bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatics Model of Serum Biomarkers to Prognosticate the Response to Programmed Death-1/Ligand-1 Targeted Immunotherapy in Metastatic Non–Small Cell Lung Cancer
Authors: Tarhoni Imad , Multani Maneet , Fughhi Ibtihaj , Gerard David , Fidler Mary , Batus Marta , Bonomi Philip , Borgia Jeffrey
Published: September 2019

Introduction

Immune-checkpoint inhibitors revolutionized the therapeutic paradigm for metastatic non–small cell lung cancer (NSCLC). The average response, however, still hovers at 20%, demonstrating the urgent need for biomarkers predictive of response. High-throughput laboratory technology promises to serve as an insightful and robust tool to recognize and select patterns of biomarkers in serum. We applied machine learning on serum immune-checkpoint biomarkers for prognostication of response to immunotherapy in advanced NSCLC.

Method

Pretreatment sera from 106 advanced NSCLC cases who failed frontline chemotherapy were evaluated for 16 soluble immune-checkpoint molecules using the Human Immuno-Oncology Checkpoint Protein Panel (MilliporeSigma). This panel constituted BTLA, CD27, CD28, TIM-3, HVEM, CD40, GITR, GITRL, LAG-3, TLR-2, PD-1, PD-L1, CTLA-4, CD80, CD86, and ICOS. Primary data points were collected and calculated via a Luminex FLEXMAP 3D system (xPONENT v4.0.3 Luminex Corp). The minimum follow-up after treatment was 12 months. Response patterns were categorized based on their overall survival (OS) as long-term responders (>12 months) or short-term responders (<12 months). Values were analyzed with the clinical outcomes using “Survminer” and “survival” R packages to determine the log-rank-based cutoff values associated with overall survival. Finally, machine learning methods were implemented using “caret” and “rpart” R packages to fit a classification model to predict the response pattern. The model was trained and tested on random fractions of the cohort.

Results

BTLA4, HVEM, CD40, GITRL, LAG-3, PD-1, CD80, and CD86 serum levels significantly correlated with OS (all P values ≤.02 and HR of 0.27, 0.5, 4.59, 0.17, 0.12, 0.48, 3.64, and 0.37, respectively). The algorithm composing PD-1, LAG-3, CD86, and CTLA4 predicted the response pattern with PPV of 81%, specificity of 87%, and accuracy of 75%.

Conclusion

The serum immune-checkpoint predictive model might assist in the tissue and gene-based profiling of immune-checkpoints to predict the benefit from immunotherapy.
Importance of Predictive Biomarkers and Epigenetics in Health: Novel Solutions in Clinical Care
Authors: Jaffe Russell , Mani Jayashree
Published: September 2019

Introduction/Objective

Chronic health issues precipitate from a myriad of origins. We underline three common underlying causes: cumulative repair deficits, oxidative damage and metabolic acidosis. A unique set of predictive biomarkers (PBs) addressing these aspects is presented that has been developed on the premise that epigenetics influence 92% and genetics influence the remaining 8% of health. Together with an individualized and personalized treatment plan, this approach has shown to provide best health outcomes.

Methods

(1) To tailor therapeutic management of chronic conditions, predictive tests that have a variance of 5% or less are used and their “least risk, most gain” goal values are adhered to instead of usual or normal statistical ranges. This helps confirm specific individual need and facilitates effective monitoring of outcome results. Repair deficit is measured by hsCRP, oxidative damage measured by homocysteine, Omega 3 index, and 8OhdG; immune intolerance indicated by lymphocyte response assays and metabolic acidosis indicated by urine pH assessment. (2) Individualized nutrient protocols are formulated based on predictive biomarker results. (3) A metabolically alkalinizing diet is initiated with the goal to providing a buffering effect on cellular chemistry. For example, dietary sugars and refined flours are the single biggest triggers of inflammation driving hyperinsulinemia leading to a biochemical cascade that alters gene expression promoting inflammation.

Results

This proactive approach is evidence based and has been shown to lower costs while enhancing individual outcomes when compared to current best standards of care, reducing risks, and adding “years to life and life to years.”

Conclusion

There is a difference between known tests and functional predictive tests—identifies individual epigenetic risks better. Least risk-highest gain goal values are more relevant than normal lab values. Choosing the right kind of high-sensitivity biomarkers and adopting an associated lifestyle plan can improve quality of clinical care.
Evaluation of the Proliferation of Breast Cancer Cells Among Women in Osun State, Southwest Nigeria
Authors: Iyiola Sina , Ifeoma Enweani , Ngokere Anthony , Avwioro Godwin , Komolafe Akinwumi
Published: September 2019

Objectives

Nigeria has one of the highest morbidity rates from breast cancer; therefore, this work examined the proliferation rate of breast cancer and the hospital presentation time lag among women in Osun State, Nigeria.

Methods

This cross-sectional study was carried out in Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife and Ladoke Akintola University Teaching Hospital, Oshogbo, Nigeria. The request cards and tissue blocks were sorted from the year 2014 to 2017. The time lag it took the patients to report at the hospitals was retrieved from the request cards. The breast tissue blocks were sectioned, stained with H&E, and graded. A representative tissue block was selected for each patient. Sections obtained from the blocks were stained with Mki67 antibody using a diaminobenzidine horseradish peroxidase technique. The cells were semiquantitatively scored as percentage of tumor cells stained brown. The mean ± SD was calculated.

