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The purpose of this scoping review was to identify available sources of evidence on the epidemiology of transfusion-related acute lung injury (TRALI) and whether meta-analysis on the incidence of TRALI is feasible. TRALI is a serious complication and the second leading cause of death related to blood transfusion. Estimates of the incidence of TRALI would provide a useful benchmark for research to reduce TRALI.We searched the Medline, EMBASE, and PubMed databases for publications related to the incidence of TRALI and hemovigilance. We included all studies irrespective of language or country. Both full-text articles and conference abstracts were included. Participants of the studies must all have received a blood transfusion. Reviews and case studies were excluded.We identified 427 articles or abstracts to include for review. More than half were abstracts, and the majority were published after 2010. Reported TRALI definitions varied, but only 27.2% of studies reported any definition for TRALI. TRALI rates were reported using different denominators, such as per blood unit (54.1%), patient (34.4%), and transfusion episode (14.8%). Study populations and contexts were mostly general (75.6% and 80.3%, respectively). There was also variation in study design with most being observational (90.6%) and only 13.1% of all studies used modern donor restriction policies.There was substantial variation in reporting in studies on TRALI incidence. Meta-analysis of TRALI rates may be feasible in specific circumstances where reporting is clear. Future studies should clearly report key items, such as a TRALI definition.

Non-pathogen reduction platelet bacterial risk control strategies in the US FDA guidance include at least one culture. Almost all of these strategies have a culture hold time of ≥12 h. Studies have reported time to detection (TTD) of bacterial cultures inoculated with bacteria from contaminated platelets, but these data and estimates of risk associated with detection failures have not been synthesized.We performed a literature search to identify studies reporting TTD for samples obtained from spiked platelet components. Using extracted data, regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components are transfused to a patient. We then used published data on time of transfusion (ToT) to estimate the risk of detection failures in practice.The search identified 1427 studies, of which 16 were included for analysis. TTD data were available for 16 different organisms, including 14 in aerobic cultures and 11 in anaerobic cultures. For inocula of 1 colony forming unit (CFU), the average TTD for aerobic organisms was 19.2 h while it was 24.9 h in anaerobic organisms, but there was substantial overall variation. A hold time of 12 versus 24 h had minimal effect for most organisms.TTD variation occurs between bacterial species and within a particular species. Under typical inventory management, the relative contribution of culture detection failures is much smaller than the residual risk from sampling failures. Increasing the hold period beyond 12 h has limited value.

Investigating dispersal in animal populations can be difficult, particularly for taxa that are hard to directly observe such as those that are small or rare. A promising solution may come from new approaches that use genome-wide sequence data to detect close kin dyads and estimate dispersal parameters from the distribution of these dyads. These methods have so far only been applied to mosquito populations. However, they should have broad applicability to a range of taxa, although no assessment has yet been made on their performance under different dispersal conditions and study designs. Here we develop an R package and Shiny app, kindisperse, that can be used to estimate dispersal parameters from the spatial distribution of close kin. Kindisperse can handle study designs that target different life stages and allows for a range of dispersal kernel shapes and organismal life histories; we provide implementation examples for a vertebrate (Antechinus) and an invertebrate (Aedes). We use simulations run in kindisperse to compare the performance of two published close kin methodologies, showing that one method produces unbiased estimates whereas the other produces downward-biased estimates. We also use kindisperse simulations to investigate how study design affects dispersal estimates, and we provide guidelines for the size and shape of sample sites as well as the number of close kin needed for accurate estimates. kindisperse is easily adaptable for application to a variety of research contexts ranging from invasive pests to threatened species where non-invasive DNA sampling can be used to detect close kin.

Heterozygosity is a metric of genetic variability frequently used to inform the management of threatened taxa. Estimating observed and expected heterozygosities from genome-wide sequence data has become increasingly common, and these estimates are often derived directly from genotypes at single nucleotide polymorphism (SNP) markers. While many SNP markers can provide precise estimates of genetic processes, the results of ‘downstream’ analysis with these markers may depend heavily on ‘upstream’ filtering decisions. Here we explore the downstream consequences of sample size, rare allele filtering, missing data thresholds and known population structure on estimates of observed and expected heterozygosity using two reduced-representation sequencing datasets, one from the mosquito Aedes aegypti (ddRADseq) and the other from a threatened grasshopper, Keyacris scurra (DArTseq). We show that estimates based on polymorphic markers only (i.e. SNP heterozygosity) are always biased by global sample size (N), with smaller N producing larger estimates. By contrast, results are unbiased by sample size when calculations consider monomorphic as well as polymorphic sequence information (i.e. genome-wide or autosomal heterozygosity). SNP heterozygosity is also biased when differentiated populations are analysed together while autosomal heterozygosity remains unbiased. We also show that when nucleotide sites with missing genotypes are included, observed and expected heterozygosity estimates diverge in proportion to the amount of missing data permitted at each site. We make three recommendations for estimating genome-wide heterozygosity: (a) autosomal heterozygosity should be reported instead of (or in addition to) SNP heterozygosity; (b) sites with any missing data should be omitted and (c) populations should be analysed in independent runs. This should facilitate comparisons within and across studies and between observed and expected measures of heterozygosity.

