bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation
Authors: Camargo Jose F. , Komanduri Krishna V.
Published: June 2017

Despite the refinements in molecular methods for the detection of cytomegalovirus (CMV) and the advent of highly effective preemptive strategies, CMV remains a leading cause of morbidity and mortality in hematopoietic cell transplant (HCT) recipients. CMV can cause tissue-invasive disease including pneumonia, hepatitis, colitis, retinitis, and encephalitis. Mortality in HCT recipients with CMV disease can be as high as 60%. CMV infection has been associated with increased risk of secondary bacterial and fungal infections, increased risk of graft-versus- host disease, and high rates of non-relapse mortality following HCT. The risk of CMV is highly dependent on the donor (D) and the recipient (R) serostatus (D−/R+ > D+/R+ > D+/R− > D−/R−). Among allogeneic HCT recipients, high-dose corticosteroids, T-cell depletion, graft- versus-host disease, and mismatched or unrelated donors constitute the main predisposing factors. However, not all seropositive individuals with these risk factors develop CMV, which strongly suggests that host factors, such as those regulating CMV-specific T-cell responses, play a major role in predisposition to CMV in HCT recipients. Here, we discuss emerging concepts in CMV infection in HCT with emphasis on immunological factors that govern CMV reactivation and the applicability of immune monitoring to understand correlates of pathogenesis and its potential to guide clinical decision making.
Long-term complications after hematopoietic cell transplantation
Authors: Majhail Navneet S.
Published: June 2017

The prevalence of autologous and allogeneic hematopoietic cell transplantation (HCT) survivors continues to increase. Among patients whose disease remains in remission for the first 2— 5 years after transplantation, it is estimated that approximately 80–90% will be alive over the subsequent 10 years. However, the relative mortality rates of such patients continue to remain higher than those of their general population peers, with late complications contributing to significant long-term morbidity and mortality. Late effects in HCT survivors include secondary cancers, organ specific complications, late infections, quality of life impairments, psychosocial issues, sexual and fertility concerns, financial toxicity, and issues around return to work/school. A patient-centric and multidisciplinary approach to HCT survivorship care with collaborative and coordinated care from transplant centers and community healthcare providers is necessary to ensure their long-term health. Lifelong follow-up of HCT survivors is recommended, with established guidelines serving as the template for providing screening and preventive care based on patient-specific exposures. This review discussed common late complications, models for care delivery, and gaps and priorities for future research in the field of HCT survivorship.
High dose chemotherapy and autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma
Authors: Akhtar Saad
Published: June 2017

Primary treatment for adult and pediatric patients with Hodgkin lymphoma (HL) using current multiagent anthracycline-based chemotherapy with or without radiation therapy will cure approximately >70% of the patients; >95% for early stage with a favorable risk profile and 70–75% with advanced stage and high risk features. Managing refractory and relapsed disease, however, remains a challenge. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage 40–70% of patients with relapsed or refractory HL. Two randomized trials in relapsed and refractory patients showed superior progression free survival. This presentation addresses some of the salient differences and changes in the management that have evolved over the last decade and have either already affected, or are likely to affect the outcome of HDC auto-SCT. The following will discussed. 1. Historic trials and other emerging issues impacting the outcome of HDC auto-SCT. 2. Changes in the primary treatment and response adapted therapy. 3. Evaluation and validation of prognostic factors at the time of first failure. 4. Selection of salvage chemotherapy. 5. Conditioning regimens. 6. Consolidation after HDC auto-SCT. 7. Management of failures of HDC auto-SCT. 8. Availability of financial resources in various healthcare systems. Enrolment in clinical trials should be encouraged.
Practical risk score for 5‐, 10‐, and 20‐year prediction of dementia in elderly persons: Framingham Heart Study
Authors: Li Jinlei , Ogrodnik Matthew , Devine Sherral , Auerbach Sanford , Wolf Philip A. , Au Rhoda
Published: June 2017

Introduction

With a rapidly aging population, general practitioners are confronting the challenge of how to determine those who are at greatest risk for dementia and potentially need more specialized follow‐up to mitigate symptoms early in its course. We created a practical dementia risk score and provided individualized estimates of future dementia risk.

Methods

Using the Framingham Heart Study data, we built our prediction model using Cox proportional hazard models and developed a point system for the risk score and risk estimates.

Results

The score system used total points ranging from −1 to 31 and stratifies individuals into different levels of risk. We estimated 5‐, 10‐, and 20‐year dementia risk prediction and incorporated these into the points system.