Results

Out of 240 breast cancer patients sampled, 6 (2.5%), 97 (40.4), and 137 (57.1%), respectively, were grades 1, 2, and 3. The mean value of MKi67 was 23.90 ± 20.38, median 16.00. The mean value for grade 2 cancer was 15.31 ± 14.34; grade 3 cancer was 37.95 ± 22.47. Only 21.9% of breast cancer patients came to clinic within 3 months of lumps awareness in their breasts while 64.5% attended clinic after 6 months.

Conclusions

Breast cancer among the Osun State women was not very aggressive when comparing the Mki67 values obtained in this study with the values obtained in the developed world. Greater percentages of women with breast cancer waited too long before presenting themselves at the hospital. Thus, a high morbidity rate was recorded.
CDC and Clinical Laboratory Partners: Analysis of Biosafety Gaps Revealed During the Ebola Outbreak
Authors: Cornish Nancy , Campbell Sheldon , Weirich Elizabeth
Published: September 2019

Objectives

Patient care and public health in the United States depend on timely and reliable clinical laboratory testing. A third of the roughly 500 million yearly patient visits to health care providers involve at least one laboratory test, and approximately 70% of medical decisions are based upon test results. However, the performance of clinical laboratory testing could be compromised by patient specimens potentially contaminated with highly infectious materials. The importance of biosafety in clinical laboratories was highlighted during the 2014 Ebola crisis, where fears about safety resulted in some institutions refusing or delaying tests on patient specimens, which resulted in delayed diagnoses and contributed to patient deaths.

Methods

In collaboration with subject matter experts from academia, medical centers, and federal institutions, the Centers for Disease Control and Prevention has reviewed the capability of clinical laboratories to safely test patient specimens potentially contaminated with highly infectious materials, like Ebola. Current biosafety guidance for clinical laboratories has been largely based on biosafety practices in research laboratories, so the guidelines do not always correspond to clinical laboratories and may be incomplete or occasionally inconsistent. While essential to patient care, clinical laboratories are also unique environments with specialized equipment, processes, and therefore distinct challenges. Here we discuss the complexity of clinical laboratories and describe how applying current biosafety guidance to clinical laboratories may be difficult and confusing at best or inappropriate and harmful at worst. We describe biosafety gaps and opportunities for improvement in the areas of ethics; risk assessment and management; automated and manual laboratory disciplines; specimen collection, processing, and storage; test utilization; waste management; laboratory personnel training and competency assessment; and accreditation processes.

Conclusion

These identified gaps in knowledge and practice could inform future research and education in clinical laboratory biosafety.
An Institutional Review of Pathologist Approval of Send-Out Testing: A Look at Financial Impact
Authors: Peterson Daniel , Foulis Philip , Agosti Steven
Published: September 2019

Introduction

Beginning in 2012, the Choosing Wisely campaign sought to identify tests or procedures whose necessity should be questioned to ensure that they are truly necessary. This study aims to look at the inappropriate usage of relatively uncommon “send-out” laboratory tests that, although rare for the majority of patients, carry a much higher financial cost than more common “in-house” tests. The study objective is to gain an understanding of the fiscal impact of pathology approval of send-out test orders.

Methods

The laboratory records of send-out tests that were either approved or cancelled by the pathology department based on explicit test specific criteria were reviewed from 2004 to May 8, 2018. This review totaled 49,935 unique patients, 115,484 unique accessions for a send-out test order, and 588 unique send-out tests that did not meet criteria encompassing a menu of 725 send-out tests. The cost of each send-out test, number of cancelled tests, and number of approved tests were examined to reveal which cancelled test orders accounted for the most savings.

Conclusion

This study showed that, with no policy in place for pathology approval of send-out testing, inappropriate test orders may contribute to 30% of the cost of all send-out testing. The three areas of testing that contributed to the costliest amount of inappropriate ordering (41% of overall savings) were cytogenetics, FISH, and HIV/HCV treatment susceptibility testing. This information may be used to address the root cause of the issue by educating clinicians as to the appropriate clinical indications of certain send-out tests, the tests most commonly inappropriately ordered, and the tests that require the greatest discretion when ordering. Further study is necessary to address possible interventions that may resolve the root cause of inappropriate send-out test orders.
Implementation of an Algorithmic Approach to Molecular Infectious Disease Laboratory Testing on Cerebrospinal Fluid Samples
Authors: Maris Alexander , Hughes Caitlin , Antoine-Reid Thessicar , Schmitz Jonathan
Published: September 2019

