bluuebunny/crossref_metadata_2025 huggingface dataset:
Sharp Constant in Third-order Hardy–Sobolev–Maz’ya Inequality in the Half Space of Dimension Seven
Authors: Hong Qing
Published: March 2019

This paper is concerned with the sharp constant in higher-order Hardy–Sobolev–Maz’ya inequalities in the half space $\mathbb{R}^{n}_{+}$. These inequalities were recently established by Lu and Yang [26]. We prove that, in the case of dimension seven, the sharp constant in the third-order Hardy–Sobolev–Maz’ya inequality coincides with the sharp third-order Sobolev constant. This provides an analogue of the corresponding results of Benguria, Frank, and Loss [3] and Lu and Yang [26], in which the sharp constant in the first-order inequality in dimension three and the sharp constant in the second-order inequality in dimension five are addressed respectively.
Immunogenicity and Safety of a Sabin Strain–Based Inactivated Polio Vaccine: A Phase 3 Clinical Trial
Authors: Hu Yuemei , Wang Jianfeng , Zeng Gang , Chu Kai , Jiang Deyu , Zhu Fengdong , Ying Zhifang , Chen Lei , Li Changgui , Zhu Fengcai , Yin Weidong
Published: March 2019

Background

The Sabin strain–based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in developing countries.

Methods

The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy infants aged 60–90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations, respectively.

Results

A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol population. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P < .01); 94.8% and 84.0%, respectively, for type 2 (P < .01); and 98.9% and 97.7%, respectively, for type 3 (P = .11). A total of 599 and 600 participants in the sIPV and IPV groups, respectively, were included in the safety population. Fever was the most common adverse event, occurring in 61.6% and 49.8% of participants in the experimental and control arms, respectively (P < .01).

Conclusions

The sIPV demonstrated an immunogenicity profile noninferior to that of the conventional IPV and had a good safety profile.

Clinical Trials Registration

NCT03526978.
Integrating the Ecosystem Services Paradigm into Environmental Law: A Mechanism to Protect Mangrove Ecosystems?
Authors: Bell-James Justine
Published: March 2019

The ecosystem services paradigm is a widely recognised concept in ecology and environmental management, but one that is not uniformly incorporated into environmental law. This article argues that the integration of this paradigm into law can assist with protection of critical environmental resources, using mangrove ecosystems as an example. This article commences with a defence of the ecosystem services paradigm, followed by a discussion of the ecosystem services provided by mangroves. It argues that a comprehensive analysis of existing laws is a necessary first step towards legal reform, and to this end, it proposes a rubric for assessment of laws and legal frameworks. This rubric is applied to laws in Queensland, Australia, as a case study. It concludes by identifying major deficiencies in the recognition of mangrove ecosystem services in existing laws, and calling for reform in this area.
Estimating the Age of Forensically Useful Blowfly, Sarconesia chlorogaster (Diptera: Calliphoridae), Using Larval Length and Weight
Authors: Lecheta Melise Cristine , Moura Mauricio Osvaldo
Published: March 2019

Determining the age of an insect collected in a corpse is a key element to estimate the minimum postmortem interval in forensic entomology. Along with models of accumulated degree-hours, the estimation of the age based on larval weight and length is among the most common methods for this purpose. Sarconesia chlorogaster (Wiedemann, 1830), along with other Calliphoridae, is an important species in forensics in South America. However, studies analyzing the weight and length of S. chlorogaster larvae during development have not yet been done. In this work, we develop growth models based on the weight and length of larvae in different temperatures and provide formulas that can be used to estimate the age of the larvae based on the weight and length for each temperature. Larvae were reared at six temperatures (10, 15, 20, 25, 30, 35°C), and the measurements of larval length and weight were taken during all development until they stopped feeding. For the measurements, we attempted to use methodologies that can be easily replicated and do not require equipment that could be of difficult access. The results of this work come to complement and improve the use of S. chlorogaster in forensic applications.
Mass calibration of the CODEX cluster sample using SPIDERS spectroscopy – I. The richness–mass relation
Authors: Capasso R , Mohr J J , Saro A , Biviano A , Clerc N , Finoguenov A , Grandis S , Collins C , Erfanianfar G , Damsted S , Kirkpatrick C , Kukkola A
Published: March 2019

