bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of organ doses following high dose rate (HDR) brachytherapy of breast cancer: a Geant4 Monte Carlo simulation study
Authors: Aidil M S , Hashikin N A A , Yeong C H , Guatelli S , Ng K H , Malaroda A , Rosenfeld A B , Perkins A C
Published: June 2019

This study aimed to evaluate the absorbed doses received by the organs at risk (OARs) following Iridium-192 (192Ir) high dose rate (HDR) brachytherapy of the left breast. The MIRD5 adult female anthropomorphic phantom, readily available in the Geant4 Monte Carlo package was used. However, the left breast was modified from 195 to 145 cm3, to represent a breast following lumpectomy. Left breast was chosen due to its higher cancer occurrence than the right breast. The HDR sources were constructed with an outer cylindrical dimension of 4.5 mm (length) × 0.9 mm (diameter). Various influencing parameters were studied, i.e. catheter arrangement (single versus dual plane), source inter-dwell distances (5 versus 10 mm), and different radionuclides, i.e. Cobalt-60 (60Co) and 192Ir, by delivering a total treatment dose of 32 Gy to the left breast. Absorbed doses to the OARs (e.g. left lung, heart, right breast, spleen, etc.) were then evaluated. A maximum left lung dose of 1.5 Gy was recorded, while doses to the other OARs were all below 1 Gy. The treatment using dual plane catheter arrangement contributed to a slightly higher dose to the OARs, despite equal dose to the breast. There was no dose difference between different inter-dwell distances used in this study. 60Co resulted in a slightly higher left lung dose than that of 192Ir, while the results were the opposite for the other OARs. HDR brachytherapy allows high dose to be delivered to the breast within a short period of time, with minimal absorbed doses to the OARs.
Picket fence test of Agility MLCs using linac log data
Authors: Sakaria Kasmayanti , Shaheera Midi Nur , Zin Hafiz M
Published: June 2019

The multileaf collimator (MLC) performance is critical during intensity modulated radiotherapy (IMRT) delivery. Picket fence test is typically performed by acquiring images of MLC gaps using film or electronic portal imaging device (EPID) to assess the MLC positional accuracy as part of a comprehensive weekly quality assurance (QA) programme. This study aims to investigate the accuracy of MLC position of Agility MLCs (Elekta, Stockholm, Sweden) using linac log data. The positions of MLCs were tracked during picket fence test using Elekta’s propriety optical tracking system on the linac head. The data were recorded at four cardinal gantry angles over six weeks. The fluence from the picket fence was constructed using the tracked MLC positions and compared with the fluence obtained from EPID. The fluence of the picket fence pattern constructed from the tracking data of MLC position showed that the measured range of gap size error within -0.3 mm to 0.8 mm. The average MLC positional error tracked was 0.07 mm ± 0.14 mm (mean ± 1 SD). Gap size measured from tracking data was within the range of the results obtained from EPID. Tracking the MLC position using the optical tracking system provide a more accurate test method for routine QA of the MLC performance. Over the period of investigation, it was found that the MLC performance was within the tolerance of ± 1 mm recommended by AAPM TG142.
Study of detectors response on the scatter radiation of 6 MV flattening filter free beams
Authors: Pratiwi R D T , Ryangga D , Pawiro S A
Published: June 2019

Small field dosimetry which related to the use of Flattening Filter Free (FFF) beams is a great challenge because of the perturbation effects caused by the size of the detector’s active volume or detector’s materials. This phenomenon encourages researchers to do a further study about detector response. In this study, scatter and primary radiation from 6 MV FFF photon beams were studied to evaluate the detector response in small fields for a better understanding of the contribution of every phenomenon. Ion chamber and Gafchromic films were used in three measurement configurations representing open field measurement and approximations of both primary and scatter part of the beam, described as follows: (i) detectors positioned under steel block, exposing the detectors only to scatter part of radiation field, (ii) detectors positioned inside mini phantom, approximating the detector response to primary radiation with minimum scatter, (iii) detectors positioned in the standard open field, which was the superposition of the primary and scatter radiation. The results show that detector responses were heavily depended on its design (i.e. active volume) especially in small beams. The detector response in the open field could be reproduced from the blocked and primary beam set-up with a discrepancy ranging from 1.0% to 36%. Moreover, the volume averaging and other phenomenon affecting the detector response could be observed in the blocked beam.
Biodegradable Samarium-153–labelled microspheres for hepatic radioembolization: preparation, characterization and radiolabelling evaluation after neutron activation
Authors: How Wong Yin , Yee Tan Hun , Kasbollah Azahari , Johan Jeet Abdullah Basri , Nazri Md Shah Mohammad , Hong Yeong Chai
Published: June 2019