Rapid turnaround time for infectious disease laboratory testing is critical for the encephalitic/meningitic patient. Clinicians and emergency medicine providers often will bundle cerebrospinal fluid (CSF) studies (cell counts, glucose, protein) with molecular infectious disease laboratory (MIDL) assays, up front, to expedite clinical decision making about antimicrobial therapy and hospital admission. Many patients, however, ultimately do not have CSF pleocytosis and, predictably, have negative MIDL results. We quantified patients who had MIDL testing ordered, without concurrent CSF pleocytosis, to justify a mandated algorithm for CSF MIDL testing. Four months of MIDL CSF results were reviewed (viral monoplex PCRs); 274 patients were identified. Forty-seven percent of patients (128/274) were neonates (<2 months old) and thus may not have had the immunologic capacity to mount a pleocytosis to CNS infection. Of the remaining 53% of patients (>2 months old), who would have been expected to generate a CSF pleocytosis, 55% (81/146) had one or more MIDL studies ordered without CSF pleocytosis; 3.4% of these patients (5/146) did not have CSF cell counts ordered. Among all patients, 7.7% (21/274) had positive MIDL results (1 HSV1; 2 HSV2; 18 enterovirus). Seventeen patients had CSF pleocytosis; the 4 patients without CSF pleocytosis were neonates (3) or had no cell counts ordered (1). A ratio of 700 RBC to 1 WBC was used to approximate the expected number of CSF WBC in bloody taps (10%; 28/274). We show that over half of patients >2 months old had MIDL studies ordered without CSF pleocytosis; all patients with positive MIDL results had CSF pleocytosis or were neonates or had no cell counts ordered. An algorithm will be implemented in which all neonates with concern for CNS infection will have CSF MIDL tests ordered; among nonneonates, only those with documented CSF pleocytosis may have MIDL assays ordered (with rare exceptions; eg, leukopenia).
A Comparison of Ordering Pattern of Laboratory Send-Out Tests Between Naturopathic Doctors and General Practitioners in a Pediatric Population
Authors: Liao Hsuan-Chieh , Baird Geoffrey , Dickerson Jane
Published: September 2019

Objectives

Naturopathy is defined as the practice of medicine for the treatment of human diseases with natural agents. It also emphasizes prevention and promotion of health through the self-healing process of the body. Even without any illness or symptoms, naturopathic doctors (NDs) often advocate for and use unique lab tests to make clinical judgments. Tests that are performed outside of the ordering institution, send-out tests, are at increased risk of ordering the wrong or unnecessary test and misinterpreting test results. Here we evaluate the laboratory send-out tests that were ordered by NDs and general practitioners (GPs) at a tertiary pediatric care center to identify opportunities for improved laboratory stewardship.

Methods

We performed a retrospective analysis from Seattle Children’s laboratory send-out tests, which were ordered between January 1, 2018, and December 31, 2018. We compared the tests ordered by NDs with general practitioners in our practice, by grouping the following provider specialties: adolescent medicine, family medicine, or pediatrics. All the requests were reviewed and categorized by test type: heavy metal, allergen, infectious disease, hormone and vitamin, hematology and immunology, toxicology, oncology, genetics, and others. Ordering frequency and abnormal rate from each category were analyzed. The abnormal rate was defined as percentage of abnormal results divided by total number of ordered tests.

Results

During the 12-month period, there were 20,312 send-out tests; 1,028 (5.1%) of them were ordered by 83 NDs for 329 patients, and 3,862 (19.0%) of them were ordered by 462 GPs for 2,139 patients. The most frequently ordered tests by NDs were heavy metal screens (506 tests, 49.2% of total), allergen panels (31.7%), and infectious disease tests (7.0%). The corresponding abnormal rates were 8.5%, 0.9%, and 8.3%, respectively, with an overall abnormal rate of 6.6%. For GPs, the most frequently ordered tests were hormone and vitamin analyses (1,346 tests, 34.9% of total), hematology and immunology tests (22.5%), and heavy metal screens (10.8%). The corresponding abnormal rates were 18.1%, 35.9%, and 18.8% and overall abnormal rate was 17.8%.

Conclusion

We observed different ordering patterns between GPs and NDs, with rates of abnormal findings significantly higher from the tests ordered by GPs. These data suggest some of the tests ordered by NDs have low positive predictive value or clinical significance and could be potentially mis- or overutilized. Understanding the patterns and the variety of testing from different providers can help target interventions to improve laboratory stewardship in this area.
Improving Adherence to the HIV Testing Algorithm With Resident Physician Intervention
Authors: Johnson Kimberly , Buchan Blake , Colon-Franco Jessica
Published: September 2019

Introduction

The CDC recommends the following algorithm for HIV testing: (1) a screening HIV-1/HIV-2 Ag/Ab immunoassay, (2) HIV-1/HIV-2 antibody differentiation immunoassay, and, if these results are discordant, (3) HIV-1 nucleic acid test (NAT). Final interpretation of this algorithm depends on its completion. To assess the adherence of this algorithm, a retrospective chart review was performed to reveal that 31% of discordant results were not followed up by NAT. A prospective interventional study was devised to improve adherence to the algorithm.

