bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient and facility variation in costs of catheter ablation for atrial fibrillation
Authors: Perino Alexander C. , Fan Jun , Schmitt Susan K. , Kaiser Daniel W. , Heidenreich Paul A. , Narayan Sanjiv M. , Wang Paul J. , Chang Andrew Y. , Turakhia Mintu P.
Published: June 2018

Background

Cost‐effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the US healthcare system and the relationship between cost and outcomes.

Methods and results

We performed a retrospective cohort study using data from the MarketScan® commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 to 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30‐day and 1‐year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced healthcare utilization in higher cost quintiles with reductions in rehospitalization at 30‐days (Quintile 1: 16.1%, Quintile 5: 8.8%, P < 0.001) and 1‐year (Quintile 1: 34.8%, Quintile 5: 25.6%, P < 0.001), which remained significant in multivariate analysis.

Conclusions

Although median costs of AF ablation are below amounts used in prior cost‐effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects.
Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study
Authors: Sunagawa Sumito , Shirakura Takashi , Hokama Noboru , Kozuka Chisayo , Yonamine Masato , Namba Toyotaka , Morishima Satoko , Nakachi Sawako , Nishi Yukiko , Ikema Tomomi , Okamoto Shiki , Matsui Chieko , Hase Naoki , Tamura Mizuho , Shimabukuro Michio , Masuzaki Hiroaki
Published: June 2018

Aims/Introduction

There is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally‐ and systemically‐activated xanthine oxidase (XO), a rate‐limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus and metabolic syndrome (MetS).

Materials and Methods

We enrolled 60 patients with type 2 diabetes mellitus and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly‐sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters.

Results

The value of plasma XO activity was correlated with indices of insulin resistance and the level of circulating liver transaminases. In contrast, the level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with the serum uric acid level.

Conclusions

Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and MetS. Through assessing the plasma XO activity, patients showing normal levels of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncovering metabolic risks in type 2 diabetes mellitus and MetS patients.
Risk factors of post‐endoscopic submucosal dissection electrocoagulation syndrome for colorectal neoplasm
Authors: Ito Sayo , Hotta Kinichi , Imai Kenichiro , Yamaguchi Yuichiro , Kishida Yoshihiro , Takizawa Kohei , Kakushima Naomi , Tanaka Masaki , Kawata Noboru , Yoshida Masao , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki
Published: June 2018

Background and Aim

Colorectal endoscopic submucosal dissection (ESD) is used for the treatment of large colorectal superficial neoplasms. However, there have been no large studies on electrocoagulation syndrome developing after colorectal ESD. The aim of this study was to clarify the incidence and clinical risk factors of post‐ESD electrocoagulation syndrome (PECS).

Methods

A total of 692 patients (median age: 70 years; 395 men) with 692 lesions, who underwent colorectal ESD at a tertiary cancer center between July 2010 and December 2015, were eligible. PECS was clinically diagnosed based on the presence of localized abdominal tenderness matching the ESD enforcement site and fever (> 37.5 °C) or an inflammatory response (C‐reactive protein level > 0.5 mg/dL or leukocytosis > 10 000 cells/μL), without obvious findings of perforation, which developed at > 6 h post‐ESD. Outcomes of the procedure, the incidence of PECS, and risk factors associated with PECS were assessed.

Results

The incidence of PECS was 4.8% (33 patients), and all patients improved by conservative treatment. On multivariate analysis, the female sex (odds ratio [OR] 2.6; 95% confidence interval [95% CI]: 1.2–5.7), tumor location at the cecum (OR 14.5; 95% CI: 3.7–53.7 vs rectum), and the presence of submucosal fibrosis (OR 2.8; 95% CI: 1.1–7.5) were found to be independent risk factors of PECS.

Conclusions

This study identified the risk factors for PECS. Patients with high‐risk factors of PECS require careful management after colorectal ESD.
The subfornical organ: A novel site for prolactin action
Authors: Kamesh A. , Black E. A. E. , Ferguson A. V.
Published: June 2018

Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL‐R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood‐brain barrier. Accordingly, areas of the brain that do not possess a blood‐brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL‐R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real‐time polymerase chain reaction, we found that PRL‐R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch‐clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 μmol L‐1 PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, −6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L‐1 to 1 μmol L‐1, the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K+ current in 67% of SFO neurones in voltage‐clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL‐R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.
Addressing Gaps in Cardiopulmonary Resuscitation Education: Training Middle School Students in Hands‐Only Cardiopulmonary Resuscitation
Authors: Magid Kate H. , Heard Debra , Sasson Comilla
Published: June 2018

BACKGROUND

Training middle school students to perform hands‐only cardiopulmonary resuscitation (HOCPR) is a potential method to increase overall rates of bystander cardiopulmonary resuscitation (CPR). We aimed to examine the feasibility of teaching this population CPR using teacher‐implemented education sessions guided by American Heart Association (AHA) training kits and resources.

