bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term surveillance biopsy: Is it necessary after pediatric heart transplant?
Authors: Peng David M. , Ding Victoria Y. , Hollander Seth A. , Khalapyan Tigran , Dykes John C. , Rosenthal David N. , Almond Christopher S. , Sakarovitch Charlotte , Desai Manisha , McElhinney Doff B.
Published: December 2018

Due to limited and conflicting data in pediatric patients, long‐term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB‐detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2 year of post‐HT biopsy data were reviewed for RSB‐detected rejections occurring >2 year post‐HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan‐Meier freedom from rejection rates by patient characteristics and used the log‐rank test to assess differences in rejection probabilities. We identified the best‐fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB‐detected rejection >2 year post‐HT. The overall empirical rate of RSB‐detected rejection >2 year post‐HT was 2.9/100 patient‐years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR = 0.98; 95% CI 0.78‐1.23; P = 0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB‐detected rejection under multivariable Cox analysis (P = 0.008). Most pediatric patients did not have RSB‐detected rejection beyond 2 years post‐HT, and the majority of those who did were older at time of HT. Indiscriminate long‐term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection.
Increased virulence of Globodera pallida during repeated rearing on different resistant potato cultivars explained by a simple model
Authors: Beniers J. E. , Nöllen Y. , van Eck H. J. , Schouten H. J.
Published: December 2018

Selection for virulence of Globodera pallida on potato cultivars was studied for four generations under controlled conditions. The reproduction rate (Pf/Pi) of a mixed Pa2/3 population increased by a factor of 61 during rearing on the partially resistant potato cv. Darwina compared to rearing on the susceptible cv. Irene. This was a result of selection for virulence on cv. Darwina, and achieving the Hardy–Weinberg equilibrium on cv. Irene. Increased virulence also significantly raised the reproduction rate on several other Solanum genotypes. These changes could be explained reasonably well by the monogenic inheritance of a virulence factor breaking the Grp1 locus. The virulence changes were probably mainly evoked by this gene only, inherited from S. vernei 1‐3 or S. vernei 24/20. The Grp1 locus has probably provided the differential S. vernei hybrid (VTn)2 62‐33‐3 with its resistance to the Pa2 group and not to the Pa3 group. Alternation of cultivars did not halt selection if the cultivars highly differentiated between the Pa2 and Pa3 populations. Only when alternation was with cultivars that harboured a different resistance gene against Pa3 was selection for virulence delayed. Differences in virulence levels (i.e. reproduction rates) within the nematode population determined the rate of selection, not the resistance level itself. Selection of a Pa3 population for three generations on cv. Karakter not only increased the reproduction rate on cv. Karakter itself by a factor 4.2, but also raised the reproduction on other potato genotypes. A simple monogenic model could explain these changes in virulence.
Chronic granulamatous disease: Two decades of experience from a paediatric immunology unit in a country with high rate of consangineous marriages
Authors: Kutukculer Necil , Aykut Ayca , Karaca Neslihan E. , Durmaz Asude , Aksu Guzide , Genel Ferah , Pariltay Erhan , Cogulu Özgür , Azarsız Elif
Published: December 2018

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X‐linked recessive (XR‐CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR‐CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane‐bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive‐AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow‐up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.
Monoclonal antibody against human Tim‐3 enhances antiviral immune response
Authors: Li Ge , Hou Chunmei , Dou Shuaijie , Zhang Jiacheng , Zhang Yanling , Liu Yiqiong , Wang Zhiding , Xiao He , Wang Renxi , Chen Guojiang , Li Yan , Feng Jiannan , Shen Beifen , Han Gencheng
Published: December 2018

T cell immunoglobulin and mucin domain protein 3 (Tim‐3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim‐3 is related to immune exhaustion in tumour and viral infection. To overcome Tim‐3‐mediated immune tolerance, we developed a novel monoclonal antibody against human Tim‐3 (L3G) and investigated its roles in inhibiting Tim‐3 signalling and overcoming immune tolerance in T cells and monocytes/macrophages. The administration of L3G to cultured peripheral blood mononuclear cells (PBMCs) significantly increased the production of IFN‐γ and IL‐2 and the expression of type I interferon. The administration of L3G also increased the production of IFN‐γ, IL‐8 and type I interferon in U937 cells and primary monocytes. We investigated the mechanisms by which L3G enhances pro‐inflammatory cytokine expression, and our data show that L3G enhances STAT1 phosphorylation in both monocytes/macrophages and T cells. Finally, in an H1N1 infection model of PBMCs and U937 cells, L3G decreased the viral load and enhanced the expression of interferon. Thus, we developed a functional antibody with therapeutic potential against Tim‐3‐mediated infection tolerance.
Emerging role of stem cell memory‐like T cell in immune thrombocytopenia
Authors: Cao Jiang , Zhang Changxiao , Han Xiao , Cheng Hai , Chen Wei , Qi Kunming , Qiao Jianlin , Sun Zengtian , Wu Qingyun , Zeng Lingyu , Niu Mingshan , Li Li , Xu Kailin
Published: December 2018