Methods

A retrospective chart review was performed on all HIV testing performed from January 2017 to June 2018. The patients with discordant results without NAT were identified. These results then prompted a prospective interventional study. Starting in November 2018, a daily automated report was created to identify patients with discordant results and no NAT ordered after 48 hours. This report prompted the client services department to either call the provider if they were an outside client and tell them to contact the pathology resident, or call the resident directly if the provider was an internal client. The resident then provided guidance to order NAT. The total number of patients with discordant results with the intervention was monitored for adherence to the algorithm indicated by clinicians ordering the NAT. Preliminary data from November 2018 to March 2019 were analyzed and compared to the original data.

Results

The retrospective data revealed a total of 71 patients with discordant results and 22 (31%) did not have NAT testing. The preliminary prospective data revealed a total of 27 patients with discordant results and 3 (11%) did not have NAT testing. These data were found to be statistically significant with P = .04 with a chi-square test.

Conclusion

Resident physician intervention has significantly improved the adherence to the HIV testing algorithm based on preliminary data.
Opsoclonus Myoclonus Ataxia Syndrome With Anti–Glutamic Acid Decarboxylase Antibody Positive: Response to Plasma Exchange
Authors: Taherian Mehran , Aghighi Maryam , Petras Melissa
Published: September 2019

Objectives

Opsoclonus myoclonus syndrome (OMS) is a very rare neurological disorder of probably autoimmune origin. Glutamic acid decarboxylase antibody (GAD-Ab) is one of many antibodies that have been associated with OMS. Common treatments include intravenous immunoglobulin (IVIG) and corticosteroids. To our knowledge, this is the fourth case of GAD-Ab-positive OMS reported and the first one responsive to plasma exchange (PLEX).

Clinical Presentation

The patient is a 77-year-old male who presented with new-onset tremors and gait disorder. He had been diagnosed with OMS and positive GAD-Ab 2 years ago. At the time of diagnosis, his condition was not responsive to IVIG or corticosteroids and seemed to improve following PLEX. He made a near full recovery and was prescribed a low dose of mycophenolate. The patient reported worsening in tremor and gait over the last several days. This was the first time he had signs of clinical relapse since diagnosis. His labs were notable for hyponatremia, elevated glucose, and acute kidney injury. Brain CT showed intracranial atherosclerosis and age-indeterminate generalized cortical atrophy, perhaps due to chronic microangiopathic white matter changes. GAD-Abs assessed on this admission were zero (normal is less than 5), whereas they were 143 before treatment 2 years ago, although no GAD-Ab titer was measured after PLEX. The patient received five sessions of PLEX with overall improvement.

Conclusion

We reported a rare case of OMS with positive GAD-Ab who responded to PLEX. GAD-Ab may be a predictive marker of patient symptoms and is recommended to be measured in patients with OMS before and after treatment.
Distribution of Blood Types and ABO Gene Frequencies in Egypt
Authors: Abdelmonem Mohamed , Fyala Amira , Boraik Ayman , Shedid Mohamed , Mohamed Amira Husseiny , Abdel-Rhman Mohammad
Published: September 2019

ABO blood group was first discovered by Landsteiner in 1901. Currently, there are more than 30 blood group systems, but ABO system remains the most clinically important of all blood groups in transfusion practice. The ABO blood group system antibodies are naturally occurring without any exposure to RBCs through transfusion or pregnancy, unlike the other blood group systems.

Method

The study was performed on a total of 40,591 healthy blood donors in Egypt. ABO and Rh (D) groupings were performed on all donors’ samples. Data on the frequency of ABO and Rh(D) blood groups were reported in numbers and percentages.

Results

The study showed that type A is the most common blood group (35.12%) in Egypt followed by O at 31.94%, followed by B at 23.12%, while AB had the least prevalence at 9.74%; A > O > B > AB. Our study showed that 91.78% of the donor population were Rh positive and 8.22% were Rh negative. The frequencies of the IA, IB, and IO alleles were calculated using the Hardy-Weinberg law of equilibrium. The calculated gene frequencies are 0.2537 for IA (p), 0.1812 for IB (q), and 0.5651 for IO (r). In the Egyptian population, O (r) records the highest value, followed by B (q) and A (p); O > B > A. The homozygous types were as follows: OO, 31.94%; AA, 6.43%; and BB, 3.28%. The heterozygous types were AO, 28.67%; BO, 20.47%; and AB, 9.78%.

Conclusions

The study provides the first accurate ABO gene frequency data as well as information on the distribution of ABO blood group Rh groups of various alleles in the Egyptian population. This information is very helpful in the effective management of the blood bank inventory. It will help transfusion services planning for future health challenge and improve blood transfusion practice.
Agreement of Enzyme-Linked Immunosorbent Assay With Rapid Plasma Reagin and Treponema pallidum Hemagglutination Assay for Screening and Diagnosis of Syphilis at National Blood Bank Service in Addis Ababa, Ethiopia
Authors: Ibrahim Jemal , Afework Ejigayehu , Hussein Mintewab
Published: September 2019

Objectives

To determine the agreement of enzyme-linked immunosorbent assay (ELISA) with rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) at the National Blood Bank Service in Addis Ababa, Ethiopia.

Methods

The study was conducted from January to June 2016 on 190 syphilis ELISA positive and 190 negative samples stored at the National Blood Bank Service (NBBS) laboratory, Addis Ababa, Ethiopia, from July 2015 to December 2015. A systematic random sampling method was used to select samples. The data were analyzed by SPSS version 20 software. The overall percent agreement, kappa value, sensitivity, specificity, positive predictive value, and negative predictive value of the tests were calculated.