METHODS

We conducted a national HOCPR training campaign in middle schools during the 2014‐2015 school year. Participating schools utilized AHA CPR training kits to train seventh and eighth grade students. We assessed pretest/posttest knowledge and comfort in performing HOCPR.

RESULTS

We recruited 1131 schools and trained approximately 334,610 students in HOCPR. The average pretest score on knowledge questions was 50% and the average posttest score was 84%. Most students (76%) felt comfortable performing HOCPR after the education session. Overall, 98% of teachers said they would continue to implement CPR training in the future.

CONCLUSIONS

Large‐scale, teacher‐implemented CPR education sessions in the middle school setting are a successful approach to increase middle school student's knowledge and comfort in performing HOCPR and to increase overall bystander CPR rates.
Determining parents' patterns of behaviour when searching for online information on their child's health
Authors: Yardi Shruti , Caldwell Patrina HY , Barnes Elizabeth H , Scott Karen M
Published: June 2018

Aim

The internet has enabled parents to become informed medical consumers and take an active role in their child's treatment. We aimed to determine parents' online medical information‐seeking behaviour about their child's health. This included sources of information, reasons for searching, use and assessment of information and whether parents wanted assistance with searching and assessing information.

Methods

A questionnaire was distributed to 331 parents and carers of inpatients and outpatients at Children's Hospital at Westmead in 2015. Most questions involved tick‐box responses and a few free‐text responses. Responses were tabulated and described by frequencies and percentages. Associations between participant demographics and responses were examined using chi‐square tests.

Results

In all, 308 (93%) questionnaires were returned. Most participants (90%) reported searching for medical information about their child's health. Of these, 96% searched the internet, and of these, 63% used a smartphone. The most common reason for searching before seeing the doctor was to prepare questions. The most common reasons for searching after seeing the doctor were to know more and because participants had more questions. Only half (57%) ascertained whether an information source was reliable. Most wanted guidance on searching (69%) and assessing reliability (77%).

Conclusions

Almost all parents search for online information about their child's health, but most are unsure whether the information they find is trustworthy and are hesitant to act on or present it to their child's doctor. Health professionals could discuss this with parents during consultations to dispel potential misunderstandings and provide guidance on searching and assessing.
Detection of arboreal feeding signs by Asiatic black bears: effects of hard mast production at individual tree and regional scales
Authors: Tochigi K. , Masaki T. , Nakajima A. , Yamazaki K. , Inagaki A. , Koike S.
Published: June 2018

Arboreal feeding signs are among several field indicators of the use of tree crowns by the Asiatic black bear (Ursus thibetanus) to sit and eat fruit; however, it is unclear which factors influence this sign formation in hard mast species. Here, we investigated the influence of seed production by individual trees and at a regional scale by major hard mast species on the detection of arboreal feeding signs. For 7 years, we quantitatively assessed seed production by 374–481 trees each year of three dominant hard mast species (Quercus crispula, Quercus serrata and Castanea crenata) in the Ashio‐Nikko Mountains of central Japan and checked for the presence or absence of arboreal feeding signs in these trees. We estimated individual tree energy values and regional mast energy values across these three species and evaluated the influence of each factor on the detection probability of arboreal feeding signs. Arboreal feeding signs were more likely in individual trees with larger mast energy values and during poor mast years. There was no difference among species in the relative importance of individual tree energy or regional mast energy. Interaction of factors was also detected: the magnitude of the positive effect of individual tree energy on the detection of arboreal feeding signs was larger in poorer mast years, and the negative effect of regional mast energy was more conspicuous in the case of trees with greater mast energy. Thus, bears may maximize their feeding efficiency on hard mast in various ways, depending on regional mast availability; during poor mast years, bears are more likely to climb trees with higher individual tree energy values and leave arboreal feeding signs. Arboreal feeding signs cannot be used as an indicator of bear density unless both individual tree energy and regional mast energy values are monitored.
Distance, elevation and environment as drivers of diversity and divergence in bumble bees across latitude and altitude
Authors: Jackson Jason M. , Pimsler Meaghan L. , Oyen Kennan Jeannet , Koch‐Uhuad Jonathan B. , Herndon James D. , Strange James P. , Dillon Michael E. , Lozier Jeffrey D.
Published: June 2018