A biocompatible and biodegradable radioactive samarium-153 (153Sm)-labelled Poly-(L-lactic acid) (PLLA) microspheres was developed for hepatic radioembolization. Samarium acetylacetonate was encapsulated in PLLA microspheres using oil-in-water solvent evaporation method. Physicochemical characterization of the microspheres were analysed using Field Emission Scanning Electron Microscopy, Energy Dispersive X-ray spectroscopy and particle size analyser. The prepared microspheres were irradiated in a nuclear reactor with a neutron flux of 1.49 × 1012 n.cm-2.s-1, converting 152Sm to 153Sm (Emax = 807.6 keV, half-life = 46.3 h). Gamma spectroscopy was carried out to determine the presence of radionuclide impurities while the in-vitro radiolabelling efficiency was performed to analyse the retention of 153Sm on the microspheres. The Sm-labelled PLLA microspheres was found spherical with the diameters within 20-60 μm, as indicated by the scanning electron microscopy and particle size distribution results. Gamma spectrometry suggested that no long half-life radioimpurities present after neutron activation. The 153Sm-labelled PLLA microspheres has achieved a nominal activity of 5.9 GBq.g-1 after 6 h neutron activation. The formulation showed more than 97% radiolabelling efficiency in saline and human blood plasma over 550 h. The 153Sm-labelled PLLA microspheres are potentially useful for hepatic radioembolization due to their biodegradability, favourable radiation characteristics and excellent radiolabelling efficiency. The preparation of the formulation does not involve ionizing radiation and hence reduces the costs of production.
Introducing stereotactic radiotherapy safely: credentialing centres and staff
Authors: Perkins A , Aland T , Dally M , Jhala E , Bailey N , Shannon D , Anderson L
Published: June 2019

Stereotactic radiotherapy treatments use high doses of radiation delivered in relatively few fractions compared with conventional radiotherapy. Specialist planning, immobilization and image guidance techniques are needed to achieve accurate treatment. Because doses are high and fractions few, the consequences of treatment errors are more severe than for conventional therapy. A credentialing program for staff and equipment is one strategy that can be used to reduce risk. The Icon Group runs a network of 20 radiotherapy centres in Australia. There has been a rapid growth of stereotactic treatments at Icon. In order to reduce the risks of introducing stereotactic therapy, an in-house credentialing and endorsement program was developed. A multi-disciplinary working group comprising medical physicists, radiation oncologists and radiation therapists was established to develop endorsement policies and procedures. Elements considered included the purchase, commissioning and quality assurance of equipment, the establishment and documentation of safe work practices and staff competency assessment. The endorsement program is in the process of being implemented across the Icon network.
Remobilization and fate of sulphur in mustard
Authors: Borpatragohain Priyakshee , Rose Terry J , Liu Lei , Barkla Bronwyn J , Raymond Carolyn A , King Graham J
Published: June 2019

Background and Aims

Sulphur (S) is an essential macronutrient involved in numerous metabolic pathways required for plant growth. Crops of the plant family Brassicaceae require more S compared with other crops for optimum growth and yield, with most S ultimately sequestered in the mature seeds as the storage proteins cruciferin and napin, along with the unique S-rich secondary metabolite glucosinolate (GSL). It is well established that S assimilation primarily takes place in the shoots rather than roots, and that sulphate is the major form in which S is transported and stored in plants. We carried out a developmental S audit to establish the net fluxes of S in two lines of Brassica juncea mustard where seed GSL content differed but resulted in no yield penalty.

Methods

We quantified S pools (sulphate, GSL and total S) in different organs at multiple growth stages until maturity, which also allowed us to test the hypothesis that leaf S, accumulated as a primary S sink, becomes remobilized as a secondary source to meet the requirements of GSL as the dominant seed S sink.

Key Results

Maximum plant sulphate accumulation had occurred by floral initiation in both lines, at which time most of the sulphate was found in the leaves, confirming its role as the primary S sink. Up to 52 % of total sulphate accumulated by the low-GSL plants was lost through senesced leaves. In contrast, S from senescing leaves of the high-GSL line was remobilized to other tissues, with GSL accumulating in the seed from commencement of silique filling until maturity.

Conclusion

We have established that leaf S compounds that accumulated as primary S sinks at early developmental stages in condiment type B. juncea become remobilized as a secondary S source to meet the demand for GSL as the dominant seed S sink at maturity.
X—Two Shoes and a Fountain: Ecstasis, Mimesis and Engrossment in Heidegger’s The Origin of the Work of Art
Authors: Mulhall Stephen
Published: June 2019

In this essay, I argue for three interpretative claims about the philosophical strategies and examples employed in the first of Heidegger’s three lectures on ‘The Origin of the Work of Art’. I argue that his initial response to a Van Gogh painting is intended to dramatize a confusion rather than to articulate an insight; that his invocation of a poem by C. F. Meyer serves a number of functions overlooked by other commentators; and that Heidegger’s overall approach is best understood in terms of Michael Fried’s conception of modernism in painting.
Chicdiff: a computational pipeline for detecting differential chromosomal interactions in Capture Hi-C data
Authors: Cairns Jonathan , Orchard William R , Malysheva Valeriya , Spivakov Mikhail
Published: June 2019

Capture Hi-C is a powerful approach for detecting chromosomal interactions involving, at least on one end, DNA regions of interest, such as gene promoters. We present Chicdiff, an R package for robust detection of differential interactions in Capture Hi-C data. Chicdiff enhances a state-of-the-art differential testing approach for count data with bespoke normalization and multiple testing procedures that account for specific statistical properties of Capture Hi-C. We validate Chicdiff on published Promoter Capture Hi-C data in human Monocytes and CD4+ T cells, identifying multitudes of cell type-specific interactions, and confirming the overall positive association between promoter interactions and gene expression.