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by autoantibody‐mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T‐lymphocyte dysfunctions. Increasing studies have indicated that stem cell memory‐like T cell (TSCM) plays an important role in the development of multiple autoimmune diseases. This study aimed to explore the clinical correlation between the TSCM subset and ITP. The percentages of peripheral blood naïve T cells (TNs), TSCMs, central memory T cells (TCMs), effector memory T cells (TEMs) and effector T cells (TEs) among CD4+ and CD8+ T cells in 20 ITP patients before and after treatment were detected using flow cytometry. Our results showed that the percentages of peripheral blood CD4+ and CD8+ T cells in ITP patients were imbalanced. The percentage of CD8+ TSCMs in peripheral blood before treatment in ITP patients was significantly higher than that in healthy controls, whereas the percentages of the other T cell subsets did not exhibit significant differences. Our study further analysed the correlation between the change in the percentage of CD8+ TSCMs and the treatment efficacy. The results showed that the percentage of peripheral blood CD8+ TSCMs in ITP patients after glucocorticoid treatment significantly decreased and the changes of the percentages of CD8+ TSCMs before and after treatment in complete response (CR) and response (R) patients were obvious. Our finding showed that the imbalance of the percentage of CD8+ TSCMs might be involved in the development of ITP and might serve as a novel indicator of efficacy.
Oil Discovery, Political Institutions and Economic Diversification
Authors: Alsharif Nouf , Bhattacharyya Sambit
Published: December 2018

Diversification is touted as a desirable policy objective for oil‐rich nations because it reduces exposure to volatility. However, the empirical relationship between petroleum and diversification is not well understood. Here, we test the effect of giant oil discoveries on diversification using a panel dataset of 136 countries observed over the period from 1962 to 2012. We notice non‐oil sector export concentration 8 years after a discovery. However, we do not observe any effect on the structure of employment in non‐resource and manufacturing sectors. Democratic political institutions moderate the export and employment concentration effects of petroleum discovery.
HIV, HCMV and mycobacterial antibody levels: a cross‐sectional study in a rural Ugandan cohort
Authors: Stockdale Lisa , Nash Stephen , Nalwoga Angela , Gibson Lorna , Painter Hannah , Raynes John , Asiki Gershim , Newton Robert , Fletcher Helen
Published: December 2018

Objectives

A growing evidence base implicates human cytomegalovirus (HCMV) as a risk factor for TB disease. We investigated total IgG and mycobacteria‐specific antibodies in a cross‐sectional study nested within a rural Ugandan General Population Cohort (GPC), in relation to HIV infection and the magnitude of HCMV IgG response.

Methods

Sera from 2189 individuals (including 27 sputum‐positive TB cases) were analysed for antibodies against mycobacteria (Ag85A, PPD, LAM, ESAT6/CFP10) and HCMV, tetanus toxoid (TT) and total IgG.

Results

Anti‐mycobacterial antibodies increased with age until approximately 20 years, when they plateaued. Higher HCMV exposure (measured by IgG) was associated with lower levels of some anti‐mycobacterial antibodies, but no increase in total IgG. HIV infection was associated with a decrease in all anti‐mycobacterial antibodies measured and with an increase in total IgG.

Conclusions

The increase in anti‐mycobacterial antibodies with age suggests increasing exposure to non‐tuberculous mycobacteria (NTM), and to M.tb itself. HIV infection is associated with decreased levels of all mycobacterial antibodies studied here, and high levels of HCMV IgG are associated with decreased levels of some mycobacterial antibodies. These findings point towards the importance of humoral immune responses in HIV/TB co‐infection and highlight a possible role of HCMV as a risk factor for TB disease.
Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency
Authors: Simon Toby L. , FitzGerald Peter , Kühne Mirjam , Farrar Connie , Knowles Jonathan , Bycholski Keith , Zenker Othmar
Published: December 2018

BACKGROUND

To ensure that immunoglobulin (Ig) products have adequate functional antibody, the US Food and Drug Administration (FDA) requires that Ig lots contain minimum levels of measles neutralizing antibody; the current minimum is 0.48 x US Reference Ig 176.

STUDY DESIGN AND METHODS

In the first part of the study, measles antibody titers were measured in donor plasma samples collected in 2007, 2011, and 2017. In the second part, trough or steady‐state serum levels of measles neutralizing antibody were measured in two studies of patients with primary immunodeficiency (PID) who were treated with intravenous (Study 1; N = 46) or subcutaneous (Study 2; N = 18) Ig replacement therapy, meeting previous requirements for lot potency (≥0.6 x US Reference Ig 176). Serum measles neutralizing antibody titers were then estimated for conditions in which the potency of the Ig replacement product was 0.48 or 0.30 x US Reference Ig 176.

RESULTS

Measles antibody titers in donated plasma samples declined in donors born after 1963. In the two studies of patients with PID who were treated with intravenous or subcutaneous Ig replacement therapy, all patients exhibited trough (intravenous Ig) or steady‐state (subcutaneous Ig) measles neutralizing antibody titers above 0.12 IU/mL, which has been shown to protect against clinical measles in the general population. Estimates suggest that all patients except one would have continued to meet this standard if the Ig lot potency had been 0.48 or 0.30 x US Reference Ig 176.