Identifying drivers of dispersal limitation and genetic differentiation is a key goal in biogeography. We examine patterns of population connectivity and genetic diversity using restriction site‐associated DNA sequencing (RADseq) in two bumble bee species, Bombus vosnesenskii and Bombus bifarius, across latitude and altitude in mountain ranges from California, Oregon and Washington, U.S.A. Bombus vosnesenskii, which occurs across a broader elevational range at most latitudes, exhibits little population structure while B. bifarius, which occupies a relatively narrow higher elevation niche across most latitudes, exhibits much stronger population differentiation, although gene flow in both species is best explained by isolation with environmental niche resistance. A relationship between elevational habitat breadth and genetic diversity is also apparent, with B. vosnesenskii exhibiting relatively consistent levels of genetic diversity across its range, while B. bifarius has reduced genetic diversity at low latitudes, where it is restricted to high‐elevation habitat. The results of this study highlight the importance of the intersect between elevational range and habitat suitability in influencing population connectivity and suggest that future climate warming will have a fragmenting effect even on populations that are presently well connected, as they track their thermal niches upward in montane systems.
Demographic expansion and genetic load of the halophyte model plant Eutrema salsugineum
Authors: Wang Xiao‐Juan , Hu Quan‐Jun , Guo Xin‐Yi , Wang Kun , Ru Da‐Fu , German Dmitry A. , Weretilnyk Elizabeth A. , Abbott Richard J. , Lascoux Martin , Liu Jian‐quan
Published: June 2018

The halophyte model plant Eutrema salsugineum (Brassicaceae) disjunctly occurs in temperate to subarctic Asia and North America. This vast, yet extremely discontinuous distribution constitutes an ideal system to examine long‐distance dispersal and the ensuing accumulation of deleterious mutations as expected in expanding populations of selfing plants. In this study, we resequenced individuals from 23 populations across the range of E. salsugineum. Our population genomic data indicate that E. salsugineum migrated “out of the Altai region” at least three times to colonize northern China, northeast Russia and western China. It then expanded its distribution into North America independently from northeast Russia and northern China, respectively. The species colonized northern China around 33.7 thousand years ago (kya) and underwent a considerable expansion in range size approximately 7–8 kya. The western China lineage is likely a hybrid derivative of the northern China and Altai lineages, originating approximately 25–30 kya. Deleterious alleles accumulated in a stepwise manner from (a) Altai to northern China and North America and (b) Altai to northeast Russia and North America. In summary, E. salsugineum dispersed from Asia to North America and deleterious mutations accumulated in a stepwise manner during the expansion of the species’ distribution.
Divergent evapotranspiration partition dynamics between shrubs and grasses in a shrub‐encroached steppe ecosystem
Authors: Wang Pei , Li Xiao‐Yan , Wang Lixin , Wu Xiuchen , Hu Xia , Fan Ying , Tong Yaqin
Published: June 2018

Previous evapotranspiration (ET) partitioning studies have usually neglected competitions and interactions between antagonistic plant functional types. This study investigated whether shrubs and grasses have divergent ET partition dynamics impacted by different water‐use patterns, canopy structures, and physiological properties in a shrub‐encroached steppe ecosystem in Inner Mongolia, China.

The soil water‐use patterns of shrubs and grasses have been quantified by an isotopic tracing approach and coupled into an improved multisource energy balance model to partition ET fluxes into soil evaporation, grass transpiration, and shrub transpiration.

The mean fractional contributions to total ET were 24 ± 13%, 20 ± 4%, and 56 ± 16% for shrub transpiration, grass transpiration, and soil evaporation respectively during the growing season. Difference in ecohydrological connectivity and leaf development both contributed to divergent transpiration partitioning between shrubs and grasses.

Shrub‐encroachment processes result in larger changes in the ET components than in total ET flux, which could be well explained by changes in canopy resistance, an ecosystem function dominated by the interaction of soil water‐use patterns and ecosystem structure. The analyses presented here highlight the crucial effects of vegetation structural changes on the processes of land–atmosphere interaction and climate feedback.
Pleistocene glacial cycles drive isolation, gene flow and speciation in the high‐elevation Andes
Authors: Nevado Bruno , Contreras‐Ortiz Natalia , Hughes Colin , Filatov Dmitry A.
Published: June 2018

Mountain ranges are amongst the most species‐rich habitats, with many large and rapid evolutionary radiations. The tempo and mode of diversification in these systems are key unanswered questions in evolutionary biology. Here we study the Andean Lupinus radiation to understand the processes driving very rapid diversification in montane systems.