Objective To report patient‐reported outcomes of minimally invasive sacroiliac (SI) joint fusion as a case series. Methods This study was a retrospective cohort study of patients 18 years of age and older who underwent a minimally invasive SI joint fusion by a single surgeon between 1 January 2013 and 31 December 2015. Routine demographic data, characteristics, and relevant surgical and clinical data were all collected for this group. In addition, patients completed preoperative and postoperative visual analog scale (VAS) and Short Form 36 (SF‐36) questionnaires to assess outcomes. Patient selection for SI fusion was based on short‐term resolution of symptoms (80% or greater relief) with an image‐guided intra‐articular injection of local anesthetic. Routine statistical analysis was performed using the Wilcoxon signed rank test, Fisher's exact test, or χ2 analysis as appropriate. Results This study included 19 patients comprising 24 SI fusions, with a mean follow‐up of 58 months. The average patient age was 50 years and the average surgical blood loss was 25 cc. Men comprised 79% of the cohort. The VAS score improved from 7 to 3 (P = 0.0001). SF‐36 physical function, role limitations due to physical health, and role limitations due to emotional health improved to a statistically significant extent. General health was not significantly changed. Every patient showed improvement in their SF‐36 physical function scores (mean 40 preoperatively to 55 at final follow up) and 18 of 19 showed improvement in the VAS score (mean 7 preoperatively to 3 at final follow‐up). Conclusion In appropriately selected patients, minimally invasive SI joint fusion results in decreased pain and improved physical functioning of patients, which is sustained for more than 4 years post‐procedure., Minimally invasive SI fusion involves the percutaneous placement of three implants across the SI joint from lateral to medial while sparing the sacral foramina. The implants are coated for bony ingrowth.

Population genomic approaches can characterise dispersal across a single generation through to many generations in the past, bridging the gap between individual movement and intergenerational gene flow. These approaches are particularly useful when investigating dispersal in recently altered systems, where they provide a way of inferring long-distance dispersal between newly established populations and their interactions with existing populations. Human-mediated biological invasions represent such altered systems which can be investigated with appropriate study designs and analyses. Here we apply temporally-restricted sampling and a range of population genomic approaches to investigate dispersal in a 2004 invasion ofAedes albopictus(the Asian tiger mosquito) in the Torres Strait Islands (TSI) of Australia. We sampled mosquitoes from 13 TSI villages simultaneously and genotyped 373 mosquitoes at genome-wide single nucleotide polymorphisms (SNPs): 331 from the TSI, 36 from Papua New Guinea (PNG), and 4 incursive mosquitoes detected in uninvaded regions. Within villages, spatial genetic structure varied substantially but overall displayed isolation by distance and a neighbourhood size of 232–577. Close kin dyads revealed recent movement between islands 31–203 km apart, and deep learning inferences showed incursiveAe. albopictushad travelled to uninvaded regions from both adjacent and non-adjacent islands. Private alleles and a coancestry matrix indicated direct gene flow from PNG into nearby islands. Outlier analyses also detected four linked alleles introgressed from PNG, with the alleles surrounding 12 resistance-associated cytochrome P450 genes. By treating dispersal as both an intergenerational process and a set of discrete events, we describe a highly interconnected invasive system.

Background The US Food and Drug Administration (FDA) issued a guidance for bacterial risk control strategies for platelet components in September 2019 that includes strategies using secondary bacterial culture (SBC). While an SBC likely increases safety, the optimal timing of the SBC is unknown. Our aim was to develop a model to provide insight into the best time for SBC sampling. Study design and methods We developed a mathematical model based on the conditional probability of a bacterial contamination event. The model evaluates the impact of secondary culture sampling time over a range of bacterial contamination scenarios (lag and doubling times), with the primary outcome being the optimal secondary sampling time and the associated risk. Results Residual risk of exposure decreased with increasing inoculum size, later sampling times for primary culture, and using higher thresholds of exposure (in colony-forming units per milliliter). Given a level of exposure, the optimal sampling time for secondary culture depended on the timing of primary culture and on the expiration time. In general, the optimal sampling time for secondary culture was approximately halfway between the time of primary culture and the expiration time. Conclusion Our model supports that the FDA guidance is quite reasonable and that sampling earlier in the specified secondary culture windows may be most optimal for safety.

Dispersal is a key biological process serving several functions including connectivity among populations. Habitat fragmentation caused by natural or anthropogenic structures may hamper dispersal, thereby disrupting genetic connectivity. Investigating factors affecting dispersal and gene flow is important in the current era of anthropogenic global change, as dispersal comprises a vital part of a species' resilience to environmental change. Using finescale landscape genomics, we investigated gene flow and genetic structure of the Sooty Copper butterfly (Lycaena tityrus) in the Alpine Ötz valley system in Austria. We found surprisingly high levels of gene flow in L. tityrus across the region. Nevertheless, ravines, forests, and roads had effects on genetic structure, while rivers did not. The latter is surprising as roads and rivers have a similar width and run largely in parallel in our study area, pointing towards a higher impact of anthropogenic compared with natural linear structures. Additionally, we detected eleven loci potentially under thermal selection, including ones related to membranes, metabolism, and immune function. This study demonstrates the usefulness of molecular approaches in obtaining estimates of dispersal and population processes in the wild. Our results suggest that, despite high gene flow in the Alpine valley system investigated, L. tityrus nevertheless seems to be vulnerable to anthropogenically-driven habitat fragmentation. With anthropogenic rather than natural linear structures affecting gene flow, this may have important consequences for the persistence of species such as the butterfly studied here in altered landscapes.

Background Understanding pest incursion pathways is critical for preventing new invasions and for stopping the transfer of alleles that reduce the efficacy of local control methods. The mosquitoes Aedes albopictus (Skuse) and Ae. aegypti (Linnaeus) are both highly invasive disease vectors, and through a series of ongoing international incursions are continuing to colonize new regions and spread insecticide resistance alleles among established populations. This study uses high-resolution molecular markers and a set of 241 reference genotypes to trace incursion pathways of Ae. albopictus into mainland Australia, where no successful invasions have yet been observed. We contrast these results with incursion pathways of Ae. aegypti, investigated previously. Results Assignments successfully identified China, Japan, Singapore and Taiwan as source locations. Incursion pathways of Ae. albopictus were entirely different to those of Ae. aegypti, despite broad sympatry of these species throughout the Indo-Pacific region. Incursions of Ae. albopictus appeared to have come predominantly along marine routes from key trading locations, while Ae. aegypti was mostly linked to aerial routes from tourism hotspots. Conclusion These results demonstrate how genomics can help decipher otherwise cryptic incursion pathways. The inclusion of reference genotypes from the Americas may help resolve some unsuccessful assignments. While many congeneric taxa will share common incursion pathways, this study highlights that this is not always the case, and incursion pathways of important taxa should be specifically investigated. Species differences in aerial and marine incursion rates may reflect the efficacy of ongoing control programmes such as aircraft disinsection. © 2020 Society of Chemical Industry.