Results

From 190 positive sera, 151 (80%) were confirmed as positive by TPHA, and 39 (20%) were found false positive; 59 (31.1%) of them were positive and 131 (68.9%) were false positive by RPR. From 190 negative sera, all were negative by RPR and TPHA. The sensitivity, specificity, positive predictive value, and negative predictive value of TPHA were 99.9%, 85%, 79%, and 100%, respectively, while RPR was 62%, 99%, 100%, and 63%, respectively. Overall percent agreement of ELISA with TPHA was 90% and corresponding kappa value was 0.795, and ELISA with RPR was 66% with a kappa value of 0.375.

Conclusion

TPHA was very sensitive; there was substantial agreement with ELISA. Whereas RPR was highly specific and less sensitive, there was fair agreement with ELISA. TPHA can be used interchangeably with ELISA to screen blood in blood bank laboratories.
Economics, Race, and the Postwar US Novel: A Quantitative Literary History
Authors: Sinykin Daniel , So Richard Jean , Young Jessica
Published: September 2019

How has the language of economics, as codified by economics as a discipline, entered the US novel in the postwar period? Have economists influenced novelists at the level of language, and if so, how and how much? We begin with the belief, inferred from current scholarship on economics and culture, but never before empirically tested, that economic language became more prevalent around 1980, especially among white men—a belief that we strive to complicate and give nuance. Readers may detect an irony in the relationship between our method and case study. No academic discipline has valorized the use of quantification for social analysis more than economics. As a discipline, its language has become saturated with the language of modeling. Cultural and literary critics have long argued that economics has even harmed society by creating false accounts of how humans behave and think. Can we take their tools, however, and make them ours as a way to critique economics itself?
Quantifying hydrologic controls on local- and landscape-scale indicators of coastal wetland loss
Authors: Stagg Camille L , Osland Michael J , Moon Jena A , Hall Courtney T , Feher Laura C , Jones William R , Couvillion Brady R , Hartley Stephen B , Vervaeke William C
Published: September 2019

Background and Aims

Coastal wetlands have evolved to withstand stressful abiotic conditions through the maintenance of hydrologic feedbacks between vegetation production and flooding. However, disruption of these feedbacks can lead to ecosystem collapse, or a regime shift from vegetated wetland to open water. To prevent the loss of critical coastal wetland habitat, we must improve understanding of the abiotic–biotic linkages among flooding and wetland stability. The aim of this research was to identify characteristic landscape patterns and thresholds of wetland degradation that can be used to identify areas of vulnerability, reduce flooding threats and improve habitat quality.

Methods

We measured local- and landscape-scale responses of coastal wetland vegetation to flooding stress in healthy and degrading coastal wetlands. We hypothesized that conversion of Spartina patens wetlands to open water could be defined by a distinct change in landscape configuration pattern, and that this change would occur at a discrete elevation threshold.

Key Results

Despite similarities in total land and water cover, we observed differences in the landscape configuration of vegetated and open water pixels in healthy and degrading wetlands. Healthy wetlands were more aggregated, and degrading wetlands were more fragmented. Generally, greater aggregation was associated with higher wetland elevation and better drainage, compared with fragmented wetlands, which had lower elevation and poor drainage. The relationship between vegetation cover and elevation was non-linear, and the conversion from vegetated wetland to open water occurred beyond an elevation threshold of hydrologic stress.

Conclusions

The elevation threshold defined a transition zone where healthy, aggregated, wetland converted to a degrading, fragmented, wetland beyond an elevation threshold of 0.09 m [1988 North American Vertical Datum (NAVD88)] [0.27 m mean sea level (MSL)], and complete conversion to open water occurred beyond 0.03 m NAVD88 (0.21 m MSL). This work illustrates that changes in landscape configuration can be used as an indicator of wetland loss. Furthermore, in conjunction with specific elevation thresholds, these data can inform restoration and conservation planning to maximize wetland stability in anticipation of flooding threats.
Neurobehavioral Outcomes in School-Aged Children with Primary Snoring
Authors: Hagström Kati , Saarenpää-Heikkilä Outi , Himanen Sari-Leena , Lampinlampi Anna-Maria , Rantanen Kati
Published: September 2019

Objective

We assess behavioral and attentional problems and neurocognitive functioning in school-aged children with primary snoring (PS).

Methods

Seventeen children with PS and 27 non-snoring peers aged 6–10 years took part in the study. All children underwent a polysomnography (PSG) at the Sleep Laboratory. Snoring was defined by parents and with PSG. Children with obstructive sleep apnea were excluded. The parents completed the Sleep Disturbance Scale for Children. Parents and teachers assessed behavioral and attentional problems with the Child Behavior Checklist and the Conners’ Rating Scale-Revised. Neuropsychological assessment included the Wechsler Intelligence Scale for Children and the Developmental Neuropsychological Assessment (NEPSY test).

