A concise review of glycerol derivatives for use as fuel additives.

Due to renewable fuel mandates worldwide, the increase in biodiesel production has caused an oversupply of low-cost glycerol on the markets, which can negatively affect the sustainability of the biodiesel industry as a whole. In order to avoid that scenario, the transformation of glycerol into value-added products has been investigated, and the production of additives for internal combustion engine fuels is one good example of glycerol valorization. The present work presents a summary of the literature describing the most important chemical pathways through which glycerol can be converted into fuel additives, to be subsequently mixed with either gasoline, biodiesel, or diesel fuel. The focus is on the three major categories, namely glycerol acetals/ketals, ethers, and esters (acetates). Moreover, the effectiveness of the different glycerol-derived compounds is illustrated through several examples from the literature. Finally, a few research gaps on the topic are identified and suggestions for future work are described.

Medical correlates of first-term attrition in US Navy personnel.

INTRODUCTION: First-term attrition (FTA), or failure of a military service member to complete their initial service contract, is a major financial burden and source of lost manpower in the US Navy. The objective of the present study was to examine medical correlates of FTA using healthcare and disability rating data. METHODS: In this retrospective cohort study, all US Navy-enlisted personnel between the years 2003 and 2018 with FTA (n=58 777) and regular discharge (n=203 084) were identified for analysis from accession dates in the Career History Archival Medical and Personnel System. Medical diagnoses from outpatient and inpatient records were abstracted from the Military Health System Data Repository. For a subgroup of the study population discharged with a disability rating (n=12 880), diagnoses were identified from the Integrated Disability Evaluation System. The FTA and regular discharge groups were compared using relative risks (RRs) and 95% CIs, and per cent differences for the disability subgroup analysis. RESULTS: Compared with regular discharges, those with FTA were more likely to have outpatient and inpatient diagnoses for mental health disorders. Personality disorder yielded the strongest association with FTA in both outpatient (RR=10.45, 95% CI 9.79 to 11.16) and inpatient settings (RR=18.97, 95% CI 14.16 to 25.42). Other disorders associated with FTA included schizophrenia, substance-related disorders, poisoning by psychotropic agents and adjustment disorders. In the disability analysis, the FTA group relative to regular discharges had the largest per cent differences for 'arthritis, degenerative (hypertrophic or osteoarthritis)' (10.8% vs 2.5%) and 'tibia and fibula, impairment' (3.0% vs 0.4%). CONCLUSIONS: This study provides evidence that FTA is associated with both mental and physical health conditions. Mental and physical factors related to FTA require further examination, particularly whether pre-enlistment screening or early career intervention could lead to mitigation strategies. Future research should extend this analysis to other services and population subgroups.

Soil texture and climate limit cultivation of the arsenic hyperaccumulator Pteris vittata for phytoextraction in a long-term field study.

Long term field studies are required to bridge gaps between research and practical application of arsenic phytoextraction with the arsenic-hyperaccumulating fern Pteris vittata. In a 4-year field study, we investigated the effects of nutrient application (compost, inorganic or organic nitrogen, inorganic or organic phosphorus) and soil texture (13 % and 35 % clay) on arsenic phytoextraction with P. vittata in moderately contaminated soils (74-79 mg As/kg in the 0-15 cm depth interval). We found the highest phytoextraction rates, 5 ± 1 kg As/ha/y, in a coarse-textured compost-amended soil after 2 years of phytoextraction. Phytoextraction rates decreased over time, likely due to decreased root growth in mature stands, indicating plants should be replaced every 2-3 years to maintain phytoextraction efficiency. Across soil textures, nitrogen or phosphorus application led to a 60 % decrease in mean frond arsenic concentrations, leading to mean phytoextraction rates 54 % lower than in control ferns. In the fine-textured soil, frond arsenic concentrations were 54 % lower than in the coarse-textured soil, and fewer ferns survived from year 3 to 4. Across soil textures, compost application increased fern survival. We show that phytoextraction with P. vittata is limited to specific soil and climate conditions, narrower than those under which P. vittata grows in the wild.

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.

The relationship between time to diagnose and diagnostic accuracy among internal medicine residents: a randomized experiment.