Availability and implementation

Chicdiff is implemented as an R package that is publicly available at https://github.com/RegulatoryGenomicsGroup/chicdiff.

Supplementary information

Supplementary data are available at Bioinformatics online.
Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo
Authors: Tsolenyanu Enyonam , Bancroft Rowan E , Sesay Abdul K , Senghore Madikay , Fiawoo Mawouto , Akolly Djatougbe , Godonou Mawussi A , Tsogbale Novissi , Tigossou Segla D , Tientcheu Leopold , Dagnra Anoumou , Atakouma Yawo , Sylvanus Ndow Peter , Worwui Archibald , Landoh Dadja E , Mwenda Jason M , Biey Joseph N , Ntsama Bernard , Kwambana-Adams Brenda A , Antonio Martin
Published: June 2019

Background

Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region.

Methods

Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction.

Results

Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2–5 years.

Conclusions

Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo.
Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children
Authors: Turner Paul , Leab Phana , Ly Sokeng , Sao Sena , Miliya Thyl , Heffelfinger James D , Batmunkh Nyambat , Lessa Fernanda C , Walldorf Jenny A , Hyde Terri B , Ork Vichit , Hossain Md Shafiqul , Gould Katherine A , Hinds Jason , Cooper Ben S , Ngoun Chanpheaktra , Turner Claudia , Day Nicholas P J
Published: June 2019

Background

Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years.

Methods

There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012–December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE).

Results

Comparing 2014 with 2016–2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6–21.8) for all pneumococci and 39.2% (95% CI 26.7–46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7–33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4–35.8) by 2018, with a decrease of 36.3% (95% CI 23.8–46.9) for VT IPD and an increase of 101.4% (95% CI 62.0–145.4) for non-VT IPD.

Conclusions

Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.
Validation of the Strengths and Difficulties Self-Report in Norwegian Sign Language
Authors: Aanondsen Chris Margaret , Jozefiak Thomas , Heiling Kerstin , Rimehaug Tormod
Published: June 2019

The majority of studies on mental health in deaf and hard-of-hearing (DHH) children report a higher level of mental health problems. Inconsistencies in reports of prevalence of mental health problems have been found to be related to a number of factors such as language skills, cognitive ability, heterogeneous samples as well as validity problems caused by using written measures designed for typically hearing children. This study evaluates the psychometric properties of the self-report version of the Strengths and Difficulties Questionnaire (SDQ) in Norwegian Sign Language (NSL; SDQ-NSL) and in written Norwegian (SDQ-NOR). Forty-nine DHH children completed the SDQ-NSL as well as the SDQ-NOR in randomized order and their parents completed the parent version of the SDQ-NOR and a questionnaire on hearing and language-related information. Internal consistency was examined using Dillon–Goldstein’s rho, test–retest reliability using intraclass correlations, construct validity by confirmatory factor analysis (CFA), and partial least squares structural equation modeling. Internal consistency and test–retest reliability were established as acceptable to good. CFA resulted in a best fit for the proposed five-factor model for both versions, although not all fit indices reached acceptable levels. The reliability and validity of the SDQ-NSL seem promising even though the validation was based on a small sample size.
Long-term Risk of Advanced Neoplasia After Colonic Low-grade Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study
Authors: De Jong Michiel E , Van Tilburg Sanne B , Nissen Loes H C , Kievit Wietske , Nagtegaal Iris D , Horjus Carmen S , Römkens Tessa E H , Drenth Joost P H , Hoentjen Frank , Derikx Lauranne A A P
Published: June 2019

Background and Aims

The long-term risk of high-grade dysplasia [HGD] and colorectal cancer [CRC] following low-grade dysplasia [LGD] in inflammatory bowel disease [IBD] patients is relatively unknown. We aimed to determine the long-term cumulative incidence of advanced neoplasia [HGD and/or CRC], and to identify risk factors for advanced neoplasia in a nationwide IBD cohort with a history of LGD.

Methods

This is a nationwide cohort study using data from the Dutch National Pathology Registry [PALGA] to identify all IBD patients with LGD between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We determined the cumulative incidence of advanced neoplasia and identified risk factors via multivariable Cox regression analysis.

