenqiang , Peng Yong , Du Yanfang , Wang Yuebin , Yin Yuejia , Zhang Xuehai , Liu Qing , Deng Min , Li Nan , Cui Xiyan , Hao Dongyun , Yan Jianbing
Published: October 2017

Flowering time is a vital trait to control the adaptation of flowering plants to different environments. CCT-domain containing genes are considered to play an important role in plants flowering. Among 53 maize CCT family genes, 28 of them were located in the flowering time QTL regions and 16 genes were significant associated with flowering time based on candidate gene-based association mapping analysis. Furthermore, a CCT gene named as ZmCOL3 was validated to be a flowering repressor upstream of ZmCCT which is one of the key genes regulating maize flowering. The overexpressed ZmCOL3 could delay flowering time about 4 days whether in long day or short day conditions. The absent of one cytosine in 3’UTR and the present of 551bp fragment in promoter regions are likely the causal polymorphisms which may contribute to the maize adaptation from tropical to temperate regions. ZmCOL3 could transactivate ZmCCT transcription or interfere circadian clock to inhibit flowering which was integrated in the modified model of maize photoperiod pathway.

Highlight

Maize CCT genes influence flowering time in different latitude environments and one of them named ZmCOL3 is a flowering time repressor which could transactivate ZmCCT transcription to delay flowering.
Re-examining the effects of supplier integration on operations performance: a relational view
Authors: He Yuanqiong , Sun Hongyi , Ni Wenbin , Ng Stephen C.H.
Published: October 2017

Purpose

The importance of supplier integration (SI) in improving firms’ performance has been previously identified but the effects of SI are complicated, as the relationship between supplier and buyer is full of uncertainty. The purpose of this paper is to re-examine the effects of SI on operations performance from a relational view.

Design/methodology/approach

Two strategies of integrating suppliers are theoretically presented: information sharing and joint decision making. Hypotheses are then developed on when SI influences operations performance, using product complexity and competitive intensity as moderating factors. The hypotheses are tested using a global survey data set, made up of 763 manufacturing firms from 22 countries.

Findings

The results indicate a positive relationship between SI and operations performance and that the moderating roles of product complexity and competition intensity are significant, but product complexity does not have significant moderation effects on the relationships between joint decision making and product quality/cost reduction.

Research limitations/implications

The moderators of product complexity and competitive intensity are not comprehensive. Future study into how and under what circumstances SI has the greatest effect will be of benefit.

Originality/value

This study makes theoretical contributions by exploring the strategies of SI through a relational view, and examining the effects of SI through the moderating roles of product complexity and competition intensity.
Contextualizing the 1990 campus security act and campus sexual assault in intersectional and historical terms
Authors: Graham Rebecca Dolinsky , Konradi Amanda
Published: October 2017

Purpose

Residential college campuses remain dangerous – especially for women students who face a persistent threat of sexual violence, despite passage of the 1990 Campus Security Act and its multiple amendments. Campuses have developed new programming, yet recent research confirms one in five women will experience some form of sexual assault before graduating. Research on campus crime legislation does not describe in detail the context in which it developed. The purpose of this paper is to draw attention to the effects of early rhetorical frames on the ineffective policy.

Design/methodology/approach

The authors discuss the rhetorical construction of “campus crime,” and related “criminals” and “victims,” through content analysis and a close interpretive reading of related newspaper articles.

Findings

The 1986 violent rape and murder of Jeanne Clery at Lehigh University in Pennsylvania became iconic in media descriptions of campus crime. Media drew attention to the racial and classed dimensions of the attack on Clery, but elided the misogyny central to all sexual assaults. This reinforced a stereotype that “insiders” on campuses, primarily white and middle class, were most vulnerable to “outsider” attacks by persons of color. Colleges and universities adopted rhetoric of “endangerment” and “unreason” and focused on what potential victims could do to protect themselves, ignoring the role of students in perpetrating crime.

Research limitations/implications

This analysis does not link rhetoric in newspapers to legislative discussion. Further analysis is necessary to confirm the impact of particular claims and to understand why some claims may have superseded others.

Originality/value

This analysis focuses critical attention on how campus crime policy is shaped by cultural frames.
The effects of board experience and independence on mitigating agency conflict
Authors: Agyemang Badu Ebenezer , Appiah Kingsley Opoku
Published: October 2017

Purpose

The purpose of this paper is to investigate the impact of board experience and independence on mitigating agency conflict between shareholders and managers.