We use galaxy dynamical information to calibrate the richness–mass scaling relation of a sample of 428 galaxy clusters that are members of the CODEX sample with redshifts up to z ∼ 0.7. These clusters were X-ray selected using the ROSAT All-Sky Survey (RASS) and then cross-matched to associated systems in the redMaPPer (the red sequence Matched-filter Probabilistic Percolation) catalogue from the Sloan Digital Sky Survey. The spectroscopic sample we analyse was obtained in the SPIDERS program and contains ∼7800 red member galaxies. Adopting NFW mass and galaxy density profiles and a broad range of orbital anisotropy profiles, we use the Jeans equation to calculate halo masses. Modelling the scaling relation as $\lambda \propto \text{A}_{\lambda } {M_{\text{200c}}}^{\text{B}_{\lambda }} ({1+z})^{\gamma _{\lambda }}$, we find the parameter constraints $\text{A}_{\lambda }=38.6^{+3.1}_{-4.1}\pm 3.9$, $\text{B}_{\lambda }=0.99^{+0.06}_{-0.07}\pm 0.04$, and $\gamma _{\lambda }=-1.13^{+0.32}_{-0.34}\pm 0.49$, where we present systematic uncertainties as a second component. We find good agreement with previously published mass trends with the exception of those from stacked weak lensing analyses. We note that although the lensing analyses failed to account for the Eddington bias, this is not enough to explain the differences. We suggest that differences in the levels of contamination between pure redMaPPer and RASS + redMaPPer samples could well contribute to these differences. The redshift trend we measure is more negative than but statistically consistent with previous results. We suggest that our measured redshift trend reflects a change in the cluster galaxy red sequence (RS) fraction with redshift, noting that the trend we measure is consistent with but somewhat stronger than an independently measured redshift trend in the RS fraction. We also examine the impact of a plausible model of correlated scatter in X-ray luminosity and optical richness, showing it has negligible impact on our results.
PeSHN1 regulates water-use efficiency and drought tolerance by modulating wax biosynthesis in poplar
Authors: Meng Sen , Cao Yang , Li Huiguang , Bian Zhan , Wang Dongli , Lian Conglong , Yin Weilun , Xia Xinli
Published: March 2019

Wax, a hydrophobic structure that provides an effective waterproof barrier to the leaves, is an important drought adaptation trait for preventing water loss. However, limited knowledge exists regarding the molecular mechanisms underlying wax biosynthesis in trees. Here, PeSHN1, an AP2/ethylene response factor transcription factor, was isolated from a fast-growing poplar Populus × euramericana cv. ‘Neva’ clone. To study the potential biological functions of PeSHN1, transgenic 84K poplar (Populus alba × Populus glandulosa) plants overexpressing PeSHN1 were generated. PeSHN1 overexpression resulted in decreased transpiration, increased water-use efficiency (WUE) and increased drought tolerance. The transgenic poplar plants exhibited increased wax accumulation and altered wax composition, mainly because of a substantial increase in long-chain (>C30) fatty acids, aldehydes and alkanes. Gene expression analyses revealed that many genes involved in wax biosynthesis were induced in the PeSHN1 overexpression plants. In addition, chromatin immunoprecipitation-PCR assays and dual luciferase assays revealed that at least one of those genes, LACS2, is likely targeted by PeSHN1. Moreover, the PeSHN1 overexpression plants maintained higher photosynthetic activity and accumulated more biomass under drought stress conditions. Taken together, these results suggest that PeSHN1 regulates both WUE and drought tolerance in poplar by modulating wax biosynthesis and that altered PeSHN1 expression could represent a novel approach (altering the wax trait on leaf surfaces to increase WUE) for breeding drought-tolerant plants.
Bilateral horizontal salter osteotomies with anterior symphyseal closure using a nylon tape in the treatment of exstrophy of the bladder
Authors: Aly Ahmad S.
Published: March 2019

The aim of this case series study is to describe the orthopedic management of bladder exstrophy and to report on the intermediate-term outcomes following bilateral horizontal Salter osteotomies with anterior symphyseal closure using a nylon tape. This retrospective study included seven patients (five boys and two girls) who underwent bilateral horizontal osteotomies after reconstruction of the urogenital deformity using the Cantwell–Ransley technique and symphyseal closure by nylon tape number 2–5. the age range was between 7 months and 8 years (median age = 17 months). Three patients had recurrent bladder exstrophy after they underwent “ramotomy” early in their life, whereas four were operated primarily. All patients were followed up over 2 years, with a mean follow-up duration of 3.27 years (2–5 years). Petrie cast was applied, with both legs abducted and internally rotated till bony union had been achieved. This allowed free handling of the wounds and catheters. Removal of k-wires was performed in an outpatient clinic after the complete union of bony osteotomies had been achieved (6–8 weeks). Satisfactory bladder closure was achieved in all patients. None of the patients had a bone infection or nonunion at the osteotomy sites. No postoperative wound dehiscence has occurred for up to 5 years. The foot progression angle improved from 37°–70° (median = 45°) preoperatively to 0°–15° (median = 5°) postoperatively. Symphyseal diastasis was closed well in all of our patients in postoperative plain radiography compared with 5.8–11 cm (median = 8.2 cm) diastasis preoperatively. One patient had a superficial wound infection. Another patient had a sutured bladder neck by a nylon tape during the symphyseal closure. Bilateral horizontal Salter osteotomies with anterior symphyseal closure using nylon tape are safe and effective in the management of bladder exstrophy, especially in older children and in extreme diastasis (> 6 cm); with improvement in the gait as it corrects the acetabular external rotation.
Divergent Intramedullary Nailing (DIN): A Modified Intramedullary Nailing Technique to Treat Paediatric Distal Tibial Fractures
Authors: Harly Edouard , Angelliaume Audrey , Lalioui Abdelfetah , Pfirrmann Clémence , Harper Luke , Lefèvre Yan
Published: March 2019

Introduction:

Elastic stable intramedullary nailing (ESIN) allows for efficient reduction and stabilization of fractures of the tibial shaft in children and adolescents. However, for fractures of the distal third of the tibia, traditional ESIN could be inappropriate, thus compromising the stability and the healing of the fracture. The aim of this study was to present and to assess a new technique of modified ESIN to treat fracture of the distal third of the tibia, called divergent intramedullary nailing (DIN).