Results

We identified 4284 patients with colonic LGD with a median follow-up of 6.4 years after initial LGD diagnosis. The cumulative incidence of subsequent advanced neoplasia was 3.6, 8.5, 14.4 and 21.7%, after 1, 5, 10 and 15 years, respectively. The median time to develop advanced neoplasia after LGD was 3.6 years. Older age [≥ 55 years] at moment of LGD (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.44–2.06), male sex [HR 1.33, 95% CI 1.10–1.60], and follow-up at an academic [vs non-academic] medical centre [HR 1.37, 95% CI 1.07–1.76] were independent risk factors for advanced neoplasia following LGD.

Conclusions

In a large nationwide cohort with long-term follow-up of IBD patients with LGD, the cumulative incidence of advanced neoplasia was 21.7% after 15 years. Older age at LGD [≥55 years], male sex and follow-up by a tertiary IBD referral centre were independent risk factors for advanced neoplasia development after initial LGD.
Phantasmata of Dance: Time and Memory within Choreographic Constraints
Authors: Casini Silvia
Published: June 2019

This article contributes to the scholarly discussion of the relationship between cinema and dance using Giorgio Agamben’s understanding of dance as gesture. To render Agamben’s critical framework operative, however, one needs to consider his reference to the concept of phantasmata (images) taken from Domenico da Piacenza’s Renaissance treatise on choreography. Agamben returns to this treatise to support his argument that dance is concerned first and foremost with time and memory rather than space and the present. To notate dance as a sequence of moving images is not simply to make visible on screen a series of bodily movements in space. Rather, it means acknowledging that dancing is primarily a mental activity. Taking Agamben’s reflections on dance and using Maya Deren’s work on screen dance as a case-study, this article discusses how cinema and dance together prompt us to undo the economy of bodily movements, restoring the body to us transfigured.
Distinct Influence of Omega-3 Fatty Acids on the Plasma Metabolome of Healthy Older Adults
Authors: Xyda Souzana-Eirini , Vuckovic Ivan , Petterson Xuan-Mai , Dasari Surendra , Lalia Antigoni Z , Parvizi Mojtaba , Macura Slobodan I , Lanza Ian R
Published: June 2019

Omega-3 polyunsaturated fatty acids (n3-PUFA) are well recognized for their potent triglyceride-lowering effects, but the potential influence of these bioactive lipids on other biological processes, particularly in the context of healthy aging, remains unknown. With the goal of gaining new insight into some less well-characterized biological effects of n3-PUFAs in healthy older adults, we performed metabolomics of fasting peripheral blood plasma collected from 12 young adults and 12 older adults before and after an open-label intervention of n3-PUFA (3.9 g/day, 2.7 g eicosapentaenoic [EPA], 1.2 g docosahexaenoic [DHA]). Proton nuclear magnetic resonance (1H-NMR) based lipoprotein subclass analysis revealed the expected reduction in total triglyceride (TG), but also demonstrated that n3-PUFA supplementation reduced very low-density lipoprotein (VLDL) particle number, modestly increased high-density lipoprotein (HDL) cholesterol, and shifted the composition of HDL subclasses. Further metabolite profiling by 1H-NMR and mass spectrometry revealed pronounced changes in phospholipids, cholesterol esters, diglycerides, and triglycerides following n3-PUFA supplementation. Furthermore, significant changes in hydroxyproline, kynurenine, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) following n3-PUFA supplementation provide further insight into some less well-recognized biological effects of n3-PUFA supplementation, including possible effects on protein metabolism, the kynurenine pathway, and glucose metabolism.
Effects of Weight History on the Association Between Directly Measured Adiposity and Mortality in Older Adults
Authors: Baker Joshua F , Ziolkowski Susan L , Long Jin , Leonard Mary B , Stokes Andrew
Published: June 2019

Background

It is controversial whether an altered relationship between adiposity and mortality occurs with aging. We evaluated associations between adiposity and mortality in younger and older participants before and after considering historical weight loss.

Methods

This study used whole-body dual-energy x-ray absorptiometry data from the National Health and Nutrition Examination Survey in adults at least 20 years of age. Fat mass index (FMI), determined by dual-energy x-ray absorptiometry, was converted to age-, sex-, and race-specific Z-Scores. Percent change in weight from the maximum reported weight was determined and categorized. Cox proportional hazards models assessed associations between quintile of FMI Z-Score and mortality. Sequential models adjusted for percent weight change since the maximum weight.

Results

Participants with lower FMI were more likely to have lost weight from their maximum, particularly among older participants with lower FMI. Substantially greater risk of mortality was observed for the highest quintile of FMI Z-Score compared to the second quintile among younger individuals [HR 2.50 (1.69, 3.72) p < .001]. In contrast, a more modest association was observed among older individuals in the highest quintile [HR 1.23 (0.99, 1.52) p = .06] (p for interaction <.001). In both the younger and older participants, the risks of greater FMI Z-Score were magnified when adjusting for percent weight change since maximum reported weight.

