bluuebunny/crossref_metadata_2025 huggingface dataset:
Software‐aided cytochrome P450 reaction phenotyping and kinetic analysis in early drug discovery
Authors: Cece‐Esencan Esra Nurten , Fontaine Fabien , Plasencia Guillem , Teppner Marieke , Brink Andreas , Pähler Axel , Zamora Ismael
Published: December 2015

Rationale

Cytochrome P450 (CYP450) reaction phenotyping (CRP) and kinetic studies are essential in early drug discovery to determine which metabolic enzymes react with new drug entities. A new semi‐automated computer‐assisted workflow for CRP is introduced in this work. This workflow provides not only information regarding parent disappearance, but also metabolite identification and relative metabolite formation rates for kinetic analysis.

Methods

Time‐course experiments based on incubating six probe substrates (dextromethorphan, imipramine, buspirone, midazolam, ethoxyresorufin and diclofenac) with recombinant human enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and human liver microsomes (HLM) were performed. Liquid chromatography/high‐resolution mass spectrometry (LC/HRMS) analysis was conducted with an internal standard to obtain high‐resolution full‐scan and MS/MS data. Data were analyzed using Mass‐MetaSite software. A server application (WebMetabase) was used for data visualization and review.

Results

CRP experiments were performed, and the data were analyzed using a software‐aided approach. This automated‐evaluation approach led to (1) the detection of the CYP450 enzymes responsible for both substrate depletion and metabolite formation, (2) the identification of specific biotransformations, (3) the elucidation of metabolite structures based on MS/MS fragment analysis, and (4) the determination of the initial relative formation rates of major metabolites by CYP450 enzymes.

Conclusions

This largely automated workflow enabled the efficient analysis of HRMS data, allowing rapid evaluation of the involvement of the main CYP450 enzymes in the metabolism of new molecules during drug discovery. Copyright © 2015 John Wiley & Sons, Ltd.
Glutamine deamidation: an indicator of antiquity, or preservational quality?
Authors: Schroeter Elena R. , Cleland Timothy P.
Published: December 2015

Rationale

Much credence has been given in the paleoproteomic community to glutamine deamidation as a proxy for the age of proteins derived from fossil and subfossil material, and this modification has been invoked as a means for determining the endogeneity of molecules recovered from very old fossil specimens.

Methods

We re‐evaluated the relationship between glutamine deamidation and geologic time by examining previously published data from five recent mass spectrometry studies of archeaological fossils. Deamidation values recovered for fossils were graphed against their reported chronologic age using WebPlotDigitizer.

Results

The experimental data that has been produced from fossil material to date show that the extent of glutamine deamidation does not correspond to the absolute age of the specimens being examined, but rather show extreme variation between specimens of similar age and taxonomic affinity.

Conclusions

Because deamidation rates and levels can be greatly affected by numerous chemical and environmental factors, we propose that glutamine deamidation is better suited as an indicator of preservational quality and/or environmental conditions than a mark of the endogeneity or authenticity of ancient proteins. Copyright © 2015 John Wiley & Sons, Ltd.
An experiment to assess the effects of diatom dissolution on oxygen isotope ratios
Authors: Smith Andrew C. , Leng Melanie J. , Swann George E. A. , Barker Philip A. , Mackay Anson W. , Ryves David B. , Sloane Hilary J. , Chenery Simon R. N. , Hems Mike
Published: December 2015

Rationale

Current studies which use the oxygen isotope composition from diatom silica (δ18Odiatom) as a palaeoclimate proxy assume that the δ18Odiatom value reflects the isotopic composition of the water in which the diatom formed. However, diatoms dissolve post mortem, preferentially losing less silicified structures in the water column and during/after burial into sediments. The impact of dissolution on δ18Odiatom values and potential misinterpretation of the palaeoclimate record are evaluated.

Methods

Diatom frustules covering a range of ages (6 samples from the Miocene to the Holocene), environments and species were exposed to a weak alkaline solution for 48 days at two temperatures (20 °C and 4 °C), mimicking natural dissolution post mucilage removal. Following treatment, dissolution was assessed using scanning electron microscope images and a qualitative diatom dissolution index. The diatoms were subsequently analysed for their δ18O values using step‐wise fluorination and isotope ratio mass spectrometry.

Results

Variable levels of diatom dissolution were observed between the six samples; in all cases higher temperatures resulted in more frustule degradation. Dissolution was most evident in younger samples, probably as a result of the more porous nature of the silica. The degree of diatom dissolution does not directly equate to changes in the isotope ratios; the δ18Odiatom value was, however, lower after dissolution, but in only half the samples was this reduction outside the analytical error (2σ analytical error = 0.46‰).