We use genomic and transcriptomic data of multiple species and populations, and apply phylogenomic and demographic analyses to test whether diversification proceeded without interspecific gene flow – as expected if Andean orogeny and geographic isolation were the main drivers of diversification – or if diversification was accompanied by gene flow, in which case other processes were probably involved.

We uncover several episodes of gene flow between species, including very recent events likely to have been prompted by changes in habitat connectivity during Pleistocene glacial cycles. Furthermore, we find that gene flow between species was heterogeneously distributed across the genome.

We argue that exceptionally fast diversification of Andean Lupinus was partly a result of Late Pleistocene glacial cycles, with associated cycles of expansion and contraction driving geographic isolation or secondary contact of species. Furthermore, heterogeneous gene flow across the genome suggests a role for selection and ecological speciation in rapid diversification in this system.
Soil texture mediates tree responses to rainfall intensity in African savannas
Authors: Case Madelon F. , Staver A. Carla
Published: June 2018

Rainfall variability is a major determinant of soil moisture, but its influence on vegetation structure has been challenging to generalize. This presents a major source of uncertainty in predicting vegetation responses to potentially widespread shifts in rainfall frequency and intensity. In savannas, where trees and grasses coexist, conflicting lines of evidence have suggested, variously, that tree cover can either increase or decrease in response to less frequent, more intense rainfall.

Here, we use remote sensing products and continent‐wide soil maps for sub‐Saharan Africa to analyze how soil texture and fire mediate the response of savanna tree cover to rainfall climatology.

Tree cover increased with mean wet‐season rainfall and decreased with fire frequency, consistent with previous analyses. However, responses to rainfall intensity varied: tree cover dramatically decreased with rainfall intensity on clayey soils, at high rainfall, and with rainfall spread over longer wet seasons; conversely, on sandy soils, at low rainfall, and with shorter wet seasons, tree cover instead increased with rainfall intensity.

Tree cover responses to rainfall climatology depend on soil texture, accounting for substantial variation in tree cover across African savannas. Differences in underlying soils may lead to divergent responses of savannas to global change.
Risk factors for persistent hyperparathyroidism in children with stable renal function after kidney transplantation
Authors: Kim Da Hyun , Lee Joo Hoon , Han Duck Jong , Park Young Seo
Published: June 2018

This study aimed to investigate the risk factors for PHPT in children with stable renal function who received KT. We retrospectively analyzed the clinical findings and laboratory results of patients who underwent KT below 19 years of age, between 1996 and 2016 at our hospital. Patients were followed up for more than 1 year after KT. We calculated the mean ± standard deviation or median [minimum – maximum] for each parameter. We included a total of 46 patients (male:female = 26:20). Twelve patients (26.1%) were included in the PHPT group, and 34 (73.9%) were in the nPTH group. The dialysis duration was 57.1 ± 49.9, 44 [0‐145] months in the PHPT group and 23.5 ± 25.8, 15 [1‐121] months in the nPTH group (P = .040). The post‐KT total CO2 level was significantly higher in the PHPT group (P = .022). The pre‐ (P = .021) and post‐KT (P = .005) and 3‐month average (P = .018) iPTH levels were also significantly higher in PHPT group. The height z‐score showed a negative correlation, and the pre‐KT, 3‐month average phosphorus and alkaline phosphate levels showed positive correlations with iPTH levels, at 1 year after KT. Patients who undergo prolonged durations of dialysis, have increased iPTH levels before and after KT, and have low bicarbonate levels after KT are at risk of PHPT and should be monitored carefully.
Clinical course of human herpesvirus 6 infection in pediatric living donor liver transplantation
Authors: Yasui Toshihiro , Suzuki Tatsuya , Yoshikawa Tetsushi , Yatsuya Hiroshi , Kawamura Yoshiki , Miura Hiroki , Hara Fujio , Watanabe Shunsuke , Uga Naoko , Naoe Atsuki
Published: June 2018