Results

The PS group had significantly more parent-reported internalizing, total, and attentional problems than the control group. Teachers did not report behavioral problems in the PS group. The PS and control groups had equal IQ scores and similar core neurocognitive functions, except for one visuospatial subtest. The PS group had significantly more inspiratory flow limitation and increased diaphragmatic electromyography compared with the controls. Parents reported significantly more daytime sleepiness in the PS group. Daytime sleepiness and snoring time were consistently associated with more behavioral and attentional problems. Flow limitation and more oxygen saturation values under 90% were associated with attentional problems, higher oxygen desaturation index, and lower mean oxygen saturation percentage with reduced language functions.

Conclusions

Snoring with an increase in respiratory effort without apneas and hypopneas and parent-reported daytime sleepiness may be linked to daytime symptoms. School-aged children with PS are at risk for behavioral and attentional problems, but not cognitive impairments.
PPNID: a reference database and molecular identification pipeline for plant-parasitic nematodes
Authors: Qing Xue , Wang Meng , Karssen Gerrit , Bucki Patricia , Bert Wim , Braun-Miyara Sigal
Published: September 2019

Motivation

The phylum Nematoda comprises the most cosmopolitan and abundant metazoans on Earth and plant-parasitic nematodes represent one of the most significant nematode groups, causing severe losses in agriculture. Practically, the demands for accurate nematode identification are high for ecological, agricultural, taxonomic and phylogenetic researches. Despite their importance, the morphological diagnosis is often a difficult task due to phenotypic plasticity and the absence of clear diagnostic characters while molecular identification is very difficult due to the problematic database and complex genetic background.

Results

The present study attempts to make up for currently available databases by creating a manually-curated database including all up-to-date authentic barcoding sequences. To facilitate the laborious process associated with the interpretation and identification of a given query sequence, we developed an automatic software pipeline for rapid species identification. The incorporated alignment function facilitates the examination of mutation distribution and therefore also reveals nucleotide autapomorphies, which are important in species delimitation. The implementation of genetic distance, plot and maximum likelihood phylogeny analysis provides more powerful optimality criteria than similarity searching and facilitates species delimitation using evolutionary or phylogeny species concepts. The pipeline streamlines several functions to facilitate more precise data analyses, and the subsequent interpretation is easy and straightforward.

Availability and implementation

The pipeline was written in vb.net, developed on Microsoft Visual Studio 2017 and designed to work in any Windows environment. The PPNID is distributed under the GNU General Public License (GPL). The executable file along with tutorials is available at https://github.com/xueqing4083/PPNID.

Supplementary information

Supplementary data are available at Bioinformatics online.
Bugs: Rethinking the History of Computing
Authors: McKinney Cait , Mulvin Dylan
Published: September 2019

This paper argues that scholars of computing, networks, and infrastructures must reckon with the inseparability of “viral” discourses in the 1990s. This co-assembled history documents the reliance on viral analogies and explanations honed in the HIV/AIDS crisis and its massive loss of life, widespread institutional neglect, and comprehensive technological failures. As the 1990s marked a period of intense domestication of computing technologies in the global North, we document how public figures, computer experts, activists, academics, and artists used the intertwined discourses surrounding HIV and new computer technologies to explicate the risks of vulnerability in complex, networked systems. The efficacy of HIV as an analogy is visible in the circulation of viral concepts, fears surrounding interdependence, and emergent descriptions of precarity in the face of a widespread “infrastructure crisis.” Through an analysis of this decade, we show how HIV/AIDS discourses indelibly marked the domestication of computing, computer networks, and nested, digitized infrastructures.
Potentially inappropriate medications in older adults: a population-based cohort study
Authors: Roux Barbara , Sirois Caroline , Simard Marc , Gagnon Marie-Eve , Laroche Marie-Laure
Published: September 2019

Background

Non-optimal medication use among older adults is a public health concern. A concrete picture of potentially inappropriate medication (PIM) use is imperative to ensure optimal medication use.

Objective

To assess the prevalence of PIMs in community-dwelling older adults and identify associated factors.

Methods

A retrospective population-based cohort study was conducted using the Quebec Integrated Chronic Disease Surveillance System (QICDSS). The QICDSS includes data on drug claims for community-dwelling older adults with chronic diseases or at risk of developing chronic diseases aged ≥65 years who are insured by the public drug insurance plan. Individuals aged ≥66 years who were continuously insured with the public drug plan between 1 April 2014 and 31 March 2016 were included. PIMs were defined using the 2015 Beers criteria. We conducted multivariate robust Poisson regression analyses to explore factors associated with PIM use.

Results

A total of 1 105 295 individuals were included. Of these, 48.3% were prescribed at least one PIM. The most prevalent PIMs were benzodiazepines (25.7%), proton-pump inhibitors (21.3%), antipsychotics (5.6%), antidepressants (5.0%) and long-duration sulfonylureas (3.3%). Factors associated with PIM exposure included being a woman [rate ratio (RR): 1.20; 95% confidence interval (CI): 1.20–1.21], increased number of medications and having a high number of chronic diseases, especially mental disorders (RR: 1.50; 95% CI: 1.49–1.51).