Using unique assessment data for players from a German Bundesliga club’s youth academy, we tested four core hypotheses on how player ratings and rater or ratee-related characteristics reflect the (prospective) optimism bias and (retrospective) positivity bias. The results indicate not only that the ratings of predicted and remembered performance are indeed higher than the talents’ actual performance throughout a season, but that these differences depend positively on the rater’s organizational experience and negatively on the amount of ratee data available. They also suggest that (prospective) anticipation is even more positively biased than (retrospective) recollection of player performances, underscoring the asymmetry between looking forward and looking backward.

Scarlet Macaws Ara macao have the largest geographical distribution of any Neotropical psittacine, occupying a variety of lowland forest habitats from Mexico to Brazil. Two subspecies, Ara macao macao and Ara macao cyanoptera, are currently recognized based on wing chord length and plumage coloration, with formal descriptions suggesting genetic introgression in southern Nicaragua and northern Costa Rica. The present study aimed to investigate the extent of genetic diversification within A. macao by analysing mitochondrial sequence data from contemporary and historical samples. Phylogenetic reconstruction and population aggregation analysis confirmed two distinct phylogeographical groups, with a high degree of intraspecific genetic structure and no evidence of a putative hybrid zone. Whole mitochondrial genome sequencing further confirmed substantial divergence (~ 1.8%) between the cyanoptera and macao lineages. These results demonstrate a separation of A. macao into two distinct evolutionary entities and highlight a non‐uniform distribution of intraspecific diversity, suggesting current conservation designations may warrant re‐evaluation.

BACKGROUND Risk-adjusted benchmarking could be useful to compare blood utilization between hospitals or individual groups, such as physicians, while accounting for differences in patient complexity. The aim of this study was to analyze the association of red blood cell (RBC) use and diagnosis-related group (DRG) weights across all inpatient hospital stays to determine the suitability of using DRGs for between-hospital risk-adjusted benchmarking. Specific hierarchical organizational units (surgical vs. nonsurgical patients, departments, and physicians) were also evaluated. STUDY DESIGN AND METHODS We studied blood use among all adult inpatients, and within organizational units, over 4 years (May 2014 to March 2018) at an academic center. Number of RBCs transfused, all patient refined (APR)-DRGs, and other variables were captured over entire hospital stays. We used multilevel generalized linear modeling (zero-inflated negative binomial) to study the relationship between RBC utilization and APR-DRG. RESULTS A total of 97,955 hospital stays were evaluated and the median APR-DRG weight was 1.2. The association of RBCs transfused and APR-DRG weight was statistically significant at all hierarchical levels (incidence rate ratio = 1.22; p

Biological invasions are increasing globally in number and extent despite efforts to restrict their spread. Knowledge of incursion pathways is necessary to prevent new invasions and to design effective biosecurity protocols at source and recipient locations. This study uses genome‐wide single nucleotide polymorphisms (SNPs) to determine the origin of 115 incursive Aedes aegypti(yellow fever mosquito) detected at international ports in Australia and New Zealand. We also genotyped mosquitoes at three point mutations in the voltage‐sensitive sodium channel (Vssc) gene: V1016G, F1534C and S989P. These mutations confer knockdown resistance to synthetic pyrethroid insecticides, widely used for controlling invertebrate pests. We first delineated reference populations using Ae. aegypti sampled from 15 locations in Asia, South America, Australia and the Pacific Islands. Incursives were assigned to these populations using discriminant analysis of principal components (DAPC) and an assignment test with a support vector machine predictive model. Bali, Indonesia, was the most common origin of Ae. aegypti detected in Australia, while Ae. aegypti detected in New Zealand originated from Pacific Islands such as Fiji. Most incursives had the same allelic genotype across the three Vsscgene point mutations, which confers strong resistance to synthetic pyrethroids, the only insecticide class used in current, widely implemented aircraft disinsection protocols endorsed by the World Health Organization (WHO). Additionally, all internationally assigned Ae. aegypti had Vssc point mutations linked to pyrethroid resistance that are not found in Australian populations. These findings demonstrate that protocols for preventing introductions of invertebrates must consider insecticide resistance, and highlight the usefulness of genomic data sets for managing global biosecurity objectives.

Our objective was to determine the clinical services offered by American Board of Obesity Medicine (ABOM) Diplomates and whether guideline concordant services varied by clinical practice attributes. We conducted a cross-sectional analysis of the 2019 ABOM Diplomate survey (response rate 19.2%). Respondents (n = 494) self-reported services offered: nutrition, exercise, mental health, minimally invasive bariatric procedures, perioperative bariatric surgical care and FDA-approved anti-obesity medications. We graded concordance of services offered with three evidence-based obesity guidelines, and then conducted bivariate analyses comparing concordance by practice attributes. Most responding ABOM Diplomates offered nutrition (90.1%), exercise (67.8%) and mental health (76.7%). Few offered minimally invasive procedures (24.3%), and most provided perioperative surgical care (63.0%). Most (83.4%) prescribed FDA-approved medications-typically both short- and long-term agents (70.9%). Few Diplomates had low concordance with the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) guidelines (24.7%). Those who managed more obesity-related conditions and endorsed AHA/ACC/TOS guideline use had higher concordance with these recommendations. No differences in guideline concordance existed by population, clinical effort or location. We found similar findings regarding concordance with ) American Association of Clinical Endocrinologists/American College of Endocrinology and Obesity Medicine Association guidelines. In conclusion, most responding ABOM Diplomates offer evidence-based obesity medicine services. Clinicians may therefore have increased confidence in patient receipt of evidence-based care when referring to an ABOM Diplomate.

