bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of near‐surface wind speed and gustiness on horizontal and vertical porous medium gas transport and gas exchange with the atmosphere
Authors: Poulsen T. G. , Furman A. , Liberzon D.
Published: January 2018

Effects of wind speed and wind gustiness on horizontal and vertical subsurface gas transport and subsurface–atmosphere gas exchange were investigated experimentally using a 40 cm × 40 cm, 35‐cm‐deep stainless steel container, filled with a dry granular porous medium (crushed basalt) of 2–4‐mm grain size. Experiments used CO2 and O2 as tracer gases and were conducted under both steady and gusty wind at speeds ranging from 0 to 5.6 m s−1. Tracer gas breakthrough curves were measured at 20 locations within the porous medium to assess both horizontal and vertical gas movement. Results indicated that horizontal gas movement in wind‐exposed porous materials is important, especially near the wind‐exposed surface, and suggested considerable effects of both wind speed and wind gustiness on both horizontal and vertical gas transport inside the porous medium as well as subsurface–atmospheric gas exchange. Although wind‐induced subsurface gas transport is likely to be multidimensional, one‐dimensional model simulations indicated that vertical transport is an adequate approximation of the resulting average gas transport and exchange with the atmosphere over a larger area.

Highlights

Experimental assessment of near‐surface gas movement in wind‐exposed porous medium

Near‐surface gas movement in wind‐exposed porous media occurs both horizontally and vertically.

Wind speed and wind gustiness affect gas movement near the soil–atmosphere interface.

Wind‐induced bulk subsurface‐to‐atmosphere gas mass transport may be approximated as vertical.
Value of clinical features to differentiate refractory epilepsy from mimics: a prospective longitudinal cohort study
Authors: Labate A. , Mumoli L. , Curcio A. , Tripepi G. , D'Arrigo G. , Ferlazzo E. , Aguglia U. , Indolfi C. , Quattrone A. , Gambardella A.
Published: January 2018

Background and purpose

Misdiagnosis of refractory epilepsy (rE) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE.

Methods

Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry.

Results

Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non‐epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut‐off age at 35 years and above. Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about 70% in rE. A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures.

Conclusions

This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions.
Intravenous thrombolysis for acute ischaemic stroke in patients on direct oral anticoagulants
Authors: Touzé E. , Gruel Y. , Gouin‐Thibault I. , De Maistre E. , Susen S. , Sie P. , Derex L.
Published: January 2018

Background and purpose

Whereas intravenous thrombolysis (IVT) is allowed for acute ischaemic stroke in patients on vitamin K antagonists with international normalized ratio ≤1.7, there are no similar recommendations for patients on direct oral anticoagulants (DOACs), notably due to the lack of coagulation tests to assess the therapeutic effects. Although the literature is scarce, consisting of small case series and retrospective studies, considering the frequency of this situation the French Vascular Neurology Society and the French Study Group on Haemostasis and Thrombosis have worked on a joint position paper to provide a practical position regarding the emergency management of ischaemic stroke in patients on DOACs.

Method

Based on a review of the literature, the authors wrote a first text that was submitted to a broad panel of members from the two societies. The text was then amended by the authors to address experts’ comments and to reach a consensus.

Results

In patients with normal renal function and who stopped the DOAC for at least 48 h, the management should not differ from that in patients without oral anticoagulant. In patients who are still on DOACs, mechanical thrombectomy is encouraged preferentially when applicable in first line. Otherwise, when specific tests are available, values <50 ng/ml indicate that IVT is allowed. In the absence of specific tests, standard tests (thrombin time, prothrombin time and activated partial thromboplastin time) can be used for dabigatran and rivaroxaban, although interpretation of these tests may be less reliable. In some patients on dabigatran, idarucizumab may be used before IVT.

Conclusions

In this expert opinion paper, it is suggested that IVT can be performed in patients selected according to the time elapsed since the drug was last taken, renal function, type of hospital where the patient is admitted and plasma concentration of DOAC.
Hunt or hide: How insularity and urbanization affect foraging decisions in lizards
Authors: De Meester Gilles , Lambreghts Yorick , Briesen Bjorn , Smeuninx Tom , Tadić Zoran , Van Damme Raoul
Published: January 2018