Conclusions

We have shown that dissolution can have a small negative impact on δ18Odiatom values, causing reductions of up to 0.59‰ beyond analytical error (0.46‰) at natural environmental temperatures. These findings need to be considered in palaeoenvironmental reconstructions using δ18Odiatom values, especially when interpreting variations in these values of <1‰. Copyright © 2015 John Wiley & Sons, Ltd.
The Effects of Regional Hydrologic Alteration on Fish Community Structure in Regulated Rivers
Authors: Macnaughton Camille J. , McLaughlin Fraser , Bourque Guillaume , Senay Caroline , Lanthier Gabriel , Harvey‐Lavoie Simonne , Legendre Pierre , Lapointe Michel , Boisclair Daniel
Published: December 2015

Alterations to temporal patterns of river flow regimes resulting from damming and flow regulation practices may have negative consequences for freshwater communities. However, little has been performed to develop a holistic approach to assess the effects of hydrologic alterations on fish communities across a wide range of rivers and between different regulation strategies. To address this, we used daily and hourly hydrologic data from gauges in 10 regulated and 14 unregulated Canadian rivers. Building on the Ecological Limits of Hydrologic Alteration concept, hydrologic alterations for many ecologically relevant flow indices were combined to obtain river‐specific hydrologic alteration scores. Extensive community surveys to estimate fish abundance, biomass, diversity indices and habitat guild representation provided data for the derivation of similar river‐specific biotic alteration scores relative to unregulated river conditions. Our results indicate that biological impairment consisting of significant biotic alteration relative to the means from unregulated rivers was directly related to increasing flow alteration scores, with the smallest fish and flow alteration scores observed in run‐of‐river systems and the greatest alteration scores under hydro‐peaking regimes. Our approach not only examined the relationship between river‐specific hydrologic alteration scores and the associated biotic responses, but also provided a more comprehensive assessment of the flow‐response alteration relationship between regulation practices, which may better inform future environmental flow management guidelines. Copyright © 2015 John Wiley & Sons, Ltd.
Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress
Authors: Gammoh Omar S. , Al‐Smadi Ahmed , Al‐Awaida Wajdy , Badr Mujtaba M. , Qinna Nidal A.
Published: December 2015

Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross‐talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM‐A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose‐6‐phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright © 2015 John Wiley & Sons, Ltd.
The Family and Family Relationships, 1500-1900
Authors: O’Day Rosemary
Published: December 2015

While historians have written with ease about the state and the church, the family has so far defied historical analysis. As the primary cell of human social organisation, upon which both state and church depend, it is of crucial importance. In this concise, informative and stimulating book, Rosemary O’Day seeks to explain the difficulties facing the historian of the family and to suggest strategies for their solution. She compares families and households in time, space and economy over the period 1500–1914 and draws together the important existing work.
John Fowles
Authors: Acheson James
Published: December 2015

This vibrant collection of original essays sheds new light on all of Fowles' writings, with a special focus on The French Lieutenant’s Woman as the most widely studied of Fowles' works. The impressive cast of contributors offers an outstanding range of expertise on Fowles, providing fresh reassessments and new perspectives.
A general framework for architecture composability
Authors: Attie Paul , Baranov Eduard , Bliudze Simon , Jaber Mohamad , Sifakis Joseph
Published: December 2015

Architectures depict design principles: paradigms that can be understood by all, allow thinking on a higher plane and avoiding low-level mistakes. They provide means for ensuring correctness by construction by enforcing global properties characterizing the coordination between components. An architecture can be considered as an operator
A
that, applied to a set of components

B

, builds a composite component

A
(
B
)

meeting a characteristic property

Φ

. Architecture composability is a basic and common problem faced by system designers. In this paper, we propose a formal and general framework for architecture composability based on an associative, commutative and idempotent architecture composition operator

⊕

. The main result is that if two architectures
A
1
and
A
2
enforce respectively safety properties

Φ
1

and

Φ
2

, the architecture

A
1

⊕

A
2

enforces the property

Φ
1

∧

Φ
2

, that is both properties are preserved by architecture composition. We also establish preservation of liveness properties by architecture composition. The presented results are illustrated by a running example and a case study.
Thinking concretely or abstractly: The influence of fit between goal progress and goal construal on subsequent self‐regulation
Authors: Park Jooyoung , Hedgcock William M.
Published: December 2015