The objective of the current study was to develop a population pharmacokinetics (PK) model for erythropoietin (Epo) in premature infants and healthy adults to characterize the variation in PK, and to study the differences in Epo PK in these 2 populations. Thirteen very low-birth-weight premature infants (

Background Ancillary testing including immunohistochemistry and molecular diagnostics has become an increasingly important component for the evaluation of cytologic specimens. Ancillary testing is important not only for diagnosis but also for predictive and prognostic evaluation. While a number of substrates are appropriate for ancillary testing, cell block specimens are commonly utilized and the success of ancillary testing depends on cell-block cellularity. Methods Forty-six pairs of cases each fixed in both formalin and CytoLyt were each analyzed by two evaluators for overall cellularity. Linear regression was used to assess inter-rater reliability of cell counts for each method. Cellularity scores for each case were obtained by averaging the scores for each rater and cellularity was compared between the methods. Results Inter-rater agreement was very good for both methods. The coefficient of determination was 1.0 and 0.99 for the CytoLyt and formalin methods respectively. Cell blocks using the CytoLyt method have lower levels of cellularity than cell blocks performed by the formalin method. Conclusions Cell blocks prepared using a formalin fixative yield significantly greater cellularity than those produced by the CytoLyt method. Formalin fixation appears to optimize cellularity of cell blocks useful for ancillary testing.

Background Rapid on-site evaluation (ROSE) can increase adequacy and reduce needle passes in fine-needle aspiration cytology (FNAC) procedures. However, ROSE increases the cost of FNAC. Costs may be reduced if ROSE is performed by an alternate evaluator (AE), such as a cytotechnologist (CT), endoscopist, or pulmonologist, rather than a cytopathologist (CP). Studies have shown that AEs can perform ROSE with high accuracy but are generally not as accurate as CPs. The objective of this study was to evaluate the impact of AEs on the cost-effectiveness of ROSE. Methods A cost model, based on a mathematical sampling model, was developed. The cost model was used to compare the impact of the evaluator type on overall costs. Results CTs were likely to be cost-effective for simple procedures and were unlikely to be cost-effective for only the most complex procedures. The model demonstrated the tradeoff in cost savings from using AEs and the potential costs associated with repeated procedures due to the lower accuracy of AEs. Conclusions The cost-effectiveness of AEs is context-dependent. AEs can be cost-effective even if they are less accurate than CPs. AEs are likely to be cost-effective in most contexts.

Aims To assess the association between cytomegalovirus and Type 2 diabetes among 6664 participants from the National Health and Nutrition Examination Survey. Methods We used existing data from adults aged 20-49 years who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. Cytomegalovirus status was determined using cytomegalovirus-specific immunoglobulin G antibodies. Prevalent Type 2 diabetes was assessed through self-report or a plasma fasting glucose of ≥7 mmol/l. Logistic regression models were used to evaluate the association between Type 2 diabetes and cytomegalovirus seropositivity after adjustment for age, gender, race/ethnicity, smoking status, education, BMI and physical activity. Results In a univariate model, the crude odds of Type 2 diabetes were 47% higher in those who were cytomegalovirus-seropositive vs cytomegalovirus-seronegative. The association was attenuated and no longer significant after adjustment for age and other covariates: the odds ratio for diabetes was 1.09 (95% CI 0.71 to 1.66) for cytomegalovirus-seropositive vs -seronegative individuals. Conclusions Our study suggests that the association between cytomegalovirus and Type 2 diabetes is explained by age and other risk factors for diabetes.

The current reference method in the United States for measuring in vivo population red blood cell (RBC) kinetics utilizes chromium-51 (51 Cr) RBC labeling for determining RBC volume, 24-hour posttransfusion RBC recovery, and long-term RBC survival. Here we provide evidence supporting adoption of a method for kinetics that uses the biotin-labeled RBCs (BioRBCs) as a superior, versatile method for both regulatory and investigational purposes. RBC kinetic analysis using BioRBCs has important methodologic, analytical, and safety advantages over 51 Cr-labeled RBCs. We critically review recent advances in labeling human RBCs at multiple and progressively lower biotin label densities for concurrent, accurate, and sensitive determination of both autologous and allogeneic RBC population kinetics. BioRBC methods valid for RBC kinetic studies, including successful variations used by the authors, are presented along with pharmacokinetic modeling approaches for the accurate determination of RBC pharmacokinetic variables in health and disease. The advantages and limitations of the BioRBC method-including its capability of determining multiple BioRBC densities simultaneously in the same individual throughout the entire RBC life span-are presented and compared with the 51 Cr method. Finally, potential applications and limitations of kinetic BioRBC determinations are discussed.

BACKGROUND Critically ill preterm very-low-birthweight (VLBW) neonates (birthweight ≤ 1.5 kg) frequently develop anemia that is treated with red blood cell (RBC) transfusions. Although RBCs transfused to adults demonstrate progressive decreases in posttransfusion 24-hour RBC recovery (PTR24 ) during storage-to a mean of approximately 85% of the Food and Drug Administration-allowed 42-day storage-limited data in infants indicate no decrease in PTR24 with storage. STUDY DESIGN AND METHODS We hypothesized that PTR24 of allogeneic RBCs transfused to anemic VLBW newborns: 1) will be greater than PTR24 of autologous RBCs transfused into healthy adults and 2) will not decrease with increasing storage duration. RBCs were stored at 4°C for not more than 42 days in AS-3 or AS-5. PTR24 was determined in 46 VLBW neonates using biotin-labeled RBCs and in 76 healthy adults using 51 Cr-labeled RBCs. Linear mixed-model analysis was used to estimate slopes and intercepts of PTR24 versus duration of RBC storage. RESULTS For VLBW newborns, the estimated slope of PTR24 versus storage did not decrease with the duration of storage (p = 0.18) while for adults it did (p