Design/methodology/approach

This paper uses a panel data of 137 firms listed on stock exchanges in Ghana and Nigeria over a period of seven years. System generalized method of moments and other estimation techniques were adopted for the study. Using agency and resource dependence theories, board experience and independence ignored in previous studies are selected for the study.

Findings

The findings of this paper indicate a negative and statistically significant relationship between board experience, board independence, and agency conflict. A further examination using an agency score computed from the principal factor analysis of the four main agency proxies indicates a significant and negative relationship between board independence and agency conflict, but a negative and statistically non-significant relation between board experience and agency conflict.

Practical implications

The authors’ evidence has important implications for countries that are currently or contemplating pursuing board reforms to recommend the appointment of more independent and experience directors to corporate board.

Originality/value

This paper introduces a new proxy for assessing human and social capital of directors to test the integration hypothesis of a unique data set from Ghana and Nigeria toward mitigating agency conflict.
Identifying potential offenders on the basis of police records: development and validation of the ProKid risk assessment tool
Authors: Wientjes Jacqueline , Delsing Marc , Cillessen Antonius , Janssens Jan , Scholte Ron
Published: October 2017

Purpose

The purpose of this paper is to describe the development and validation of the ProKid risk assessment tool, which was designed to enable Dutch police officers to identify youths with elevated risk of committing violent and/or property crimes.

Design/methodology/approach

The ProKid algorithms were based on the results of logistic regression analyses of police data from a sample of 31,769 adolescents in the former police regions “Amsterdam-Amstelland” and “Gelderland-Midden”. For the validation, logistic regression analyses were performed on police data of youths in the police region “Amsterdam-Amstelland” who had been in contact with the police in 2011 (n=39,977). Furthermore, receiver operating characteristic analyses were performed to assess the instrument’s accuracy.

Findings

Results indicated that higher ProKid risk categories were associated with greater odds of being registered as a suspect of either a violent or property offence. The instrument was found to have good predictive accuracy. Area under the curve values ranged from 0.83 to 0.84 for violent offences and from 0.82 to 0.83 for property offences.

Practical implications

The current study demonstrates that ProKid is a valid and accurate tool to be used by police officers to identify youths with elevated risk of future violent and property offending. The automated assessment procedure enables a quick screening of large numbers of both non-offenders and offenders. This study confirms the value of official police records for assessing the risk of future offending for preventive purposes.

Originality/value

The present study demonstrates the validity of a risk assessment tool based on Dutch police records for both non-offenders and offenders.
Tax evasion and welfare fraud: do punishments fit the crime or the perception of the crime?
Authors: Marriott Lisa , Sim Dalice
Published: October 2017

Purpose

Individuals with fewer resources often receive more punitive treatment in the justice system than those who are more privileged. This situation is frequently justified with reference to societal preferences. To test the accuracy of this justification, the purpose of this study is to report on the extent to which the different treatments of tax evaders and welfare fraudsters in the Australian and New Zealand justice systems reflect the views of these societies.

Design/methodology/approach

Attitudes are captured in a survey with 3,000 respondents in Australia and New Zealand.

Findings

When asked directly, the majority of respondents (58 per cent) perceive no difference in people committing welfare fraud or tax evasion. However, responses to presented scenarios on tax evasion and welfare fraud show different tolerances for each crime. When provided with scenarios including crimes and criminals, results show that survey respondents see tax evasion as a less serious crime. However, when asked about their own propensity to commit the same offence, respondents indicate that they are more likely to engage in welfare fraud than tax evasion. The authors also report on factors that have an impact on individual’s attitudes towards tax evasion and welfare fraud.

Social implications

The survey results do not clearly show more punitive attitudes towards tax evasion or welfare fraud. Thus, the authors do not find support for the suggestion that the harsher treatment of welfare fraud can be justified with reference to society’s views.

Originality/value

The study reports on original survey research.
Local councils’ environmental sustainability reporting: who really counts?
Authors: Othman Radiah , Laswad Fawzi , Nath Nirmala
Published: October 2017

Purpose

The purpose of this paper is to examine local councils’ response to the Environmental Reporting Act 2015(ERA), stakeholder identification and implications for the state of the environment management and monitoring of by local councils in New Zealand.

Design/methodology/approach

Informed by stakeholder salience theory, this study uses an interpretative approach in analysing survey data collected from all 78 local councils. Ninety-two key individuals responded to the survey which was administered a month before the Environmental Reporting Bill was passed as an Act.

Findings

The findings suggest that focus and priorities of the councils varied depending on the influential power of various group stakeholders. Legal requirements were a very significant factor for reporting environmental sustainability information and the availability of funding and resources posed a significant challenge. Environmental sustainability was considered as both a risk and an opportunity. Compliance with legislation was the utmost priority of the local councils.