CONCLUSION

These studies provide supporting evidence that the lot release specification can be safely lowered from 0.48 to 0.30 x US Reference Ig 176, which will accommodate declining measles neutralizing antibody levels in donor plasma.
Estimating the revenue costs of tax treaties in developing countries
Authors: Janský Petr , Šedivý Marek
Published: December 2018

(12764) Petr Janský Marek Šedivý Tax treaties between countries influence how much tax revenues governments receive from multinational enterprises. These treaties often reduce the withholding tax rates on outgoing dividend and interest payments. We provide illustrative estimates of costs for these two taxes for 14 developing countries in sub‐Saharan Africa and Asia in a first multi‐country comparison of this kind. These might be overestimates because we assume that foreign direct investments are not influenced by the tax treaties. We estimate that the highest potential tax revenue losses are within hundreds of millionsUS$and around 0.1% ofGDP, with Philippines incurring the highest losses both inUS$and relative toGDP. We also find that around 95% of the losses is due to dividends and that only four investor countries—Japan, Netherlands, Switzerland and Singapore—are together responsible for more than half of the losses. We discuss the limitations of these estimates and how future research could improve their quality as well as coverage.
Competitive pressure, innovation and trade protection: Evidence from US patent data
Authors: Liebman Benjamin H. , Reynolds Kara M.
Published: December 2018

Recent theoretical models have suggested that the relationship between competition and innovation may best be characterised as an inverted‐U shape: firms in industries with low levels of competition are more likely to innovate in the wake of increased competition as they attempt to escape competition, while those in highly competitive industries will decrease innovation in the wake of increased competition as the profit incentive to innovate dissipates. Results from other studies have found positive as well as negative relationships between innovation and competition. In a parallel literature, trade economists have produced conflicting results regarding the impact of trade liberalisation on innovation. One stream of research has shown that increased access to imported intermediate goods increases productivity, suggesting a positive relationship between imports and innovation. Others have hypothesised that firms may use the technology embodied in intermediate inputs as a substitute for domestic innovation. In this paper, we merge these divergent literatures and investigate whether innovation, as measured by the production of patents by US manufacturers, has been impacted by market competition and tariff reductions. Our empirical findings indicate that insulation from imports in the form of higher tariffs on final goods was associated with innovation until the late 1980s, while falling tariffs on intermediate goods appear to have facilitated innovation during the 1990s. We also find evidence of the inverted U‐shaped relationship between market competition and innovation.
When Sports Challenge Authority: A Case Study of Gatekeeping During the 2017 Chinese Ping-Pong Boycott
Authors: Xu Qingru , Billings Andrew C.
Published: December 2018

At the World Tour Platinum China Open in 2017, 3 leading Chinese table tennis players and two coaches withdrew from the Games to protest the sudden removal of Head Coach Liu Guoliang, triggering unprecedented public uproar online. Applying gatekeeping theory, this study explored how mainland Chinese media controlled information flow during the crisis. A thematic analysis uncovered 3 primary gatekeeping behaviors: repetition, selection, and manipulation. Findings suggest that the party-state, not media institutions, was the dominant gatekeeper in mainland China. The Chinese media system and sports system were both subject to strict government control during a crisis that challenged authority.
Examining the Sport Daily Deal: An Assessment Across Industry Segments
Authors: Cianfrone Beth A. , Braunstein-Minkove Jessica R. , Tavormina Alyssa L.
Published: December 2018

Sport executives concerned with maximizing ticket sales often explore different communication channels to reach potential consumers. Advertising and selling discounted tickets through daily deals (e.g., Groupon and Living Social) is an increasingly popular method, yet there is little research on the extent to which sport organizations are using daily deals. A mixed-method design was employed to examine sport organizations’ use of daily deals, including how sport daily deals are most commonly used and the rationale for their use. In Phase 1, a content analysis of Groupon and LivingSocial daily deals e-mailed over 31 days in 11 U.S. cities provided a framework for exploring the types, frequency, and characteristics of sport ticketing deals. In Phase 2, the perspectives of 7 sport-organization executives served as guiding metrics in developing a deeper understanding of daily-deal usage. Findings can inform sport marketers’ ticketing and promotional strategies and provide a basis for theoretical daily-deal application.
Breakdown of the Stokes-Einstein relation above the melting temperature in a liquid phase-change material
Authors: Wei Shuai , Evenson Zach , Stolpe Moritz , Lucas Pierre , Angell C. Austen
Published: December 2018

Failure of classic equation linking diffusion and viscosity points to new thinking on switch kinetics of phase-change materials.
Cavity quantum-electrodynamical polaritonically enhanced electron-phonon coupling and its influence on superconductivity
Authors: Sentef M. A. , Ruggenthaler M. , Rubio A.
Published: December 2018