Discussion

This risk score system provides a practical tool because all included predictors are easy to assess by practitioners. It can be used to estimate future probabilities of dementia for individuals.
Organizing Leviathan
Authors: Dahlström Carl , Lapuente Victor
Published: June 2017

Why are some countries less corrupt and better governed than others? Challenging conventional explanations on the remarkable differences in quality of government worldwide, this book argues that the organization of bureaucracy is an often overlooked but critical factor. Countries where merit-recruited employees occupy public bureaucracies perform better than those where public employees owe their post to political connections. The book provides a coherent theory of why, and ample evidence showing that meritocratic bureaucracies are conducive to lower levels of corruption, higher government effectiveness, and more flexibility to adopt modernizing reforms. Data comes from both a novel dataset on the bureaucratic structures of over 100 countries as well as from narratives of particular countries, with a special focus on the relationship between politicians and bureaucrats in Spain and Sweden. A notable contribution to the literature in comparative politics and public policy on good governance, and to corruption studies more widely.
What Is the Applicability of a Novel Surveillance Concept of Ventilator-Associated Events?
Authors: Jansson Miia , Ala-Kokko Tero , Ahvenjärvi Lauri , Karhu Jaana , Ohtonen Pasi , Syrjälä Hannu
Published: June 2017

BACKGROUND

In 2013, the Centers for Disease Control and Prevention released a novel surveillance concept called the “ventilator-associated event,” which focused surveillance on objective measures of complications among patients that underwent invasive ventilations.

OBJECTIVE

To evaluate the concordance and possible differences in efficacy (ie, disease severity and outcomes) between 2 surveillance paradigms: (1) infection-related ventilator-associated complications (iVAC) and (2) on conventional ventilator-associated pneumonia (VAP).

DESIGN

Prospective, observational, single-center cohort study.

PATIENTS

This study included 85 adult patients that received invasive ventilation for at least 2 consecutive calendar days in a 22-bed, adult, mixed medical-surgical intensive care unit in Finland between October 2014 and June 2015.

RESULTS

Among these patients, 9 (10.1 per 1,000 days of mechanical ventilation) developed iVAC (10.6%) and 20 (22.4 per 1,000 days of mechanical ventilation) developed conventional VAP (23.5%). The iVAC indicators were most often caused by atelectasis and fluid overload. Compared with patients with conventional VAP, patients with iVAC had significantly worse respiratory status but no other differences in disease severity or outcomes.

CONCLUSIONS

The incidence of conventional VAP was >2-fold that of iVAC, and the surveillance paradigms for VAP and iVAC capture different patterns of disease. Our results suggest that this novel surveillance concept, although based on objective measures of declining oxygenation, actually identified deteriorations of oxygenation due to noninfectious causes.

Infect Control Hosp Epidemiol 2017;38:983–988
Building community capacity and resilience through Emergency Services Cadets
Authors: Baisden Sally
Published: June 2017

The Queensland Emergency Services Cadets Program (ESCP) is a unique experiential education program that engages with young people aged from twelve to seventeen years, the majority of whom face the particular challenges of living in rural, remote and urban disadvantaged communities. The ESCP aims to build capacity and resilience in individuals, families and communities by providing young people with opportunities to develop skills, increase confidence, foster greater connection and belonging to community, and provide a sense of purpose through emergency preparedness. This article explores how ESCP positively impacts on cadets’ lives by delivering a capacity-building program that teaches disaster response and emergency management skills; allows all participants to enter on an even platform; draws on the cooperation and support of multiple emergency services, local councils, schools, businesses, community resources and dedicated volunteers; and is provided at no cost to participants. By positioning young people as capable and competent, and supporting them to learn and demonstrate their skills and knowledge within their community, the article argues the ESCP delivers specific and tangible developmental outcomes for young people and their communities. Specific outcomes discussed include the empowerment of cadets to become self-determining, the strengthening of the community’s collective knowledge and the promotion of a positive image of young people within their community.
SoundSurfers
Authors: Hesnan Jen , Dolan Eoin
Published: June 2017

SoundSurfers is a youth-led program of Foroige Ireland that provides a safe, dynamic and creative environment for young people aged from ten to eighteen years to empower themselves through music technology, practice and public performance. This article analyses young people’s experiences of SoundSurfers within the context of recent research on effective youth programs. It demonstrates how the program engages young people from disadvantaged backgrounds and describes how national education organisations such as Camara Education Ireland and its TechSpace program can successfully equip skilled youth workers for this work. By fostering a diverse community of participants supported by skilled youth workers, young people can develop mutual respect and share common interests through peer-supported activities. The authors illustrate how offering mainstream creative provision enables a process that builds interdependence and empathy in young people. The SoundSurfers inter-agency approach is also highlighted to emphasise the positive opportunities and outcomes that can arise from this approach.
'Stories from beyond'
Authors: Skattebol Jennifer
Published: June 2017