Foraging decisions should reflect a balance between costs and benefits of alternative strategies. Predation risk and resource availability in the environment may be crucial in deciding how cautious individuals should behave during foraging. These costs and benefits will vary in time and context, meaning that animals should be able to adjust their foraging behaviour to new or altered environments. Studying how animals do this is essential to understand their survival in these environments. In this study, we investigated the effect of both insularity and urbanization on risk‐taking and neophobia during foraging in the Dalmatian wall lizard (Podarcis melisellensis). Small islets tend to have both a lower number of predators and less resources. Therefore, islet populations were expected to show more risk‐taking behaviour and less neophobia in a foraging context. Previous studies on behaviour of urban lizards have yielded inconsistent results, but due to a lack of both predators and arthropod prey in urban habitats, we expected urban lizards to also take more risks and behave less neophobic. We sampled several inhabited and uninhabited locations on Vis (Croatia) and surrounding islets. Risk‐taking behaviour was tested by measuring the latency of lizards to feed in the presence of a predator model, and neophobia by measuring the latency to feed in the presence of a novel object. We found that islet lizards do indeed take more risks and were less vigilant, but not less neophobic. Urban and rural lizards did not differ in any of these behaviours, which is in sharp contrast with previous work on mammals and birds. The behavioural differences between islet and island lizards were novel, but not unexpected findings and are in line with the theory of “island tameness”. The effect of urbanization on the behaviour of animals seems to be more complex and might vary among taxa.
The NMR solution structure of Mycobacterium tuberculosis F‐ATP synthase subunit ε provides new insight into energy coupling inside the rotary engine
Authors: Joon Shin , Ragunathan Priya , Sundararaman Lavanya , Nartey Wilson , Kundu Subhashri , Manimekalai Malathy S. S. , Bogdanović Nebojša , Dick Thomas , Grüber Gerhard
Published: January 2018

Mycobacterium tuberculosis (Mt) F1F0 ATP synthase (α3:β3:γ:δ:ε:a:b:b′:c9) is essential for the viability of growing and nongrowing persister cells of the pathogen. Here, we present the first NMR solution structure of Mtε, revealing an N‐terminal β‐barrel domain (NTD) and a C‐terminal domain (CTD) composed of a helix‐loop‐helix with helix 1 and ‐2 being shorter compared to their counterparts in other bacteria. The C‐terminal amino acids are oriented toward the NTD, forming a domain‐domain interface between the NTD and CTD. The Mtε structure provides a novel mechanistic model of coupling c‐ring‐ and ε rotation via a patch of hydrophobic residues in the NTD and residues of the CTD to the bottom of the catalytic α3β3‐headpiece. To test our model, genome site‐directed mutagenesis was employed to introduce amino acid changes in these two parts of the epsilon subunit. Inverted vesicle assays show that these mutations caused an increase in ATP hydrolysis activity and a reduction in ATP synthesis. The structural and enzymatic data are discussed in light of the transition mechanism of a compact and extended state of Mtε, which provides the inhibitory effects of this coupling subunit inside the rotary engine. Finally, the employment of these data with molecular docking shed light into the second binding site of the drug Bedaquiline.

Database

Structural data are available in the PDB under the accession number 5YIO.
Woman‐Hating: On Misogyny, Sexism, and Hate Speech
Authors: Richardson‐Self Louise
Published: January 2018

Hate speech is one of the most important conceptual categories in anti‐oppression politics today; a great deal of energy and political will is devoted to identifying, characterizing, contesting, and (sometimes) penalizing hate speech. However, despite the increasing inclusion of gender identity as a socially salient trait, antipatriarchal politics has largely been absent within this body of scholarship. Figuring out how to properly situate patriarchy‐enforcing speech within the category of hate speech is therefore an important politico‐philosophical project. My aim in this article is twofold: first, I argue that sexist speech, though oppressive, is not hate speech. Second, I argue that misogynistic speech is hate speech, even when it is intradivisional (that is, when it targets only subsets of women). This is important because recognizing that the concepthate speechapplies to certain forms of patriarchy‐enforcing speech is another step in clarifying what is wrong with the practice, and how bad it is in relation to other abuses. Consequently, this article provides a more nuanced account of the kinds of expressions that can and should count as instances of hate speech.
Osteopontin contributes to effective neutrophil recruitment, IL‐1β production and apoptosis in Aspergillus fumigatus keratitis
Authors: Zhao Guiqiu , Hu Ming , Li Cui , Lee Jieun , Yuan Kelan , Zhu Guoqiang , Che Chengye
Published: January 2018

Fungal keratitis is a major cause of corneal ulcers, resulting in significant visual impairment and blindness. A phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) mediates cluster formation of the host fungal receptors and enhances the phagocytosis and clearance of pathogenic fungi. However, whether OPN production and function occurs in fungal keratitis is unknown. OPN expression in Aspergillus fumigatus keratitis patient corneas was assessed by quantitative polymerase chain reaction (qRT‐PCR) and immunofluorescence. Human neutrophils, THP‐1 macrophages and corneal epithelial cells (HCECs) stimulated with A. fumigatus were utilized for in vitro experiments. Mouse models of A. fumigatus keratitis were developed by intrastromal injection for in vivo experiments. Using siRNAs, neutralizing antibodies, recombinant proteins and inhibitors, the production and role of OPN in A. fumigatus infection was assessed by clinical evaluation, qRT‐PCR, immunofluorescence, western blotting and bioluminescence image acquisition. We observed increased corneal OPN expression in A. fumigatus keratitis patients and mouse models compared to controls. OPN production in response to A. fumigatus infection was dependent on LOX‐1 and Erk1/2. Compared to controls, OPN knockdown impaired proinflammatory cytokine IL‐1β production, which was dependent on 4E‐BP1. OPN knockdown decreased myeloperoxidase levels, and resulted in decreased neutrophil recruitment, higher fungal load and increased apoptosis in mouse A. fumigatus keratitis. Our results indicate that OPN is a critical component of the antifungal immune response and is essential for effective neutrophil recruitment, inflammatory cytokine production and apoptosis in A. fumigatus keratitis.
Estimating the Cost‐of‐Equity Capital Using Empirical Asset Pricing Models
Authors: Kirby Chris
Published: January 2018