Research limitations/implications

The results suggest that stakeholders with power received more attention from the local councils. In addition, the tension between the central government, the elected representatives and the public became apparent.

Originality/value

This paper offers insight on how the local councils viewed risks, opportunities and potential implications of a new legislation, and whether the stakeholders were considered in these contexts.
Mental models and cognitive discomfort
Authors: Bourmistrov Anatoli
Published: October 2017

Purpose

The purpose of the study is to examine whether public servants as users of accounting information are responsive to changes in the content of an accounting report and, if so, how responsive they are.

Design/methodology/approach

The study applies a theoretical framework, linking accounting information and accounting use by focusing on users’ “mental models”. The empirical context for the study is a municipality located in Northwest Russia. Three public servants were followed over several days for the purpose of studying their use of a formal accounting report. Later, those users were also presented with a different version of the same accounting report that was re-constructed by the researcher based on normative accounting theory. The study documents the responses of public servants and presents those in a narrative form.

Findings

The study reveals that though the original formal financial accounting report is extensively used, the public servants mostly reject the usefulness of the modified version of the report. The modified accounting report puts public servants in a “discomfort” zone, where the users’ mental models come in conflict with the information in the modified report. Following that, the study uncovers that the use of the traditional accounting report is based on three different mental models developed by users over time and guiding the use of accounting. Those mental models are described by three metaphors: “balanced matrix”, “water tank” and “fair rules”.

Originality/value

There is an unreasonable expectation that change in the public sector accounting system from cash toward accrual information will improve the quality of decision-making by public servants. The claim needs evidence that change in the accounting information supply will actually lead to change in information use. The paper demonstrates that change in use requires more substantial change in the users’ mental models. This change is difficult, time-demanding and requires the development of tailor-made training programs. The paper is also a response to van Helden’s (2016) call for more observational studies that can give a more accurate picture of use.
Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano Prefecture, Japan
Authors: Ogawa Eisaku , Okuyama Ryuhei , Seki Tomoko , Kobayashi Aya , Oiso Naoki , Muto Masahiko , Nakagawa Hidemi , Kawada Akira
Published: October 2017

A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non‐metropolitan regional area.
‘Shew Yourselves as Men’: Gender, Citizenship and Political Propaganda in the 1773 and 1774 Worcester Election Contests
Authors: Blomgren Alvar
Published: October 2017

This case study of the 1773 and 1774 election contests in the city of Worcester investigates how members of the local oligarchy, and the political opposition to that oligarchy, drew on contemporary discourses on citizenship to convince the electorate that their candidate would become a worthy representative of their city in parliament, and to refute the claims of their opponents. Since independence was absolutely essential to the voters’ identities as male householder citizens, this became the main issue of conflict. The candidate of the opposition interest, Sir Watkin Lewes, sought to establish himself as the guardian of the independence of the citizens of Worcester against the corrupt corporation. The candidates of the corporation, Thomas Bates Rous and his successor, Colonel Nicholas Lechmere, instead claimed that Lewes was the real threat, as his anti‐corruption campaign deprived the voters of the usual fruits of the election. While such claims also entailed an appeal by the local elite to the financial interest of the voters, the need to justify this incentive ideologically, and the high portion of voters who turned their backs on their patrons, does suggest the power embedded in the concept of citizenship in the political life at the level of the localities. Gendered and classed conceptions of citizenship, furthermore, were employed as offensive weapons in the political propaganda surrounding the elections, as each faction sought to discredit the other by claiming that they were neither manly enough, nor of the proper social status, to qualify as worthy political subjects. Thus, citizenship was not only fundamentally gendered in the masculine, but also highly hierarchical and equally intertwined with contemporary notions of class.
7 December 1916: Asquith, Lloyd George and the Crisis of Liberalism
Authors: Morgan Kenneth O.
Published: October 2017