Cavity photons can enhance the coupling between electrons and lattice vibrations and affect important properties of 2D materials.
Intrinsic properties of human germinal center B cells set antigen affinity thresholds
Authors: Kwak Kihyuck , Quizon Nicolas , Sohn Haewon , Saniee Avva , Manzella-Lapeira Javier , Holla Prasida , Brzostowski Joseph , Lu Jinghua , Xie HengYi , Xu Chenguang , Spillane Katelyn M. , Tolar Pavel , Pierce Susan K.
Published: December 2018

Human germinal center B cells are intrinsically designed for optimal affinity-based selection.
Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Reactivation
Authors: Papp Bernadett , Motlagh Naeem , Smindak Richard J. , Jin Jang Seung , Sharma Aria , Alonso Juan D. , Toth Zsolt
Published: December 2018

The lytic cycle of KSHV is involved not only in the dissemination of the virus but also viral oncogenesis, in which the effect of RTA on the host transcriptome is still unclear. Using genomics approaches, we identified a core set of host genes which are rapidly and directly induced by RTA in the early phase of KSHV lytic reactivation. We found that RTA does not need viral cofactors but requires its host cofactor RBP-Jκ for inducing many of its core RIGs. Importantly, we show a critical role for two of the core RIGs in efficient lytic reactivation and replication, highlighting their significance in the KSHV lytic cycle. We propose that the unbiased identification of RTA-induced host genes can uncover potential therapeutic targets for inhibiting KSHV replication and viral pathogenesis.
Appraisal of a scoring instrument for training and testing neonatal intubation skills
Authors: Bouwmeester Romy N , Binkhorst Mathijs , Yamada Nicole K , Geurtzen Rosa , van Heijst Arno F J , Halamek Louis P , Draaisma Jos M T , Hogeveen Marije
Published: December 2018

Objective

To determine the validity, reliability, feasibility and applicability of a neonatal intubation scoring instrument.

Design

Prospective observational study.

Setting

Simulation-based research and training centre (Center for Advanced Pediatric and Perinatal Education), California, USA.

Subjects

Forty clinicians qualified for neonatal intubation.

Interventions

Videotaped elective intubations on a neonatal patient simulator were scored by two independent raters. One rater scored the intubations twice. We scored the preparation of equipment and premedication, intubation performance, tube position/fixation, communication, number of attempts, duration and successfulness of the procedure.

Main outcome measures

Intraclass correlation coefficients (ICC) were calculated for intrarater and inter-rater reliability. Kappa coefficients for individual items and mean kappa coefficients for all items combined were calculated. Construct validity was assessed with one-way analysis of variance using the hypothesis that experienced clinicians score higher than less experienced clinicians. The approximate time to score one intubation and the instrument’s applicability in another setting were evaluated.

Results

ICCs for intrarater and inter-rater reliability were 0.99 (95% CI 0.98 to 0.99) and 0.89 (95% CI 0.35 to 0.96), and mean kappa coefficients were 0.93 (95% CI 0.85 to 1.01) and 0.71 (95% CI 0.56 to 0.92), respectively. There were no differences between the more and less experienced clinicians regarding preparation, performance, communication and total scores. The experienced group scored higher only on tube position/fixation (p=0.02). Scoring one intubation took approximately 15 min. Our instrument, developed in The Netherlands, could be readily applied in the USA.

Conclusions

Our scoring instrument for simulated neonatal intubations appears to be reliable, feasible and applicable in another centre. Construct validity could not be established.
How to use… iron studies
Authors: Hanna Martin , Fogarty Michael , Loughrey Clodagh , Thompson Anthony , Macartney Christine , Thompson Andrew , McNaughten Ben
Published: December 2018

Iron studies are frequently requested in paediatric practice. They are useful both as a diagnostic tool and as a way of monitoring certain conditions, particularly those causing iron overload. This article outlines the physiology of iron metabolism and discusses laboratory aspects of performing iron studies, including factors influencing interpretation. Clinical scenarios are used to highlight how the tests can be used in different clinical situations.
Type 3 neovascularisation (retinal angiomatous proliferation) treated with antivascular endothelial growth factor: real-world outcomes at 24 months
Authors: Invernizzi Alessandro , Teo Kelvin , Nguyen Vuong , Daniell Mark , Squirrell David , Barthelmes Daniel , Gillies Mark C
Published: December 2018

Aims

To compare 24 months outcomes of eyes with retinal angiomatous proliferations (RAPs) treated with antivascular endothelial growth factor (anti-VEGF) with a group of controls diagnosed with other neovascular age-related macular degeneration (nAMD) subtypes in a real-world setting.

Methods

Treatment-naïve nAMD eyes that commenced anti-VEGF between January 2006 and November 2015 were identified from a registry of nAMD treatment outcomes. Cases were defined as eyes diagnosed with RAP. Three controls per case were selected among nAMD eyes with non-RAP lesions and matched on baseline visual acuity (VA), year of treatment initiation, anti-VEGF agent first injected and follow-up. Baseline VA was compared with 12 and 24 months VA. Change in VA, number of injections received, proportion of visits with active nAMD and time to first inactivation were compared between RAPs and controls.