Empirical asset pricing models seek to capture characteristic‐based patterns in the cross‐section of average stock returns. I propose a new approach for constructing these models, and investigate its performance with respect to estimating the cost‐of‐equity capital. Using a model that accounts for the cross‐sectional relation between five characteristics and average stock returns, I obtain cost‐of‐equity estimates that outperform those produced by the Fama‐French five‐factor model in out‐of‐sample tests. Because the proposed approach builds directly on standard cross‐sectional regression techniques, it provides complete flexibility in choosing the firm characteristics used to formulate the cost‐of‐equity estimates.
Reduced orienting to audiovisual synchrony in infancy predicts autism diagnosis at 3 years of age
Authors: Falck‐Ytter Terje , Nyström Pär , Gredebäck Gustaf , Gliga Teodora , Bölte Sven ,   the EASE team
Published: January 2018

Background

Effective multisensory processing develops in infancy and is thought to be important for the perception of unified and multimodal objects and events. Previous research suggests impaired multisensory processing in autism, but its role in the early development of the disorder is yet uncertain. Here, using a prospective longitudinal design, we tested whether reduced visual attention to audiovisual synchrony is an infant marker of later‐emerging autism diagnosis.

Methods

We studied 10‐month‐old siblings of children with autism using an eye tracking task previously used in studies of preschoolers. The task assessed the effect of manipulations of audiovisual synchrony on viewing patterns while the infants were observing point light displays of biological motion. We analyzed the gaze data recorded in infancy according to diagnostic status at 3 years of age (DSM‐5).

Results

Ten‐month‐old infants who later received an autism diagnosis did not orient to audiovisual synchrony expressed within biological motion. In contrast, both infants at low‐risk and high‐risk siblings without autism at follow‐up had a strong preference for this type of information. No group differences were observed in terms of orienting to upright biological motion.

Conclusions

This study suggests that reduced orienting to audiovisual synchrony within biological motion is an early sign of autism. The findings support the view that poor multisensory processing could be an important antecedent marker of this neurodevelopmental condition.
Effects of Survey Mode on Consumer Assessment of Healthcare Providers and Systems (CAHPS) Hospice Survey Scores
Authors: Parast Layla , Elliott Marc N. , Hambarsoomian Katrin , Teno Joan , Anhang Price Rebecca
Published: January 2018

Objectives

To examine the effect of mode of survey administration on response rates and response tendencies for the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Hospice Survey and develop appropriate adjustments.

Design

Survey response data were obtained after sampling and fielding of the CAHPS Hospice Survey in 2015. Sampled caregivers and decedents were randomized to one of three modes: mail only, telephone only, and mixed mode (mail with telephone follow‐up). Linear regression analysis was used to examine the effect of mode on individual responses to questions (6 composite measures and 2 global measures that examine hospice quality).

Setting

U.S. hospice programs (N = 57).

Participants

Primary caregivers of individuals who died in hospice (N = 7,349).

Measurements

Outcomes were 8 hospice quality measures (6 composite measures, 2 global measures). Analyses were adjusted for differences in case‐mix (e.g., decedent age, payer for hospice care, primary diagnosis, length of final episode of hospice care, respondent age, respondent education, relationship of decedent to caregiver, survey language, and language spoken at home) between hospices.

Results

Response rates were 42.6% for those randomized to mail only, 37.9%, for those randomized to telephone only, and 52.6% for those randomized to mixed mode (P < .001 for difference). There were significant mode effects (P < .05) for 10 of the 24 questions that compose the quality measures, with mail‐only respondents being significantly more likely to report better experiences than telephone‐only respondents.