Conclusions

Older people with low fat mass report greater historical weight loss, potentially explaining substantially altered relationships between fat mass and mortality in older individuals. As a result, epidemiologic studies performed in older populations will likely underestimate the causal risks of excess adiposity.
The effect of entrepreneurial origin on firms’ performance: the case of Portuguese academic spinoffs
Authors: Barbosa Natália , Faria Ana Paula
Published: June 2019

We investigate the role of entrepreneurial origin on firms’ performance by comparing academic spinoff firms with their non-academic counterparts. Academic spinoffs grow through resources accumulation and internationalization; yet they do not translate these advantages into productivity gains. The access to upstream complementary resources appears to play a chief role in explaining the academic spinoffs’ superior performance. Academic spinoffs are contributing to economic development by creating new jobs, but their relevance as a source of sustained economic value is limited so far.
Macrococcus canis contains recombinogenic methicillin resistance elements and the mecB plasmid found in Staphylococcus aureus
Authors: Chanchaithong Pattrarat , Perreten Vincent , Schwendener Sybille
Published: June 2019

Objectives

To analyse the genetic context of mecB in two Macrococcus canis strains from dogs, compare the mecB-containing elements with those found in other Macrococcus and Staphylococcus species, and identify possible mobilizable mecB subunits.

Methods

Whole genomes of the M. canis strains Epi0076A and KM0218 were sequenced using next-generation sequencing technologies. Multiple PCRs and restriction analysis confirmed structures of mecB-containing elements, circularization and recombination of mecB subunits.

Results

Both M. canis strains contained novel composite pseudo (Ψ) staphylococcal cassette chromosome mec (SCCmec) elements. Integration site sequences for SCC flanked and subdivided composite ΨSCCmecEpi0076A (69569 bp) into ΨSCC1Epi0076A-ΨSCCmecEpi0076A-ΨSCC2Epi0076A and composite ΨSCCmecKM0218 (24554 bp) into ΨSCCKM0218-ΨSCCmecKM0218. Putative γ-haemolysin genes (hlgB and hlgC) were found at the 3′ end of both composite elements. ΨSCCmecKM0218 contained a complete mecB gene complex (mecIm-mecR1m-mecB-blaZm) downstream of a new IS21-family member (ISMaca1). ΨSCCmecEpi0076A carried a blaZm-deleted mecB gene complex similar to that reported in ‘Macrococcus goetzii’ CCM4927T. A second mecB gene was found on the 81325 bp MDR plasmid pKM0218 in KM0218. This plasmid contained a complete Tn6045-associated mecB gene complex distinct from that of ΨSCCmecKM0218. pKM0218 was almost identical to the mecB-containing plasmid recently reported in Staphylococcus aureus (overall 99.96% nucleotide identity). Mobilization of mecB within an unconventional circularizable structure was observed in Epi0076A as well as chromosomal plasmid insertion via recombination of mecB operons in KM0218.

Conclusions

Our findings provide evidence of both the continuing evolution of mecB-containing elements in macrococci and M. canis as a potential source of the mecB-containing plasmid found in staphylococci.
Assessing clinical heterogeneity in sepsis through treatment patterns and machine learning
Authors: Fohner Alison E , Greene John D , Lawson Brian L , Chen Jonathan H , Kipnis Patricia , Escobar Gabriel J , Liu Vincent X
Published: June 2019

Objective

To use unsupervised topic modeling to evaluate heterogeneity in sepsis treatment patterns contained within granular data of electronic health records.

Materials and Methods

A multicenter, retrospective cohort study of 29 253 hospitalized adult sepsis patients between 2010 and 2013 in Northern California. We applied an unsupervised machine learning method, Latent Dirichlet Allocation, to the orders, medications, and procedures recorded in the electronic health record within the first 24 hours of each patient’s hospitalization to uncover empiric treatment topics across the cohort and to develop computable clinical signatures for each patient based on proportions of these topics. We evaluated how these topics correlated with common sepsis treatment and outcome metrics including inpatient mortality, time to first antibiotic, and fluids given within 24 hours.

Results

Mean age was 70 ± 17 years with hospital mortality of 9.6%. We empirically identified 42 clinically recognizable treatment topics (eg, pneumonia, cellulitis, wound care, shock). Only 43.1% of hospitalizations had a single dominant topic, and a small minority (7.3%) had a single topic comprising at least 80% of their overall clinical signature. Across the entire sepsis cohort, clinical signatures were highly variable.

Discussion

Heterogeneity in sepsis is a major barrier to improving targeted treatments, yet existing approaches to characterizing clinical heterogeneity are narrowly defined. A machine learning approach captured substantial patient- and population-level heterogeneity in treatment during early sepsis hospitalization.