BACKGROUND: Diagnostic errors have been attributed to cognitive biases (reasoning shortcuts), which are thought to result from fast reasoning. Suggested solutions include slowing down the reasoning process. However, slower reasoning is not necessarily more accurate than faster reasoning. In this study, we studied the relationship between time to diagnose and diagnostic accuracy. METHODS: We conducted a multi-center within-subjects experiment where we prospectively induced availability bias (using Mamede et al.'s methodology) in 117 internal medicine residents. Subsequently, residents diagnosed cases that resembled those bias cases but had another correct diagnosis. We determined whether residents were correct, incorrect due to bias (i.e. they provided the diagnosis induced by availability bias) or due to other causes (i.e. they provided another incorrect diagnosis) and compared time to diagnose. RESULTS: We did not successfully induce bias: no significant effect of availability bias was found. Therefore, we compared correct diagnoses to all incorrect diagnoses. Residents reached correct diagnoses faster than incorrect diagnoses (115 s vs. 129 s, p < .001). Exploratory analyses of cases where bias was induced showed a trend of time to diagnose for bias diagnoses to be more similar to correct diagnoses (115 s vs 115 s, p = .971) than to other errors (115 s vs 136 s, p = .082). CONCLUSIONS: We showed that correct diagnoses were made faster than incorrect diagnoses, even within subjects. Errors due to availability bias may be different: exploratory analyses suggest a trend that biased cases were diagnosed faster than incorrect diagnoses. The hypothesis that fast reasoning leads to diagnostic errors should be revisited, but more research into the characteristics of cognitive biases is important because they may be different from other causes of diagnostic errors.

Sport-specific differences in dynamic visual acuity and gaze stabilization in division-I collegiate athletes.

BACKGROUND: The vestibular-ocular reflex (VOR) integrates the vestibular and ocular systems to maintain gaze during head motion. This reflex is often negatively affected following sport-related concussion. Objective measures of gaze stability, a function mediated by the VOR, such as the computerized dynamic visual acuity test (DVAT) and gaze stabilization test (GST), may have utility in concussion management. However, normative data specific to sport, sex, or concussion history have not been established in collegiate athletes. OBJECTIVE: The objective of this study was to establish normative values for the DVAT and GST in collegiate athletes and explore the effect of sport, sex, and concussion history on VOR assessments. METHODS: The DVAT and GST were completed by 124 collegiate athletes (72 male, 52 female, mean±SD, age: 19.71±1.74 years, height: 173.99±13.97 cm, weight: 80.06±26.52 kg) recruited from Division-I athletic teams (football, soccer and cheerleading). The DVAT and GST were performed in the rightward and leftward directions during a single session in a standardized environment. Normative values for DVAT and GST measures were expressed as percentiles. Non-parametric statistics were used to compare differences between groups based on sex, sport, and concussion history. Alpha was set a-priori at 0.05. RESULTS: Overall, the median LogMAR unit for 124 athletes completing the DVAT was 0 (IQR = 0.17) for both leftward and rightward. The median velocities achieved on the GST were 145 °/sec and 150 °/sec (IQR = 45 and 40) for the leftward and rightward directions respectively. Significant differences were observed between sports (p = 0.001-0.17) for the GST with cheerleading demonstrating higher velocities than the other sports. However, no significant differences were identified based on sex (p≥0.09) or history of concussion (p≥0.15). CONCLUSIONS: Normative estimates for the DVAT and GST may assist in the clinical interpretation of outcomes when used in post-concussion evaluation for collegiate athletes. Although sex and previous concussion history had no effect on the DVAT or GST, performance on these measures may be influenced by type of sport. Sport-related differences in the GST may reflect VOR adaptations based on individual sport-specific demands.

Mesoscope: A Web-based Tool for Mesoscale Data Integration and Curation.

Interest is growing for 3D models of the biological mesoscale, the intermediate scale between the nanometer scale of molecular structure and micrometer scale of cellular biology. However, it is currently difficult to gather, curate and integrate all the data required to define such models. To address this challenge we developed Mesoscope (mesoscope.scripps.edu/beta), a web-based data integration and curation tool. Mesoscope allows users to begin with a listing of molecules (such as data from proteomics), and to use resources at UniProt and the PDB to identify, prepare and validate appropriate structures and representations for each molecule, ultimately producing a portable output file used by CellPACK and other modeling tools for generation of 3D models of the biological mesoscale. The availability of this tool has proven essential in several exploratory applications, given the high complexity of mesoscale models and the heterogeneity of the available data sources.

Cuttlefish: Color Mapping for Dynamic Multi-Scale Visualizations.

Visualizations of hierarchical data can often be explored interactively. For example, in geographic visualization, there are continents, which can be subdivided into countries, states, counties and cities. Similarly, in models of viruses or bacteria at the highest level are the compartments, and below that are macromolecules, secondary structures (such as α-helices), amino-acids, and on the finest level atoms. Distinguishing between items can be assisted through the use of color at all levels. However, currently, there are no hierarchical and adaptive color mapping techniques for very large multi-scale visualizations that can be explored interactively. We present a novel, multi-scale, color-mapping technique for adaptively adjusting the color scheme to the current view and scale. Color is treated as a resource and is smoothly redistributed. The distribution adjusts to the scale of the currently observed detail and maximizes the color range utilization given current viewing requirements. Thus, we ensure that the user is able to distinguish items on any level, even if the color is not constant for a particular feature. The coloring technique is demonstrated for a political map and a mesoscale structural model of HIV. The technique has been tested by users with expertise in structural biology and was overall well received.