Conclusion

Unlike results observed in previous mode experiments for hospital CAHPS, hospice primary caregivers tend to respond more negatively by telephone than by mail. Valid comparisons of hospice performance require that reported hospice scores be adjusted for survey mode.
The variation in chemical composition of barley feed with or without enzyme supplementation influences nutrient digestibility and subsequently affects performance in piglets
Authors: Clarke L. C. , Sweeney T. , Curley E. , Duffy S. K. , Rajauria G. , O'Doherty J. V.
Published: January 2018

This study investigates the effect of dietary supplementation of a β‐glucanase and β‐xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty‐four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a β‐glucanase and β‐xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a β‐glucanase and β‐xylanase enzyme supplement. Piglets offered the low quality barley‐based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley‐based diet had reduced faecal scores compared to piglets offered the low quality barley‐based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley‐based diet compared to piglets offered the low quality barley‐based diet. The inclusion of a β‐glucanase and β‐xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley‐based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of β‐glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.
Separating Introduction Effects from Selectivity Effects: The Differences in Employment Patterns of Codetermined Firms
Authors: Gralla Rafael , Kraft Kornelius
Published: January 2018

This study examines differences in employment growth between firms with and without works councils by separating introduction effects from potential selectivity effects. Using a difference‐in‐differences framework, we show that firms with works councils have higher employment growth before adopting a works council. However, employment growth declines after introduction. We identify the reason for lower employment growth in reduced hiring rates, while dismissal rates remain constant.
The Global Adoption of National Policies Protecting Children from Violent Discipline in Schools and Homes, 1950–2011
Authors: Brehm Hollie Nyseth , Boyle Elizabeth Heger
Published: January 2018

With a focus on the relationship between women's and children's rights and theories of globalization, we conduct an event history analysis of more than 150 countries between 1950 and 2011 to assess the factors associated with policies banning corporal punishment in schools and homes. Our research reveals that formal condemnation of corporal punishment in schools is becoming a global norm; policies banning corporal punishment in the home, in contrast, are being adopted more slowly. We find that the percentage of women in parliament is associated with the adoption of anti-corporal punishment policies in both schools and homes, suggesting a nexus between women's and children's issues. Countries with more ethnic diversity are slower to adopt home policies, however. We propose that minority groups in these countries may be resistant to laws because of the risk of selective or prejudicial enforcement. In terms of globalization, more aid is associated with both school and home policies, and countries that have ratified the Convention on the Rights of the Child are more likely to adopt home policies. Surprisingly, international nongovernmental organizations are not significantly associated with either type of policy adoption.
Knowledge, attitude and practice among Health Visitors in the United Kingdom toward children's oral health
Authors: Oge Ozkem Azmi , Douglas Gail V. A. , Seymour Diane , Adams Cheryll , Csikar Julia
Published: January 2018

Objectives

The purpose of this study was to determine knowledge, attitude, and practical behavior of health visitors regarding children's oral health in the United Kingdom (UK).

Methods

A web‐based self‐administered survey with 18 closed and 2 open ended questions was distributed to a convenience sample of approximately 9,000 health visitors who were currently employed in the United Kingdom and a member of the Institute of Health Visiting.

Results

A total of 1,088 health visitors completed the survey, resulting in a response rate of 12%. One‐third of the health visitors reported that they had not received oral health training previously. Almost all agreed that oral health advice/promotion should be included in their routine health visiting contacts. Previous oral health training/education was associated with an increase in oral health knowledge; confidence in entering a discussion with parents/caregivers and willingness to be involved in dental referral process.

Conclusions

The results of our study support the need for health visitors to receive oral health training in oral health promotion including oral health risk assessment, guidance on evidence based up‐to‐date prevention measures, increasing the dental attendance prevalence at early stages and awareness of including specific oral health guidelines/fact sheets into their regular practice.
A critical interrogation of the relation between the ecosystem approach and ecosystem services
Authors: De Lucia Vito
Published: January 2018

This article offers a critical interrogation of the relationship between two emerging conceptual frameworks whose importance has grown quickly within the context of international environmental law: the ecosystem approach and ecosystem services. Both premised on the concept of the ecosystem, their origin is parallel, but their present and future is convergent and increasingly intertwined. The ecosystem approach, increasingly deployed in a variety of normative and regulatory contexts, has become a key strategy for the integrated management of human activities, and has been characterized as a paradigm shift in environmental law and governance. Ecosystem services, mainstreamed by the Millennium Ecosystem Assessment series in the early 2000s, refer to the benefits people obtain from ecosystems. The relationship between the two concepts is arguably underexplored. This article aims at filling this gap from a particular critical legal perspective, and will read this relationship in terms of a ‘biopolitical entanglement’.
Who cares about the day after tomorrow? Pension issues when households are myopic or time inconsistent
Authors: Börsch‐Supan Axel , Härtl Klaus , Leite Duarte Nuno
Published: January 2018