Conclusion

Almost one out of two community-dwelling older adults use a PIM. It is imperative to reduce the use of PIMs, by limiting their prescription and by promoting their deprescribing, which necessitates not only the active involvement of prescribers but also patients.
Influence of labeling on the glycan affinities and specificities of glycan-binding proteins. A case study involving a C-terminal fragment of human galectin-3
Authors: Kitova Elena N , Han Ling , Vinals Daniel F , Kitov Pavel I , Derda Ratmir , Klassen John S
Published: September 2019

Glycan interactions with glycan-binding proteins (GBPs) play essential roles in a wide variety of cellular processes. Currently, the glycan specificities of GBPs are most often inferred from binding data generated using glycan arrays, wherein the GBP is incubated with oligosaccharides immobilized on a glass surface. Detection of glycan–GBP binding is typically fluorescence-based, involving the labeling of the GBP with a fluorophore or with biotin, which binds to fluorophore-labeled streptavidin, or using a fluorophore-labeled antibody that recognizes the GBP. While it is known that covalent labeling of a GBP may influence its binding properties, these effects have not been well studied and are usually overlooked when analyzing glycan array data. In the present study, electrospray ionization mass spectrometry (ESI-MS) was used to quantitatively evaluate the impact of GBP labeling on oligosaccharide affinities and specificities. The influence of three common labeling approaches, biotinylation, labeling with a fluorescent dye and introducing an iodination reagent, on the affinities of a series of human milk and blood group oligosaccharides for a C-terminal fragment of human galectin-3 was evaluated. In all cases labeling resulted in a measurable decrease in oligosaccharide affinity, by as much as 90%, and the magnitude of the change was sensitive to the nature of the ligand. These findings demonstrate that GBP labeling may affect both the absolute and relative affinities and, thereby, obscure the true glycan binding properties. These results also serve to illustrate the utility of the direct ESI-MS assay for quantitatively evaluating the effects of protein labeling on ligand binding.
A rapid assessment of the political economy of health at district level, with a focus on maternal, newborn and child health, in Bangladesh, Indonesia, Nepal and the Philippines
Authors: Hipgrave David B , Anderson Ian , Sato Midori
Published: September 2019

Low- and middle-income countries (LMICs) face many challenges and competing demands in the health sector, including maternal and newborn mortality. The allocation of financial and human resources for maximum health impact is important for social and economic development. Governments must prioritize carefully and allocate scarce resources to maximum effect, but also in ways that are politically acceptable, financially and institutionally feasible, and sustainable. Political economy analysis (PEA)—that gets what, when and why—can help explain that prioritization process. We used PEA to investigate how four Asian LMICs (Bangladesh, Indonesia, Nepal and the Philippines) allocate and utilize resources for maternal, newborn and child health (MNCH). Using mixed research methods including a literature review, field interviews at national and sub-national level, and policy, process and budget analysis in each country, we examined three political economy issues: (1) do these countries demonstrably prioritize MNCH at policy level; (2) if so, is this reflected in the allocation of financial and other resources and (3) if resources are allocated to MNCH, do they achieve the intended outputs and outcomes through actual programme implementation? We also considered the influence of transnational developments. We found that all four countries demonstrate political commitment to health, including MNCH. However, the health sector receives comparatively low public financing, governments often do not follow through on plans or pronouncements, and capacity for related action varies widely. Poor governance and decentralization, lack of data for monitoring and evaluation of progress, and weak public sector human resource capacity were frequent problems; engagement of the private or non-government sectors is an important consideration. Opportunities exist to greatly improve equity and MNCH outcomes in these nations, using a mix of evidence, improved governance, social engagement and the media to influence decisions, increase resource allocation to and improve accountability in the health sector.
Impact of integrated healthcare: Taiwan’s Family Doctor Plan
Authors: Liang Li-Lin
Published: September 2019

Integration of health services has been pursued worldwide. Diversity in integration approaches and in the contexts in which integrated programmes operate, however, hinders comparative analysis of care integration in both high-income countries (HICs) and low- and middle-income countries (LMICs). This study evaluates an HIC programme implemented in a delivery system resembling those of LMICs, especially its weak primary care system. The programme, Taiwan’s Family Doctor Plan (FDP), targets high-cost and chronic patients, incorporating key elements of integrated care, viz., case management, multidisciplinary teams and care pathways. This study estimates the effects of shifting from usual to integrated care and locates contextual factors that may distort programme implementation. To estimate programme effects, difference-in-differences analysis is applied to a balanced panel comprising >160 000 patients over 2009–13. Because physician participation is voluntary, a propensity score matching method is used to match providers. The research findings reveal that introduction of the FDP has not reoriented the model of care from fragmented towards integrated health services. It reduces continuity of care and has no effect on co-ordination of care. Regarding quality of care, the FDP is shown to have no effect on avoidable admissions and increases drug injections and emergency department visits. Several contextual factors may serve as barriers that impede elements of FDP from generating desirable outcomes. These include absence of registration and gatekeeping systems; limited capacities of clinics; and preponderance of fee-for-service remuneration. These findings suggest that HIC design elements may not be directly transferrable to settings with weak primary care systems, as is typical of LMIC healthcare. Changes at the system level, such as establishing regular sources of care, may be necessary before elements of integrated care are introduced to a weaker primary care system.
Responses of ecological indicators to fishing pressure under environmental change: exploring non-linearity and thresholds
Authors: Fu Caihong , Xu Yi , Grüss Arnaud , Bundy Alida , Shannon Lynne , Heymans Johanna J , Halouani Ghassen , Akoglu Ekin , Lynam Christopher P , Coll Marta , Fulton Elizabeth A , Velez Laure , Shin Yunne-Jai
Published: September 2019