A retrospective cohort study comparing dairy calf treatment decisions by farm personnel with veterinary observations of clinical signs.

Antimicrobials are frequently administered to calves with diarrhea, despite evidence suggesting questionable efficacy. Even if efficacious, providing the appropriate therapy to an animal requires accurate disease detection. The objective of this study was to use previously collected data and compare clinical scoring by a veterinarian to treatment decisions by on-farm personnel. Data describing daily clinical scores and farm treatments were previously collected from 4 farms for calves from birth to age 28 d. In this data set, a total of 460 calves were enrolled. Daily observations and clinical assessments were made on each farm by the same veterinarian, for a total of 12,101 calf observation days. Farm personnel made all treatment decisions based on their own observations, and these treatments were recorded by study personnel. Overall, the cumulative incidence of a calf exhibiting at least one abnormal clinical sign over the 28-d observation period was 0.93, with cumulative incidences of 0.85 and 0.33 for diarrhea and dehydration, respectively. The cumulative incidence of any treatment (including antibiotics and electrolytes) was 0.85, although the majority of treatments used an antimicrobial. The farm-specific probabilities that a calf with clinical signs of dehydration or diarrhea, respectively, received fluid or electrolyte therapy ranged from 0.08 to 0.27 and 0.03 to 0.12. These probabilities were greater for the day a clinical sign was first observed. The farm-specific probabilities that a calf with clinical signs of diarrhea received an antimicrobial was 0.23 to 0.65, and the probability that a calf exhibiting clinical signs of respiratory disease received an antimicrobial was 0.33 to 0.76. The first observation of diarrhea had similar probabilities to those for all observations of diarrhea. There was greater probability of treatment for calves with their first observed abnormal respiratory signs. Probabilities that treatment with antimicrobials, or fluids or electrolytes, was associated with an abnormal clinical sign were low-that is, calves received treatments in the absence of any abnormal clinical signs. This study illustrates incongruity between treatment decisions by calf treaters (the designated personnel on each farm responsible for calf health assessment and treatment decisions) and those of an observer using a clinical scoring system to identify calves with abnormal clinical signs. These findings indicate opportunities and the need for dairy farmers and advisors to evaluate calf treatment protocols, reasons for treatment, and training programs for calf health and disease detection, as well as to develop monitoring programs for treatment protocol compliance and health outcomes following therapy.

Spatial variability in size at maturity of golden king crab (Lithodes aequispinus) and implications for fisheries management.

Many crab fisheries around the world are managed by size, sex and season, where males are given at least one opportunity to reproduce before being harvested. Golden king crab (Lithodes aequispinus) supports a commercial fishery in Southeast Alaska and legal size is based on growth and maturity information from other parts of their range. Size-at-maturity estimates varied for crabs among seven management areas in Southeast Alaska, where male maturity estimates increased in size with increases in latitude, while maturity estimates across their North Pacific range decreased in size with increases in latitude. Depth, temperature and harvest history were not related to variation observed in male maturity estimates. Management implications from this research include reducing legal size in some areas to maximize harvest potential and increasing in others to allow male crabs the opportunity to reproduce before being harvested. A more conservative strategy would incorporate the largest maturity estimate, thus increasing the legal size which would have a negative impact to the commercial fishery, but allow male crabs the opportunity to reproduce before being harvested. This study shows the importance of understanding how life-history characteristics change over space and the challenge incorporating spatial variability for improved fisheries management.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients.

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Umbilical cord blood graft engineering: challenges and opportunities.

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specific T-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

Gene expression associated with intersterility in Heterobasidion.

Intersterility (IS) is thought to prevent mating compatibility between homokaryons that belong to different species. Although IS in Heterobasidion is regulated by the genes located at the IS loci, it is not yet known how the IS genes influence sexual compatibility and heterokaryon formation. To increase our understanding of the molecular events underlying IS, we studied mRNA abundance changes during IS compatible and incompatible interactions over time. The clustering of the transcripts into expression profiles, followed by the application of Gene Ontology (GO) enrichment pathway analysis of each of the clusters, allowed inference of biological processes participating in IS. These analyses identified events involved in mating and sexual development (i.e., linked with IS compatibility), which included processes associated with cell-cell adhesion and recognition, cell cycle control and signal transduction. We also identified events potentially involved in overriding mating between individuals belonging to different species (i.e., linked with IS incompatibility), which included reactive oxygen species (ROS) production, responses to stress (especially to oxidative stress), signal transduction and metabolic biosynthesis. Our findings thus enabled detection and characterization of gene expression changes associated with IS in Heterobasidion, as well as identification of important processes and pathways associated with this phenomenon. Overall, the results of this study increase current knowledge regarding the molecular mechanisms underpinning IS in Heterobasidion and allowed for the establishment of a vital baseline for further studies.