Pension economics has traditionally guided pension policy with the help of formal models based on individuals who think in a life‐cycle context with perfect foresight, full information, and in a time‐consistent manner. Associated macro models were mostly based on a single country. This paper sheds light on several aspects of pension economics when these assumptions do not hold using—to our knowledge—the first multi‐country model of procrastinating households. Our focus is on the interaction between the share of procrastinators in a country, the speed and extent of population aging, and the size of an existing PAYG‐DB pension system. Starting from the insight that procrastination reduces the volume of savings, we focus on three questions that are particularly relevant for the quickly aging Asian economies: What are the consequences for the balance between pay‐as‐you‐go and fully funded pension systems? Where will retirement savings be invested in a globally linked world with very different pension systems and demographics? How large are global spillover effects of pension reforms in one region for the other regions in the world?
Stress reactions following acute situations involving moral challenges among health care professionals
Authors: Larsson Gerry , Nilsson Sofia , Hyllengren Peder , Ohlsson Alicia , Waaler Gudmund , Kallenberg Kjell
Published: January 2018

Many health care professionals have to make morally difficult decisions during acute, stressful situations. The aim was to explore the applicability of an existing qualitatively developed model of individual reactions among professional first responders following such situations using a quantitative approach. According to the model, the interaction of antecedent individual and contextual characteristics affect the immediate emotional reactions to acute, stressful events involving a moral dilemma. Continuous coping efforts and the quality of social support will also affect the long‐term positive and negative reactions to the event. The participants (n= 204, about 50% response rate) represented three Swedish health care professions stationed at a university hospital and a regional hospital: Physicians (n= 50), nurses (n= 94) and “others” (n=60, mainly social welfare officers and assistant nurses). Except for the personality dimension emotional stability which was measured using an established instrument, all measurement scales were operationalizations of codes and categories from the qualitative study (ten scales altogether). Four multiple regression analyses were performed with long‐term positive and negative reactions in everyday acute and morally extremely taxing situations respectively as dependent variables. The outcome showed that long‐term positive reactions covaried with much use of the coping strategies Emotional distancing and Constructive emotional confrontation and a perception of a well‐functioning Formal social support. Regarding long‐term negative reactions, higher age and little use of Emotional distancing accounted for much of the variance. Immediate emotional reactions also contributed significantly. Conclusion: the results largely supported the model concepts and their assumed relationships.
Breakthrough Exophiala dermatitidis infection during prophylactic administration of micafungin during second umbilical cord blood transplantation after graft failure
Authors: Watanabe Naoki , Gotoh Akihiko , Shirane Shuichi , Hamano Yasuharu , Hirai Yuji , Shimizu Maika , Nakamura Ayako , Matsumoto Kana , Morita Kunihiko , Mori Takeshi , Ohsaka Akimichi , Komatsu Norio
Published: January 2018

Exophiala dermatitidis infections in patients with hematological malignancies are very rare. Our patient had a blood stream infection caused by E. dermatitidis following the second umbilical cord blood transplantation (UCBT) after graft failure during the first UCBT. To our knowledge, this is the first report describing a breakthrough fungal infection caused by E. dermatitidis during the prophylactic administration of micafungin (MCFG). Therefore, MCFG‐treated patients should be monitored for breakthrough E. dermatitidis infection during hematopoietic stem cell transplantation.
A cluster of donor‐derived Cryptococcus neoformans infection affecting lung, liver, and kidney transplant recipients: Case report and review of literature
Authors: Camargo Jose F. , Simkins Jacques , Schain Denise C. , Gonzalez A. Adrian , Alcaide Maria L. , Anjan Shweta , Guerra Giselle , Roth David , Kupin Warren L. , Mattiazzi Adela , Tan Yaohong , Milikowski Clara , Morris Michele I. , Abbo Lilian M.
Published: January 2018

Donor‐derived infections (DDIs) are a very rare but potentially devastating complication of solid organ transplantation. Here we present a cluster of proven donor‐derived cryptococcal infection in the kidney, liver, and lung recipients from a single donor. Remarkably, the onset of illness in the kidney and liver recipients occurred more than 8‐12 weeks after transplantation, which is beyond the incubation period previously reported for donor‐derived cryptococcosis. DDI should always be considered in the differential diagnosis of transplant recipients admitted with febrile illness, even when presenting beyond the first month post‐transplant. Communication between reference laboratories, transplant centers, and organ procurement organizations is critical to improve outcomes.
Reduction in late onset cytomegalovirus primary disease after discontinuation of antiviral prophylaxis in kidney transplant recipients treated with de novo everolimus
Authors: Devresse Arnaud , Leruez‐Ville Marianne , Scemla Anne , Avettand‐Fenoel Véronique , Morin Lise , Lebreton Xavier , Tinel Claire , Amrouche Lucile , Lamhaut Lionel , Timsit Marc Olivier , Zuber Julien , Legendre Christophe , Anglicheau Dany
Published: January 2018

Background

Donor (D)+/recipient (R)− serostatus is closely associated with a higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis is conventionally used in such patients, but late onset CMV infection/disease still occurs after the discontinuation of prophylaxis.