Lived experiences are the bones of this article: the lived experiences of delivering the resources needed for secure futures to young people in highly disadvantaged contexts. At the heart of the article is a biography of a young woman who captures the imagination. I share her story because the strength of her internal assets and her interest in articulating them contrast with her risk factors and the immediate impression of her demeanour. This article details the process of discovering these strengths through an interview that was part of a service evaluation. It offers a detailed walk through the processes that researchers and practitioners take to find the internal strengths of young people. In placing myself — an evaluation researcher — within the story, I offer a complete service landscape picture stretching from the lived experience of being under-resourced to the efficacy of interventions and then on to the production of policy evidence. Evidence is now a central plank in the struggle to close equality gaps, but its production is typically invisible. I set the scene with a brief account of myself — the storyteller — and then I turn to the question of what we broadly know about disadvantage experienced by young Australians. This is followed by a detailed account of the production of evaluation evidence. This inter-subjective account of the researcher and the researched, enables the story of a young woman who embodied and lived these ‘statistics’ to take flight. It offers insights into her assets and how they interact with the resourcing and policy landscape as she experiences it. Finally, I connect this story of how we find out about assets to the good practices identified in Seymour’s Youth Development Research Project, which organises the articles in this issue.
Making the most of youth development
Authors: Seymour Kathryn , Bull Melissa , Homel Ross , Wright Paul
Published: June 2017

There is a growing international emphasis on the use of research-based evidence to inform youth program policy, practice and funding priorities, and on involving young people as subjects and actors in gathering this evidence. Youth development organisations and programs increasingly are expected to engage in research that informs their program development and illustrates their effectiveness. Research partnerships that provide community access to external research expertise are one way by which youth organisations and programs can strengthen their internal research capacity. This article explores the youth-inclusive community–university partnership underpinning the Queensland Youth Development Research Project, and examines some of the multifaceted methodological and ethical dimensions of this approach across three dimensions of research: planning, doing and finishing. Successful youth-inclusive research requires paying attention to the diversity of challenges characteristic of youth research. These challenges, influenced by the complexity of child, young adult and older adult relationships, highlight the fundamental importance of understanding how power is expressed and mediated in youth research. Overall, the article argues that youth-inclusive research can be shaped to bring broader benefits to research, scholars, young people and the wider community beyond the aim of simply improving the research process itself.
Nicholas L. Holt, ed., 'Positive Youth Development Through Sport', 2nd ed., New York: Routledge, 2016, ISBN 9 7811 3889 1814, 244 pp., £29.99 p/b, £100 h/b
Authors: Whitten Tyson
Published: June 2017

Nicholas L. Holt, ed., Positive Youth Development Through Sport, 2nd ed., New York: Routledge, 2016, ISBN 9 7811 3889 1814, 244 pp., £29.99 p/b, £100 h/b
Peter Kelly and Annelies Kamp (eds), 'A Critical Youth Studies for the 21st Century', Boston, MA: Brill, 2015, ISBN 9 7890 0424 3750, 629 pp., €159
Authors: Williams Corrie
Published: June 2017

Peter Kelly and Annelies Kamp (eds), A Critical Youth Studies for the 21st Century, Boston, MA: Brill, 2015, ISBN 9 7890 0424 3750, 629 pp., €159
Positive relationships in community youth development organisations
Authors: Gibbs Robyn
Published: June 2017

When relationships within a community organisation are productive, staff are more likely to be happy, to understand and to be effective in their role. In youth-focused organisations delivering volunteer-led youth programs, a productive organisational relationship is essential to ensure effective recruitment, development and retention of staff, and the delivery of quality programs. This article provides a unique examination of the organisational relationships within Girl Guides Australia, between the volunteers who govern the organisation and those who deliver the youth program. The results of an extensive Australia-wide review of the adult volunteer training program are discussed, and changes to the ways in which relationships are fostered and understood in the organisation are outlined. The review has led to new understandings that modern volunteering requires changes to the ways in which organisational relationships are managed and supported, with a move away from compulsory ongoing training to a focus on volunteers as lifelong learners. Above all, this article shows how productive organisational relationships are when underpinned by founding relationships on openness and honesty, supporting relationships using learning and development, and building relationships using a quality people-management framework.
Radiocarbon Data from the Vicinity of Four South Korean Nuclear Power Plants in 2013–2014
Authors: Lee J H , Kim C H , Kang J , Song S , Yun M H , Kim J C
Published: June 2017

Radiocarbon (14C) is a radionuclide generated mainly through neutron-induced reactions in all types of nuclear reactors. Since most of the 14C released into the environment is in the form of gaseous emissions (CO2 and hydrocarbons), terrestrial plants are the primary indicators of increased 14C levels near nuclear power plants (NPPs). In 2013–2014, we collected samples of silver grasses (including common reed) and pine needles within 3 km of four South Korean NPP centers and measured 14C activities using accelerator mass spectrometry (AMS) at Seoul National University. The highest 14C activities were observed, respectively, in Wolsong>Hanul>Kori>Hanbit [220, 143, 127, and 123% modern carbon (pMC)].
Sample Preparation at the Jena 14C Laboratory
Authors: Steinhof A , Altenburg M , Machts H
Published: June 2017