Distribution and evolution of het gene homologs in the basidiomycota.

In filamentous fungi a system known as somatic incompatibility (SI) governs self/non-self recognition. SI is controlled by a regulatory signaling network involving proteins encoded at the het (heterokaryon incompatible) loci. Despite the wide occurrence of SI, the molecular identity and structure of only a small number of het genes and their products have been characterized in the model fungi Neurospora crassa and Podospora anserina. Our aim was to identify and study the distribution and evolution of putative het gene homologs in the Basidiomycota. For this purpose we used the information available for the model fungi to identify homologs of het genes in other fungi, especially the Basidiomycota. Putative het-c, het-c2 and un-24 homologs, as well as sequences containing the NACHT, HET or WD40 domains present in the het-e, het-r, het-6 and het-d genes were identified in certain members of the Ascomycota and Basidiomycota. The widespread phylogenetic distribution of certain het genes may reflect the fact that the encoded proteins are involved in fundamental cellular processes other than SI. Although homologs of het-S were previously known only from the Sordariomycetes (Ascomycota), we also identified a putative homolog of this gene in Gymnopus luxurians (Basidiomycota, class Agaricomycetes). Furthermore, with the exception of un-24, all of the putative het genes identified occurred mostly in a multi-copy fashion, some with lineage and species-specific expansions. Overall our results indicated that gene duplication followed by gene loss and/or gene family expansion, as well as multiple events of domain fusion and shuffling played an important role in the evolution of het gene homologs of Basidiomycota and other filamentous fungi.

A within-trial cost-effectiveness analysis of primary care referral to a commercial provider for weight loss treatment, relative to standard care--an international randomised controlled trial.

BACKGROUND: Due to the high prevalence of overweight and obesity there is a need to identify cost-effective approaches for weight loss in primary care and community settings. OBJECTIVE: We evaluated the cost effectiveness of two weight loss programmes of 1-year duration, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP). DESIGN: This analysis was based on a randomised controlled trial of 772 adults (87% female; age 47.4±12.9 years; body mass index 31.4±2.6 kg m(-2)) recruited by health professionals in primary care in Australia, United Kingdom and Germany. Both a health sector and societal perspective were adopted to calculate the cost per kilogram of weight loss and the ICER, expressed as the cost per quality adjusted life year (QALY). RESULTS: The cost per kilogram of weight loss was USD122, 90 and 180 for the CP in Australia, the United Kingdom and Germany, respectively. For SC the cost was USD138, 151 and 133, respectively. From a health-sector perspective, the ICER for the CP relative to SC was USD18 266, 12 100 and 40 933 for Australia, the United Kingdom and Germany, respectively. Corresponding societal ICER figures were USD31,663, 24,996 and 51,571. CONCLUSION: The CP was a cost-effective approach from a health funder and societal perspective. Despite participants in the CP group attending two to three times more meetings than the SC group, the CP was still cost effective even including these added patient travel costs. This study indicates that it is cost effective for general practitioners (GPs) to refer overweight and obese patients to a CP, which may be better value than expending public funds on GP visits to manage this problem.

Clinical trials and tribulations--lessons from pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a dreadful disease that lacks adequate therapy. A number of treatment trials have been performed and have utilized a variety of primary efficacy endpoints. Endpoints that provide the most useful efficacy information are clinical endpoints that are directly related to how a patient feels, functions or survives. Unfortunately, there are no properly established patient-reported outcome measures or measures of functional status in IPF, making survival the most robust primary efficacy endpoint. Clinically meaningful events such as hospitalization can also provide important efficacy information. The use of non-validated surrogate endpoints as primary outcome measures often leads to uncertainty when interpreting trial results.

Inexpensive and safe DNA gel electrophoresis using household materials.

Gel electrophoresis is the single most important molecular biology technique and it is central to life sciences research, but it is often too expensive for the secondary science classroom or homeschoolers. A simple safe low-cost procedure is described here that uses household materials to construct and run DNA gel electrophoresis. Plastic containers are fitted with aluminum foil electrodes and 9-V batteries to run food-grade agar-agar gels using aquarium pH buffers and then stained with gentian violet. This activity was tested in a high school biology classroom with significantly positive responses on postactivity reflective surveys. The electrophoresis activity addresses several Life Science Content Standard C criteria, including aspects of cell biology, genetics, and evolution. It also can be used to teach aspects of motion and force in the physical science classroom.

Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease.

Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published. Using data from the National Center for Health Statistics from 1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p<0.0001); males: 72.0 versus 74.4 yrs (p<0.0001)). Decedents with pulmonary fibrosis had a significantly greater risk of VTE. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone. These data suggest a link between a pro-fibrotic and a pro-coagulant state.