On 7 December 1916, in a dramatic coup, Lloyd George supplanted Asquith and became prime minister. This marked the death of a great party and has generated huge controversy. For long, Lloyd George was condemned as the culprit but latterly his reputation has risen sharply. Asquith and Lloyd George came from very different wings of the party, imperialist and Little Englander. Asquith seemed the supreme insider, Lloyd George a supreme Welsh outsider. However in peacetime government, they formed a tremendous partnership. Their close association continued to the formation of the first coalition in May 1915. Then serious division came over military conscription, with Lloyd George moving towards his old foes, the Unionists. As minister for munitions, then secretary for war, he became publicly very critical of the conduct of the war. A great conflict arose over his demand for a new war committee. This was directed against the generals: he did not wish to become prime minister. It looked as if a compromise was possible. On 3 December 1916 Asquith agreed to such a committee but, fatally, reversed his view the next day, Crucial was his misjudgment of the Unionist leaders, especially Balfour. On 6 December the king asked Lloyd George to form a government. Asquith seriously exaggerated his own strength while Lloyd George now had growing Unionist support, the backing of Labour and of a majority of Liberal MPs mobilised by Addison. So Asquith fell and a governmental revolution followed – a new small war cabinet, a cabinet secretariat under Hankey, a secretariat of private advisors in the ‘Garden Suburb’ and an inexorable move towards prime ministerial (or quasi‐presidential) government. In May 1918, the ‘Maurice debate’ saw the Liberals divided into pro‐ and anti‐government factions; they were crushed at the subsequent general election. The party was thereafter haunted by December 1916 and responsibility was bitterly contested. Yet it should be remembered that before 7 December 1916, the two Liberal leaders formed a dynamic and commanding partnership, which changed British politics profoundly and irreversibly.
Analysis of the genetic diversity and structure of the Spanish apple genetic resources suggests the existence of an Iberian genepool
Authors: Pereira‐Lorenzo S. , Urrestarazu J. , Ramos‐Cabrer A.M. , Miranda C. , Pina A. , Dapena E. , Moreno M.A. , Errea P. , Llamero N. , Díaz‐Hernández M.B. , Santesteban L.G. , Laquidain M.J. , Gogorcena Y. , Urbina V. , Dalmases J. , Ascasíbar‐Errasti J. , Royo J.B.
Published: October 2017

The nature and structure of genetic diversity in the Spanish apple germplasm preserved at the national level was widely unknown, since studies performed to date on this topic have been exclusively carried out at the regional scale. Here, 1453 accessions from Spanish collections of Malus × domestica were evaluated with a common set of 13 SSR (Simple Sequence Repeats) markers in order to estimate genetic diversity, to identify the underlying genetic structure and to unravel the relationships among them and among a wide set of international cultivars for reference. In total, 737 unique genotypes were identified, 581 diploids and 156 triploids. Using a model‐based Bayesian clustering procedure, two reconstructed populations were obtained for diploid genotypes; one retaining only Spanish cultivars (42% of genotypes), and a second containing all foreign cultivars the latter exhibiting evidence supporting the existence of a secondary sub‐structure. Similarly, analysis performed on the 156 triploid genotypes also revealed two reconstructed populations; one exclusively associated with local Spanish genotypes (44%). The Jaccard coefficient allowed clustering by UPGMA (Unweighted Pair Group Method) diploid and triploid genotypes, and remarkable differences in allelic composition among the different partitioning levels were found. AMOVA analyses showed moderate but significant differentiation among the main groups (0.08 ≤ FST ≤ 0.12). Our results highlight an important fraction of the Spanish apple germplasm that constitutes a differentiated genepool with respect to the international and commercial apple cultivars. Moreover, the extent of the Spanish genetic diversity was spatially distributed along the northern Iberian Peninsula, suggesting an extensive migration of genotypes along the country. This study is the first valuable action for genetic conservation of apple at the national scale, and constitutes a decisive step towards the definition of a Spanish core collection that will be useful for further studies in dissecting the genetic control of important horticultural traits through genome‐wide association analysis in apple.
A discussion on disease severity index values. Part II: using the disease severity index for null hypothesis testing
Authors: Chiang K.S. , Liu H.I. , Tsai J.W. , Tsai J.R. , Bock C.H.
Published: October 2017

A disease severity index (DSI) is a single number for summarising a large amount of information on disease severity. The DSI has most often been used with data based on a special type of ordinal scale comprising a series of consecutive ranges of defined numeric intervals, generally based on the percent area of symptoms presenting on the specimen(s). Plant pathologists and other professionals use such ordinal scale data in conjunction with a DSI (%) for treatment comparisons. The objective of this work is to explore the effects on both of different scales (i.e. those having equal or unequal classes, or different widths of intervals) and of the selection of values for scale intervals (i.e. the ordinal grade for the category or the midpoint value of the interval) on the null hypothesis test for the treatment comparison. A two‐stage simulation approach was employed to approximate the real mechanisms governing the disease‐severity sampling design. Subsequently, a meta‐analysis was performed to compare the effects of two treatments, which demonstrated that using quantitative ordinal rating grades or the midpoint conversion for the ranges of disease severity yielded very comparable results with respect to the power of hypothesis testing. However, the principal factor determining the power of the hypothesis test is the nature of the intervals, not the selection of values for ordinal scale intervals (i.e. not the mid‐point or ordinal grade). Although using the percent scale is always preferable, the results of this study provide a framework for developing improved research methods where the use of ordinal scales in conjunction with a DSI is either preferred or a necessity for comparing disease severities.
Mode of action and efficacy of iprodione against the root‐knot nematode Meloidogyne incognita
Authors: d'Errico G. , Giacometti R. , Roversi P. F. , d'Errico F. P. , Woo S. L.
Published: October 2017