This article examines the relationship between goal progress and construal level and its influence on subsequent goal pursuit. Using action identification theory, we hypothesized that greater perceived goal progress leads to higher‐level construals and that the fit between goal progress and goal construal is more likely to enhance self‐regulation than non‐fit. Our findings indicate that, compared with lesser perceived goal progress, greater perceived goal progress induces higher‐level construals (studies 1a–2a). Moreover, as people perceive greater goal progress, abstract goal construal (i.e., “why”) is more likely to promote goal‐consistent behavior than concrete goal construal (i.e., “how”; studies 2a–2b). We also observed that this fit between goal progress and goal construal influences actual self‐regulatory behavior (study 3).
Point–counterpoint: Resource heterogeneity, performance, and competitive advantage
Authors: Ketokivi Mikko
Published: December 2015

This JOM Forum is an exchange of ideas on the antecedents and consequences of resource heterogeneity. Two sets of authors examine in a point–counterpoint style the usefulness of the resource based view (or resource based theory) in operations management research.
Cell‐free circulating tumour DNA as a liquid biopsy in breast cancer
Authors: De Mattos‐Arruda Leticia , Caldas Carlos
Published: December 2015

Recent developments in massively parallel sequencing and digital genomic techniques support the clinical validity of cell‐free circulating tumour DNA (ctDNA) as a ‘liquid biopsy’ in human cancer. In breast cancer, ctDNA detected in plasma can be used to non‐invasively scan tumour genomes and quantify tumour burden. The applications for ctDNA in plasma include identifying actionable genomic alterations, monitoring treatment responses, unravelling therapeutic resistance, and potentially detecting disease progression before clinical and radiological confirmation. ctDNA may be used to characterise tumour heterogeneity and metastasis‐specific mutations providing information to adapt the therapeutic management of patients. In this article, we review the current status of ctDNA as a ‘liquid biopsy’ in breast cancer.
Characterization of persistent pain after hysterectomy based on gynaecological and sensory examination
Authors: Pokkinen Satu M. , Nieminen Kari , Yli-Hankala Arvi , Kalliomäki Maija-Liisa
Published: December 2015

Background and aims

Previous studies have shown that pelvic pain is common after hysterectomy. It is stated that only a minor part of that pain can be defined as persistent postsurgical pain. Our primary aim was to find out if the pelvic pain after hysterectomy may be classified as postsurgical. Secondary aims were to characterize the nature of the pain and its consequences on the health related quality of life.

Methods

We contacted the 56 women, who had reported having persistent pelvic pain six months after hysterectomy in a previously sent questionnaire. Sixteen women participated. Clinical examinations included gynaecological examination and clinical sensory testing. Patients also filled in quality of life (SF-36) and pain questionnaires.

Results

Ten out of sixteen patients still had pain at the time of examination. In nine patients, pain was regarded as persistent postsurgical pain and assessed probable neuropathic for five patients. There were declines in all scales of the SF-36 compared with the Finnish female population cohort.

Conclusions

In this study persistent pelvic pain after vaginal or laparoscopic hysterectomy could be defined as persistent postsurgical pain in most cases and it was neuropathic in five out of nine patients. Pain had consequences on the health related quality of life.

Implications

Because persistent postsurgical pain seems to be the main cause of pelvic pain after hysterectomy, the decision of surgery has to be considered carefully. The management of posthysterectomy pain should be based on the nature of pain and the possibility of neuropathic pain should be taken into account at an early postoperative stage.
Prisoners of Reason
Authors: Amadae S. M.
Published: December 2015

Is capitalism inherently predatory? Must there be winners and losers? Is public interest outdated and free-riding rational? Is consumer choice the same as self-determination? Must bargainers abandon the no-harm principle? Prisoners of Reason recalls that classical liberal capitalism exalted the no-harm principle. Although imperfect and exclusionary, modern liberalism recognized individual human dignity alongside individuals' responsibility to respect others. Neoliberalism, by contrast, views life as ceaseless struggle. Agents vie for scarce resources in antagonistic competition in which every individual seeks dominance. This political theory is codified in non-cooperative game theory; the neoliberal citizen and consumer is the strategic rational actor. Rational choice justifies ends irrespective of means. Money becomes the medium of all value. Solidarity and good will are invalidated. Relationships are conducted on a quid pro quo basis. However, agents can freely opt out of this cynical race to the bottom by embracing a more expansive range of coherent action.
The Intellectual in Modern Chinese History
Authors: Cheek Timothy
Published: December 2015