Methods:

We performed a retrospective monocentric study. All patients less than 16 years old, managed in our pediatric orthopaedics department, and operated upon according to the DIN technique for a displaced and/or unstable fracture of the distal third of the tibia were included. Demographic and surgical data were collected. X-rays were performed preoperatively, postoperatively, at 6 weeks, and every 6 months. The surgical technique starts as does the classic ESIN. However, nails are not curved, so that they cross only once at the proximal part of the tibia; they are divergent and supported by the medial and lateral distal part of the tibial shaft. This allows for reduction and stabilization of the fracture.

Results:

A total of 13 patients were included, with a mean age of 10 years and a mean follow-up of 32 months. The size of the nail varied between 2.5 and 4 mm. The mean surgical time was 54 minutes. The DIN technique provided a satisfying reduction (coronal and sagittal angulation <3 degrees) for the 13 fractures. In addition, there was no secondary displacement at 6 weeks. All patients were healed at 6 months, with no clinical torsion or axis malalignment.

Conclusions:

The current study confirms the feasibility and the efficiency of the DIN method to treat fracture of the distal third of the tibia.
Infusing, sustaining, and replenishing compassion in health care organizations through compassion practices
Authors: McClelland Laura E. , Vogus Timothy J.
Published: March 2019

Background

Human suffering is prevalent and costly in health care organizations. Recent research links the use of compassion practices with improved patient experience and employee well-being, but little is known about how these practices create and sustain compassion to address workplace suffering and enhance care quality.

Purpose

This study examines the dynamics of compassion practices, specifically how compassion practices create and sustain compassion in caregiving work.

Methodology

We conducted a qualitative field study at two acute care hospitals utilizing three forms of data collection: semistructured interviews, nonparticipant observation, and archival data. Data were analyzed utilizing thematic coding.

Results

Both organizations attempted to foster workplace compassion through their hiring, socialization, employee support, and rewards practices.

Conclusion

Organizations enable compassion through common organizational practices that perform three functions: (a) infusing the organization with new members and resources to enact compassion, (b) sustaining compassion by reinforcing its appropriateness in the workplace, and (c) replenishing compassion resources by improving and restoring employee well-being and ability to provide high-quality compassionate care.

Practice Implications

This study provides managers with a detailed guide for how health care organizations use compassion practices as a managerial tool to address two key challenges: (a) high rates of employee ill-being due to the demanding nature of the work and (b) providing high-quality compassionate care.
An international, consensus-derived Core Outcome Set for Cardiac Arrest effectiveness trials: the COSCA initiative
Authors: Haywood Kirstie L. , Whitehead Laura , Perkins Gavin D.
Published: March 2019

Purpose of review

Accurate and relevant assessment is essential to determining the impact of ill-health and the relative benefit of healthcare. This review details the recent development of a core outcome set for cardiac arrest effectiveness trials – the COSCA initiative.

Recent findings

The reported heterogeneity in outcome assessment and a lack of outcome reporting guidance were key triggers for the development of the COSCA. The historical failure of existing research to adequately capture the perspective of survivors and their family members in defining survival is described. Working collaboratively with international stakeholders – including survivors, family members and advocates – as research partners and participants ensured that a range of perspectives were considered throughout all stages of COSCA development. Three core domains and methods of assessment were recommended: survival – at 30 days or hospital discharge; neurological function assessed at 30 days or hospital discharge with the modified Rankin Scale; and health-related quality of life assessed at 90 days (as a minimum) with one of three generic measures.

The COSCA recommendation describes a small group of outcomes that should be reported as a minimum across large, randomized clinical effectiveness trials for cardiac arrest.
Emotional Awareness and Cognitive Performance in Borderline Intellectual Functioning Young Adolescents
Authors: Smirni Daniela , Smirni Pietro , Di Martino Giovanni , Operto Francesca Felicia , Carotenuto Marco
Published: March 2019

According toDSM-5andICD-10, borderline intellectual functioning (BIF) should not be classified properly as a disorder. However, BIF people may present relevant problems of adaptive functioning in several areas of daily activities, and they seem to be more vulnerable to mental diseases. Young adolescence may be considered a particular period for emotional information processing. The “own and others' emotions” awareness can play a crucial role in many daily life situations, such as decision making, interpersonal relationships, and decoding of facial expressions. On this background, a BIF young adolescents group underwent a neuropsychological assessment including emotional and cognitive domains, and was compared with a healthy young adolescents control group (HC). In the overall sample, a significant negative correlation between general intellectual abilities and emotional awareness was found. The BIF group showed a significantly greater level of alexithymia and a poorer performance in higher cognitive tasks than HC group. As hypothesized, a border cognitive functioning influences mentalization processes as ability to discriminate and monitor emotions, as well as higher domains of cognition.
Estrogen Receptor-α Quantification in Breast Cancer: Concordance Between Immunohistochemical Assays and mRNA-In Situ Hybridization for ESR1 Gene
Authors: Thomsen Christian , Nielsen Søren , Nielsen Boye S. , Pedersen Sine H. , Vyberg Mogens
Published: March 2019