The ban and restriction on the use of several synthetic chemicals for controlling plant parasitic nematodes, and concern about their side effects necessitate the availability of effective methods of control with low toxicity to humans and non‐target organisms. Therefore, efficacy and mode of action of iprodione, a dicarboximide fungicide, was evaluated against the root‐knot nematode Meloidogyne incognita, in vitro and in vivo conditions, in comparison with the nematicides fenamiphos, fosthiazate and oxamyl at 7.00, 1.66 and 1.66 mL/5 L water, respectively. In vitro, iprodione showed nematostatic rather than nematicidal activity against second‐stage juveniles of M. incognita in contrast to fenamiphos, fosthiazate and oxamyl which were nematicidal. In the in vivo experiment with tomato, iprodione controlled M. incognita less than fenamiphos, fosthiazate and oxamyl. No visual symptoms of phytotoxicity were observed. Therefore, iprodione can be a useful chemical for controlling nematode populations if included in an Integrated Pest Management program.
Influence of cell distribution and diabetes status on the association between mitochondrial DNA copy number and aging phenotypes in the InCHIANTI study
Authors: Moore Ann Zenobia , Ding Jun , Tuke Marcus A. , Wood Andrew R. , Bandinelli Stefania , Frayling Timothy M. , Ferrucci Luigi
Published: October 2017

Mitochondrial DNA copy number (mtDNA‐CN) estimated in whole blood is a novel marker of mitochondrial mass and function that can be used in large population‐based studies. Analyses that attempt to relate mtDNA‐CN to specific aging phenotypes may be confounded by differences in the distribution of blood cell types across samples. Also, low or high mtDNA‐CN may have a different meaning given the presence of diseases associated with mitochondrial damage. We evaluated the impact of blood cell type distribution and diabetes status on the association between mtDNA‐CN and aging phenotypes, namely chronologic age, interleukin‐6, hemoglobin, and all‐cause mortality, among 672 participants of the InCHIANTI study. After accounting for white blood cell count, platelet count, and white blood cell proportions in multivariate models, associations of mtDNA‐CN with age and interleukin‐6 were no longer statistically significant. Evaluation of a statistical interaction by diabetes status suggested heterogeneity of effects in the analysis of mortality (P < 0.01). The magnitude and direction of associations between mtDNA‐CN estimated from blood samples and aging phenotypes are influenced by the sample cell type distribution and disease status. Therefore, accounting for these factors may aid understanding of the relevance of mitochondrial DNA copy number to health and aging.
Nifedipine Prevents Apoptosis of Alcohol‐Exposed First‐Trimester Trophoblast Cells
Authors: Bolnick Alan D. , Bolnick Jay M. , Kohan‐Ghadr Hamid‐Reza , Kilburn Brian A. , Hertz Michael , Dai Jing , Drewlo Sascha , Armant D. Randall
Published: October 2017

Background

Maternal alcohol abuse leading to fetal alcohol spectrum disorder (FASD) includes fetal growth restriction (FGR). Ethanol (EtOH) induces apoptosis of human placental trophoblast cells, possibly disrupting placentation and contributing to FGR in FASD. EtOH facilitates apoptosis in several embryonic tissues, including human trophoblasts, by raising intracellular Ca2+. We previously found that acute EtOH exposure increases trophoblast apoptosis due to signaling from both intracellular and extracellular Ca2+. Therefore, nifedipine, a Ca2+ channel blocker that is commonly administered to treat preeclampsia and preterm labor, was evaluated for cytoprotective properties in trophoblast cells exposed to alcohol.

Methods

Human first‐trimester chorionic villous explants and the human trophoblast cell line HTR‐8/SVneo (HTR) were pretreated with 12.5 to 50 nM of the Ca2+ channel blocker nifedipine for 1 hour before exposure to 50 mM EtOH for an additional hour. Intracellular Ca2+ concentrations were monitored in real time by epifluorescence microscopy, using fluo‐4‐AM. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), accumulation of cytoplasmic cytochrome c, and cleavage rates of caspase 3 and caspase 9.