Summary Species invasion is an important disturbance to ecosystems worldwide, yet knowledge about the impacts of invasive species on bacterial communities remains sparse. Using a novel approach, we simultaneously detected phenotypic and derived taxonomic change in a natural bacterioplankton community when subjected to feeding pressure by quagga mussels, a widespread aquatic invasive species. We detected a significant decrease in diversity within one hour of feeding, and a total diversity loss of 11.6 ± 4.1 % after 3h. This loss of microbial diversity was caused by the selective removal of high nucleic acid (HNA) populations (29 ± 5% after 3h). We were able to track the community diversity at high temporal resolution by calculating phenotypic diversity estimates from flow cytometry data of minute amounts of sample. Through parallel flow cytometry and 16S rRNA gene amplicon sequencing analysis of environments spanning a broad diversity range, we showed that the two approaches resulted in highly correlated diversity measures and captured the same seasonal and lake-specific patterns in community composition. Based on our results, we predict that selective feeding by IDMs directly impacts the microbial component of the carbon cycle, as it may drive bacterioplankton communities toward less diverse and potentially less productive states. This article is protected by copyright. All rights reserved.

Objective Examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). Methods Prospective multi-center cohort study of HNC patients receiving Intensity-Modulated Radiation Therapy (IMRT) or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices, were measured in 372 subjects pre-RT and 216 at 6 months from start of RT. Results Mean stimulated whole salivary flow declined from 1.09 ml/min to 0.47 ml/min at 6 months (p < 0.0001). Mean maximal mouth opening reduced from 45.58 mm to 42.53 mm at 6 months (p < 0.0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ 0.0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < 0.0001). Conclusions Despite advances in RT techniques, HNC patients experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life. This article is protected by copyright. All rights reserved.

N-methylimidazolidin-4-one organocatalysts were studied in the gas phase. Protonated and sodium-cationized (sodiated) molecules are conveniently accessible by electrospray mass spectrometry. Protonation enables three different closed-shell paths of ring cleavage leading to iminium ions. The fragmentation pattern is largely unaffected by exocyclic substituents and thus is valuable to characterize the substance type as N-methylimidazolidin-4-ones. Sodiated species show a distinctly different fragmentation that is less useful for characterization purposes: apart from signal loss due to dissociation of Na+ , the observation of benzyl radical loss is by far predominant. Only in absence of a benzyl substituent, an analogue of the third ring cleavage (loss of [C2 H5 NO]) is observed. Copyright © 2017 John Wiley & Sons, Ltd.

Background Biotin-labeled red blood cells (BioRBCs) are used for in vivo kinetic studies. Because BioRBC dosing occasionally induces antibodies, a sensitive and specific anti-BioRBC detection assay is needed. Study design and methods Aims were to 1) develop a gel card assay to evaluate existing, naturally occurring and BioRBC-induced plasma antibodies, 2) compare gel card and tube agglutination detection results, and 3) test for a relationship of antibody induction and BioRBC dose. Reagent BioRBCs were prepared using sulfo-NHS biotin ranging from densities 18 (BioRBC-18) to 1458 (BioRBC-1458) µg/mL RBCs. Results Among BioRBC-exposed subjects, gel card and tube agglutination results were concordant in 21 of 22 adults and all 19 infant plasma samples. Gel card antibody detection sensitivity was more than 10-fold greater than tube agglutination. Twelve to 16 weeks after BioRBC exposure, induced anti-antibodies were detected by gel card in three of 26 adults (12%) at reagent densities BioRBC-256 or less, but in none of 41 infants. Importantly, induced anti-BioRBC antibodies were associated with higher BioRBC dose (p = 0.008); no antibodies were detected in 18 subjects who received BioRBC doses less than or equal to BioRBC-18. For noninduced BioRBC antibodies, six of 1125 naive adults (0.3%) and none of 46 naive infants demonstrated existing anti-BioRBC antibodies using reagent BioRBC-140 or -162. Existing anti-BioRBCs were all neutralized by biotin compounds, while induced antibodies were not. Conclusions The gel card assay is more sensitive than the tube agglutination assay. We recommend reagent BioRBC-256 for identifying anti-BioRBCs. Use of a low total RBC biotin label dose (≤ BioRBC-18) may minimize antibody induction.

The purpose of the current study was to survey and interview caregivers of children with disabilities (ages 2–5 years) to obtain their input as to whether current playground equipment meets their child's needs. A total of 149 participants agreed to participate. Caregivers (i) indicated that their child with a disability could not fully participate in the playground's offerings, (ii) felt that the playground was not appropriate for their child with a disability and (iii) dreamed of a fully inclusive playground that met their child's needs. The results also demonstrate that social participation barriers continue to remain for families who have children with disabilities despite the passing of international human rights standards targeting individuals with disabilities and a global focus in improving the overall well-being of children with disabilities.

Background In 2018, the Milan System for Reporting Salivary Gland Cytopathology was published defining a diagnostic categorization scheme with known malignancy risks and clinical follow up recommendations. Inter-observer reproducibility of the categories was not defined. Methods Salivary gland fine-needle aspirations (FNA) were reviewed over a 5 year period and classified by three independent observers. Inter-observer reproducibility was estimated using observed agreement and chance corrected agreement (Cohen's kappa). Results Four hundred and eight cases were reviewed with chance corrected agreement of 0.42 for the original Milan System and 0.48 for a modified system using "similar follow up" categories. Categories 4A and 6B showed substantial agreement (kappa =0.71 and 0.72). Conclusion The Milan System shows moderate over all agreement between observers. Strongest inter-observer agreement was seen for categories 4A and 6B.