The different categories of samples and their treatments at the radiocarbon (14C) laboratory in Jena, Germany, are described. The Jena 14C laboratory is dedicated to studying the global carbon cycle through the analysis of soil, plant, gas, charcoal, and wood samples. The respective preparation procedures for different samples types are presented, including wet-chemistry pretreatments for soil decalcification, charcoal purification using an acid–base–oxidation procedure (ABOx), and α-cellulose extraction from wood and leaves. In particular, investigations of the background corrections for each sample type are emphasized. Furthermore, an investigation of the contamination resulting from the storage of graphite is presented. Four storage conditions are investigated for storage times up to 30 months.
Identification of quantitative trait loci underlying lutein content in soybean seeds across multiple environments
Authors: TENG W. L. , FENG W. J. , ZHANG J. Y. , XIA N. , GUO J. , LI W. , WU D. P. , ZHAO X. , HAN Y. P. , LI W. B.
Published: June 2017

Lutein benefits human health significantly, including that of the eyes, skin and heart. Therefore, increasing lutein content in soybean seeds is an important objective for breeding programmes. However, no information about soybean lutein-related quantitative trait loci (QTL) has been reported, as of 2016. The aim of the present study was to identify QTLs underlying the lutein content in soybean seeds. A population including 129 recombinant inbred lines was developed from the cross between ‘Dongnong46’ (lutein 13·10 µg/g) and ‘L-100’ (lutein 23·96 µg/g), which significantly differed in seed lutein contents. This population was grown in ten environments including Harbin in 2012, 2013, 2014 and 2015; Hulan in 2013, 2014 and 2015; and Acheng in 2013, 2014 and 2015. A total of 213 simple sequence repeat markers were used to construct the genetic linkage map, which covered approximately 3623·39 cM, with an average distance of 17·01 cM between markers. In the present study, eight QTLs associated with lutein content were found initially, which could explain 1·01–19·66% of the observed phenotypic variation in ten different tested environments. The phenotypic contribution of qLU-1 (located near BARC-Satt588 on chromosome 9 (Chr 9; linkage group (LG) K)) was >10% across seven tested environments, while qLU-2 (located near Satt192 of Chr 12 (LG H)) and qLU-3 (located near Satt353 of Chr12 (LGH)) could explain 5–10% of the observed phenotypic variation in more than seven environments, respectively. qLU-5, qLU-6, qLU-7 and qLU-8 could be detected in more than four environments. These eight QTLs were novel, and have considerable potential value for marker-assistant selection of higher lutein content in soybean lines.
ADAM SMITH ON JUSTICE, SOCIAL JUSTICE, AND ULTIMATE JUSTICE
Authors: Otteson James R.
Published: June 2017

Adam Smith argues that virtue falls into two broad categories: “justice,” which he calls a “negative” virtue because it principally comprises restraint from harming or injuring others; and “beneficence,” which he calls “positive” because it comprises the actions we ought to take to improve others’ situations. Smith’s conception of justice is thus quite “thin,” and some critics argue that it is indeed too thin, since it fails to incorporate substantive concerns for the well-being of others. In this essay, I lay out Smith’s conception of justice and offer a way to understand it that attempts to comprehend the various things he says about it. I then offer a cluster of objections drawing on criticisms that might fall under the heading of “social justice.” Finally, I suggest how Smith might respond to the criticisms by outlining a Smithian conception of what I call “ultimate justice.”
RECONSTRUCTING RACISM: TRANSFORMING RACIAL HIERARCHY FROM “NECESSARY EVIL” INTO “POSITIVE GOOD”
Authors: Grynaviski Jeffrey D. , Munger Michael C.
Published: June 2017

Our theoretical claim is that racism was consciously (though perhaps not intentionally) devised, and later evolved, to serve two conflicting purposes. First, racism served a legal-economic purpose, legitimating ownership and savage treatment of slaves by southern whites, preserving the value of property rights in labor. Second, racism allowed slave owners to justify, to themselves and to outsiders, how a morally "good" person could own slaves. Racism portrayed African slaves as being less than human (and therefore requiring care, as a positive duty of the slave owner, as a man cares for his children, who cannot care for themselves), or else as being other than human (and therefore being spiritually no different from cattle or horses, and therefore requiring only the same considerations for maintenance and husbandry). The interest of the historical narrative presented here is the emergence of racial chattel slavery as a coherent and fiercely defended ideal, rather than the "necessary evil" that had been the perspective of the Founders. The reason that this is important is that the ideology of racism persisted far beyond the destruction of the institution of slavery, through Reconstruction, Jim Crow, and in some ways persisting even today. This work is an example of the problems of assuming that there is a "feedback" mechanism by which moral intuitions are updated and perfected; to the contrary, as suggested by Douglass North, even socially inferior ideologies can prove extremely persistent.
REPUBLICANISM AND GLOBAL INSTITUTIONS: THREE DESIDERATA IN TENSION
Authors: Ronzoni Miriam
Published: June 2017