This vivid narrative history of Chinese intellectuals and public life provides a guide to making sense of China today. Timothy Cheek presents a map and a method for understanding the intellectual in the long twentieth century, from China's defeat in the Sino-Japanese war in 1895 to the 'Prosperous China' since the 2008 Beijing Olympics. Cheek surveys the changing terrain of intellectual life over this transformative century in Chinese history to enable readers to understand a particular figure, idea or debate. The map provides coordinates to track different times, different social worlds and key concepts. The historical method focuses on context and communities during six periods to make sense of ideas, institutions and individual thinkers across the century. Together they provide a memorable account of the scenes and protagonists, and arguments and ideas, of intellectuals and public life in modern China.
Inflectional Paradigms
Authors: Stump Gregory
Published: December 2015

Sometimes dismissed as linguistically epiphenomenal, inflectional paradigms are, in reality, the interface of a language's morphology with its syntax and semantics. Drawing on abundant evidence from a wide range of languages (French, Hua, Hungarian, Kashmiri, Latin, Nepali, Noon, Old Norse, Sanskrit, Turkish, Twi and others), Stump examines a variety of mismatches between words' content and form, including morphomic patterns, defectiveness, overabundance, syncretism, suppletion, deponency and polyfunctionality. He demonstrates that such mismatches motivate a new grammatical architecture in which two kinds of paradigms are distinguished: content paradigms, which determine word forms' syntactic distribution and semantic interpretation, and form paradigms, which determine their inflectional realization. In this framework, the often nontrivial linkage between a lexeme's content paradigm and its stems' form paradigm is the nexus at which incongruities of content and form are resolved. Stump presents clear and precise analyses of a range of morphological phenomena in support of this theoretical innovation.
The World's Search for Sustainable Development
Authors: Sanwal Mukul
Published: December 2015

This text traces the evolution of sustainable development and climate change from the time it emerged in international consultations and agreements. The three sections of the book, focusing on the framework, climate change and sustainable development, seek to cover the essentials of the politics of natural resource usage at the global level. The book explores the evolution of sustainable development and climate change within the framework of the United Nations, and the way the concept has been defined through intergovernmental meetings, agreements and consensus within the multilateral system. It also explores the best ways of reducing the risk to the planet while enabling societies to pursue sustainable development paths. The challenges call for a transformation of social systems to facilitate a broadly acceptable change. The book also explores the adoption of low-carbon models different from the high-carbon socio-technical systems and related social practices.
Print Media and the History of Women’s Sport in Africa: The Kenyan Case of Barriers to International Achievement
Authors: Sikes Michelle
Published: December 2015

This article explores one source through which African women’s sport history can be drawn and interpreted: the sport sections of African newspapers. In the case of Kenya, the major dailies,Daily NationandThe East African Standard, are repositories of information pertaining to the challenges that confronted female athletes. Taking into account the history and development of these media, the article addresses the question of why did Kenyan women lag behind their male counterparts in entering the sport at an international level? Focusing on the early post-colonial period, it is argued that institutional barriers abroad as well as economic and cultural factors at home disproportionately disadvantaged female runners in their career progression. These conclusions would be difficult to substantiate without investigating the Kenyan press, a valuable source for anyone seeking to access information about the lives of the women who have contributed to Africa’s sport history.
Radiation model of a xenon flash lamp in a laser amplifier pump cavity
Authors: Wu Yongzhong , Zhu Jianqiang , Zhang Zhixiang , Li Yangshuai
Published: December 2015

Understanding the radiation model of a flash lamp is essential for the reflector design of a laser amplifier. Reflector design often involves several simplifying assumptions, like a point or Lambertian source; either of these assumptions may lead to significant errors in the output distribution. In practice, source non-idealities usually result in sacrificing the amplifier’s gain coefficient. We propose a novel test technique for attaining the xenon flash lamp absolute spectral intensity at various angles of view, and then accurately predict radiation distributions and generate the reflector shape. It is shown that due to the absorption of emitted radiation by the lamp itself, the behavior of the radiation model at various wavelengths is different. Numerical results of xenon plasma absorption coefficient were compared with the measured data. A reasonable agreement was obtained for the absorption coefficient parameters. Thus, this work provides a useful analytical tool for the engineering design of laser amplifier reflectors using xenon flash lamps as pumps.
A Novel, Sporicidal Formulation of Ethanol for Glove Decontamination to Prevent Clostridium difficile Hand Contamination During Glove Removal
Authors: Tomas Myreen E. , Nerandzic Michelle M. , Cadnum Jennifer L. , Mana Thriveen S. C. , Jencson Annette , Sunskesula Venkata , Kundrapu Sirisha , Wilson Brigid M. , Donskey Curtis J.
Published: December 2015

Decontamination of gloves before removal could reduce the risk for contamination of hands of personnel caring for patients with Clostridium difficile infection. We demonstrated that a novel sporicidal formulation of ethanol rapidly reduced C. difficile spores on gloved hands without adverse odor, respiratory irritation, or staining of clothing.