Background Long-term pain affects brain in response to attention tasks. This study aimed to verify the relationship between performance in a computerized visual attention test (CVAT) and response to duloxetine in fibromyalgia patients. Duloxetine is approved for the treatment but the response is not immediate. Methods Patients were drawn from a sample of 74 patients with chronic pain. These patients were selected because they kept their subjective perceptions of pain as severe after 1 week of duloxetine treatment. All patients were tested in the CVAT on two occasions: the first appointment and 7 days after starting duloxetine. Results After 6 weeks, the group was subdivided into responsive and non-responsive patients. Responsiveness was defined by a subjective improvement from severe to low-intensity or no-pain after the sixth week of duloxetine treatment. Responsive patients showed objective attentional improvements in the second test. Non-respondent patients did not exhibit changes in attentional performance in the second test as compared to the first one. Conclusions The data were interpreted considering that persistent pain in fibromyalgia is maintained by central sensitization that may be associated with functional changes in the dorsolateral prefrontal cortex and the posterior parietal cortex. In responsive patients, duloxetine treatment may be responsible for a partial recovery of these regions. This may explain the early attentional improvement observed in the responsive patients after 1 week of treatment. Thus, attentional performance may help to predict which patients will respond to duloxetine treatment even before they can demonstrate subjective improvements in pain perception. Significance This study shows that an improvement in an attentional test is a reliable predictor of the treatment response even without any improvement in the perception of pain.

Background Evaluation of the nuclear to cytoplasmic ratio is commonly used for assessment of the presence of malignancy and for grading and typing of malignant neoplasms. Despite its widespread usage, little information exists regarding the accuracy and reproducibility of non-automated assessment. Methods Forty-seven cells obtained from Papanicolaou stained urine cytologies were assessed by quantitative image analysis for nuclear area and cell area. The nuclear/cytoplasmic ratio was calculated. Visual estimates of the N/C ratio were made by six pathologists. Statistical analysis was performed to determine accuracy, precision, and interrater reliability. Results True N/C ratios varied from 0.02 to 0.81. 27% of cases demonstrated a true N/C ratio between 0.5 and 0.7. Quantitative estimates of N/C ratios were less precise and less accurate at high N/C ratios. The coefficient of variation was 27%. The majority of raters demonstrated decreased accuracy and precision of estimates as N/C ratio increased. Overall classification accuracy was 73%. Accuracy of classification was 53% for cases with a true N/C ratio between 0.4 and 0.8. Absolute interrater agreement was 75%. Chance corrected agreement (kappa) was 0.54. Conclusions Visual quantitation of N/C ratio showed only a fair correlation with actual N/C ratio with correlation decreasing with increasing N/C ratio. In the critical range, 0.5–0.7 N/C ratio both interobserver correlation and correlation with true N/C ratio may be insufficiently accurate for precise category assignment as used in the Paris System. Diagn. Cytopathol. 2017;45:107–112. © 2016 Wiley Periodicals, Inc.

Although dissimilatory sulfate-reducing bacteria (SRB) are generally described as strictly anaerobic organisms with regard to growth, several reports have shown that some SRB, particularly Desulfovibrio species, are quite resistant to O2 . For example, SRB remain viable in many aerobic environments while some even reduce O2 to H2 O. However, reproducible aerobic growth of SRB has not been unequivocally documented. Desulfovibrio magneticus is a SRB that is also a magnetotactic bacterium (MTB). MTB biomineralize magnetosomes which are intracellular, membrane-bounded, magnetic iron mineral crystals. The ability of D. magneticus to grow aerobically in several different media under air where an O2 concentration gradient formed, or under O2 -free N2 gas was tested. Under air, cells grew as a microaerophilic band of cells at the oxic-anoxic interface in media lacking sulfate. These results show that D. magneticus is capable of aerobic growth with O2 as a terminal electron acceptor. This is the first report of consistent, reproducible aerobic growth of SRB. This finding is critical in determining important ecological roles SRB play in the environment. Interestingly, the crystal structure of the magnetite crystals of D. magneticus grown under microaerobic conditions showed significant differences compared with those produced anaerobically providing more evidence that environmental parameters influence magnetosome formation.

Objective To compare in vitro biomechanical properties of the tube knot (TB) to a crimp clamp (CC) system, and square knot (SQ) using 3 monofilament materials. Study Design In vitro biomechanical study. Sample Population Suture loops (n=20 per material/knot construct). Methods Monotonic tensile loading (300 mm/min single pull to failure) was performed on knots tied using 3 knots (TB, 5-throw SQ, and CC system) with each of 3 materials (40# Securos® nylon, #2 polypropylene, and #2 nylon). Ultimate tensile strength, elongation, and stiffness were measured and compared by sequential 1- and 2-way ANOVA. Results Ultimate tensile strength was greatest with 40# nylon CC (mean ± SD, 293.6 ± 26.2 N), followed by TB (289.8 ± 9.2 N) and SQ (252.2 ± 8.5 N) with no significant difference between CC and TB. TB with #2 polypropylene (158.1 ± 7.4 N) and #2 nylon (126.3 ± 5.5 N) had significantly greater tensile strength than SQ with #2 polypropylene (143.6 ± 5.3 N) and #2 nylon (110.7 ± 6.2 N). Elongation at failure was significantly greater in 40# nylon TB (25.3 ± 3.2 mm) and SQ (10.8 ± 1.6 mm) compared to CC (5.3 ± 1.0 mm). Both material and knotting method had an effect on ultimate tensile strength, elongation at failure, and stiffness, based on 2-way ANOVA. Conclusion Ultimate tensile strength of TB was equivalent to that of CC; however, elongation at failure was greatest for TB, which may be of concern for clinical applications.

We investigated the etiology of attentional control (AC) and four different anxiety symptom types (generalized, obsessive-compulsive, separation, and social) in an adolescent sample of over 400 twin pairs. Genetic factors contributed to 55% of the variance in AC and between 43 and 58% of the variance in anxiety. Negative phenotypic associations between AC and anxiety indicated that lower attentional ability is related to increased risk for all 4 anxiety categories. Genetic correlations between AC and anxiety phenotypes ranged from −.36 to −.47, with evidence of nonshared environmental covariance between AC and generalized and separation anxiety. Results suggest that AC is a phenotypic and genetic risk factor for anxiety in early adolescence, with somewhat differing levels of risk depending on symptomatology.