Results

The increase in intracellular Ca2+ upon exposure to EtOH in both villous explants and HTR cells was completely blocked (p < 0.05) when pretreated with nifedipine, accompanied by inhibition of EtOH‐induced release of cytochrome c, caspase activities, and TUNEL.

Conclusions

This study indicates that nifedipine can interrupt the apoptotic pathway downstream of EtOH exposure and could provide a novel strategy for future interventions in women with fetuses at risk for FASD.
Continuation of lithium after a diagnosis of chronic kidney disease
Authors: Kessing L. V. , Feldt‐Rasmussen B. , Andersen P. K. , Gerds T. A. , Licht R. W.
Published: October 2017

Objective

To investigate whether continued lithium or anticonvulsant treatment after a first diagnosis of chronic kidney disease (CKD) was associated with progression to irreversible end‐stage kidney disease.

Methods

Nationwide cohort study including all individuals in Denmark in a period from 1995 to 2012 with a diagnosis of CKD and (i) a history of lithium treatment (N = 754, among whom 238 patients had a diagnosis of bipolar disorder) or (ii) a history of anticonvulsant treatment (N = 5.004, among whom 199 patients had a diagnosis of bipolar disorder). End‐stage CKD was defined as chronic dialysis or renal transplantation.

Results

Continuing lithium (HR = 0.58 (95% CI: 0.37–0.90) and continuing anticonvulsants (HR = 0.53 (95% CI: 0.44–0.64) were associated with decreased rates of end‐stage CKD. In the subcohorts of patients with a diagnosis of bipolar disorder, continuing lithium was associated with decreased end‐stage CKD (HR = 0.40 (95% CI: 0.17–0.98), whereas continuing anticonvulsants was not (HR = 0.70 (95% CI: 0.21–2.37). There were no interactions of continuing lithium and anticonvulsants.

Conclusion

After an initial diagnosis of CKD, patients who are selected by their physicians to continue lithium treatment may not necessarily have an increased risk of developing end‐stage CKD. Shifting to an anticonvulsant per se may not be associated with an advantage; however, this requires further investigation.
The immune profile induced is crucial to determine the effects of immunocastration over gonadal function, fertility, and GnRH‐I expression
Authors: Siel Daniela , Loaiza Alexandra , Vidal Sonia , Caruffo Mario , Paredes Rodolfo , Ramirez Galia , Lapierre Lisette , Briceño Cristóbal , Pérez Oliver , Sáenz Leonardo
Published: October 2017

Problem

Immunocastration or vaccination against the GnRH‐I hormone is a promising alternative to reproductive control in different animal species. Given the low immunogenicity of this hormone, the use of adjuvants becomes necessary.

Method of Study

This study evaluated the effects of three adjuvants that induce different immune response profiles over gonadal function, fertility, and expression of GnRH‐I. Female mice (n = 6) were vaccinated at days 1 and 30 with a recombinant antigen for immunocastration and different adjuvants that induced preferentially Th1/Th2, Th2, and Th1 immune profiles.

Results

Th1/Th2 response is the most efficient to block reproductive activity in vaccinated animals, reducing the number of luteal bodies and pre‐ovulatory follicles. Th2 and Th1/Th2 responses induced an increase in GnRH‐I at the hypothalamus.

Conclusion

The immune profile induced by different adjuvants is essential on the effects over fertility, gonadal function, and hypothalamic GnRH‐I expression in immunocastrated animals.
Uteroplacental insufficiency in rats induces renal apoptosis and delays nephrogenesis completion
Authors: Cuffe J. S. M. , Briffa J. F. , Rosser S. , Siebel A. L. , Romano T. , Hryciw D. H. , Wlodek M. E. , Moritz K. M.
Published: October 2017

Aim

Uteroplacental insufficiency in rats reduces nephron endowment, leptin concentrations and programmes cardiorenal disease in offspring. Cross‐fostering growth‐restricted (Restricted) offspring onto a mother with normal lactation restores leptin concentrations and nephron endowment. This study aimed to determine whether the reduced nephron endowment in Restricted offspring is due to delayed glomerular formation and dysregulation of renal genes regulating branching morphogenesis, apoptosis or leptin signalling. Furthermore, we aimed to investigate whether cross‐fostering Restricted offspring onto Control mothers could improve glomerular maturation and restore renal gene abundance.

Methods

Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on gestation day 18 (E18). Kidneys were collected at E20, postnatal day 1 (PN1) and PN7. An additional cohort was cross‐fostered onto separate mothers at birth and kidneys collected at PN7.

