With super SDMs (machine learning, open access big data, and the cloud) towards more holistic global squirrel hotspots and coldspots.

Species-habitat associations are correlative, can be quantified, and used for powerful inference. Nowadays, Species Distribution Models (SDMs) play a big role, e.g. using Machine Learning and AI algorithms, but their best-available technical opportunities remain still not used for their potential e.g. in the policy sector. Here we present Super SDMs that invoke ML, OA Big Data, and the Cloud with a workflow for the best-possible inference for the 300 + global squirrel species. Such global Big Data models are especially important for the many marginalized squirrel species and the high number of endangered and data-deficient species in the world, specifically in tropical regions. While our work shows common issues with SDMs and the maxent algorithm ('Shallow Learning'), here we present a multi-species Big Data SDM template for subsequent ensemble models and generic progress to tackle global species hotspot and coldspot assessments for a more inclusive and holistic inference.

Defining Critical Genes During Spherule Remodeling and Endospore Development in the Fungal Pathogen, Coccidioides posadasii.

Coccidioides immitis and C. posadasii are soil dwelling dimorphic fungi found in North and South America. Inhalation of aerosolized asexual conidia can result in asymptomatic, acute, or chronic respiratory infection. In the United States there are approximately 350,000 new infections per year. The Coccidioides genus is the only known fungal pathogen to make specialized parasitic spherules, which contain endospores that are released into the host upon spherule rupture. The molecular determinants involved in this key step of infection remain largely elusive as 49% of genes are hypothetical with unknown function. An attenuated mutant strain C. posadasii Δcts2/Δard1/Δcts3 in which chitinase genes 2 and 3 were deleted was previously created for vaccine development. This strain does not complete endospore development, which prevents completion of the parasitic lifecycle. We sought to identify pathways active in the wild-type strain during spherule remodeling and endospore formation that have been affected by gene deletion in the mutant. We compared the transcriptome and volatile metabolome of the mutant Δcts2/Δard1/Δcts3 to the wild-type C735. First, the global transcriptome was compared for both isolates using RNA sequencing. The raw reads were aligned to the reference genome using TOPHAT2 and analyzed using the Cufflinks package. Genes of interest were screened in an in vivo model using NanoString technology. Using solid phase microextraction (SPME) and comprehensive two-dimensional gas chromatography - time-of-flight mass spectrometry (GC × GC-TOFMS) volatile organic compounds (VOCs) were collected and analyzed. Our RNA-Seq analyses reveal approximately 280 significantly differentially regulated transcripts that are either absent or show opposite expression patterns in the mutant compared to the parent strain. This suggests that these genes are tied to networks impacted by deletion and may be critical for endospore development and/or spherule rupture in the wild-type strain. Of these genes, 14 were specific to the Coccidioides genus. We also found that the wild-type and mutant strains differed significantly in their production versus consumption of metabolites, with the mutant displaying increased nutrient scavenging. Overall, our results provide the first targeted list of key genes that are active during endospore formation and demonstrate that this approach can define targets for functional assays in future studies.

Direct detection of Coccidioides from Arizona soils using CocciENV, a highly sensitive and specific real-time PCR assay.

Coccidioides immitis and Coccidioides posadasii are soil fungi endemic to desert regions of the southwestern United States, and the causative agents of valley fever, or coccidioidomycosis. Studies have shown that the distribution of Coccidioides in soils is sporadic and cannot be explained by soil characteristics alone, suggesting that biotic and other abiotic factors should be examined. However, tools to reliably and robustly screen the large number of soils needed to investigate these potential associations have not been available. Thus, we developed a real-time polymerase chain reaction (PCR) assay for testing environmental samples by modifying CocciDx, an assay validated for testing clinical specimens to facilitate coccidioidomycosis diagnosis. For this study, we collected soil samples from previously established locations of C. posadasii in Arizona and new locations in fall 2013 and spring 2014, and screened the extracted DNA with the new assay known as CocciEnv. To verify the presence of Coccidioides in soil using an alternate method, we employed next generation amplicon sequencing targeting the ITS2 region. Results show our modified assay, CocciEnv, is a rapid and robust method for detecting Coccidioides DNA in complex environmental samples. The ability to test a large number of soils for the presence of Coccidioides is a much-needed tool in the understanding of the ecology of the organism and epidemiology of the disease and will greatly improve our understanding of this human pathogen.