Immunohistochemical (IHC) quantification of estrogen receptor-α (ER) is used for assessment of treatment regimen in breast cancer. Different ER IHC assays may produce diverging results, because of different antibody clones, protocols, and stainer platforms. Objective tissue-based techniques to assess sensitivity and specificity of IHC assays are therefore needed. We tested the usability of ER mRNA-in situ hybridization (mRNA-ISH) in comparison with assays based on clones SP1 and 6F11. We selected 56 archival specimens according to their reported ER IHC positivity, representing a wide spectrum from negative to strongly positive cases. The specimens were used to prepare 4 TMAs with 112 cores. Serial sections of each TMA were stained for ER and pan-cytokeratin (PCK) by IHC and ESR1 (ER gene) by mRNA-ISH. Digital image analysis (DIA) was used to determine ER IHC H-score. ESR1 mRNA-ISH was scored both manually and by DIA. DIA showed a nonlinear correlation between IHC and ESR1 mRNA-ISH with R2-values of 0.80 and 0.78 for the ER antibody clones SP1 and 6F11, respectively. Comparison of manual mRNA-ISH scoring categories and SP1 and 6F11 IHC H-scores showed a highly significant relationship (P<0.001). In conclusion, the study showed good correlation between mRNA-ISH and IHC, suggesting that mRNA-ISH can be a valuable tool in the assessment of the sensitivity and specificity of ER IHC assays.
Prediction of Mortality in Newborn Infants With Severe Congenital Diaphragmatic Hernia Using the Chest Radiographic Thoracic Area*
Authors: Dassios Theodore , Ali Kamal , Makin Erica , Bhat Ravindra , Krokidis Miltiadis , Greenough Anne
Published: March 2019

Objectives:

To evaluate whether the preoperative chest radiographic thoracic area in newborn infants with congenital diaphragmatic hernia was related to the length of mechanical ventilation and the total length of stay and whether chest radiographic thoracic area predicted survival to discharge from neonatal care.

Design:

Retrospective observational cohort study.

Setting:

Tertiary neonatal unit at King’s College Hospital National Health Service Foundation Trust, London, United Kingdom.

Patients:

Newborn infants admitted with congenital diaphragmatic hernia at King’s College Hospital in a 10-year period (2007–2017).

Interventions:

The chest radiographic thoracic area was assessed by free hand tracing of the perimeter of the thoracic area as outlined by the diaphragm and the rib cage and excluded the mediastinal structures and abdominal contents in the thorax and calculated using the Sectra PACS software (Sectra AB, Linköping, Sweden).

Measurements and Main Results:

Eighty-four infants with congenital diaphragmatic hernia (70 left-sided) were included with a median (interquartile range) gestation of 36 weeks (34–39 wk). Fifty-four (64%) survived to discharge from neonatal care. In the infants who survived the chest radiographic thoracic area was not related to the length of mechanical ventilation (r = 0.136; p = 0.328) or the total duration of stay (r = 0.095; p = 0.495). The median (interquartile range) chest radiographic thoracic area was higher in infants who survived (1,780 mm2 [1,446–2,148 mm2]) compared with in the deceased infants (1,000 mm2 [663–1,449 mm2]) after correcting for confounders (adjusted p = 0.01). Using receiver operator characteristics analysis, the chest radiographic thoracic area predicted survival to discharge from neonatal care with an area under the curve of 0.826. A chest radiographic thoracic area higher than 1,299 mm2 predicted survival to discharge with 85% sensitivity and 73% specificity.

Conclusions:

The chest radiograph in infants with severe congenital diaphragmatic hernia can predict survival from neonatal care with high sensitivity and moderate specificity.
Bleeding Scales Applicable to Critically Ill Children: A Systematic Review
Authors: Nellis Marianne E. , Levasseur Julie , Stribling Judy , Faustino E. Vincent S. , Zantek Nicole D. , Sheth Sujit , Karam Oliver
Published: March 2019

Objectives:

To summarize current bleeding scales and their validation to assess applicability to bleeding in critically ill children.

Data Sources:

We conducted electronic searches of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and Web of Science Core Collection databases from database inception to 2017.

Study Selection:

Included studies contained a bleeding score, bleeding measurement tool, or clinical measurement of hemorrhage.

Data Extraction:

We identified 2,097 unique citations; 20 full-text articles were included in the final review.

Data Synthesis:

Of the 18 studies that included subjects (two others were expert consensus definitions), seven (39%) were pediatric-only, seven (39%) were adult-only, and four (22%) included both adults and children. Nine (50%) occurred with inpatients (two studies in critical care units), seven (39%) involved outpatients and two (11%) included both inpatients and outpatients. Thirty-nine percent of the scales were developed for those with idiopathic thrombocytopenic purpura and only two (12%) described critically ill patients. The majority (80%) included need for treatment (either RBC transfusion or surgical intervention). The majority (65%) did not report measures of reliability or validation to clinical outcomes.