Recently, republicans have been increasingly arguing that the ideal of nondomination can ground both a more plausible account of global justice and better insights for global institutional design than liberal egalitarianism does. What kind of global institutions, however, does nondomination require? The essay argues that a global institutional blueprint based on the republican ideal of nondomination is a multifaceted endeavor. Republican institutions should aim to fulfill three different desiderata: 1) avoiding excessive concentration of power; 2) bringing informal asymmetrical power under institutional control; 3) furthering an active, vigilant citizenry. The three desiderata often pull in different directions. At the global level in particular, they do not converge on a verdict over whether we should switch to a cosmopolitan institutional order, stick to a world of states, or opt for something altogether different. As a result, there is no straightforward pathway leading from the vindication of nondomination as the central principle of global justice to a clear vision for a global institutional order. The issue is, instead, a matter of careful balancing.
THE GENERATIVE APPROACH TO SLA AND ITS PLACE IN MODERN SECOND LANGUAGE STUDIES
Authors: Rothman Jason , Slabakova Roumyana
Published: June 2017

This article has two main goals. The first is to summarize and comment on the current state of affairs of generative approaches to SLA (GenSLA), 35 years into its history. This discussion brings the readership of SSLA up to date on the questions driving GenSLA agendas and clears up misconceptions about what GenSLA does and does not endeavor to explain. We engage key questions, debates, and shifts within GenSLA such as focusing on the deterministic role of input in language acquisition, as well as expanding the inquiry to new populations and empirical methodologies and technologies used. The second goal is to highlight the place of GenSLA in the broader field of SLA. We argue that various theories of SLA are needed, showing that many existing SLA paradigms are much less mutually exclusive than commonly believed (cf. Rothman & VanPatten, 2013; Slabakova, Leal, & Liskin-Gasparro, 2014, 2015; VanPatten & Rothman, 2014)—especially considering their different foci and research questions.
Initial experience with a new quantitative assessment tool for fluorescent imaging in peripheral artery disease
Authors: Rieß Henrik Christian , Duprée Anna , Behrendt Christian-Alexander , Kölbel Tilo , Debus Eike Sebastian , Larena-Avellaneda Axel , Russ Detlef , Wipper Sabine
Published: June 2017

Abstract. Background: Perioperative evaluation in peripheral artery disease (PAD) by common vascular diagnostic tools is limited by open wounds, medial calcinosis or an altered collateral supply of the foot. Indocyanine green fluorescent imaging (ICG-FI) has recently been introduced as an alternative tool, but so far a standardized quantitative assessment of tissue perfusion in vascular surgery has not been performed for this purpose. The aim of this feasibility study was to investigate a new software for quantitative assessment of tissue perfusion in patients with PAD using indocyanine green fluorescent imaging (ICG-FI) before and after peripheral bypass grafting. Patients and methods: Indocyanine green fluorescent imaging was performed in seven patients using the SPY Elite system before and after peripheral bypass grafting for PAD (Rutherford III-VI). Visual and quantitative evaluation of tissue perfusion was assessed in an area of low perfusion (ALP) and high perfusion (AHP), each by three independent investigators. Data assessment was performed offline using a specially customized software package (Institute for Laser Technology, University Ulm, GmbH). Slope of fluorescent intensity (SFI) was measured as time-intensity curves. Values were compared to ankle-brachial index (ABI), slope of oscillation (SOO), and time to peak (TTP) obtained from photoplethysmography (PPG). Results: All measurements before and after surgery were successfully performed, showing that ABI, TTP, and SOO increased significantly compared to preoperative values, all being statistically significant (P < 0.05), except for TTP (p = 0.061). Further, SFI increased significantly in both ALP and AHP (P < 0.05) and correlated considerably with ABI, TTP, and SOO (P < 0.05). Conclusions: In addition to ABI and slope of oscillation (SOO), the ICG-FI technique allows visual assessment in combination with quantitative assessment of tissue perfusion in patients with PAD. Ratios related to different perfusion patterns and SFI seem to be useful tools to reduce factors disturbing ICG-FI measurements.
Behavioral Problems in Preschool Children Stemming from Perinatal Stroke
Authors: Daseking Monika , Petermann Franz , Rana Madiha , Sanders Julia
Published: June 2017

Abstract. Background: Perinatal stroke results in damage to the maturing brain and often leads to neurological deficits as well as mental and psychosocial impairments. This study identifies mental impairments emerging in preschool aged children following perinatal strokes. Methods: Scores on CBCL / 4-18 and CPM for 63 children following perinatal stroke were evaluated. Results: The study revealed a high incidence of behavioral disorders (39.7 %), especially on the CBCL subscales Social Problems and Attention Problems. Stroke type and involvement of the middle cerebral artery exerted the largest influence. A total of 48.3 % of the children exhibited below-average intelligence, though there was no significant correlation between intelligence and behavioral problems. Conclusion: In addition to cognitive and physical impairments, the psychological consequences of the disease must also be taken into account.
Kognitive Störungen bei Patienten mit Herzerkrankungen – ein Überblick
Authors: Heidler Maria-Dorothea
Published: June 2017