Conclusion

Using topic modeling based on treatment patterns may enable more precise clinical characterization in sepsis and better understanding of variability in sepsis presentation and outcomes.
Quality of Care and Outcomes of Patients With Gynecologic Malignancies Treated at Safety-Net Hospitals
Authors: Gamble Charlotte R , Huang Yongmei , Tergas Ana I , Khoury-Collado Fady , Hou June Y , St. Clair Caryn M , Ananth Cande V , Neugut Alfred I , Hershman Dawn L , Wright Jason D
Published: June 2019

Background

Although safety-net hospitals (SNH) provide a valuable role serving vulnerable patients, the quality of gynecologic oncology care at these hospitals remains inadequately documented. We examined the quality of care at SNH for women with gynecologic cancers.

Methods

We used the National Cancer Database to identify hospitals that treated patients with uterine, ovarian, or cervical cancer from 2004 to 2015. Hospitals with the greatest proportion of uninsured patients or Medicaid beneficiaries were defined as SNH. Quality metrics were derived from evidence-based recommendations. Thirty-day mortality, readmission rates, and 5-year survival were calculated. Multivariable models were developed to determine the association between treatment at SNH and outcomes.

Results

Overall, 594 750 patients diagnosed with gynecologic cancer were treated at 1340 hospitals. Compared with non-SNH, patients at SNH were younger, more frequently racial minorities, low income, and had more aggressive histologies and advanced-stage tumors. SNH had lower rates of minimally invasive surgery for uterine cancer (62.3% vs 75.9%, P < .0001), debulking for ovarian cancer (83.6% vs 86.9%, P < .05), and lymph node assessment for all three cancer types (P < .05). Rates of chemotherapy for uterine and ovarian cancer was greater whereas concurrent chemoradiation for cervical cancer was lower (P < .05 for all). Thirty-day mortality and readmission rates were equivalent. Mortality was moderately worse for patients with stage IV ovarian cancer and stage II–III cervical cancer (P < .05) but were otherwise equivalent.

Conclusions

After adjusting for patient and tumor characteristics, women with gynecologic cancers treated at SNH receive lower-quality surgical care and equivalent medical care and a subset of these patients has modest decreases in survival.
Pancreatic neuroendocrine microadenomatosis presenting as a functional VIPoma
Authors: Krainev Alexei A , Mathavan Viney K , Klink Daniel F , Saxe Jonathan M , Ong Gabie K B , Murphy Jamie K
Published: June 2019

Pancreatic microadenomas are benign tumors of neuroendocrine origin less than 5 mm in size. Whereas most microadenomas are non-functional; a few rare functional pancreatic microadenomas have been described in the setting of multiple endocrine neoplasia type one (MEN-1). In this report, we describe a unique case of multiple functional microadenomas of the pancreatic head in a patient who presented with persistent secretory diarrhea, refractory hypokalemia, metabolic acidosis and elevated plasma vasoactive intestinal peptide (VIP) levels. Following extensive serologic, radiographic and endoscopic work up, our patient underwent open pancreaticoduodenectomy with subsequent resolution of diarrheal symptoms and electrolyte abnormalities on postoperative follow up.
Deconvolution of nucleic-acid length distributions: a gel electrophoresis analysis tool and applications
Authors: Ziraldo Riccardo , Shoura Massa J , Fire Andrew Z , Levene Stephen D
Published: June 2019

Next-generation DNA-sequencing (NGS) technologies, which are designed to streamline the acquisition of massive amounts of sequencing data, are nonetheless dependent on various preparative steps to generate DNA fragments of required concentration, purity and average size (molecular weight). Current automated electrophoresis systems for DNA- and RNA-sample quality control, such as Agilent’s Bioanalyzer® and TapeStation® products, are costly to acquire and use; they also provide limited information for samples having broad size distributions. Here, we describe a software tool that helps determine the size distribution of DNA fragments in an NGS library, or other DNA sample, based on gel-electrophoretic line profiles. The software, developed as an ImageJ plug-in, allows for straightforward processing of gel images, including lane selection and fitting of univariate functions to intensity distributions. The user selects the option of fitting either discrete profiles in cases where discrete gel bands are visible or continuous profiles, having multiple bands buried under a single broad peak. The method requires only modest imaging capabilities and is a cost-effective, rigorous alternative characterization method to augment existing techniques for library quality control.
Haemodiafiltration does not lower protein-bound uraemic toxin levels compared with haemodialysis in a paediatric population
Authors: Snauwaert Evelien , Van Biesen Wim , Raes Ann , Glorieux Griet , Vande Walle Johan , Roels Sanne , Vanholder Raymond , Askiti Varvara , Azukaitis Karolis , Bayazit Aysun , Canpolat Nur , Fischbach Michel , Saoussen Krid , Litwin Mieczyslaw , Obrycki Lukasz , Paglialonga Fabio , Ranchin Bruno , Samaille Charlotte , Schaefer Franz , Schmitt Claus Peter , Spasojevic Brankica , Stefanidis Constantinos J , Shroff Rukshana , Eloot Sunny
Published: June 2019

Background

Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment.

Methods

In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5–20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months.

Results

For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01).