Conclusions:

There is a lack of validated bleeding scales to adequately assess bleeding and outcomes in critically ill children. Validated scales of bleeding are necessary and urgently needed.
Age Matching of Elderly Liver Grafts With Elderly Recipients Does Not Have a Synergistic Effect on Long-term Outcomes When Both Are Carefully Selected
Authors: Gilbo Nicholas , Jochmans Ina , Sainz-Barriga Mauricio , Nevens Frederik , van der Merwe Schalk , Laleman Wim , Verslype Chris , Cassiman David , Verbeke Len , van Malenstein Hannah , Roskams Tania , Pirenne Jacques , Monbaliu Diethard
Published: March 2019

Background

Older donors and recipients are increasingly considered for liver transplantation. Both donor and recipient age have a negative impact on outcomes. Large registry analyses show that older donors are frequently matched to older recipients. Whether age-related risks accumulate in a synergic negative effect on outcomes because of donor-recipient age matching is poorly understood.

Methods

We investigated the impact of donor-recipient age interaction on patient and death-censored graft survival in multivariate Cox regressions in 849 transplants (January 2000 to December 2015).

Results

Donors 70 years or older did not affect long-term patient or graft survival. Recipient age independently increased the risk of death (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05, P < 0.0001), but donor-recipient age interaction was noninfluential. The negative impact of recipient age on patient survival was significant as early as 6 months after transplantation (HR, 1.06; 95% CI, 1.03-1.09; P = 0.00008). The adjusted risk of death was significant for patients aged 60 to 69 years (HR, 1.995; 95% CI, 1.40-2.85; P < 0.0001) and 70 years or older (HR, 2.001; 95% CI, 1.10-2.66; P = 0.04). In contrast, the risk of graft loss was not influenced by recipient age (HR, 1.02; 95% CI, 0.996-1.04; P = 0.11) or age interaction.

Conclusions

Older livers can be safely used in older recipients without jeopardizing graft and patient survival if other risk factors are minimized.
Molecular characterization and antifungal susceptibility testing of Candida nivariensis from blood samples – an Iranian multicentre study and a review of the literature
Authors: Arastehfar Amir , Daneshnia Farnaz , Salehi Mohammad-Reza , Zarrinfar Hossein , Khodavaisy Sadegh , Haas Pieter-Jan , Roudbary Maryam , Najafzadeh Mohammad-Javad , Zomorodian Kamiar , Charsizadeh Arezoo , Brouwer Carlo , Pan Weihua , Hagen Ferry , Boekhout Teun
Published: March 2019

Purpose. Identification of the emerging yeast species Candida nivariensis among presumptively identified Iranian Candida glabrata isolates.

Methodology. Clinical C. glabrata species complex isolates from blood (n=100; 46.9%), vaginal swabs (n=20; 9.4%), bronchoalveolar lavage (n=10; 4.7%) and sputum (n=12; 5.6%) from 68 patients from Iran were investigated. Isolates were characterized by CHROMagar, multiplex PCRs, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), amplified fragment length polymorphism (AFLP) fingerprinting, internal transcribed spacer (ITS)/large subunit (LSU) rDNA and FKS1/FKS2 sequencing, and the European Committee on Antimicrobial Susceptibility Testing broth microdilution method. A comprehensive literature review was conducted and all the relevant clinical and microbiological data were collected.

Results. Four C. nivariensis isolates were recovered from blood samples of three subjects and were all consistently identified by nine-plex PCR, Bruker MALDI-TOF MS, and LSU and ITS rDNA sequencing. AFLP genotyping clustered the isolates into two groups. Sequencing of the FKS1 and FKS2 hotspots showed no accountable amino acid substitutions. All isolates were susceptible to amphotericin B, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin and micafungin.

Conclusion. In total, 4 out of 213 clinical C. glabrata species complex candidemia isolates were C. nivariensis. Improvement of the BioMerieux Vitek MS database is required to accurately identify C. nivariensis and it is advised to alternatively use CHROMagar and/or PCR-based techniques. As other species within the Nakaseomyces clade may cause infection and showed high MIC values for antifungals, inclusion of their spectra into the MALDI-TOF MS database seems relevant. Due to developing resistance to fluconazole and insufficient efficacy of caspofungin, the combination of catheter removal plus treatment with caspofungin, or voriconazole, or micafungin might be effective for patients.
Phenotyping women based on dietary macronutrients, physical activity and body weight using machine-learning tools
Authors: Ramyaa Ramyaa , Hosseini Omid , Krishnan Giri P , Krishnan Sridevi
Published: March 2019

Background

Nutritional phenotyping is a promising approach to achieve personalized nutrition. While conventional statistical approaches haven’t enabled personalizing well yet, machine-learning tools may offer solutions that haven’t been evaluated yet.

Objective

The primary aim of this study was to use energy balance components – input (dietary energy intake and macronutrient composition), output (physical activity) to predict energy stores (body weight) as a way to evaluate their ability to identify potential phenotypes based on these parameters.