Differentiation between active and latent viral infection is critical for analysis of HHV‐6‐associated disease. HHV‐6 infection has been associated with several clinical manifestations; however, the precise role of HHV‐6 in pediatric LDLT remains unclear. This retrospective cohort study included 33 pediatric patients who received LDLT. All of the recipients were monitored for HHV‐6 infection using viral isolation and real‐time PCR. HHV‐6 infection was observed in 14 of 33 (42.4%) recipients, and HHV‐6B infection occurred within 2 weeks after LDLT in 10 of 14 (71.4%) recipients. HHV‐6 was isolated from 10 of 33 (30.3%) recipients. Multivariate analysis showed that independent predictors of HHV‐6B infection were age (OR 0.975; 95% CI 0.943‐0.999; P = .041), PELD (OR 1.091; P = .038), and biliary atresia (OR 16.48; P = .035). The occurrence of unexplained fever was significantly higher in recipients with HHV‐6B infection (11/14) compared with uninfected recipients (6/19) (P = .013). Additionally, ALT levels at 8 and 9 weeks after transplantation were significantly higher in the recipients with HHV‐6B infection. Younger age, high MELD/PELD score, and biliary atresia as an underlying disease were identified as risk factors for viral infection.
Against Creativity
Authors: Hills Alison , Bird Alexander
Published: June 2018

Creativity is typically defined as a disposition to produce valuable ideas. We argue that this is a mistake and defend a new definition of creativity in terms of the imagination. It follows that creativity has instrumental value at most and then only in the right circumstances. We consider the role of tradition and judgment in worthwhile creativity and argue that there is frequently a tension between greater creativity and the production of value.
Quantifying proximal patellar tendon changes during adolescence in elite ballet dancers, a 2‐year study
Authors: Rudavsky A. , Cook J. , Docking S.
Published: June 2018

Patellar tendon pathology appears to develop in young athletes. It is not known how this tendon develops through adolescence. This longitudinal study investigated proximal patellar tendon development during the adolescent growth spurt in young ballet dancers and identified whether puberty (estimated by maturity offset) had an effect on tendon development. Fifty two dancers (32 female and 20 male dancers, ages 11‐18 at baseline) had ultrasound images of their tendons every 6 months for 2 years. Changes in tendon size (anterior‐posterior diameter) on grayscale images and echogenicity, as quantified using ultrasound tissue characterization, were recorded each time. Maturity offset was calculated used to estimate peak height velocity (adolescent growth spurt). Maturity offset did not affect effect tendon composition before peak height velocity; however, after participants passed peak height velocity, maturity offset increased the composition of stable echopattern (P < .05): a 4% differential increase in type I echopattern, indicative of normal tendon structure, and a decrease in type III echopattern (more disorganized echopattern) by 0.7% per year. Anterior‐posterior thickness increased by 0.2 mm/y (P < .05) measured 2 cm below the patella. Following peak height velocity, the proximal patellar tendon attachment increased in thickness and demonstrated a more stable echopattern representative of aligned fibrillar structure. Future research is required to further understand this normal maturation and the factors that support this process, with the aim of reducing the development of patellar tendon pathology in the adolescent jumping athlete.
Granulomatous inflammation in BK polyomavirus–associated nephropathy
Authors: Zhang Yang , Ahmed Hiba , Haririan Abdolreza , Ugarte Richard , Papadimitriou John C. , Drachenberg Cinthia B.
Published: June 2018

Evolving BK polyomavirus–associated nephropathy (BKPyVAN) is characterized by tubulointerstitial inflammation that closely resembles acute T‐cell–mediated allograft rejection if tubulitis is significant. The cellular composition of the inflammation varies during the course of BKPyVAN, and clusters of plasma cells may herald resolution of the infection. Less commonly, BKPyVAN can present with a predominance of histiocytes and granuloma formation. Granulomatous interstitial nephritis is uncommon in biopsies of either native or transplant kidneys. In both settings, this distinctive type of inflammatory response requires a systematic approach with careful clinicopathological assessment to determine its etiology. We present three patients with granulomatous BKPyVAN in the first year post‐transplantation. These allograft biopsies at 4, 6, and 12 months post‐transplant exemplify spontaneously resolving BKPyVAN, resolving infection after immunosuppression reduction, and early BKPyVAN, respectively. In immunosuppressed patients, BKPyVAN should be added to the relatively broad differential diagnosis of granulomatous tubulointerstitial nephritis.
Rejuvenation of allogenic red cells: benefits and risks
Authors: Aujla H. , Woźniak M. , Kumar T. , Murphy G. J. ,   REDJUVENATE Investigators
Published: June 2018

Background and objectives

To review preclinical and clinical studies that have evaluated the effects of red cell rejuvenation in vivo and in vitro and to assess the potential risks and benefits from their clinical use.

Materials and methods

A systematic review and narrative synthesis of the intervention of red cell rejuvenation using a red cell processing solution containing inosine, pyruvate, phosphate and adenine. Outcomes of interest in vitro were changes in red cell characteristics including adenosine triphosphate (ATP), 2,3‐diphosphoglycerate (2,3‐DPG), deformability and the accumulation of oxidized lipids and other reactive species in the red cell supernatant. Outcomes in vivo were 24‐h post‐transfusion survival and the effects on oxygen delivery, organ function and inflammation in transfused recipients.