Zusammenfassung. Patienten mit Herzerkrankung leiden unter zahlreichen kognitiven Defiziten, die mit steigendem Alter und der Schwere der kardialen Erkrankung zunehmen. Die Genese kognitiver Defizite und ihre Wechselwirkung mit Herzerkrankungen ist multifaktoriell, potenziell sind sie jedoch durch eine adäquate medizinische Behandlung der Herzerkrankung modifizierbar. Oft haben neuropsychologische Störungen wie beeinträchtigte Aufmerksamkeits-, Gedächtnis- oder Exekutivfunktionen nachhaltige Auswirkungen auf die Lebensqualität und auf das Outcome kardiologischer Rehabilitationsmaßnahmen und können Herzerkrankungen verschlimmern (bspw. durch die Aufrechterhaltung eines ungesunden Lebensstils oder unzureichende Medikamentenadhärenz). Ein routinemäßig angewandtes neuropsychologisches Screening könnte helfen, kognitiv beeinträchtigte Patienten zu identifizieren, um medizinische und rehabilitative Maßnahmen optimieren zu können.
The Future of Earth Looks Drier…but Just How Dry?
Authors: Stanley Sarah
Published: June 2017

New analysis of soil moisture projections from climate models could help resolve a discrepancy between expected increases in aridity and precipitation over land.
The State of Planetary and Space Sciences in Africa
Authors: Baratoux David , Chennaoui-Aoudjehane Hasnaa , Gibson Roger , Lamali Atmane , Reimold Wolf , Sapah Marian , Chabou Moulley , Habarulema John , Jessell Mark , Mogessie Aberra , Benkhaldoun Zouhair , Nkhonjera Elyvin , Mukosi Ndivhuwo , Kaire Maram , Rochette Pierre , Sickafoose Amanda , Martínez-Frías Jesús , Hofmann Axel , Folco Luigi , Rossi Angelo , Faye Gayane , Kolenberg Katrien , Tekle Kelali , Belhai Djelloul , Elyajouri Meriem , Koeberl Christian , Abdeen Mamdouh
Published: June 2017

Africa has an enormous potential to provide insights into planetary and space sciences, but it has remained largely untapped. Fostering a new generation of scientists promises far-reaching benefits.
APC‐targeted proinsulin expression inactivates insulin‐specific memory CD8+ T cells in NOD mice
Authors: Reeves Peta LS , Rudraraju Rajeev , Liu Xiao , Wong F Susan , Hamilton‐Williams Emma E , Steptoe Raymond J
Published: June 2017

Type 1 diabetes (T1D) results from T‐cell‐mediated autoimmune destruction of pancreatic β cells. Effector T‐cell responses emerge early in disease development and expand as disease progresses. Following β‐cell destruction, a long‐lived T‐cell memory is generated that represents a barrier to islet transplantation and other cellular insulin‐replacement therapies. Development of effective immunotherapies that control or ablate β‐cell destructive effector and memory T‐cell responses has the potential to prevent disease progression and recurrence. Targeting antigen expression to antigen‐presenting cells inactivates cognate CD8+ effector and memory T‐cell responses and has therapeutic potential. Here we investigated this in the context of insulin‐specific responses in the non‐obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. Insulin‐specific CD8+ memory T cells transferred to mice expressing proinsulin in antigen‐presenting cells proliferated in response to transgenically expressed proinsulin and the majority were rapidly deleted. A small proportion of transferred insulin‐specific Tmem remained undeleted and these were antigen‐unresponsive, exhibited reduced T cell receptor (TCR) expression and H‐2Kd/insB15‐23 tetramer binding and expressed co‐inhibitory molecules. Expression of proinsulin in antigen‐presenting cells also abolished the diabetogenic capacity of CD8+ effector T cells. Therefore, destructive insulin‐specific CD8+ T cells are effectively inactivated by enforced proinsulin expression despite tolerance defects that exist in diabetes‐prone NOD mice. These findings have important implications in developing immunotherapeutic approaches to T1D and other T‐cell‐mediated autoimmune diseases.
CD11a/ICAM‐1 blockade combined with IL‐2 targeting therapy causes a paradoxical acceleration of type 1 diabetes
Authors: Brenu Ekua W , Bartley Timothy J , Wright Casey M , Hamilton‐Williams Emma E
Published: June 2017

Enhancement of regulatory T‐cell (Treg) function is the goal of many immunotherapies aimed at treating type 1 diabetes (T1D). The use of interleukin (IL)‐2 is hindered by its effects on other populations such as effector T cells and NK cells. Combination therapies aimed at suppressing effector T cells while using IL‐2 to expand Tregs could be beneficial and have been trialed in T1D patients. We have investigated a combination therapy using IL‐2 and αCD11a blocking antibody to simultaneously expand Tregs and suppress the activation and migration of autoreactive T cells. When non‐obese diabetic mice were treated with low‐dose IL‐2/anti‐IL‐2 complexes (IL‐2c) and αCD11a, significant Treg expansion occurred in both the spleen and pancreas. Activation and IFNγ production by islet‐specific T cells was robustly suppressed in the periphery following IL‐2c/αCD11a treatment. Surprisingly, combination therapy accelerated diabetes onset compared with control treatments. Analysis of IL‐2 responsive populations found that combination therapy increased the activation of CD8+ T cells and natural killer (NK) cells specifically within the pancreas despite concomitant Treg expansion. Blocking effector T‐cell migration with the inhibitor FTY720 together with IL‐2c treatment also resulted in intra‐pancreatic expansion of effector cell populations. Thus, inhibiting effector T‐cell migration into the islets unleashes islet‐resident pathogenic effectors in the presence of low doses of exogenous IL‐2.
Murine LRBA deficiency causes CTLA‐4 deficiency in Tregs without progression to immune dysregulation
Authors: Burnett Deborah L , Parish Ian A , Masle‐Farquhar Etienne , Brink Robert , Goodnow Christopher C
Published: June 2017