Methods

We obtained data from the Women’s Health Initiative –Observational Study (WHI-OS) from BioLINCC. We chose dietary macronutrients – carbohydrate, protein, fats, fiber, sugars & physical activity variables – energy expended from mild, moderate and vigorous intensity activity h/wk to predict current body weight either numerically (as kg of body weight) or categorically (as BMI categories). Several machine-learning tools were used for this prediction – k-nearest neighbors (kNN), decision trees, neural networks (NN), Support Vector Machine (SVM) regressions and Random Forest. Further, predictive ability was refined using cluster analysis, in an effort to identify putative phenotypes.

Results

For the numerical predictions, kNN performed best (Mean Approximate Error (MAE) of 2.71kg, R2 of 0.92, Root mean square error (RMSE) of 4.96kg). For categorical prediction, ensemble trees (with nearest neighbor learner) performed best (93.8% accuracy). K-means cluster analysis identified 11 clusters suggestive of phenotypes, based on significantly improved predictive accuracy. Within clusters, individual macronutrient gain and loss modeling identified that some clusters were strongly predicted by dietary carbohydrate while others by dietary fat.

Conclusions

Machine-learning tools in nutritional epidemiology could be used to identify putative phenotypes.
Bocaparvovirus, Erythroparvovirus and Tetraparvovirus in New World Monkeys from Central America
Authors: Chaves-Friedlander A. , Ibarra-Cerdena C.N. , López-Pérez A.M. , Monge O. , Avendaño R. , Ureña-Saborio H. , Chavarría M. , Zaldaña K. , Sánchez L. , Ortíz-Malavassi E. , Suzan G. , Foley J. , Gutiérrez-Espeleta G.A.
Published: March 2019

Parvoviruses in the genera Bocaparvovirus (HBoV), Erythroparvovirus (B19) and Tetraparvovirus (PARV4) are the only autonomous parvoviruses known to be associated with human and non-human primates based on studies and clinical cases in humans worldwide and non-human primates in Asia and Africa. Here, the presence of these pathogenic agents was assessed by PCR in blood and feces from 55 howler monkeys, 112 white-face monkeys, 3 squirrel monkeys, and 127 spider monkeys in Costa Rica and El Salvador. Overall, 3.7% of the monkeys had HboV DNA, 0.67% had B19 DNA, and 14.1% had PARV4 DNA, representing the first detection of these viruses in New World monkeys. Sex was significantly associated with the presence of HBoV, males having risk up to nine times compared with females. Captivity was associated with increased prevalence for PARV4 and when all viruses were analyzed together. This work underscores the importance of future research aimed at understanding how these viruses behave in natural environments of the Neotropics, and what variables may favor their presence and transmission.
Global state of deworming coverage and inequity in low-income and middle-income countries: a spatiotemporal study of household health surveys
Authors: Lo Nathan C. , Heft-Neal Sam , Coulibaly Jean T. , Leonard Leslie , Bendavid Eran , Addiss David G.
Published: March 2019

Introduction

Mass deworming against soil-transmitted helminthiasis (STH) is a hallmark program in the neglected tropical diseases portfolio that is designed to be equitable and “pro-poor”. However, the extent to which current deworming treatment programs achieve equitable coverage across wealth class and gender remains unclear, and the current public health metric of national deworming coverage does not include representation of inequity. This study develops a framework to measure both coverage and equity in global deworming to guide future programmatic evaluation, investment, and metric design.

Methods

We used nationally representative, geospatial household survey data that measured mother-reported deworming receipt in pre-school age children (age 1-4 years) in the previous 6 months. We estimated global deworming coverage disaggregated by geography, wealth quintile and gender and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming receipt and ecological correlates of equitable deworming.

Findings

Our study included 820,883 pre-school age children living in 50 STH-endemic countries between 2004 and 2017. Globally, the mean global deworming coverage in pre-school children was estimated at 36%. The sub-national coverage ranged from 0.5% to 87.5%, and within-country variation was greater than between-country variation in coverage. The equity index was undesirable (deworming was consistently concentrated in the wealthier populations) in every endemic region of 12 countries. Of the 31 study countries that WHO reported achieving the goal of 75% national coverage, 26 had persistent inequity in deworming as defined by the mean equity index. Deworming equity modestly improved over time, and within-country variation in inequity decreased over time. We did not detect differences in deworming equity by gender. We found the strongest household correlates of deworming to be vitamin A supplementation and receipt of three doses of diphtheria-tetanus-pertussis vaccine (DTP3), while the strongest ecological predictors of equitable deworming were regions with higher coverage of health services such as DTP3 and vitamin A supplementation.

Interpretation

Although mass deworming is considered to be “pro-poor”, we find substantial inequities by wealth, despite often high reported national coverage. These inequities appear to be geographically heterogeneous, modestly improving over time, and we found no evidence of gender differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and gender with incorporation of an equity index to complement national deworming coverage.