Infect. Control Hosp. Epidemiol. 2016;37(3):337–339
Africans and Slave Marriages in Eighteenth-century Rio de Janeiro
Authors: Gomes Flávio dos Santos
Published: December 2015

During slavery in the Americas, whether plantation, mining or urban, captives, Creoles, freedpersons and Africans invented various forms of socialization, in part through family arrangements. The slave family is one of the most prominent themes in recent studies of Brazilian slavery. Until the 1970s, several authors claimed that such families did not exist; however, contemporary studies have revised many of the arguments about slaves' experiences and daily lives. Based on statistical sources (post-mortem inventories, lists of names, population censuses, and parish records) historians have demonstrated that, despite their living conditions, workdays, specific demographics, illness, mortality, etc., a considerable part of die slave population was able to establish families and compadrio relations by employing various strategies.
Juan O'Gorman, Daniel COSío Villegas, and the Mexican Historical Profession: An Interview with Josefina Zomida Vázquez
Authors: Beezley William H.
Published: December 2015

Professor Josefina Zoraida Vázquez has made an indelible imprint on the discipline of the history of Mexico. Her publications have provided an analysis of the Mexican experience through such diverse themes as the U.S. invasion (1846-1848), the evolution of national education programs, and the struggles to establish federalism and republicanism in the first decades of independence. She has written official textbooks used by all Mexican school children, appeared on numerous television programs, taught dozens of doctoral students, and assisted many scholars in both Mexico and the United States. She has been an active member of the historical profession; she organized the Congress of Mexican Historians from Mexico, the United States, and Canada in Patzcuaro in 1977 and served as the President of the same organization in Monterrey in 2003.
Continuing the Bleeding of These Pueblos Will Shortly Make Them Cadavers: The Potosi Mita, Cultural Identity, and Communal Survival in Colonial Peru
Authors: Stavig Ward
Published: December 2015

The exploitation of Andean villagers under the forced labor regime for the mines of Potosi is almost as infamous as the silver they extracted from thecerro ricois famous. Established by Viceroy Toledo in the 1570s, themita, as the system of forced labor was known, remained in place until the smoke and shot of Latin American independence struggles were in the air. For over two centuries, Spain forced thousands upon thousands ofnaturales(a common colonial term for indigenous people) from communities throughout the southern Andean highlands to lend their muscle and sweat, and all too often their blood and their lives, to keep Potosi's veins open and flowing. Through this work themitayosand their communities not only drove the colonial economy, but also were a major force in sustaining the Spanish empire and in helping forge the modern world's dominant economic system. Conversely, mita exploitation threatened the very survival of the communities subject to it. The mita was so onerous that virtually all indigenous peoples subject to the labor draft, regardless of ethnicity or class, raised an almost continuous voice of protest from their communities against the mita and its abuses. Tensions created by the mita also severely strained the bonds that linked community,curaca, and the state, which were primary ingredients in the social glue that kept colonial Andean society from coming apart. To avoid descending into the mines, and to escape such horrors as laboring over mercury vapors, many people permanently fled their communities, giving up the status oforiginarios(community members with rights such as access to land and subject to state obligations) to becomeforasteros(indigenous person not living in community of origin, or descendant of the same, without communal rights but exempt from many state obligations). In this way the mita, one of the few forces that had potential for uniting Andean peoples in opposition to the state also fractured them. Communal solidarity was severely strained and neither the shared experience of the mita nor the commonality of experience in Potosi created sufficient cohesion to overcome the ethnic and regional differences that divided them.
Left Liberalism and Race in the Evolution of Colombian Popular National Identity
Authors: Green W. John
Published: December 2015