Evans function computation for the stability of travelling waves.

In recent years, the Evans function has become an important tool for the determination of stability of travelling waves. This function, a Wronskian of decaying solutions of the eigenvalue equation, is useful both analytically and computationally for the spectral analysis of the linearized operator about the wave. In particular, Evans-function computation allows one to locate any unstable eigenvalues of the linear operator (if they exist); this allows one to establish spectral stability of a given wave and identify bifurcation points (loss of stability) as model parameters vary. In this paper, we review computational aspects of the Evans function and apply it to multidimensional detonation waves.This article is part of the theme issue 'Stability of nonlinear waves and patterns and related topics'.

Exploring the genomic diversity of black yeasts and relatives (Chaetothyriales, Ascomycota).

The order Chaetothyriales (Pezizomycotina, Ascomycetes) harbours obligatorily melanised fungi and includes numerous etiologic agents of chromoblastomycosis, phaeohyphomycosis and other diseases of vertebrate hosts. Diseases range from mild cutaneous to fatal cerebral or disseminated infections and affect humans and cold-blooded animals globally. In addition, Chaetothyriales comprise species with aquatic, rock-inhabiting, ant-associated, and mycoparasitic life-styles, as well as species that tolerate toxic compounds, suggesting a high degree of versatile extremotolerance. To understand their biology and divergent niche occupation, we sequenced and annotated a set of 23 genomes of main the human opportunists within the Chaetothyriales as well as related environmental species. Our analyses included fungi with diverse life-styles, namely opportunistic pathogens and closely related saprobes, to identify genomic adaptations related to pathogenesis. Furthermore, ecological preferences of Chaetothyriales were analysed, in conjuncture with the order-level phylogeny based on conserved ribosomal genes. General characteristics, phylogenomic relationships, transposable elements, sex-related genes, protein family evolution, genes related to protein degradation (MEROPS), carbohydrate-active enzymes (CAZymes), melanin synthesis and secondary metabolism were investigated and compared between species. Genome assemblies varied from 25.81 Mb (Capronia coronata) to 43.03 Mb (Cladophialophora immunda). The bantiana-clade contained the highest number of predicted genes (12 817 on average) as well as larger genomes. We found a low content of mobile elements, with DNA transposons from Tc1/Mariner superfamily being the most abundant across analysed species. Additionally, we identified a reduction of carbohydrate degrading enzymes, specifically many of the Glycosyl Hydrolase (GH) class, while most of the Pectin Lyase (PL) genes were lost in etiological agents of chromoblastomycosis and phaeohyphomycosis. An expansion was found in protein degrading peptidase enzyme families S12 (serine-type D-Ala-D-Ala carboxypeptidases) and M38 (isoaspartyl dipeptidases). Based on genomic information, a wide range of abilities of melanin biosynthesis was revealed; genes related to metabolically distinct DHN, DOPA and pyomelanin pathways were identified. The MAT (MAting Type) locus and other sex-related genes were recognized in all 23 black fungi. Members of the asexual genera Fonsecaea and Cladophialophora appear to be heterothallic with a single copy of either MAT-1-1 or MAT-1-2 in each individual. All Capronia species are homothallic as both MAT1-1 and MAT1-2 genes were found in each single genome. The genomic synteny of the MAT-locus flanking genes (SLA2-APN2-COX13) is not conserved in black fungi as is commonly observed in Eurotiomycetes, indicating a unique genomic context for MAT in those species. The heterokaryon (het) genes expansion associated with the low selective pressure at the MAT-locus suggests that a parasexual cycle may play an important role in generating diversity among those fungi.

Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.

BACKGROUND: The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. METHODS: Utilizing flow cytometry to identify circulating, collagen type 1+ cells, we found two populations: (i) CD45+ CD34+ (fibrocytes) and (ii) CD45+ CD34- [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) subjects. Lung resection material from a separate group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a path analysis model. RESULTS: Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes. CONCLUSION: We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

Partial Flexor Tendon Laceration Assessment: Interobserver and Intraobserver Reliability.