Results

The literature search identified 49 studies evaluating rejuvenated red cells. In vitro rejuvenation restored cellular properties including 2,3‐DPG and ATP to levels similar to freshly donated red cells. In experimental models, in vivo transfusion of rejuvenated red cells improved oxygen delivery and myocardial, renal and pulmonary function when compared to stored red cells. In humans, in vivo 24‐h survival of rejuvenated red cells exceeded 75%. In clinical studies, rejuvenated red cells were found to be safe, with no reported adverse effects. In one adult cardiac surgery trial, transfusion of rejuvenated red cells resulted in improved myocardial performance.

Conclusion

Transfusion of rejuvenated red cells reduces organ injury attributable to the red cell storage lesion without adverse effects in experimental studies in vivo. The clinical benefits of this intervention remain uncertain.
Passenger lymphocyte syndrome due to anti‐B and anti‐Jka following combined intestinal and renal transplantation
Authors: Chua C. C. , Lim H. , Testro A. , Hong F. S.
Published: June 2018

Introduction

Passenger lymphocyte syndrome (PLS) is an immune‐mediated haemolysis in which antibodies directed against recipient red‐blood‐cell (RBC) antigens are formed by viable donor B‐lymphocytes found within an allograft, leading to alloimmune destruction of recipient RBC. To our knowledge, this is the first reported case of PLS with anti‐B and anti‐Jka after combined interstitial and renal transplants at the Australian Intestinal Transplant Service.

Methods

A 47‐year‐old group B, RhD positive, Jk(a+b+) male received an ABO minor‐mismatch combined intestinal and renal transplants from a cadaveric donor who was group O RhD positive. The recipient developed clinically significant haemolysis 18 days post‐transplant with a haemoglobin nadir of 59 g/l. He was supported with donor and recipient compatible blood components, with laboratory evidence of resolution of haemolysis by day 52 post‐transplant without requiring any additional interventions.

Results

Both the recipient and donor had a negative antibody screen immediately prior to transplantation. Two alloantibodies, anti‐B and a weak anti‐Jka, were detected in the recipient's eluate.

Discussion

It is important to be vigilant about possible PLS post‐transplant especially in high‐risk populations such as those undergoing intestinal and/or multi‐visceral transplant with minor ABO‐incompatible allografts. Although PLS is a rare and self‐limiting condition, early recognition allows timely provision of compatible blood components as well as minimisation of morbidity from haemolysis.
Developing Measures of Complexity for Engineering Design
Authors: Summers Joshua D. , Shah Jami J.
Published: June 2018

Developing objective measures for evaluating the complexity of the design problems would facilitate empirical studies that require use of “equivalent” but different design problems, development of design curriculums, and comparison of computer aided design automation tools. This paper discusses the similarities and differences between design problem complexity, design process complexity, and design artifact complexity. Three fundamental aspects to complexity are identified: the size, the degree of coupling, and the solvability. Alternative methods for measuring these characteristics of the design are discussed based upon computational views of complexity, information based views of complexity, and traditional design views of complexity. A method of measuring size as it relates to complexity is proposed for measuring the information content of design. A second method is proposed for decomposing a graph-based representation of design that provides a measure of the interconnectedness as it relates to complexity. Finally, two methods are proposed for determining the solvability complexity of design based upon the effort involved and the degree of freedom of design. These measures are developed specifically for parametric and geometric problems as found in embodiment design.
Comparison of Modular Measurement Methods Based on Consistency Analysis and Sensitivity Analysis
Authors: Guo F. , Gershenson J. K.
Published: June 2018

Most modularity measures center on quantifying dependencies with components external to modules. Some modularity measures include an accounting of component similarity. What is measured as dependencies and similarities varies by measure and by context. Additionally, there is some subjectivity in the measures. Noticeably, the measures lack rigorous verification and validation. There is also a lack of quantitative comparison among the various measures. This research highlights the consistencies among the measures of modular product design and attempts to select a single measure for use in future applications. A list of eight alternative modularity measures was developed from available literature. The goal was to compare these measures to find the most representative measure with high similarity to the mainstream of all measures but also with a high sensitivity to changes in modularity. Our hypothesis is that, since many measures look somewhat similar, we are looking for one measure that is in agreement with most measures and therefore performs reliably; it should also be significantly more sensitive. Similarity was defined via consistency analysis — similar measurements rank the different product modularities in the same sequence. Sensitivity was compared by slightly changing the product architecture of example products and then quantifying which measures are more sensitive to these changes. Analysis was based on 11 products: a Fisher-price Chatter Radio, a Proctor Silex automatic drip coffeemaker, a Johnson fishing reel with pre-spooled line, a Sunbeam home hair trimmer, a Farberware ice cream scoop, a Regent halogen clamp lamp, a Bell classic portable bicycle pump, a Pur faucet mount water filter, an ANCO premium wiper blade, a Kodak single-use camera, and an Adhesive Tech mini glue gun.
Scientists aim to smoke out wildfire impacts
Authors: Cornwall Warren
Published: June 2018