Though a nation of discordant regionalism and historically weak central institutions, Colombia can paradoxically claim strong currents of popular national identity. It is well known that long centuries of relative economic isolation, coupled with Colombia's largely subsistence internal economy and torturous topography, provided few opportunities to integrate the nation's different regions. Such conditions resulted in fractured regional identities and racial compositions. What few links to the world market Colombia enjoyed before the late nineteenth century came from the mining of gold, with short episodes of tobacco and quinine exportation. Only in the 1880s and later did coffee production finally reorient the nation's economy and introduce new questions of land tenure and social relations. Colombia's fiercely partisan political system evolved during the nineteenth century, therefore, when the country was still overwhelmingly rural, inward-looking, and little more than a collection of semi-autonomous regions. Keith Christie noted that before the 1950s, regionalism was so strong that “Bogotá was essentially just another provincial capital.” As a consequence, the national army in the nineteenth century seldom proved more powerful than the many rebel armies it faced. Indeed, according to the basic Weberian definition of the “state” as the entity that controls a monopoly on the legitimate use of force, and evidenced by the fact that the national government still does not control large portions of the country's territory, Colombia's central state structures continue to be glaringly weak at the end of the twentieth century.
The effects of vitamin A supplementation with measles vaccine on leucocyte counts andin vitrocytokine production
Authors: Jensen Kristoffer Jarlov , Fisker Ane Bærent , Andersen Andreas , Sartono Erliyani , Yazdanbakhsh Maria , Aaby Peter , Erikstrup Christian , Benn Christine Stabell
Published: December 2015

As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VASv. placebo with MV, analysing leucocyte counts, whole bloodin vitrocytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP≥5 mg/l (28v. 12 %;P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γresponses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95 % CI 1·44, 10·90) but not in males (GMR 0·44; 95 % CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.
The Reform of the Chapter of Sées (1131) Reconsidered: The Evidence of the Episcopal Acta
Authors: ALLEN RICHARD
Published: December 2015

This paper reexamines the reform of the cathedral chapter of Sées in 1131. It does so by looking primarily, though not exclusively, at the almost 400 acta – that is, the charters and documents –issued by the bishops of the diocese in the period up to 1220. It shows that this underused material has the potential better to contextualise this key event in the ecclesiastical history of medieval France and radically to improve our understanding of its wider effects. It also looks in detail at the careers of the bishops during this period and shows that these prelates, contrary to popular belief, were often supportive not only of the reform established within their cathedral, but also of the wider Augustinian movement. It concludes by briefly considering what the example of Sées can tell us about the regularisation of cathedral chapters in the Middle Ages.
Congress as manager: oversight hearings and agency morale
Authors: Marvel John D. , McGrath Robert J.
Published: December 2015

Federal agencies perform many important tasks, from guarding against terrorist plots to mailing social security checks. A key question is whether Congress can effectively manage such a large and influential bureaucracy. We argue that Congress, in using oversight to ensure agency responsiveness to legislative preferences, risks harming agency morale, which could have negative long-run effects on performance and the implementation of public policy. More specifically, we argue that oversight’s effects on agency morale are conditional on whether oversight is adversarial or friendly. We assess our claims using a novel data set of the frequency and tone of hearings in which federal agencies are called to testify before Congress from 1999 to 2011 and merge it with data on agency autonomy and job satisfaction. Our findings suggest that agency morale is sensitive to congressional oversight attention, and thus speak to questions regarding democratic accountability, congressional policymaking and the implementation of public policy.
Porcine oocyte mtDNA copy number is high or low depending on the donor
Authors: Pedersen Hanne Skovsgaard , Løvendahl Peter , Larsen Knud , Madsen Lone Bruhn , Callesen Henrik
Published: December 2015

Oocyte capacity is relevant in understanding decreasing female fertility and in the use of assisted reproductive technologies in human and farm animals. Mitochondria are important to the development of a functionally good oocyte and the oocyte mtDNA copy number has been introduced as a useful parameter for prediction of oocyte competence. The aim of this study was to investigate: (i) if the oocyte donor has an influence on its oocyte's mtDNA copy number; and (ii) the relation between oocyte size and mtDNA copy number using pre- and postpubertal pig oocytes. Cumulus–oocyte complexes were collected from individual donor pigs. The oocytes were allocated into different size-groups, snap-frozen and single-oocyte mtDNA copy number was estimated by quantitative real-time PCR using the genes ND1 and COX1. Results showed that mean mtDNA copy number in oocytes from any individual donor could be categorized as either ‘high’ (≥100,000) or ‘low’ (<100,000) with no difference in threshold between pre- and postpubertal oocytes. No linear correlation was detected between oocyte size and mtDNA copy number within pre- and postpubertal oocytes. This study demonstrates the importance of the oocyte donor in relation to oocyte mtDNA copy number, irrespectively of the donor's puberty status and the oocyte's growth stage. Observations from this study facilitate both further investigations of the importance of mtDNA copy number and the unravelling of relations between different mitochondrial parameters and oocyte competence.
Prevalence of Risk Factors for Coronary Artery Disease in Pennsylvania (USA) Firefighters
Authors: Risavi Brian L. , Staszko Jason
Published: December 2015

Introduction

Firefighting is a physically demanding profession. Heart disease remains the number one killer of firefighters. Many firefighters have multiple risk factors, putting them at risk for sudden cardiac events. The purpose of this study was to describe the prevalence of risk factors for heart disease in a convenience sample of Pennsylvania (USA) firefighters.