Results

Kidneys were lighter in the Restricted group, but weight was restored with cross‐fostering. At E20, abundance of Bax, Flt1 and Vegfa was increased in Restricted offspring, while Ret and Bcl2 transcripts were increased only in Restricted females. At PN7, abundance of Gdnf and Ret was higher in Restricted offspring, as was Casp3. Restricted offspring had a wider nephrogenic zone with more immature glomeruli suggesting a delayed or extended nephrogenic period. Cross‐fostering had subtle effects on gene abundance and glomerular maturity.

Conclusion

Uteroplacental insufficiency induced apoptosis in the developing kidney and delayed and extended nephrogenesis. Cross‐fostering Restricted offspring onto Control mothers had beneficial effects on kidney growth and renal maturity, which may contribute to the restoration of nephron endowment.
New Zealand going global: The emerging relationships economy
Authors: Pawson Eric , Perkins Harvey C.
Published: October 2017

The paper examines the value‐generating strategies used in some of New Zealand's primary activities in a rapidly changing trading context in which the countries of East Asia increasingly figure. These strategies range from scaling up volume, with a consequent conspicuous impact on rural landscapes, to innovative value‐enhancing relationships linking producers, processors and consumers in processes which value landscapes for the contribution they make to provenance stories. Our argument is that higher‐value strategies are necessarily more intensely collaborative and involve a pursuit of engaged relationships, especially between onshore producers and manufacturers and consumers at a distance. We term this collaborative form of strategising as ‘the relationships economy’. We illustrate our argument using two case studies, dairying and merino. While there are great differences in scale between them, and dairying focuses significantly on volume‐generating capacity, there are players in dairying who are adopting higher‐value relationships‐based approaches similar to those developed in the merino industry. The common thread connecting the case studies is that of intentional enactment, which echoes earlier periods in New Zealand's trading history when considerable work was undertaken by industry participants to create new markets for primary products.
Ditches as species‐rich secondary habitats and refuge for meadow species in agricultural marsh grasslands
Authors: Rasran Leonid , Vogt Kati
Published: October 2017

Questions

Can drainage ditches in agricultural marsh grassland provide a suitable habitat for the persistence of fen meadow species? How does the ditch margin vegetation develop as a function of regular dredging? Is ornithologically oriented management also beneficial for plant biodiversity?

Location

Riparian marshes, Eider‐Treene‐Sorge lowland, Schleswig‐Holstein, Germany.

Methods

We performed vegetation surveys of drainage ditches along with their water body, slope and margin structures annually for 3 years. The data were analysed with respect to date and means of ditch dredging. In addition, we recorded vegetation of the surrounding agricultural grassland, measured nutrient status of the soil and the water body and sampled seed bank of the ditch slopes. We used ANOVA and multivariate methods to describe the development of the ditch vegetation and the persistence of target meadow species.

Results

Vegetation re‐development of ditch margins proceeds quite rapidly after disturbance from dredging. Dominance of mudbank species was observed only in the first year, followed by an increase of reed species and reduction of phytodiversity. Target species of wet meadow communities reach highest abundance in the second and third year and build a significant seed bank before being suppressed by reeds.

Conclusions

In heavily eutrophicated, intensively used marsh grassland, regularly disturbed ditch margins are important secondary habitats for pioneer and subdominant wetland species, which have nearly disappeared in a larger area. Current management cycles of ditch dredging every 3–4 years comply with the successional development, allowing the mudbank and wet meadow species to persist in the vegetation and seed bank. In contrast to the frequency, the form of dredging (ditch profile), which is crucial for bird protection, plays a minor role for plants. We recommend moderate disturbance (mowing of ditch margins) to suppress strong competitors in the years between dredging for additional support to target plant species.
High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study
Authors: van der Stoep M. Y. Eileen C. , Bertaina Alice , ten Brink Marloes H. , Bredius Robbert G. , Smiers Frans J. , Wanders Dominique C. M. , Moes Dirk Jan A.R. , Locatelli Franco , Guchelaar Henk‐Jan , Zwaveling Juliëtte , Lankester Arjan C.
Published: October 2017