U.S. campaign to study how plumes affect human health and environment.
New copies of old gene drove brain expansion
Authors: Pennisi Elizabeth
Published: June 2018

Research shows how genes supercharge neuron formation during human development.
Europe's science spending set for another big boost
Authors: Rabesandratana Tania
Published: June 2018

Commission seeks €97.6 billion for "Horizon Europe."
The galaxy builders
Authors: Cho Adrian
Published: June 2018

Galaxy simulations are finally producing realistic results—and surprising insights into the evolution of the universe.
A bioinspired flexible organic artificial afferent nerve
Authors: Kim Yeongin , Chortos Alex , Xu Wentao , Liu Yuxin , Oh Jin Young , Son Donghee , Kang Jiheong , Foudeh Amir M. , Zhu Chenxin , Lee Yeongjun , Niu Simiao , Liu Jia , Pfattner Raphael , Bao Zhenan , Lee Tae-Woo
Published: June 2018

I've got a feeling

Sensory (or afferent) nerves bring sensations of touch, pain, or temperature variation to the central nervous system and brain. Using the tools and materials of organic electronics, Kim
et al.
combined a pressure sensor, a ring oscillator, and an ion gel–gated transistor to form an artificial mechanoreceptor (see the Perspective by Bartolozzi). The combination allows for the sensing of multiple pressure inputs, which can be converted into a sensor signal and used to drive the motion of a cockroach leg in an oscillatory pattern.

Science
, this issue p.
998
; see also p.
966
Feedback regulation of COOLAIR expression controls seed dormancy and flowering time
Authors: Chen Min , Penfield Steven
Published: June 2018

Controls on seed dormancy

Herbivores and an inopportune cold snap can destroy fragile plant seedlings. Plants control the dormancy of their seeds in anticipation of more favorable growth conditions. Chen and Penfield analyzed the molecular controls on seed dormancy in the model plant
Arabidopsis thaliana.
Two genes and an antisense RNA, known from the process of vernalization, integrate ambient temperature to control seed dormancy via their opposing configurations.

Science
, this issue p.
1014
Vibrio2017: the Seventh International Conference on the Biology of Vibrios
Authors: Klose Karl E. , Satchell Karla J. F.
Published: June 2018

Vibrio2017, the ASM Conference on the Biology of Vibrios, was held in November 2017. The conference focused on all aspects of biology related to the bacterial genus
Vibrio
.
Control of Artifactual Variation in Reported Intersample Relatedness during Clinical Use of a Mycobacterium tuberculosis Sequencing Pipeline
Authors: Wyllie David H. , Sanderson Nicholas , Myers Richard , Peto Tim , Robinson Esther , Crook Derrick W. , Smith E. Grace , Walker A. Sarah
Published: June 2018

Contact tracing requires reliable identification of closely related bacterial isolates. When we noticed the reporting of artifactual variation between
Mycobacterium tuberculosis
isolates during routine next-generation sequencing of
Mycobacterium
spp., we investigated its basis in 2,018 consecutive
M. tuberculosis
isolates.
Mamu-B*17
+
Rhesus Macaques Vaccinated with
env
,
vif
, and
nef
Manifest Early Control of SIVmac239 Replication
Authors: Martins Mauricio A. , Tully Damien C. , Pedreño-Lopez Núria , von Bredow Benjamin , Pauthner Matthias G. , Shin Young C. , Yuan Maoli , Lima Noemia S. , Bean David J. , Gonzalez-Nieto Lucas , Domingues Aline , Gutman Martin J. , Maxwell Helen S. , Magnani Diogo M. , Ricciardi Michael J. , Bailey Varian K. , Altman John D. , Burton Dennis R. , Ejima Keisuke , Allison David B. , Evans David T. , Rakasz Eva G. , Parks Christopher L. , Bonaldo Myrna C. , Capuano Saverio , Lifson Jeffrey D. , Desrosiers Ronald C. , Allen Todd M. , Watkins David I.
Published: June 2018