Marine ecosystems are influenced by multiple stressors in both linear and non-linear ways. Using generalized additive models (GAMs) fitted to outputs from a multi-ecosystem, multi-model simulation experiment, we investigated 14 major ecological indicators across ten marine ecosystems about their responses to fishing pressure under: (i) three different fishing strategies (focusing on low-, high-, or all-trophic-level taxa); and (ii) four different scenarios of directional or random primary productivity change, a proxy for environmental change. From this work, we draw four major conclusions: (i) responses of indicators to fishing mortality in shapes, directions, and thresholds depend on the fishing strategies considered; (ii) most of the indicators demonstrate decreasing trends with increasing fishing mortality, with a few exceptions depending on the type of fishing strategy; (iii) most of the indicators respond to fishing mortality in a linear way, particularly for community and biomass-based indicators; and (iv) occurrence of threshold for non-linear-mixed type (i.e. non-linear with inflection points) is not prevalent within the fishing mortality rates explored. The conclusions drawn from the present study provide a knowledge base in indicators’ dynamics under different fishing and primary productivity levels, thereby facilitating the application of ecosystem-based fisheries management worldwide.
Lung procurement after circulatory death from donor supported on biventricular assist devices and functional assessment with portable normothermic ex vivo organ care system
Authors: Ali Jason M , Kaul Pradeep , Jenkins David P , Berman Marius
Published: September 2019

The criteria for donor organ acceptance are broadening. We describe a successful lung transplantation following donation after circulatory death of extended criteria donor supported with biventricular assist devices. During the redo sternotomy, we used the biventricular assist devices cannulae to perfuse the lungs through the pulmonary artery cannula and draining via the left and right ventricle cannula, significantly minimizing the ischaemic time. Following procurement, we utilized portable ex vivo lung system (Transmedics™ Lung OCS) to optimize, assess and eventually to proceed to a successful transplant.
Moving frames and Noether’s finite difference conservation laws I
Authors: Mansfield E L , Rojo-Echeburúa A , Hydon P E , Peng L
Published: September 2019

We consider the calculation of Euler–Lagrange systems of ordinary difference equations, including the difference Noether’s theorem, in the light of the recently-developed calculus of difference invariants and discrete moving frames. We introduce the difference moving frame, a natural discrete moving frame that is adapted to difference equations by prolongation conditions. For any Lagrangian that is invariant under a Lie group action on the space of dependent variables, we show that the Euler–Lagrange equations can be calculated directly in terms of the invariants of the group action. Furthermore, Noether’s conservation laws can be written in terms of a difference moving frame and the invariants. We show that this form of the laws can significantly ease the problem of solving the Euler–Lagrange equations, and we also show how to use a difference frame to integrate Lie group invariant difference equations. In this Part I, we illustrate the theory by applications to Lagrangians invariant under various solvable Lie groups. The theory is also generalized to deal with variational symmetries that do not leave the Lagrangian invariant. Apart from the study of systems that are inherently discrete, one significant application is to obtain geometric (variational) integrators that have finite difference approximations of the continuous conservation laws embedded a priori. This is achieved by taking an invariant finite difference Lagrangian in which the discrete invariants have the correct continuum limit to their smooth counterparts. We show the calculations for a discretization of the Lagrangian for Euler’s elastica, and compare our discrete solution to that of its smooth continuum limit.
Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir
Authors: Chesnokov Anton , Patel Mira C , Mishin Vasiliy P , De La Cruz Juan A , Lollis Lori , Nguyen Ha T , Dugan Vivien , Wentworth David E , Gubareva Larisa V
Published: September 2019

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir-resistant viruses needed for informed risk assessment.
Aggregation and Labor Supply Elasticities
Authors: Kneip Alois , Merz Monika , Storjohann Lidia
Published: September 2019

We outline a formal procedure for deriving the aggregate wage-elasticity of labor supply for a large group of heterogeneous workers who operate under uncertainty. Heterogeneity relates to preferences, income, wealth, and the labor market status. If each worker faces a small, possibly nonuniform wage change, the implied aggregate wage-elasticity can be represented by a closed-form expression. This expression captures an extensive and an intensive margin. We empirically implement the procedure for a dynamic model of individual labor supply and a micro panel of men in Germany from 2000 to 2013. We find that the extensive margin is less time-varying than the intensive margin, and that its size varies with the measure of reservation wages. Self-reported reservation wages render a larger extensive margin than other proxies. The estimated aggregate Frisch wage-elasticity varies between 0.85 and 1.06, and the two margins matter equally strongly for the unbalanced sample.