Inherited mutations in lipopolysaccharide‐responsive beige‐like anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B‐cell and antibody deficiency (common variable immunodeficiency), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9‐mediated gene targeting. These mice revealed that LRBA has a critical, cell‐autonomous role in promoting cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) accumulation within CD4 effector T cells and FOXP3+ T‐regulatory cells (Tregs). In young mice, or in chimeric mice where only half of the T cells are LRBA deficient, low CTLA‐4 was the only detectable abnormality in Tregs, whereas in old mice FOXP3 was also decreased. Low CTLA‐4 did not translate into increased CD86 on B cells unless the LRBA‐deficient mice were immunised, and neither immunisation nor chronic lymphocytic choriomeningitis virus infection precipitated immune dysregulation. LRBA deficiency did not alter antigen‐specific B‐cell activation, germinal centre (GC) formation, isotype switching or affinity maturation. Paradoxically, CD86 was decreased on GC B cells in LRBA‐deficient mice, pointing to compensatory mechanisms for controlling CD86 in the face of low CTLA‐4. These results add to the experimental rationale for treating LRBA deficiency with the CTLA4‐Ig fusion protein, Abatacept, and pose questions about the limitations of laboratory experiments in mice to reproduce human disease in natura.
Ablation-resistant carbide Zr0.8Ti0.2C0.74B0.26 for oxidizing environments up to 3,000 °C
Authors: Zeng Yi , Wang Dini , Xiong Xiang , Zhang Xun , Withers Philip J. , Sun Wei , Smith Matthew , Bai Mingwen , Xiao Ping
Published: June 2017

Ultra-high temperature ceramics are desirable for applications in the hypersonic vehicle, rockets, re-entry spacecraft and defence sectors, but few materials can currently satisfy the associated high temperature ablation requirements. Here we design and fabricate a carbide (Zr0.8Ti0.2C0.74B0.26) coating by reactive melt infiltration and pack cementation onto a C/C composite. It displays superior ablation resistance at temperatures from 2,000–3,000 °C, compared to existing ultra-high temperature ceramics (for example, a rate of material loss over 12 times better than conventional zirconium carbide at 2,500 °C). The carbide is a substitutional solid solution of Zr–Ti containing carbon vacancies that are randomly occupied by boron atoms. The sealing ability of the ceramic’s oxides, slow oxygen diffusion and a dense and gradient distribution of ceramic result in much slower loss of protective oxide layers formed during ablation than other ceramic systems, leading to the superior ablation resistance.
Imaging dynamic fingerprints of competing E2 and SN2 reactions
Authors: Carrascosa Eduardo , Meyer Jennifer , Zhang Jiaxu , Stei Martin , Michaelsen Tim , Hase William L. , Yang Li , Wester Roland
Published: June 2017

The competition between bimolecular nucleophilic substitution and base-induced elimination is of fundamental importance for the synthesis of pure samples in organic chemistry. Many factors that influence this competition have been identified over the years, but the underlying atomistic dynamics have remained difficult to observe. We present product velocity distributions for a series of reactive collisions of the type X− + RY with X and Y denoting the halogen atoms fluorine, chlorine and iodine. By increasing the size of the residue R from methyl to tert-butyl in several steps, we find that the dynamics drastically change from backward to dominant forward scattering of the leaving ion relative to the reactant RY velocity. This characteristic fingerprint is also confirmed by direct dynamics simulations for ethyl as residue and attributed to the dynamics of elimination reactions. This work opens the door to a detailed atomistic understanding of transformation reactions in even larger systems.
Missing magnetism in Sr4Ru3O10: Indication for Antisymmetric Exchange Interaction
Authors: Weickert Franziska , Civale Leonardo , Maiorov Boris , Jaime Marcelo , Salamon Myron B. , Carleschi Emanuela , Strydom André M. , Fittipaldi Rosalba , Granata Veronica , Vecchione Antonio
Published: June 2017