Background The separation of branchial cleft cysts from metastatic cystic squamous cell carcinomas in adults can be clinically and cytologically challenging. Diagnostic accuracy for separation is reported to be as low as 75% prompting some authors to recommend frozen section evaluation of suspected branchial cleft cysts before resection. We evaluated 19 cytologic features to determine which were useful in this distinction. Methods Thirty-three cases (21 squamous carcinoma and 12 branchial cysts) of histologically confirmed cystic lesions of the lateral neck were graded for the presence or absence of 19 cytologic features by two cytopathologists. The cytologic features were analyzed for agreement between observers and underwent multivariate analysis for correlation with the diagnosis of carcinoma. Results Interobserver agreement was greatest for increased nuclear/cytoplasmic (N/C) ratio, pyknotic nuclei, and irregular nuclear membranes. Recursive partitioning analysis showed increased N/C ratio, small clusters of cells, and irregular nuclear membranes were the best discriminators. Conclusion The distinction of branchial cleft cysts from cystic squamous cell carcinoma is cytologically difficult. Both digital image analysis and p16 testing have been suggested as aids in this separation, but analysis of cytologic features remains the main method for diagnosis. In an analysis of 19 cytologic features, we found that high nuclear cytoplasmic ratio, irregular nuclear membranes, and small cell clusters were most helpful in their distinction. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Low-field magnetic stimulation (LFMS) is a gated high-frequency non-invasive brain stimulation method (500 Hz gated at 2 Hz) with a proposed antidepressant effect. However, it has remained unknown how such stimulation paradigms modulate neuronal network activity and how the induced changes depend on network state. Here we examined the immediate and outlasting effects of the gated high-frequency electric field associated with LFMS on the cortical activity as a function of neuromodulatory tone that defines network state. We used a sham-controlled study design to investigate effects of stimulation (20 min of 0.5 s trains of 500 Hz charge-balanced pulse stimulation patterned at 0.5 Hz) on neural activity in mouse medial prefrontal cortex in vitro. Bath application of cholinergic and noradrenergic agents enabled us to examine the stimulation effects as a function of neuromodulatory tone. The stimulation attenuated the increase in firing rate of layer V cortical neurons during the post-stimulation period in the presence of cholinergic activation. The same stimulation had no significant immediate or outlasting effect in the absence of exogenous neuromodulators or in the presence of noradrenergic activation. These results provide electrophysiological insights into the neuromodulatory-dependent effects of gated high-frequency stimulation. More broadly, our results are the first to provide a mechanistic demonstration of how behavioral states and arousal levels may modify the effects of non-invasive brain stimulation.

Despite their homogeneous appearance, aquatic systems harbour heterogeneous habitats resulting from nutrient gradients, suspended particulate matter and stratification. Recent reports suggest phylogenetically conserved habitat preferences among bacterioplankton, particularly for particle-associated (PA) and free-living (FL) habitats. Here, we show that independent of lake nutrient level and layer, PA and FL abundance-weighted bacterial community composition (BCC) differed and that inter-lake BCC varied more for PA than for FL fractions. In low-nutrient lakes, BCC differences between PA and FL fractions were larger than those between lake layers. The reverse was true for high-nutrient lakes. Nutrient level affected BCC more in hypolimnia than in epilimnia, likely due to hypolimnetic hypoxia in high-nutrient lakes. In line with previous reports, we observed within-phylum operational taxonomic unit (OTU) habitat preference conservation, although not for all phyla, including the phylum with the highest average relative abundance across all habitats (Bacteroidetes). Consistent phylum-level habitat preferences may indicate that the functional traits that underpin ecological adaptation of freshwater bacteria to lake habitats can be phylogenetically conserved, although the levels of conservation are phylum dependent. Resolving taxa preferences for freshwater habitats sets the stage for identification of traits that underpin habitat specialization and associated functional traits that influence differences in biogeochemical cycling across freshwater lake habitats.

In this study, we present a more accurate method for correcting for range restriction (Case V) that expands upon Bryant and Gokhale's (1972) method. We further present detailed steps to incorporate the Case V method into Schmidt and Hunter's (2015) psychometric meta-analysis methods (both individual correction and artifact distribution approaches). We then evaluate the accuracy of the Case V method vis-a-vis existing methods. Monte-Carlo simulation results indicate that the Case V method provides very accurate estimates for the mean true score correlation and reasonably accurate estimates for the true standard deviation. More important, Case V almost always provides more accurate results than alternative methods (particularly, Case IV). To illustrate how the Case V method works with real data, we conduct a reanalysis of Judge, Heller, and Mount's (2002) meta-analysis examining the relationships between the Big 5 personality traits and job satisfaction. Results indicate that the true score correlations between the Big 5 traits and job satisfaction have been underestimated, whereas their true standard deviations have been overestimated. Implications for range restriction corrections in organizational research are discussed. [ABSTRACT FROM AUTHOR]

Objectives To determine the accuracy and reproducibility of differentiating between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) on fine-needle aspiration (FNA) specimens. Methods Fifty cases of NSCLC diagnosed by FNA having either concurrent core biopsies or resection as a diagnostic reference standard were selected. FNA slides were reviewed independently by five blinded observers. Two rounds of review were performed. Cases were initially categorized as SCC, favor SCC, NSCLC (type indeterminate), favor ADC, or ADC; while the indeterminate category was eliminated in the second round of review. Results The interobserver agreement was 0.22 and 0.1 with and without the indeterminate category, respectively. The overall accuracy for differentiating between SCC and ADC of the lung was 65% with the indeterminate category and 66% without. Conclusion Overall, the low interobserver agreement in our study indicates that accurate subclassification between the NSCLCs often cannot be made by cytomorphology alone. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc.