Results

157 RAPs and 469 controls were included. Baseline VA (mean (SD)) increased at 12 months (61.4 (15.5) vs 68.7 (14.7) letters, p<0.001) and remained higher (66.6 (17.3) letters) at 24 months (p<0.001) in RAPs. The change from baseline VA (mean(95% CI)) was significantly higher in RAPs than in controls at 12 months (7.3 (5.4 to 9.1) vs 4.1 (2.8 to 5.4) letters, p=0.01) and at 24 months (5.1 (2.8 to 7.3) vs 2.5 (1 to 4) letters, p=0.056). Both groups received a median of 13 injections. RAPs inactivated earlier and were less active than controls (both p<0.001).

Conclusions

RAPs responded well to anti-VEGF, with a significant improvement in VA persisting at 24 months. RAPs had better visual outcomes than controls at 12 and 24 months, tended to inactivate earlier and were less active throughout 2 years follow-up.
Core temperature up to 41.5ºC during the UCI Road Cycling World Championships in the heat
Authors: Racinais Sebastien , Moussay Sebastien , Nichols David , Travers Gavin , Belfekih Taoufik , Schumacher Yorck Olaf , Periard Julien D
Published: December 2018

Objective

To characterise the core temperature response and power output profile of elite male and female cyclists during the 2016 UCI Road World Championships. This may contribute to formulating environmental heat stress policies.

Methods

Core temperature was recorded via an ingestible capsule in 10, 15 and 15 cyclists during the team time trial (TTT), individual time trial (ITT) and road race (RR), respectively. Power output and heart rate were extracted from individual cycling computers. Ambient conditions in direct sunlight were hot (37°C±3°C) but dry (25%±16% relative humidity), corresponding to a wet-bulb globe temperature of 27°C±2°C.

Results

Core temperature increased during all races (p<0.001), reaching higher peak values in TTT (39.8°C±0.9°C) and ITT (39.8°C±0.4°C), relative to RR (39.2°C±0.4°C, p<0.001). The highest temperature recorded was 41.5°C (TTT). Power output was significantly higher during TTT (4.7±0.3 W/kg) and ITT (4.9±0.5 W/kg) than RR (2.7±0.4 W/kg, p<0.001). Heart rate increased during the TTs (p<0.001) while power output decreased (p<0.001).

Conclusion

85% of the cyclists participating in the study (ie, 34 of 40) reached a core temperature of at least 39°C with 25% (ie, 10 of 40) exceeding 40°C. Higher core temperatures were reached during the time trials than the RR.
The impact of reducing dietary aflatoxin exposure on child linear growth: a cluster randomised controlled trial in Kenya
Authors: Hoffmann Vivian , Jones Kelly , Leroy Jef L
Published: December 2018

Introduction

Observational studies have documented an association between aflatoxin (AF) exposure and reduced linear growth in infants and young children. Our objective was to assess the effectiveness of reducing AF exposure on child linear growth and serum AF levels in rural areas in Eastern Kenya.

Methods

A cluster randomised controlled design was used (28 intervention and 28 control clusters). The intervention arm received a swapping (contaminated maize was replaced with safe maize) and a stockist intervention (households were encouraged to purchase from a stockist supplied with clean maize). Women in the fifth to final month of pregnancy were invited to enrol in the study. Outcomes were child length-for-age Z-score (LAZ), the prevalence of stunting and child serum AFB1-lysine adduct level 24 (endline, primary outcomes) and 11 to 19 months (midline, secondary outcomes) after trial commencement, respectively. The trial was registered with socialscienceregistry.org.

Results

Of the 1230 unborn children enrolled in the study, 881 (72%) were included in the LAZ and 798 (65%) in the serum AFB1analysis. The intervention significantly reduced endline ln serum AFB1-lysine adduct levels (intervention effect—0.273, 95% CI −0.547 to 0.001; one-sided p=0.025), but had no effect on endline LAZ or stunting (mean LAZ at endline was −1.64). At midline, the intervention increased LAZ by 0.16 (95% CI −0.009 to 0.33; one-sided p=0.032) and reduced stunting by seven percentage points (95% CI −0.125 to −0.007; one-sided p=0.015), but had no impact on serum AFB1levels.

Conclusion

Improving access to AF-free maize substantially reduced endline serum AF, but had no effect on child linear growth. The midline analysis suggests that AF may affect linear growth at younger ages.

Trial registration number

AEARCTR-0000105.
What is the minimum number of specialist anaesthetists needed in low-income and middle-income countries?
Authors: Davies Justine I , Vreede Eric , Onajin-Obembe Bisola , Morriss Wayne W
Published: December 2018

Introduction

The number of specialist anaesthetists in most low-income and middle-income countries is below what is needed to provide a safe quality anaesthesia service. There are no estimates of the optimal number; therefore, we estimated the minimum density of specialist anaesthetists to achieve a reasonable standard of healthcare as indicated by the maternal mortality ratio (MMR).

Methods

Utilising existing country-level data of the number of physician anaesthesia providers (PAPs), MMR and Human Development Index (HDI), we developed best-fit curves to describe the relationship between MMR and PAPs, controlling for HDI. The aim was to use this relationship to estimate the number of PAPs associated with achieving the median MMR.