Methods

A convenience sample of 160 firefighters in western Pennsylvania had height, weight, waist circumference, blood pressure, and body mass index (BMI) assessed, and then were surveyed to measure their knowledge of cardiovascular risk factors. Data analysis included subgroup comparisons of age, BMI, waist circumference, and exercise for their impact on health risks in the study cohort. In particular, the researchers were interested in understanding whether the knowledge of risk was associated with lower measures of risk.

Results

Eighteen firefighters (4%) reported a history of coronary artery disease (including stents/interventions). In this group, 69% to 82% correctly identified age, hypertension (HTN), high cholesterol, smoking, obesity, sedentary lifestyle, and family history as risk factors for coronary artery disease. Fourteen percent were smokers, 41% had HTN, 38% had pre-HTN with only 12% receiving treatment, and 13.5% were treated for high cholesterol. Fifty-eight percent exercised regularly.

Conclusions

While a majority of firefighters were able to identify risk factors for coronary artery disease, many could not. Eighteen (4%) had a history of coronary artery disease, including interventions. Many had several of the risk factors indicated, which highlights the need for an organized national approach to address the medical screening/evaluation, nutrition, and exercise components of firefighter fitness.

RisaviBL, StaszkoJ. Prevalence of risk factors for coronary artery disease in Pennsylvania (USA) firefighters. Prehosp Disaster Med. 2016;31(1):102–107.
A primer on binge eating disorder diagnosis and management
Authors: Citrome Leslie
Published: December 2015

Binge eating disorder (BED) is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among U.S. adults, yet often goes unrecognized. In theDiagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BED is defined by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstancesanda sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. It can affect both men and women, regardless if they are at normal weight, overweight, or obese, and regardless of their ethnic or racial group. Psychiatric comorbidities are very common, with 79% of adults with BED also experiencing anxiety disorders, mood disorders, impulse control disorders, or substance use disorders; almost 50% of persons with BED have ≥3 psychiatric comorbidities. Multiple neurobiological explanations have been proffered for BED, including dysregulation in reward center and impulse control circuitry, with potentially related disturbances in dopamine neurotransmission and endogenous μ‐opioid signaling. Additionally, there is interplay between genetic influences and environmental stressors. Psychological treatments such as cognitive behavioral interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED; however, at present, there is one approved agent for the treatment of moderate to severe BED—lisdexamfetamine, a stimulant that was originally approved for the treatment of attention deficit hyperactivity disorder.
Position gauging of welding joints with an FMCW-based mm-wave radar system
Authors: Schrattenecker Jochen O. , Schuster Stefan , Schmid Christian M. , Scheiblhofer Werner , Ennsbrunner Helmut , Stelzer Andreas
Published: December 2015

This paper presents a position gauging system of welding joints. While the principle measurement concept was already introduced by Schrattenecker et al. in2014, here it is focused on different types of practically used welding materials. The sensor used is based on the frequency-modulated continuous-wave principle operating in the W-band. Position estimation (PoE) of different welding geometries is carried out with polarimetric scattering effects introduced by geometrical discontinuities. For the real-time calculation of the signal models a field simulation tool we developed is used. Aside from a variety of geometries, we introduce a geometrical optimization approach that increases the achievable accuracy of the measurement concept. The optimization and PoE of the different welding materials were examined in various simulations and the results were verified by measurements in the laboratory and in an industrial environment. Simulation and measurement were in good agreement.
The Fourth International Network of Twin Registries: Overview from Osaka/Research Reviews: Familial Fraternal Twinning; Twin Study of Masculine Faces; Physical Aggression and Epigenetics; Prenatal Education for Parents of Twins/Current Events: 2016 Guinness Book of World Records; Oldest Living Male Twins; Twins Reunited at Sixty-Nine; Panda Twins; Twins.com
Authors: Segal Nancy L.
Published: December 2015