Conclusions

While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research.
Knowledge, attitudes and behaviour towards needlestick injuries among junior doctors
Authors: Ong M W , Hwang J , Lim S M , Sng J
Published: June 2019

Background

Needlestick injuries (NSIs) are common healthcare-related injuries and possible consequences include blood-borne infections. Despite that, a large proportion of NSIs are not reported.

Aims

To estimate the prevalence of under-reporting of NSIs and to evaluate the knowledge, attitude and behaviour towards NSIs among junior doctors in a tertiary hospital in Singapore.

Methods

An explanatory sequential mixed-methods design was employed. Quantitative data were collected through questionnaires completed by 99 junior doctors. Descriptive statistics and bivariate analysis were performed to evaluate socio-demographic characteristics, NSI history and NSI reporting practices. Qualitative data were collected through 12 in-depth interviews. Participants were purposively recruited, and semi-structured topic guides were developed. Data were analysed using a thematic approach.

Results

Fifty-two per cent of respondents had history of NSI. Of those with history of NSI, 31% did not report injury. NSI reporters were 1.52 times as likely to be aware of how to report injury (P < 0.05), and 1.63 times as likely to feel that reporting benefits their health (P < 0.01) compared with non-reporters. NSI reporters were 83% more likely to report a clean NSI (P = 0.05). For non-reporters, the main reasons for not reporting were perceived low risk of transmission (41%) and lack of time to report (35%). Themes identified in the qualitative data include perceived benefits, perceived barriers, perceived threats, cues to action and organizational culture.

Conclusion

Under-reporting of NSIs may have significant implications for patients and healthcare workers. Addressing identified factors and instituting targeted interventions will help to improve reporting rates.
Prevalence, Magnitude, and Genotype Distribution of Urinary Cytomegalovirus (CMV) Shedding Among CMV-Seropositive Children and Adolescents in the United States
Authors: White Jodie L , Patel Eshan U , Abraham Alison G , Grabowski Mary Kate , Arav-Boger Ravit , Avery Robin K , Quinn Thomas C , Tobian Aaron A R
Published: June 2019

Background

There are limited nationally representative data on correlates of cytomegalovirus (CMV) shedding among children and adolescents. In addition, the genotype distribution of CMV infections has not been well characterized among general populations in the United States

Methods

This study characterized urinary CMV shedding among CMV immunoglobulin G-positive 6- to 19-year-olds in the US household population using data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPR) and corresponding 95% confidence intervals (CIs). Analyses were weighted and multiple imputation was performed to handle missing data (with the exception of CMV genotypes).

Results

Prevalence of urinary CMV shedding was significantly lower among 9- to 11-year-olds (20.6%; aPR = 0.61; 95% CI, 0.44–0.83) and 12- to 19-year-olds (7.0%; aPR = 0.21; 95% CI, 0.14–0.30) compared with 6- to 8-year-olds (34.4%). Among CMV shedders, the youngest age group also had the highest urinary CMV viral loads. The prevalence of urinary CMV shedding among obese individuals was significantly lower compared with lean individuals (aPR = 0.68; 95% CI, 0.47–0.99). Among CMV shedders, glycoprotein B (gB)1 (51%) was the most prevalent gB variant, followed by gB2 (29%), gB3 (21%), and gB4 (13%); glycoprotein H (gH)2 (60%) was more prevalent than gH1 (48%). Multiple (≥2) gB (14%) and multiple gH (7%) infections were detected among CMV shedders.

Conclusions

This study underscores the importance of young children even above the age of 5 years as a potential source of CMV transmission. The detection of multiple CMV strains among CMV shedders may have implications for the transmission of viral diversity as well as vaccine development.
Parental Melts and Magma Storage of a Large-volume Dacite Eruption at Vetrovoy Isthmus (Iturup Island, Southern Kuril Islands): Insights into the Genesis of Subduction-zone Dacites
Authors: Smirnov S Z , Rybin A V , Kruk N N , Timina T Yu , Sokolova E N , Kuzmin D V , Maksimovich I A , Kotov A A , Shevko A Ya , Nizametdinov I R , Abersteiner A
Published: June 2019