Funding

Bill and Melinda Gates Foundation, Stanford University Medical Scientist Training Program
Seasonal stability and dynamics of DNA methylation in plants in a natural environment
Authors: Ito Tasuku , Nishio Haruki , Tarutani Yoshiaki , Emura Naoko , Honjo Mie N. , Toyoda Atsushi , Fujiyama Asao , Kakutani Tetsuji , Kudoh Hiroshi
Published: March 2019

Organisms survive in naturally fluctuating environments by responding to long-term signals, such as seasonality, by filtering out short-term noise. DNA methylation has been considered a stable epigenetic mark but has also been reported to change in response to experimental manipulations of biotic and abiotic factors. However, it is unclear how they behave in natural environments. Here, we analyzed seasonal patterns of genome-wide DNA methylation at a single-base resolution using a single clone from a natural population of the perennial Arabidopsis halleri. The genome-wide pattern of DNA methylation was primarily stable, and most of the repetitive regions were methylated across the year. Although the proportion was small, we detected seasonally methylated cytosines (SeMCs) in the genome. SeMCs in the different contexts showed distinct seasonal patterns of methylation. SeMCs in CHH context were detected predominantly at repetitive sequences in intergenic regions. Additionally, we found that CHH methylation within AhgFLC locus showed a seasonal pattern that was negatively associated with changes in gene expression. Gene-body CG methylation (gbM) itself was generally stable across seasons, but the levels of gbM were positively associated with seasonal stability of RNA expression of the genes. These results suggest the existence of two distinct aspects of DNA methylation in natural environments: sources of epigenetic variation and epigenetic marks for stable gene expression.
The causal effect of adiposity on hospital costs: Mendelian Randomization analysis of over 300,000 individuals from the UK Biobank
Authors: Dixon Padraig , Hollingworth William , Harrison Sean , Davies Neil M , Smith George Davey
Published: March 2019

Estimates of the marginal effect of measures of adiposity such as body mass index (BMI) on healthcare costs are important for the formulation and evaluation of policies targeting adverse weight profiles. Many existing estimates of this association are affected by endogeneity bias caused by simultaneity, measurement error and omitted variables. The contribution of this study is to avoid this bias by using a novel identification strategy – random germline genetic variation in an instrumental variable analysis – to identify the presence and magnitude of the causal effect of BMI on inpatient hospital costs. We also use data on genetic variants to undertake much richer testing of the sensitivity of results to potential violations of the instrumental variable assumptions than is possible with existing approaches. Using data on over 300,000 individuals, we found effect sizes for the marginal unit of BMI more than 50% larger than multivariable effect sizes. These effects attenuated under sensitivity analyses, but remained larger than multivariable estimates for all but one estimator. There was little evidence for non-linear effects of BMI on hospital costs. Within-family estimates, intended to address dynastic biases, were null but suffered from low power. This paper is the first to use genetic variants in a Mendelian Randomization framework to estimate the causal effect of BMI (or any other disease/trait) on healthcare costs. This type of analysis can be used to inform the cost-effectiveness of interventions and policies targeting the prevention and treatment of overweight and obesity, and for setting research priorities.
High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: a cross-sectional study
Authors: Armitage Edwin P. , Senghore Elina , Darboe Saffiatou , Barry Momodou , Camara Janko , Bah Sulayman , Marks Michael , Cerami Carla , Roca Anna , Antonio Martin , Turner Claire E. , de Silva Thushan I.
Published: March 2019

Background

Scabies is a WHO neglected tropical disease common in children in low-and middle-income countries. Excoriation of scabies lesions can lead to secondary pyoderma infection, most commonly byStaphyloccocus aureusandStreptococcus pyogenes(group A streptococcus, GAS), with the latter linked to acute post-streptococcal glomerulonephritis (APSGN) and potentially rheumatic heart disease (RHD). There is a paucity of data on the prevalence of these skin infections and their bacterial aetiology from Africa.

Materials/methods

A cross-sectional study, conducted over a four-month period that included the dry and rainy season, was conducted to determine the prevalence of common skin infections in Sukuta, a peri-urban settlement in western Gambia, in children <5 years. Swabs from pyoderma lesions were cultured forS. aureusand GAS.

Results

Of 1441 children examined, 15.9% had scabies (95% CI 12.2-20.4), 17.4% had pyoderma (95% CI 10.4-27.7) and 9.7% had fungal infections (95% CI 6.6-14.0). Scabies were significantly associated with pyoderma (aOR 2.74, 95% CI 1.61-4.67). Of 250 pyoderma swabs, 80.8% were culture-positive forS. aureus, and 50.8% for GAS. Participants examined after the first rains were significantly more likely to have pyoderma than those examined before (aRR 2.42, 95% CI 1.38-4.23), whereas no difference in scabies prevalence was seen (aRR 1.08, 95% CI 0.70-1.67). Swab positivity was not affected by the season.

Conclusions

High prevalence of scabies and pyoderma were observed. Pyoderma increased significantly during rainy season. Given the high prevalence of GAS pyoderma among children, further research on the association with RHD in West Africa is warranted.