Results

We estimated that, in order to achieve a reasonable standard of healthcare, as indicated by the global median MMR, countries should aim to have at least four PAPs per 100 000 population. Existing data show that currently 80 countries have fewer than this number.

Conclusion

Four PAPs per 100 000 population is a modest target, but there is a need to increase training of doctors in many countries in order to train more specialist anaesthetists. It is important that this target is considered during the development of national workforce plans, even if a stepwise approach to workforce planning is chosen.
Long-term impact of community-based participatory women’s groups on child and maternal mortality and child disability: follow-up of a cluster randomised trial in rural Nepal
Authors: Heys Michelle , Gram Lu , Wade Angie , Haworth Edward James Norman , Osrin David , Sagar Khadkha , Shrestha Dej Krishna , Neupane Rishi Prasad , Adhikari Dhruba , Adhikari Ramesh Kant , Budhathoki Bharat , Manandhar Dharma , Costello Anthony
Published: December 2018

Background

Community-based women’s groups practising participatory learning and action (PLA) can reduce maternal and neonatal mortality in low-income countries. However, it is not clear whether these reductions are associated with subsequent increased or decreased rates of childhood death and disability. We assessed the impact on child deaths and disability beyond the perinatal period among participants in the earliest trial in Nepal 2001–2003.

Methods

Household interviews were conducted with mothers or household heads. At cluster and individual levels, we analysed disability using pairwise log relative risks and survival using multilevel logistic models.

Findings

From 6075 children and 6117 mothers alive at 4 weeks post partum, 44 419 children (73%) were available for interview a mean 11.5 years later. Rates of child deaths beyond the perinatal period were 36.6 and 52.0 per 1000 children in the intervention and control arms respectively. Rates of disability were 62.7 and 85.5 per 1000 children in the intervention and control arms respectively. Individual-level analysis, including random effects for cluster pairing and adjusted for baseline maternal literacy, socioeconomic status and maternal age, showed lower, statistically non-significant, odds of child deaths (OR 0.70 (95% CI 0.43 to 1.18) and disability (0.64 (0.39 to 1.06)) in the intervention arm.

Conclusion

Community-level exposure to women’s groups practising PLA did not significantly impact childhood death or disability or death beyond the perinatal period. Follow-up of other trials with larger sample sizes is warranted in order to explore the possibility of potential long-term survival and disability benefits with greater precision.
Educational intervention to reduce treatment of asymptomatic bacteriuria in long-term care
Authors: Lee Christine , Phillips Casey , Vanstone Jason Robert
Published: December 2018

Objective

To determine if an educational intervention can decrease the inappropriate antibiotic treatment of long-term care (LTC) residents with asymptomatic bacteriuria (ASB).

Design

Prospective chart audit between May and July 2017.

Setting

Seven LTC facilities in Regina, Saskatchewan, Canada.

Participants

Chart audits were performed on all LTC residents over 18 years of age with a positive urine culture. Educational sessions and tools were available to all clinical staff at participating LTC facilities.

Intervention

Fifteen-minute educational sessions were provided to LTC facility staff outlining the harms of unnecessary antibiotic use, antibiotic resistance and the diagnostic criteria of a urinary tract infection (UTI). Educational sessions were complimented with posters and pocket cards that summarised UTI diagnostic criteria.

Main outcome measure

The primary outcome measure was the number of residents who received inappropriate antibiotic treatment for ASB. Secondary outcome measures included the appropriateness of urine culture tests, number of tests and cost associated with inappropriate treatments.

Results

In the preintervention period, 172 urine culture and sensitivity (UC&S) tests were performed, 62 (36.0%) were positive and 50/62 (80.6%) residents had ASB based on chart review. In the postintervention period, 151 UC&S tests were performed, 50 (33.1%) were positive and 35/50 (70.0%) residents had ASB. There was a statistically significant decrease in the number of residents treated with antibiotics for ASB, from 45/50 (90%) preintervention to 22/35 (62.9%) postintervention (χ2=9.087, p=0.003).

Conclusions

An educational intervention was associated with a statistically significant decrease in inappropriate antibiotic treatment of LTC residents with ASB.
Use of social media to support student nurses: an EBN Twitter chat led by Daniel Gooding and Alison Twycross
Authors: Gooding Daniel , Swift Amelia
Published: December 2018

EBN engages readers through a range of Online social media activities to debate issues important to nurses and nursing. EBN Opinion papers highlight and expand on these debates.
UK’s initial operational response and specialist operational response to CBRN and HazMat incidents: a primer on decontamination protocols for healthcare professionals
Authors: Chilcott Robert P , Larner Joanne , Matar Hazem
Published: December 2018

The UK is currently in the process of implementing a modified response to chemical, biological, radiological and nuclear and hazardous material incidents that combines an initial operational response with a revision of the existing specialist operational response for ambulant casualties. The process is based on scientific evidence and focuses on the needs of casualties rather than the availability of specialist resources such as personal protective equipment, detection and monitoring instruments and bespoke showering (mass casualty decontamination) facilities. Two main features of the revised process are: (1) the introduction of an emergency disrobe and dry decontamination step prior to the arrival of specialist resources and (2) a revised protocol for mass casualty (wet) decontamination that has the potential to double the throughput of casualties and improve the removal of contaminants from the skin surface. Optimised methods for performing dry and wet decontamination are presented that may be of relevance to hospitals, as well as first responders at the scene of a chemical incident.
Psychology, risk, health and deployed military operations
Authors: Verrall Neil
Published: December 2018