Methods

We retrospectively analyzed the data of 215 low immunological risk patients who received kidney transplantation in our center between 2011 and 2016.

Results

Ninety‐seven patients received a combination of everolimus (EVL)/reduced doses of calcineurin inhibitors (CNI) (EVL group) de novo, and 118 received a combination of mycophenolic acid (MPA)/standard doses of CNI (MPA group) de novo. All patients received induction by basiliximab, steroids, and standardized antiviral prophylaxis depending on their CMV D/R serostatus. D+/R− recipients comprised 17% (n = 16) of the EVL group and 19% (n = 22) of the MPA group (P = .722). In the D+/R− subgroup, the 1‐year incidence of late onset CMV primary disease after the withdrawal of prophylaxis was lower in the EVL group than in the MPA group (6% vs 41%, P = .025) while the rate of CMV disease in the D+/R+ group (8% vs 6%, P = 1) and the D−/R+ group (12% vs 9%, P = 1) were similar. Kaplan‐Meier analysis of 1‐year CMV primary disease‐free survival in seronegative patients was significantly better in the EVL group (P = .029, log‐rank test).

Conclusions

Our data suggest that de novo use of EVL may reduce late onset CMV primary disease after the withdrawal of antiviral prophylaxis in kidney transplantation patients.
Norovirus causing severe gastrointestinal disease following allogeneic hematopoietic stem cell transplantation: A retrospective analysis
Authors: Swartling Lisa , Ljungman Per , Remberger Mats , Sundin Mikael , Tiveljung Annika , Mattsson Jonas , Sparrelid Elda
Published: January 2018

Background

Norovirus (NV) can cause chronic and severe gastroenteritis with possible lethal outcome in immunocompromised patients. The knowledge of NV infections in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is limited. The aim of this study was to clarify the clinical importance of NV in a large cohort of HSCT recipients.

Methods

All patients undergoing HSCT and diagnosed with NV at Karolinska University Hospital from 2006‐2012 were included in the study (63 patients). Clinical data were collected from medical records, and statistics were performed using the logistic regression method.

Results

The majority of patients (70%) had short‐term symptoms (≤14 days). However, 54% of all patients required admission or prolonged hospitalization owing to the infection. In 16% of the patients the symptoms were chronic (>30 days), and in all but one of these patients the clinical picture also was severe, with malnutrition requiring long‐term TPN, or serious dehydration. Severe combined immune deficiency (SCID) diagnosis was associated with chronic symptoms of NV infection (OR 30.3, CI 2.5‐368).

Conclusion

NV is an important pathogen in the HSCT setting, although the infection seems to be mild in most patients. Increased knowledge is needed to further identify risk factors for a severe course of NV infection in HSCT patients.
Factors and outcomes in association with sepsis differ between simultaneous pancreas/kidney and single kidney transplant recipients
Authors: Schachtner Thomas , Zaks Marina , Otto Natalie M. , Kahl Andreas , Reinke Petra
Published: January 2018

Background

As immunosuppressive therapy has improved in simultaneous pancreas/kidney transplant recipients (SPKTRs), infection has become the major limitation of disease‐free survival.

Methods

We studied all SPKTRs and deceased‐donor kidney transplant recipients (KTRs) between 2003 and 2015. Thirty‐six of 134 SPKTRs (26.9%) were diagnosed with sepsis among which 13/36 SPKTRs (36.1%) developed severe sepsis/septic shock. A control group of 98 SPKTRs without sepsis and 61/538 KTRs (11.3%) with sepsis were used for comparison.

Results

Among SPKTRs, female sex, low BMI, CMV seronegativity, CMV disease, and acute cellular rejection increased the risk for sepsis (P < .05). Patient and allograft survival was comparable among SPKTRs with and without sepsis (P > .05), but showed inferior kidney allograft function (P < .05). While urosepsis was less common among SPKTRs (45%), pneumonia (33%) and peritonitis (15%) as site of infections were more frequent (P < .05). Here, gram‐positive and fungal sepsis were more common among SPKTRs compared to KTRs (P < .05). SPKTRs showed a higher incidence and an earlier onset of sepsis compared to KTRs (P < .001). SPKTRs with severe sepsis/septic shock were more likely to show pneumonia as site of infection with gram‐positive/polymicrobial bacteremia (P < .05). Mortality from severe sepsis was 29% among SPKTRs compared to 58% among KTRs (P < .05).

Conclusion

Differences in incidence, site, causative pathogens, and onset of sepsis between SPKTRs and KTRs may be attributed to more intense immunosuppression, major surgery, and complications of diabetes among SPKTRs. Lower sepsis‐related mortality may reflect younger age and more timely diagnosis, but also supports recent findings of less sepsis‐related mortality among recipients of solid organ transplantation.
Impact of electronic health record‐based, pharmacist‐driven valganciclovir dose optimization in solid organ transplant recipients
Authors: Hensler David , Richardson Chad L. , Brown Joslyn , Tseng Christine , DeCamp Phyllis J. , Yang Amy , Pawlowski Anna , Ho Bing , Ison Michael G.
Published: January 2018

Background

Prophylaxis with valganciclovir reduces the incidence of cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under‐dosing of valganciclovir is associated with an increased risk of CMV infection and development of ganciclovir‐resistant CMV.