Accurate assessment of partial-thickness flexor tendon lacerations in the hand is difficult owing to the subjectivity of evaluation. In this study, we created 12 partial-thickness flexor tendon lacerations in a cadaveric hand, evaluated the accuracy of 6 orthopedic residents and 4 fellowship-trained hand surgeons in estimating the percentage thickness of each laceration, and assessed the groups' interobserver and intraobserver agreement. The 10 participants estimated each laceration independently and on 2 separate occasions and indicated whether they would repair it. The actual thickness of each laceration was calculated from measurements made with a pair of digital microcalipers. Overall estimates differed significantly from calibrated measurements. Estimates grouped by residents and fellowship-trained hand surgeons also differed significantly. Third-year residents were the most accurate residents, and fellowship-trained hand surgeons were more accurate than residents. Overall interobserver agreement was poor for both readings. There was moderate overall intraobserver agreement. Fellowship-trained hand surgeons and first-year residents had the highest intraobserver agreement. These results highlight the difficulty in accurately assessing flexor tendon lacerations. Accuracy appears not to improve with surgeon experience.

Aboriginal street-involved youth experience elevated risk of incarceration.

OBJECTIVES: Past research has identified risk factors associated with incarceration among adult Aboriginal populations; however, less is known about incarceration among street-involved Aboriginal youth. Therefore, we undertook this study to longitudinally investigate recent reports of incarceration among a prospective cohort of street-involved youth in Vancouver, Canada. STUDY DESIGN: Prospective cohort study. METHODS: Data were collected from a cohort of street-involved, drug-using youth from September 2005 to May 2013. Multivariate generalized estimating equation analyses were employed to examine the potential relationship between Aboriginal ancestry and recent incarceration. RESULTS: Among our sample of 1050 youth, 248 (24%) reported being of aboriginal ancestry, and 378 (36%) reported being incarcerated in the previous six months at some point during the study period. In multivariate analysis controlling for a range of potential confounders including drug use patterns and other risk factors, Aboriginal ancestry remained significantly associated with recent incarceration (adjusted odds ratio [AOR] = 1.44; 95% confidence interval [CI]: 1.12-1.86). CONCLUSIONS: Even after adjusting for drug use patterns and other risk factors associated with incarceration, this study found that Aboriginal street-involved youth were still significantly more likely to be incarcerated than their non-Aboriginal peers. Given the established harms associated with incarceration these findings underscore the pressing need for systematic reform including culturally appropriate interventions to prevent Aboriginal youth from becoming involved with the criminal justice system.

Early experience with reduction of displaced disruption of the pelvic ring using a pelvic reduction frame.

We describe our early operative experience with a new pelvic reduction frame and the standard of reduction of fractures of the pelvic ring which we achieved in the first 35 consecutive patients, with 34 acute fractures and one nonunion. The pre-operative and immediate post-operative radiographs were measured, using two methods, to find the maximum radiological displacement of the fracture and the quality of the reduction according to the criteria of Tornetta and Matta. There were 19 vertical shear fractures and 16 compression injuries. The mean age of the patients was 33.5 years (10 to 59) and mean delay to surgery was 4.6 days (0 to 16) in the 34 acute injuries. The mean operative time in isolated procedures was 103.4 minutes (SD 6.5). All but one patient had iliosacral screws implanted, 18 had screws in the anterior column, six had plates at the symphysis pubis and 12 had anterior external fixators. The mean maximum horizontal or vertical displacement was improved from 30.8 mm (SD 2.7) to a mean of 7.1 mm (SD 0.7). The reduction was assessed as excellent in ten patients, good in 18, and fair in the remainder. There was no significant influence on the quality of the reduction caused by obesity (p = 0.34), the type of fracture (p = 0.41) or delay to surgery (p = 0.83). The frame was shown to be effective, allowing the surgeon to obtain a satisfactory reduction and fixation of acute displaced disruptions of the pelvic ring.

Serum urea and total cholesterol independently predict re-hospitalisation with a cardiac-related event following an acute ST-elevation myocardial infarction.