This cross-sectional study of skin infections in The Gambia revealed prevalence of scabies, pyoderma and fungal infections in children <5 years of 15.9%, 17.4% and 9.7% respectively, with increased bacterial skin infections in the rainy season.
The representational space of observed actions
Authors: Tucciarelli Raffaele , Wurm Moritz F. , Baccolo Elisa , Lingnau Angelika
Published: March 2019

Categorizing and understanding other people’s actions is a key human capability. Whereas there exists a growing literature regarding the organization of objects, the representational space underlying the organization of observed actions remain largely unexplored. Here we examined the organizing principles of a large set of actions and the corresponding neural representations. Using multiple-regression representational similarity analysis of fMRI data, in which we accounted for variability due to major action-related features (body parts, scenes, movements, objects), we found that the semantic dissimilarity structure was best captured by patterns of activation in the lateral occipitotemporal cortex (LOTC) and the left posterior inferior parietal lobe (IPL). Together, our results demonstrate that the organization of observed actions in the LOTC and the IPL resembles the organizing principles used by participants to classify actions behaviorally, in line with the view that these regions are crucial for accessing the meaning of actions.
A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits
Authors: Foley Christopher N , Staley James R , Breen Philip G , Sun Benjamin B , Kirk Paul D W , Burgess Stephen , Howson Joanna M M
Published: March 2019

Genome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation in multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 second). We performed a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits. HyPrColoc identified 43 regions in which CHD colocalized with ≥1 trait, including 5 potentially new CHD loci. Across the 43 loci, we further integrated gene and protein expression quantitative trait loci to identify candidate causal genes.
Polygenic architecture of human neuroanatomical diversity
Authors: Biton Anne , Traut Nicolas , Poline Jean-Baptiste , Aribisala Benjamin S. , Bastin Mark E. , Bülow Robin , Cox Simon R. , Deary Ian J. , Fukunaga Masaki , Grabe Hans J. , Hagenaars Saskia , Hashimoto Ryota , Kikuchi Masataka , Muñoz Maniega Susana , Nauck Matthias , Royle Natalie A. , Teumer Alexander , Hernandez Maria Valdes , Völker Uwe , Wardlaw Joanna M. , Wittfeld Katharina , Yamamori Hidenaga ,   Alzheimer’s Disease Neuroimaging Initiative, Bourgeron Thomas , Toro Roberto
Published: March 2019

We analysed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26,000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r∼0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (∼51%) captured ∼1.5 times more genetic variance than the rest; and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF<5% captured <1/4th of the genetic variance. We also observed extensive pleiotropy across regions, with an average genetic correlation of rG∼0.45. Genetic correlations were similar to phenotypic and environmental correlations, however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture.
Effect of Foraging and Nest Defense tradeoffs on the Reproductive Success of Wood Storks (Mycteria americana)
Authors: Bruant Alexis , Picardi Simona , Frederick Peter , Basille Mathieu
Published: March 2019

In many species of birds, parental care is provided by both parents to maximize offspring survival, and there may be important trade-offs between maximizing food gathering and nest protection during the nesting period. The role of parental care in determining reproductive success was investigated in Wood Storks (Mycteria americana), and specifically how the trade-off between frequency and duration of foraging trips, and nest protection has contributed to the nesting outcome. Parental behavior of 85 pairs of Wood Storks was monitored throughout the nesting season in two breeding colonies in Palm Beach County, Florida. Wood Storks have gradually increased the frequency, but not the duration, of foraging trips as chicks developed. The ratio of hatchlings to fledglings was positively associated with the frequency of foraging trips during late chick development. Intra-specific aggressions resulting in nest takeovers have affected 32 % of the nests under study. Occurrence of nest takeovers have been higher for later-breeding pairs, and was happened primarily in the first few weeks of incubation, but was not affected by the degree of joint nest attendance of both parents. These results establish a functional link between parental effort and reproductive outcome in Wood Storks, and highlight the importance of frequent foraging trips, but not nest attendance, by parents.
Crystal structure of 1-heptafluorotolyl-closo-1,2-dicarbadodecaborane
Authors: Watson James D. , Benton Amanda , Tricas Hugo , Rosair Georgina M. , Welch Alan J.
Published: March 2019

The molecular structure of the title compound 1-(2′,3′,5′,6′-tetrafluoro-4′-trifluoromethylphenyl)-closo-1,2-dicarbadodecaborane, C9H11B10F7, features an intramolecular ortho-F...H2 hydrogen bond [2.11 (2) Å], which is responsible for an orientation of the heptafluorotolyl substituent in which the plane of the aryl ring nearly eclipses the C1—C2 cage connectivity.
Allyl 6-amino-4-(4-chlorophenyl)-5-cyano-2-methyl-4H-pyran-3-carboxylate
Authors: Krishnan G. Anantha , Mohandas T. , Kumar C. Udhaya , Pillai M. Velayutham , Sakthivel P.
Published: March 2019

In the title compound, C17H15ClN2O3, the 4H-pyran ring exhibits a shallow-boat conformation and the chlorobenzene ring occupies an axial position. The O-allyl side chain is disordered over two orientations in a 0.585 (14):0.415 (14) ratio. In the crystal, inversion dimers linked by pairs of weak N—H...N hydrogen bonds generate R
2
2(12) loops and N—H...O hydrogen bonds link the dimers into [001] chains.