Metamagnetism occuring inside a ferromagnetic phase is peculiar. Therefore, Sr4Ru3O10, a T
C
 = 105 K ferromagnet, has attracted much attention in recent years, because it develops a pronounced metamagnetic anomaly below T
C
for magnetic fields applied in the crystallographic ab-plane. The metamagnetic transition moves to higher fields for lower temperatures and splits into a double anomaly at critical fields Hc1 = 2.3 T and Hc2 = 2.8 T, respectively. Here, we report a detailed study of the different components of the magnetization vector as a function of temperature, applied magnetic field, and varying angle in Sr4Ru3O10. We discover for the first time a reduction of the magnetic moment in the plane of rotation at the metamagnetic transition. The anomaly shifts to higher fields by rotating the field from H ⊥ c to H || c. We compare our experimental findings with numerical simulations based on spin reorientation models taking into account magnetocrystalline anisotropy, Zeeman effect and antisymmetric exchange interactions. While Magnetocrystalline anisotropy combined with a Zeeman term are sufficient to explain a metamagnetic transition in Sr4Ru3O10, a Dzyaloshinskii-Moriya term is crucial to account for the reduction of the magnetic moment as observed in the experiments.
DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase
Authors: Kukushkina Viktorija , Modhukur Vijayachitra , Suhorutšenko Marina , Peters Maire , Mägi Reedik , Rahmioglu Nilufer , Velthut-Meikas Agne , Altmäe Signe , Esteban Francisco J. , Vilo Jaak , Zondervan Krina , Salumets Andres , Laisk-Podar Triin
Published: June 2017

The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5′ UTR and positive correlations in the gene ‘Body’ region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.
Mutations in human AID differentially affect its ability to deaminate cytidine and 5-methylcytidine in ssDNA substrates in vitro
Authors: Budzko Lucyna , Jackowiak Paulina , Kamel Karol , Sarzynska Joanna , Bujnicki Janusz M. , Figlerowicz Marek
Published: June 2017

Activation-induced cytidine deaminase (AID) is known for its established role in antibody production. AID induces the diversification of antibodies by deaminating deoxycytidine (C) within immunoglobulin genes. The capacity of AID to deaminate 5-methyldeoxycytidine (5 mC) and/or 5-hydroxymethyldeoxycytidine (5 hmC), and consequently AID involvement in active DNA demethylation, is not fully resolved. For instance, structural determinants of AID activity on different substrates remain to be identified. To better understand the latter issue, we tested how mutations in human AID (hAID) influence its ability to deaminate C, 5 mC, and 5 hmC in vitro. We showed that each of the selected mutations differentially affects hAID’s ability to deaminate C and 5 mC. At the same time, we did not observe hAID activity on 5 hmC. Surprisingly, we found that the N51A hAID mutant, with no detectable activity on C, efficiently deaminated 5 mC, which may suggest different requirements for C and 5 mC deamination. Homology modeling and molecular dynamics simulations revealed that the pattern of enzyme-substrate recognition is one of the important factors determining enzyme activity on C and 5 mC. Consequently, we have proposed mechanisms that explain why wild type hAID more efficiently deaminates C than 5 mC in vitro and why 5 hmC is not deaminated.
A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS
Authors: Yamamoto Seiji , Muramatsu Masashi , Azuma Erika , Ikutani Masashi , Nagai Yoshinori , Sagara Hiroshi , Koo Bon-Nyeo , Kita Satomi , O’Donnell Erin , Osawa Tsuyoshi , Takahashi Hiroyuki , Takano Ken-ichi , Dohmoto Mitsuko , Sugimori Michiya , Usui Isao , Watanabe Yasuhide , Hatakeyama Noboru , Iwamoto Takahiro , Komuro Issei , Takatsu Kiyoshi , Tobe Kazuyuki , Niida Shumpei , Matsuda Naoyuki , Shibuya Masabumi , Sasahara Masakiyo
Published: June 2017

Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31+F4/80+hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain. These cells expressed additional macrophage markers such as CD206 and CD11b. Moreover, the CD31+F4/80+cells phagocytosed apoptotic cells as functionally matured macrophages, adhered to the newly formed subventricular vascular plexus, and then divided into daughter cells. Eventually, these CD31+F4/80+cells transdifferentiated into NG2/PDGFRβ/desmin-expressing cerebrovascular pericytes, enwrapping and associating with vascular endothelial cells. These data indicate that a subset of cerebrovascular pericytes derive from mature macrophages in the very early phase of CNS vascular development, which in turn are recruited from sites of embryonic hematopoiesis such as the yolk sac by way of blood flow.
Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice
Authors: Jeengar Manish Kumar , Thummuri Dinesh , Magnusson Mattias , Naidu V. G. M. , Uppugunduri Srinivas
Published: June 2017

Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily. Uridine at medium and high dose significantly reduced the severity of colitis (DAI score) and alleviated the macroscopic and microscopic signs of the disease. The levels of proinflammatory cytokines IL-6, IL-1β and TNF in serum as well as mRNA expression in colon were significantly reduced in the uridine treated groups. Moreover, colon tissue myloperoxidase activities, protein expression of IL-6, TNF- α, COX-2, P-NFkB and P-Ikk-βα in the colon tissues were significantly reduced in medium and high dose groups. These findings demonstrated that local administration of uridine alleviated experimental colitis in male C57BL/6 mice accompanied by the inhibition of neutrophil infiltration and NF-κB signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.