A better understanding of the immune correlates of protection against HIV might facilitate the development of a prophylactic vaccine. Therefore, we investigated simian immunodeficiency virus (SIV) infection outcomes in rhesus macaques expressing the major histocompatibility complex class I allele
Mamu-B*17
. Approximately 21% of

Mamu-B*17
+

macaques spontaneously controlled chronic phase viremia after SIV infection, an effect that may involve CD8
+
T cells targeting Mamu-B*17-restricted SIV epitopes. We vaccinated

Mamu-B*17
+

macaques with genes encoding immunodominant epitopes in Vif and Nef alone (group 1) or together with
env
(group 2). Although neither vaccine regimen prevented SIV infection, 5/8 group 2 vaccinees controlled viremia to below detection limits shortly after infection. This outcome, which was not observed in group 1, was associated with vaccine-induced, nonneutralizing Env-binding antibodies. Together, these findings suggest a limited contribution of Vif- and Nef-specific CD8
+
T cells for virologic control in

Mamu-B*17
+

macaques and implicate anti-Env antibodies in containment of SIV infection.
Leveraging Existing 16S rRNA Gene Surveys To Identify Reproducible Biomarkers in Individuals with Colorectal Tumors
Authors: Sze Marc A. , Schloss Patrick D.
Published: June 2018

An increasing body of literature suggests that both individual and collections of bacteria are associated with the progression of colorectal cancer. As the number of studies investigating these associations increases and the number of subjects in each study increases, a meta-analysis to identify the associations that are the most predictive of disease progression is warranted. We analyzed previously published 16S rRNA gene sequencing data collected from feces and colon tissue. We quantified the odds ratios (ORs) for individual bacterial taxa that were associated with an individual having tumors relative to a normal colon. Among the fecal samples, there were no taxa that had significant ORs associated with adenoma and there were 8 taxa with significant ORs associated with carcinoma. Similarly, among the tissue samples, there were no taxa that had a significant OR associated with adenoma and there were 3 taxa with significant ORs associated with carcinoma. Among the significant ORs, the association between individual taxa and tumor diagnosis was equal to or below 7.11. Because individual taxa had limited association with tumor diagnosis, we trained Random Forest classification models using only the taxa that had significant ORs, using the entire collection of taxa found in each study, and using operational taxonomic units defined based on a 97% similarity threshold. All training approaches yielded similar classification success as measured using the area under the curve. The ability to correctly classify individuals with adenomas was poor, and the ability to classify individuals with carcinomas was considerably better using sequences from feces or tissue.

IMPORTANCEColorectal cancer is a significant and growing health problem in which animal models and epidemiological data suggest that the colonic microbiota have a role in tumorigenesis. These observations indicate that the colonic microbiota is a reservoir of biomarkers that may improve our ability to detect colonic tumors using noninvasive approaches. This meta-analysis identifies and validates a set of 8 bacterial taxa that can be used within a Random Forest modeling framework to differentiate individuals as having normal colons or carcinomas. When models trained using one data set were tested on other data sets, the models performed well. These results lend support to the use of fecal biomarkers for the detection of tumors. Furthermore, these biomarkers are plausible candidates for further mechanistic studies into the role of the gut microbiota in tumorigenesis.
Candida albicans-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers
Authors: Allert Stefanie , Förster Toni M. , Svensson Carl-Magnus , Richardson Jonathan P. , Pawlik Tony , Hebecker Betty , Rudolphi Sven , Juraschitz Marc , Schaller Martin , Blagojevic Mariana , Morschhäuser Joachim , Figge Marc Thilo , Jacobsen Ilse D. , Naglik Julian R. , Kasper Lydia , Mogavero Selene , Hube Bernhard
Published: June 2018

Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as
Candida albicans
, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation of
C. albicans
across intestinal epithelia
in vitro
and identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000
C. albicans
deletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin of
C. albicans
, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation of
C. albicans
through intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin.

IMPORTANCE
Candida albicans
, usually a harmless fungus colonizing human mucosae, can cause lethal bloodstream infections when it manages to translocate across the intestinal epithelium. This can result from antibiotic treatment, immune dysfunction, or intestinal damage (e.g., during surgery). However, fungal processes may also contribute. In this study, we investigated the translocation process of
C. albicans
using
in vitro
cell culture models. Translocation occurs as a stepwise process starting with invasion, followed by epithelial damage and loss of epithelial integrity. The ability to secrete candidalysin, a peptide toxin deriving from the hyphal protein Ece1, is key:
C. albicans
hyphae, secreting candidalysin, take advantage of a necrotic weakened epithelium to translocate through the intestinal layer.