Treosulfan‐based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen‐related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m2, administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m2) and 1561 ± 511 mg*h/l (14 g/m2), with an inter‐individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19–16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07–18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft‐versus‐host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long‐term disease‐specific outcome and late treatment‐related toxicity.
Evaluation of a disease risk index for adult patients undergoing umbilical cord blood transplantation for haematological malignancies
Authors: Paviglianiti Annalisa , Ruggeri Annalisa , Volt Fernanda , Sanz Guillermo , Milpied Noel , Furst Sabine , Esquirol Albert , Arcese William , Picardi Alessandra , Ferra Christelle , Ifrah Norbert , Bourhis Jean H. , Raj Kavita , von dem Borne Peter A. , Sica Simona , Menard Anne‐lise , Bloor Adrian , Kenzey Chantal , Gluckman Eliane , Rocha Vanderson
Published: October 2017

A disease risk index (DRI) has been defined for stratifying heterogeneous cohorts of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This index defines 4 distinct groups with different outcomes, dividing patients by disease type and status and considering cytogenetics for acute myeloid leukaemia and myelodysplastic syndromes (MDS). Recently, the DRI has been refined to include rare diseases and improve MDS stratification by blast percentage and response to prior therapy. Previous reports on DRI include only a small number of UCBT recipients. The current study aims to determine the applicability of the DRI for patients undergoing unrelated cord blood transplantation (UCBT). We retrospectively analysed 2530 adults receiving UCBT between 2004 and 2014. Diagnosis was acute leukaemia (AL) in 66% of the cases. Overall survival (OS) at 2 years was 56 ± 3% for patients with low DRI (n = 352), 46 ± 1% for intermediate DRI (n = 1403), 28 ± 2% for high (n = 489) and 20 ± 4% for very high DRI (n = 109) (P < 0·001). In the multivariate model, DRI remained an independent risk factor for OS. Similar findings were observed for PFS and DRI. Our results show the applicability of DRI for stratifying UCBT recipients and confirm the prognostic value of this simple and robust tool in this setting.
Cognitive and physical development in HIV‐positive children in South Africa and Malawi: A community‐based follow‐up comparison study
Authors: Sherr L. , Hensels I. S. , Tomlinson M. , Skeen S. , Macedo A.
Published: October 2017

Background

Child development is negatively impacted by HIV with children that are infected and affected by HIV performing worse than their peers in cognitive assessments.

Methods

We conducted a descriptive follow‐up comparison study (n=989) in South Africa and Malawi. We tracked child development in 135 HIV‐positive children compared to 854 uninfected children aged 4–13 years attending community‐based organizations at baseline and again 12–15 months later.

Results

Children with HIV were more often stunted (58.8% vs. 27.4%) and underweight (18.7% vs. 7.1%). They also had significantly poorer general physical functioning (M=93.37 vs. M=97.00). HIV‐positive children scored significantly lower on digit span and the draw‐a‐person task.

Conclusions

These data clearly show that HIV infection poses a serious risk for child development and that there is a need for scaled up interventions. Community‐based services may be ideally placed to accommodate such provision and deliver urgently needed support to these children.
Expression of aromatase in the rostral ventromedial medulla and its role in the regulation of visceral pain
Authors: Gao Po , Ding Xiao‐Wei , Dong Li , Luo Ping , Zhang Guo‐Hua , Rong Wei‐Fang
Published: October 2017

Aims

Estrogens are known to exert a wide spectrum of actions on brain functions including modulation of pain. Besides the circulating estrogens produced mainly by the ovaries, many brain regions are also capable of de novo synthesizing estrogens, which may exert important modulatory effects on neuronal functions. This study was aimed to test the hypothesis that aromatase, the enzyme that catalyzes the conversion of testosterone to estradiols, may be distributed in the rostral ventromedial medulla (RVM), where it may impact on visceral pain.

Methods and results

Adult female rats were treated with cyclophosphamide (CPM, 50 mg/kg, ip, once every 3 days) or saline. At approximately day 10 following the 3rd injection, CPM‐treated rats exhibited colorectal hyperalgesia as they showed significantly greater abdominal withdrawal responses (AWR) to graded colorectal distension (CRD, 0‐100 mm Hg) than the saline group. Immunofluorescent staining and Western blot assay revealed that CPM‐induced colorectal hyperalgesia was associated with significantly increased expression of aromatase and phosphorylated μ‐type opioid receptor (pMOR) and decreased expression of total MOR in the RVM. Intracisternal application of aromatase inhibitors, fadrozole, and letrozole reversed CPM‐induced colorectal hyperalgesia and restored pMOR and MOR expression in the RVM.

Conclusions

Our observations confirmed the expression of aromatase in the RVM, a pivotal brain region in descending modulation of pain and opioid analgesia. The results support the hypothesis that locally produced estrogens in the RVM may be involved in the maintenance of chronic visceral hyperalgesia and the downstream signaling may involve phosphorylation of MOR.