This article will focus on a study by the UK Defence Science and Technology Laboratory (Dstl) which investigated the risk propensity and health behaviours of UK army personnel deployed to Iraq in 2007 as part of Op TELIC. The study addressed the concept of impulsive sensation seeking and how this interacted with health behaviours associated with alcohol, smoking, driving and sex at predeployment, during deployment and postdeployment, as well as perceptions of risk and psychological well-being. There is also a description of other deployment-related risk and health research and analysis undertaken by Dstl as part of a wider discussion on the nature of both risk and health on deployed operations.
AVPP
Authors: Orosa Lois , Azevedo Rodolfo , Mutlu Onur
Published: December 2018

Value prediction improves instruction level parallelism in superscalar processors by breaking true data dependencies. Although this technique can significantly improve overall performance, most of the state-of-the-art value prediction approaches require high hardware cost, which is the main obstacle for its wide adoption in current processors. To tackle this issue, we revisit
load
value prediction as an efficient alternative to the classical approaches that predict
all
instructions. By speculating only on loads, the pressure over shared resources (e.g., the Physical Register File) and the predictor size can be substantially reduced (e.g., more than 90% reduction compared to recent works). We observe that existing value predictors cannot achieve very high performance when speculating only on load instructions. To solve this problem, we propose a new, accurate and low-cost mechanism for predicting the values of load instructions: the Address-first Value-next Predictor with Value Prefetching (AVPP). The key idea of our predictor is to predict the load address first (which, we find, is much more predictable than the value) and to use a small non-speculative Value Table (VT)—indexed by the predicted address—to predict the value next. To increase the coverage of AVPP, we aim to increase the hit rate of the VT by predicting also the load address of a
future instance
of the same load instruction and prefetching its value in the VT. We show that AVPP is relatively easy to implement, requiring only 2.5% of the area of a 32KB L1 data cache. We compare our mechanism with five state-of-the-art value prediction techniques, evaluated within the context of load value prediction, in a relatively narrow out-of-order processor. On average, our AVPP predictor achieves 11.2% speedup and 3.7% of energy savings over the baseline processor, outperforming
all
the state-of-the-art predictors in 16 of the 23 benchmarks we evaluate. We evaluate AVPP implemented together with different prefetching techniques, showing additive performance gains (20% average speedup). In addition, we propose a new taxonomy to classify different value predictor
policies
regarding predictor update, predictor availability, and in-flight pending updates. We evaluate these policies in detail.
IFNγ-Induced IFIT5 Promotes Epithelial-to-Mesenchymal Transition in Prostate Cancer via miRNA Processing
Authors: Lo U-Ging , Pong Rey-Chen , Yang Diane , Gandee Leah , Hernandez Elizabeth , Dang Andrew , Lin Chung-Jung , Santoyo John , Ma Shihong , Sonavane Rajni , Huang Jun , Tseng Shu-Fen , Moro Loredana , Arbini Arnaldo A. , Kapur Payal , Raj Ganesh V. , He Dalin , Lai Chih-Ho , Lin Ho , Hsieh Jer-Tsong
Published: December 2018

IFNγ, a potent cytokine known to modulate tumor immunity and tumoricidal effects, is highly elevated in patients with prostate cancer after radiation. In this study, we demonstrate that IFNγ can induce epithelial-to-mesenchymal transition (EMT) in prostate cancer cells via the JAK–STAT signaling pathway, leading to the transcription of IFN-stimulated genes (ISG) such as IFN-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor miRNAs (pre-miRNA) that includes pre-miR-363 from the miR-106a-363 cluster as well as pre-miR-101 and pre-miR-128, who share a similar 5′-end structure with pre-miR-363. These suppressive miRNAs exerted a similar function by targeting EMT transcription factors in prostate cancer cells. Depletion of IFIT5 decreased IFNγ-induced cell invasiveness in vitro and lung metastasis in vivo. IFIT5 was highly elevated in high-grade prostate cancer and its expression inversely correlated with these suppressive miRNAs. Altogether, this study unveils a prometastatic role of the IFNγ pathway via a new mechanism of action, which raises concerns about its clinical application.

Significance: A unique IFIT5–XRN1 complex involved in the turnover of specific tumor suppressive microRNAs is the underlying mechanism of IFNγ-induced epithelial-to-mesenchymal transition in prostate cancer.