Methods

An automated electronic health record (EHR)‐based, pharmacist‐driven program was developed to optimize dosing of valganciclovir in solid organ transplant recipients at a large transplant center. Two cohorts of kidney, pancreas‐kidney, and liver transplant recipients from our center pre‐implementation (April 2011‐March 2012, n = 303) and post‐implementation of the optimization program (September 2012‐August 2013, n=263) had demographic and key outcomes data collected for 1 year post‐transplant.

Results

The 1‐year incidence of CMV infection dropped from 56 (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI 1.06‐2.60, P = .027) for the pre‐implementation group after adjusting for potential confounders. The program also resulted in a numerical reduction in the number of ganciclovir‐resistant CMV cases (2 [0.7%] pre‐implementation vs 0 post‐implementation).

Conclusions

An EHR‐based, pharmacist‐driven valganciclovir dose optimization program was associated with reduction in CMV infections.
Targeted recruitment of male donors for allogeneic haematopoietic cell transplantation: A review of the evidence
Authors: Fingrut W. , Rikhraj K. , Allan D.
Published: January 2018

Many patients in need of a haematopoietic cell transplant cannot find a suitable HLA‐compatible donor within their families and rely on volunteers who have registered as haematopoietic stem cell donors with a stem cell donor registry. Transplant physicians mostly prefer male donors for their patients when multiple donor options exist, and organizations recruiting donors are actively targeting males in their recruitment efforts. However, significant recruitment of female donors continues worldwide and appears to be increasing. In this review, the evidence underlying transplant physician preference for male donor selection is summarized. The review will inform donor recruitment organizations contemplating a change in strategy to target potential male registrants and will equip donor recruitment staff and volunteers with a resource to better understand their recruitment efforts.
Corruption Prevention and Economic Growth: A Mediating Effect of Rule of Law
Authors: Hongdao Qian , Mumtaz Ayesha , Mukhtar Hamid , Saleem Hafiz Abdul Rahman , Azam Sonia
Published: January 2018

This article is based on the mediating effect of rule of law between control of corruption and economic growth in China. Many empirical studies have been conducted on the relationship of corruption with economic growth, income, democracy, education, employment rate and the likes. Most of them are based on linear relationship and evaluate the impact of corruption and corruption prevention on different economic and social variables. But the study under consideration is focusing upon the role of rule of law in control of corruption and economic growth in China. It puts forth a question that what kind of effects rule of law put on economic growth and corruption prevention. The top seven economies of the world have been selected and data has been extracted from the Worldwide Governance indicators of the World Bank. In order to address the above question, the study was divided into two major parts. First, the author has applied regression analyses to see the relationship among the economic growth, rule of law and corruption; and also the impact of economic growth and control of corruption on rule of law. Then, mediation analysis has been conducted to see if rule of law plays a role in control of corruption and economic growth. The results show that economic growth significantly improve the level of control of corruption and rule of law plays a partial intermediary role in the process of economic development to enhance the corruption prevention. Second, the author has discussed the condition of rule of law and corruption in the era of the current leader, Xi Jinping and before 2012.
Defining the Barriers to Women Publishing in High-Impact Journals
Authors: Overbaugh Julie
Published: January 2018

Publications are an important measure of success in science, and publications in top-tier journals are often highly prized for that reason. This commentary describes gender differences in publication of HIV-related papers that raise questions about best practices in this important aspect of science. Data are needed in cases where there are differences in the publication rates of manuscripts with female versus male senior authors so that approaches that best support diversity in science can be defined.
Lanthanide-Dependent Regulation of Methylotrophy in Methylobacterium aquaticum Strain 22A
Authors: Masuda Sachiko , Suzuki Yutaka , Fujitani Yoshiko , Mitsui Ryoji , Nakagawa Tomoyuki , Shintani Masaki , Tani Akio
Published: January 2018