Detailed mineralogical and melt and fluid inclusion constraints on magma storage, and the evolution of melts, are presented for the large-volume caldera eruption on the Vetrovoy Isthmus on Itutrup Island (Kuril Islands, Russia). The shallow magma reservoir beneath the Vetrovoy Isthmus is composed of a mush of plagio-rhyolitic melt, phenocrysts and the products of peritectic reaction(s). The melt appears to have formed as a result of partial melting of previously erupted rocks, which probably had andesitic to basaltic compositions and were metamorphosed into amphibole-bearing assemblages. The breakdown of amphibole in the partially melted precursor rocks led to the formation of early Mg-rich clino- and orthopyroxene, along with plagioclase and Fe–Ti oxides, and the release of aqueous fluids. Variations in fluid pressure are recorded by a strong increase of An contents in plagioclase. Crystallization took place at around 850°C with pressure ranging from 0·9 to 3 kbar. This study demonstrates that dacitic magmas erupted during the course of a 20 kyr voluminous eruption were the result of mixing between plagio-rhyolitic partial melts and the breakdown reaction minerals (i.e. pyroxenes, plagioclase and Fe–Ti oxides). Plagioclase and quartz were the last minerals to crystallize from these melts prior to eruption.
Dispersal ability and niche breadth act synergistically to determine zooplankton but not phytoplankton metacommunity structure
Authors: Pujoni Diego Guimarães Florencio , Barros Cristiane Freitas de Azevedo , dos Santos Juliana Barreto Oliveira , Maia-Barbosa Paulina Maria , Barbosa Francisco Antônio Rodrigues
Published: June 2019

It is well known that both niche requirements and dispersal act together to structure communities; however, it remains unclear how the underlying mechanisms create the observed patterns in nature. In plankton communities, traits related to dispersal ability (e.g. body and propagule sizes) and niche breadth (i.e. habitat generalists and habitat specialists) have recently shown promise in this regard. Here, we hypothesized that body size (a proxy for dispersal ability) and niche breadth act together to determine limnetic plankton metacommunity structure in a tropical system of natural landlocked lakes in Brazil. Our hypotheses were partially supported for zooplankton community. Copepoda showed no relation to environmental variables, and the larger-bodied Calanoida was structured only by space. The Cladocera showed the largest spatial and environmental limitation. Rotifers showed the lowest association with space; however, its pure environmental fraction was higher than expected. The phytoplankton community was largely structured by both environment and space. The spatial limitation of this group was a clear divergence from our expectations. Lastly, we revealed that intragroup variation (when species were evaluated individually) was equal or larger than between group variation, indicating that group-specific traits may play a more important role in determining metacommunity structure.
Widespread Pressure Pain Sensitivity over Nerve Trunk Areas in Women with Frequent Episodic Tension-Type Headache as a Sign of Central Sensitization
Authors: Caamaño-Barrios Leandro H , Galán-del-Río Fernando , Fernández-de-las-Peñas César , Plaza-Manzano Gustavo , Arendt-Nielsen Lars , Ortega-Santiago Ricardo
Published: June 2019

Objective

Previous studies reported the presence of widespread pressure pain sensitivity in patients with tension-type headache. However, most of the studies assessed pressure pain sensitivity over muscle tissue. Our aim was to investigate the difference in pressure pain sensitivity over musculoskeletal and nerve symptomatic and distant areas between women with frequent episodic tension-type headache (FETTH) and healthy subjects.

Methods

Thirty-two women with FETTH and 32 matched healthy women participated. Pressure pain threshold (PPT) was bilaterally assessed over several nerve trunks (greater occipital, median, radial, ulnar, common peroneal, tibialis posterior) and musculoskeletal structures (temporalis muscle, C5/C6 joint, tibialis anterior) by an assessor blinded to the subject’s condition. A four-week headache diary was used to collect the intensity, frequency, and duration of headache. The Hospital Anxiety and Depression Scale was used to determine anxiety and depressive levels.

Results

Analysis of covariance found lower widespread and bilateral PPTs over all nerve trunks and musculoskeletal structures in women with FETTH pain (P < 0.001). No significant effect of anxiety and depressive levels on PPTs was found (all P > 0.222). PPT over the temporalis muscle was significantly negatively correlated with headache intensity.

Conclusions

This study found widespread pressure pain hypersensitivity over both nerve trunks and musculoskeletal structures in women with FETTH, suggesting that the presence of central altered nociceptive processing is not just restricted to musculoskeletal areas, for example, muscles, but also pain evoked from directly provoking the nerve trunks by pressure. It is also possible that nerve tissue treatment could lead to a decrease in central sensitization and headache features.
Perturbing neutrino oscillations around the solar resonance
Authors: Martinez-Soler Ivan , Minakata Hisakazu
Published: June 2019

Atmospheric neutrinos at low energies, $E \lesssim 500$ MeV, are known to be a rich source of information on lepton mixing parameters. We formulate a simple perturbative framework to elucidate the characteristic features of neutrino oscillation at around the solar-scale enhancement due to the matter effect. The clearest message that we could extract from our perturbation theory is that CP violation in the appearance oscillation probability is large, a factor of $\sim 10$ times larger than CP violation at around the atmospheric-scale oscillation maximum. The underlying mechanism for this is that one of the suppression factors on the CP phase-dependent terms due to the smallness of $\Delta m^2_{21} / \Delta m^2_{31}$ is dynamically lifted by the solar-scale enhancement. Our framework has a unique feature as a perturbation theory in which a large $\Delta m^2_{31}$ term outside the key 1-2 sector for the solar-scale resonance does not yield sizable corrections. On the contrary, the larger the $\Delta m^2_{31}$, the smaller the higher-order corrections.