See related commentary by Liu and Gao, p. 1032
Leveraging the Electronic Health Record to Create an Automated Real‐Time Prognostic Tool for Peripheral Arterial Disease
Authors: Arruda‐Olson Adelaide M. , Afzal Naveed , Priya Mallipeddi Vishnu , Said Ahmad , Moussa Pacha Homam , Moon Sungrim , Chaudhry Alisha P. , Scott Christopher G. , Bailey Kent R. , Rooke Thom W. , Wennberg Paul W. , Kaggal Vinod C. , Oderich Gustavo S. , Kullo Iftikhar J. , Nishimura Rick A. , Chaudhry Rajeev , Liu Hongfang
Published: December 2018

Background

Automated individualized risk prediction tools linked to electronic health records (
EHR
s) are not available for management of patients with peripheral arterial disease. The goal of this study was to create a prognostic tool for
patients with peripheral arterial disease
using data elements automatically extracted from an
EHR
to enable real‐time and individualized risk prediction at the point of care.

Methods and Results

A previously validated phenotyping algorithm was deployed to an
EHR
linked to the Rochester Epidemiology Project to identify
peripheral arterial disease
cases from Olmsted County,
MN,
for the years 1998 to 2011. The study cohort was composed of 1676 patients: 593 patients died over 5‐year follow‐up. The c‐statistic for survival in the overall data set was 0.76 (95% confidence interval [CI], 0.74–0.78), and the c‐statistic across 10 cross‐validation data sets was 0.75 (95% CI, 0.73–0.77). Stratification of cases demonstrated increasing mortality risk by subgroup (low: hazard ratio, 0.35 [95% CI, 0.21–0.58]; intermediate‐high:
hazard ratio,
2.98 [95% CI, 2.37–3.74]; high:
hazard ratio,
8.44 [95% CI, 6.66–10.70], all
P
<0.0001 versus the reference subgroup). An equation for risk calculation was derived from Cox model parameters and β estimates. Big data infrastructure enabled deployment of the real‐time risk calculator to the point of care via the
EHR
.

Conclusions

This study demonstrates that electronic tools can be deployed to
EHR
s to create automated real‐time risk calculators to predict survival of patients with peripheral arterial disease. Moreover, the prognostic model developed may be translated to patient care as an automated and individualized real‐time risk calculator deployed at the point of care.
Thromboangiitis Obliterans: 110 Years Old and Little Progress Made
Authors: Olin Jeffrey W.
Published: December 2018

See Article by
Le Joncour et al
.
“So Much a Piece of Nature”: Emerson, Webster, and the Transcendental Constitution
Authors: Kirsch Geoffrey R.
Published: December 2018

This essay tracks Ralph Waldo Emerson's obsession with Daniel Webster, from early hero-worship to bitter disillusionment over the Fugitive Slave Act to posthumous vindication. It argues that Webster's trajectory parallels that of the Constitution, and concludes that the postbellum Constitution embodies Webster's positivist reverence and Emerson's faith in higher law.
A Case of Identity: MASSACHUSETTENSIS and John Adams
Authors: Nicolson Colin , Edwards Owen Dudley , Macpherson Jamie , Nicolson Kristen
Published: December 2018

This article utilises friendship as an analytical category to interpret the debate between Novanglus and Massachusettensis in 1774-75, demonstrating how the friendship of John Adams and Jonathan Sewall informed political discourse and Adams's radicalization, and validating Adams's presumption of Sewall's coauthorship of Massachusettensis with Daniel Leonard.
The Many Facets of National Culture: A Critical Appraisal
Authors: AlMutairi Shihanah , Yen Dorothy , Heller Michael
Published: December 2018

Due to its wide usage in vast fields of study, there is a lack of studies synthesizing the many aspects of national culture theory. The authors argue that given the proliferation of national culture theories in various disciplines, the need to integrate and provide an analytical review is fundamental for further research. As such, they have reviewed 110 empirical and conceptual studies on the concept of national culture and recounted the different national culture theories within. They have also assimilated the varied criticism towards each respective national culture theory and synthesized them under six discernable shortcomings: the ecological fallacy, the concept of nations as units, the complexity of culture, the construct’s conceptualization, the research approach, and the dangers of stereotyping.
Influence of Parkinson’s Disease on Judging Stair Step Height: Exploratory Study
Authors: da Conceição Núbia R. , Teixeira-Arroyo Claudia , Vitório Rodrigo , Orcioli-Silva Diego , Beretta Victor S. , de Sousa Priscila N. , Gobbi Lilian T. B.
Published: December 2018

This study investigated the effects of Parkinson’s Disease (PD) on the perceptive judgment of stair step height using both exteroceptive visual and exproprioceptive judgments. We invited 14 individuals with PD and 14 neurologically healthy older adults (OA) to perform perceptual judgment tasks for first step stairway heights of 11 and 20 cm. Initially, participants performed first the exteroceptive visual judgment and then the exproprioceptive judgment in five randomized trials for each stair height. An analysis of variance for the exteroceptive visual judgment revealed no main effects or interaction between PD versus OA groups and height. However, the analysis of variance for exproprioceptive judgment revealed a significant interaction between group and height ( F1,26 = 9.519; p = .005; Pη2 = .268) such that both groups made more errors in exproprioceptive judgment at a height of 11 cm. The OA group made more errors in exproprioceptive judgment for the 20-cm step when compared with the PD group ( p = .016) but the PD group underestimated the step height. We conclude that PD influences exproprioceptive perception of step height and that steps with smaller (vs. larger) heights induce greater exproprioceptive error.