Lanthanides have been considered unimportant for biological processes. In methylotrophic bacteria, however, a methanol dehydrogenase (MDH) encoded by
xoxF
was recently found to be lanthanide dependent, while the classic-type
mxaFI
is calcium dependent. XoxF-type MDHs are more widespread in diverse bacterial genera, suggesting their importance for methylotrophy.
Methylobacterium
species, representative methylotrophic and predominating alphaproteobacteria in the phyllosphere, contain both types and regulate their expression depending on the availability of lanthanides. RNA-seq analysis showed that the regulation takes place not only for MDH genes but also the subsequent formaldehyde oxidation pathways and respiratory chain, which might be due to the direct oxidation of methanol to formate by XoxF. In addition, a considerable number of genes of unknown function, including AT-rich genes, were found to be upregulated in the presence of lanthanides. This study provides first insights into the specific reaction of methylotrophic bacteria to the presence of lanthanides, emphasizing the biological relevance of this trace metal.
Is the association between health-related quality of life and fatigue mediated by depression in patients with multiple sclerosis? A Spanish cross-sectional study
Authors: Fernández-Muñoz Juan J , Cigarán-Méndez Margarita , Navarro-Pardo Esperanza , Pérez-de-Heredia-Torres Marta , Parás-Bravo Paula , Fernández-de-las-Peñas César
Published: January 2018

Objectives

To determine the mediating effects of depression on health-related quality of life and fatigue in individuals with multiple sclerosis (MS).

Design

A cross-sectional study.

Setting

Tertiary urban hospital.

Participants

One hundred and eight patients (54% women) with MS participated in this study.

Outcome measures

Demographic and clinical data (weight, height, medication and neurological impairment), fatigue (Fatigue Impact Scale), depression (Beck Depression Inventory-II) and health-related quality of life (Short-Form Health Survey 36) were collected.

Results

Fatigue was significantly associated with bodily pain, physical function, mental health and depression. Depression was associated with bodily pain and mental health. The path analysis found direct effects from physical function, bodily pain and depression to fatigue (all, P<0.01). The path model analysis revealed that depression exerted a mediator effect from bodily pain to fatigue (B=−0.04, P<0.01), and from mental health to fatigue (B=−0.16, P<0.01). The amount of fatigue explained by all predictors in the path model was 37%.

Conclusions

This study found that depression mediates the relationship between some health-related quality of life domains and fatigue in people with MS. Future longitudinal studies focusing on proper management of depressive symptoms in individuals with MS will help determine the clinical implications of these findings.
Mouse models of lupus: what they tell us and what they don’t
Authors: Richard Mara Lennard , Gilkeson Gary
Published: January 2018

Lupus is a complex heterogeneous disease characterised by autoantibody production and immune complex deposition followed by damage to target tissues. Animal models of human diseases are an invaluable tool for defining pathogenic mechanisms and testing of novel therapeutic agents. There are perhaps more applicable murine models of lupus than any other human disease. There are spontaneous models of lupus, inducible models of lupus, transgenic-induced lupus, gene knockout induced lupus and humanised mouse models of lupus. These mouse models of lupus have contributed significantly to our knowledge of the pathogenesis of lupus and served as valuable preclinical models for proof of concept for new therapies. Despite their utility, mouse models of lupus have their distinct limitations. Although similar, mouse and human immune systems are different and thus one cannot assume a mechanism for disease in one is translatable to the other. Efficacy and toxicity of compounds can vary significantly between humans and mice, also limiting direct translation. Finally, the heterogeneous aspects of human lupus, both in clinical presentation, underlying pathogenesis and genetics, are not completely represented in current mouse models. Thus, proving a therapy or mechanism of disease in one mouse model is similar to proving a mechanism/therapy in a limited subset of human lupus. These limitations, however, do not marginalise the importance of animal models nor the significant contributions they have made to our understanding of lupus.
Investigation of the push–pull effects on β-functionalized zinc porphyrin coordinated to C60 donor–acceptor conjugates
Authors: Thomas Michael B. , Jindasa R.G. Waruna , Hu Yi , Schmitz Benjamin , Wang Hong , D’Souza Francis
Published: January 2018

Two novel β-functionalized push–pull zinc porphyrins with amine or phenyl push-groups and cyclic imide or carboxylic esters pull-groups have been newly synthesized for light energy harvesting applications. The ethynylphenyl spacers extended the conjugation of the porphyrin π-systems, as reflected by their red-shifted absorbance and fluorescence spectra. Computational studies performed at the B3LYP/6-31G* level indicated no steric hindrance between the porphyrin π-system and the substituents. The calculated HOMO and LUMO orbitals displayed significant delocalization in 1, where the electron density in the HOMO was localized over the push groups, whereas the LUMO was extended over the porphyrin π- and pull-groups. On the other hand, 2 did not display significant orbital segregation, which is attributed to its weaker push–pull character. Electrochemical studies revealed smaller HOMO–LUMO gaps for the push–pull zinc porphyrins. As a consequence of the push–pull effects, reduction in fluorescence intensity and lifetime was observed. Femtosecond transient absorption spectral studies revealed successful formation of singlet excited state in both of the push–pull porphyrins. Donor–acceptor conjugates were subsequently built and characterized by coordinating an electron acceptor, C60Im, via metal–ligand axial coordination. Efficient photo-induced charge separation in both donor–acceptor conjugates was witnessed wherein the charge-separated states persisted tens of nanoseconds prior returning to the ground state.