The 4th International Network of Twin Registries (INTR) Consortium Meeting took place in Osaka, Japan, September 28–29, 2015. The venue was the Osaka Medical Center for Medical Innovation and Translational Research. An overview of presentations and other activities is provided. Next, 1930s research on familial fraternal twinning, preference for masculine faces, physical aggression and epigenetics, and a prenatal education program for parents of multiples are described. Current twin-related events include the 2016 Guinness Book of World Records (GWR), the oldest living male twins, newly reunited twins, the birth of panda twins and a controversial twin-based website.
The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium
Authors: Willemsen Gonneke , Ward Kirsten J. , Bell Christopher G. , Christensen Kaare , Bowden Jocelyn , Dalgård Christine , Harris Jennifer R. , Kaprio Jaakko , Lyle Robert , Magnusson Patrik K.E. , Mather Karen A. , Ordoňana Juan R. , Perez-Riquelme Francisco , Pedersen Nancy L. , Pietiläinen Kirsi H. , Sachdev Perminder S. , Boomsma Dorret I. , Spector Tim
Published: December 2015

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
Whole-Exome Sequencing in Nine Monozygotic Discordant Twins
Authors: Zhang Rong , Thiele Holger , Bartmann Peter , Hilger Alina C. , Berg Christoph , Herberg Ulrike , Klingmüller Dietrich , Nürnberg Peter , Ludwig Michael , Reutter Heiko
Published: December 2015

By definition, monozygotic (MZ) twins carry an identical set of genetic information. The observation of early post-twinning mutational events was shown to cause phenotypic discordance among MZ twin pairs. These mutational events comprise genomic alterations at different scales, ranging from single nucleotide changes to larger copy-number variations (CNVs) of varying sizes, as well as epigenetic changes. Here, we performed whole-exome sequencing (WES) in nine discordant MZ twins to identify somatic mutational events in the affected twin that might exert a dominant negative effect. Five of these MZ twin pairs were discordant for congenital heart defects (CHD), two for endocrine disorders, one for omphalocele, and one for congenital diaphragmatic hernia (CDH). Analysis of WES data from all nine MZ twin pairs using the de novo probability tool DeNovoGear detected only one apparent de novo variation inTMPRSS13in one of the CHD-affected twins. Analysis of WES data from all nine MZ twin pairs by using standard filter criteria without the de novo probability tool DeNovoGear revealed a total of 6,657 variations in which both the twin pairs differed. After filtering for variations only present in the affected twins and absent in in-house controls, 722 variations remained. Visual inspection for read quality decreased this number to 12, present only in the affected twin. However, Sanger sequencing of the overall 13 variations failed to confirm the variation in the affected twin. These results suggest that somatic mutational events in coding regions do not seem to play a major role in the phenotypic expression of MZ discordant twin pairs.
Erreichbarkeit Jugendlicher für ein Internet- und SMS-Programm zum Thema Alkohol
Authors: Haug Severin , Castro Raquel Paz , Schaub Michael P
Published: December 2015

Zusammenfassung. Zielsetzung: Internet- und Short Message Service (SMS)-basierte Interventionen eröffnen die Möglichkeit mit Hilfe von individualisierten Botschaften zu einem sensiblen Umgang mit Alkohol zu motivieren. Schulklassen sind ein geeignetes Setting um große Populationen junger Leute proaktiv für diese Interventionen zu gewinnen. Es wurden individuelle, schul- und klassenspezifische Merkmale untersucht, welche die Teilnahmebereitschaft an einem Internet- und SMS-basierten Programm zur Förderung eines sensiblen Umgangs mit Alkohol beeinflussen. Methodik: Grundlage bildeten die Daten von 964 Schülern aus Berufs- und Mittelschulen in der Schweiz, die zur Studien- und Programmteilnahme eingeladen wurden und von denen 712 (73.9 %) daran teilnahmen. Mittels einer Mehrebenenanalyse wurde der Einfluss individueller und klassenspezifischer Merkmale auf die Teilnahmebereitschaft überprüft. Ergebnisse: Auf Klassenebene war eine kleinere Anzahl Anwesender und ein geringerer Anteil an Personen mit Migrationshintergrund mit einer höheren Teilnahmebereitschaft am Programm verbunden, auf individueller Ebene waren dies ein weibliches Geschlecht, ein niedrigeres Alter und ein höherer maximaler Alkoholkonsum im letzten Monat. Schlussfolgerungen: Eine Aufteilung größerer Klassen könnte hilfreich sein, um einzelne Personen gezielter zu motivieren. Insbesondere in Klassen mit einem hohen Anteil älterer oder männlicher Jugendlicher sollte genügend Zeit und Energie für eine gezielte Motivation zur Studien- und Programmteilnahme aufgewendet werden.