Background The Papanicolaou Society of Cytopathology has developed a set of guidelines which include a diagnostic scheme with the categories “atypical” and “suspicious for malignancy.” These intermediate categories may help stratify risk of malignancy for samples obtained from the bile and pancreatic ducts. However, the reproducibility of these intermediate categories is currently unknown. Methods Twenty sequential brushing specimens of bile or pancreatic ducts from each of the categories “atypical” and “suspicious for malignancy” were identified and the slides retrieved. All 40 cases were reviewed independently by four cytopathologists blinded to the original diagnoses. Resulting review diagnoses were statistically analyzed for agreement and the Kappa statistic calculated. Agreement of the observers’ diagnoses with original diagnoses was also evaluated. Results Interobserver agreement was graded as slight to fair with observers agreeing in about 50% of cases. The corresponding kappa statistic for the category “atypical” was 0.21 and 0.18 for the category “suspicious for malignancy.” Reviewer agreement with the original reference diagnosis occurred in approximately one half of review diagnoses. Conclusion Analysis of agreement shows that interobserver agreement was only slight to fair. Despite the categories “atypical” and “suspicious for malignancy” having distinct risks of malignancy (62% versus 74%), the reproducibility of these categories is relatively poor. A single intermediate category may improve reproducibility over the scheme proposed by the Papanicolaou Society of Cytopathology while maintaining an ability to stratify risk of malignancy. Diagn. Cytopathol. 2015;43:797–801. © 2015 Wiley Periodicals, Inc.

In this article, I provide answers to the questions posed by Will Shadish about the history and development of the Schmidt-Hunter methods of meta-analysis. In the 1970s, I headed a research program on personnel selection at the US Office of Personnel Management (OPM). After our research showed that validity studies have low statistical power, OPM felt a need for a better way to demonstrate test validity, especially in light of court cases challenging selection methods. In response, we created our method of meta-analysis (initially called validity generalization). Results showed that most of the variability of validity estimates from study to study was because of sampling error and other research artifacts such as variations in range restriction and measurement error. Corrections for these artifacts in our research and in replications by others showed that the predictive validity of most tests was high and generalizable. This conclusion challenged long-standing beliefs and so provoked resistance, which over time was overcome. The 1982 book that we published extending these methods to research areas beyond personnel selection was positively received and was followed by expanded books in 1990, 2004, and 2014. Today, these methods are being applied in a wide variety of areas.

A literacy-related activity that occurs in children’s homes—talk about letters in everyday conversations—was examined using data from 50 children who were visited every 4 months between 14 and 50 months. Parents talked about some letters, including those that are common in English words and the first letter of their children’s names, especially often. Parents’ focus on the child’s initial was especially strong in families of higher socioeconomic status, and the extent to which parents talked about the child’s initial during the later sessions of the study was related to the children’s kindergarten reading skill. Conversations that included the child’s initial were longer than those that did not, and parents presented a variety of information about this letter. Learning to read is crucial for success in school and life. Consequently, researchers, educators, and policy makers are interested in finding out why some children learn to read more easily than others. Part of the answer may lie in the literacy-related activities that children participate in at home, before formal reading instruction begins. These activities may include being read to by their parents, learning to spell their names, and playing with magnets in the shapes of letters. Children who are reported by their parents to engage in such activities infrequently are on average less successful in learning to read than children who are reported to engage in them often (e.g., Burgess, Hecht, & Lonigan, 2002; Christian, Morrison, & Bryant, 1998). Shared book reading is the most studied aspect of the home literacy environment, but researchers have suggested that the construct of home literacy be expanded to include other activities (e.g., Phillips & Lonigan, 2009). Here, we focus on one potentially important but understudied activity—parents’ talk about letters of the alphabet with their young children—and how this varies across families and relates to children’s later reading performance.

Objective The aim of this article is to determine the cost effectiveness of cell free DNA (cfDNA) as a replacement forintegrated screening using a societal cost perspective. Method This study used Monte-Carlo simulation with one-way and probabilistic sensitivity analysis. Results Cell free DNA is more effective and less costly than integrated screening. The incremental cost-effectivenessratio for cfDNA relative to the integrated test was $277955 per case detected (95th percent confidence interval $881882 to $532785). Conclusion Cell free DNA screening is a cost-effective replacement for maternal serum screening when the lifetimecosts of Down syndrome live births are considered. The adoption of cfDNA screening would save approximately$277955 for each additional case detected over integrated screening. © 2014 John Wiley & Sons, Ltd. Funding sources: NoneConflicts of interest: All of the authors are employees of ARUP laboratories, which provide a wide range of clinical laboratory tests including prenatal screening tests(both maternal serum screening and cfDNA).

Background Endoscopic ultrasonographic-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the investigation of pancreatic lesions. It shows good sensitivity and excellent specificity. Diagnostic criteria have been published but not statistically validated for the diagnosis of malignancy and stratification of risk for malignancy. Methods A training set of 57 EUS-FNAs and the validation set of 107 EUS-FNAs were selected. Slides were independently evaluated by three pathologists. Sixteen morphologic features were evaluated in the training set. Average absolute agreement, kappa scores, and association with malignancy were statistically evaluated. Recursive partitioning and multivariant analyses were performed on the features tested in the training set. Agreement data, univariate-odds ratios, and discriminatory power were calculated for the diagnostic features selected from the training set. The selected morphologic features formed a scoring rule that was then applied to the validation set. Results The average absolute agreement in the training set was 72%. Anisonucleosis, nuclear crowding, macro nucleoli, single atypical epithelial cells, and intracytoplasmic mucin showed the highest interrater reliability. Anisonucleosis, macronucleoli, single atypical epithelial cells, and intracytoplasmic mucin were most predictive of malignancy. A simple scoring rule was developed combining these morphologic features and applied to the validation set. Analysis of the area under the receiver operating characteristic (ROC) curve confirmed the statistical validity of the scoring rule. Conclusion A scoring system utilizing the presence or absence of anisonucleosis, macronucleoli, single atypical epithelial cells, and mucinous metaplasia yielded good discriminatory power (area under ROC curve = 0.87). Diagn. Cytopathol. 2015;43:613–621. © 2015 Wiley Periodicals, Inc.