BACKGROUND: Although elevated serum urea and low serum sodium have been shown to be associated with increased short-term (30-day) mortality following an ST-elevation myocardial infarction (STEMI), little is known about the role of these biochemical markers as predictors of intermediate-term (1-year) re-hospitalisation. METHODS: Case notes of 90 consecutively admitted patients discharged with a primary diagnosis of an STEMI were retrospectively investigated. Baseline parameters were recorded and patients' clinical course following hospital discharge was carefully reviewed up to 1-year post-STEMI. Multivariate logistic regression analysis was performed to determine the independent association between baseline parameters and 1-year re-hospitalisation. RESULTS: The mean age of the patients was 62.8+/-1.38 years. Thirty patients (33.3%) were re-hospitalised for cardiac-related events and three patients (3.3%) died within 1 year of index STEMI. Using stepwise regression analysis, after adjusting for all independent variables, admission total cholesterol (p=0.013) and urea (p=0.04) were found to be the only significant independent predictors of re-hospitalisation or death. Admission serum sodium was non-significant (p=0.065), but only just. For each mmol/L increase in total cholesterol, a patient was 2.18 times more likely to be re-hospitalised, while for each mmol/L increase in serum urea, a patient was 1.32 times more likely to be re-hospitalised or die. When data were categorised based on high urea (> 7 mmol/L), high total cholesterol (> 5.0 mmol/L) and low sodium (< 135 mmol/L) at admission, none of these variables showed any significant increased risk of re-hospitalisation or death. This suggests that these biochemical parameters were continuously associated with risk of re-hospitalisation through the whole range of serum concentrations. CONCLUSION: In this retrospective study, independent predictors of 1-year re-hospitalisation following an STEMI include high serum urea, raised cholesterol levels and, possibly, reduced sodium levels. These simple biomarkers can be included in patients' risk stratification when following post-STEMI patients in out-patient clinics.

The population biology of coccidioides: epidemiologic implications for disease outbreaks.

Studies of field- and patient-derived isolates conducted over the past 75 years have provided a general picture of the population structure of Coccidioides, the cause of coccidioidomycosis. Premolecular studies provided a general outline of the geographical range, epidemiology and distribution of the fungus. Recent studies based on molecular markers have demonstrated that the genus is comprised of two genetically diverse, and genetically isolated, species: Coccidioides immitis and C. posadasii. Both species are composed of biogeographically distinct populations. Structure for two of these populations (C. immitis from central California, and C. posadasii from southern Arizona) indicates that frequent genetic recombination occurs within the entire geographic range of each population, even though sex has never been observed in the genus. Outbreaks of coccidioidomycosis are not the result of the spread of a single clonal isolate, but are caused by a diversity of genotypes. Although it is now possible to match patient isolates to populations, the lack of apparent structure within each population and the current paucity of environmental isolates limit map-based epidemiological approaches to understanding outbreaks. Therefore, a comprehensive database comprised of soil-derived isolates from across the biogeographic range of Coccidioides will improve the utility of this approach. Appropriate collection of environmental isolates will assist the investigation of remaining questions regarding the population biology of Coccidioides. The comparative genomics of representative genotypes from both species and all populations of Coccidioides will provide a thorough set of genetic markers in order to resolve the population genetics of this pathogenic fungus.

Quantifying Aphanomyces euteiches in Alfalfa with a Fluorescent Polymerase Chain Reaction Assay.

ABSTRACT A polymerase chain reaction (PCR) assay using a set of specific primers and a dual-labeled probe (TaqMan) was developed to quantify the amount of Aphanomyces euteiches DNA in alfalfa plants exhibiting varying levels of disease severity. The study included isolates of race 1 and race 2 of A. euteiches. The assay also discriminated between alfalfa populations for resistance based on analysis of DNA extracted from bulked plant samples. Analysis of individual plants and bulked plant samples of standard check populations with both pathogen isolates resulted in Spearman rank correlations between pathogen DNA content and disease severity index ratings that were greater than 0.75 and highly significant (P < 0.0005). In experiments with a race 1 isolate, the amount of pathogen DNA present in the resistant check WAPH-1 was significantly less than in the susceptible check Saranac. In experiments with a race 2 isolate, the amount of pathogen DNA in the resistant check WAPH-5 was significantly less than in either of the susceptible checks, Saranac and WAPH-1. Discrimination between commercial cultivars based on quantitative PCR analysis of bulked plant samples was similar to classification based on visual assessment of disease severity.

Clear cell carcinoma of the palate.

A case of minor salivary gland clear cell adenocarcinoma of the palate with metastasis to the lungs in a 53-year-old female is presented. Histologically, the cells were characterized by glycogen rich clear cells arranged in solid nests, trabeculae, surrounded by hyalinized fibrous stroma. We believe this represents an aggressive form of this type of tumor.

Oral management of the patient with cancer in the head and neck region.

Cancer therapies--including surgery, radiation, and chemotherapy--may unfavorably affect the oral/dental health of patients. Existing dental problems can also result in serious complications that may be prevented by dental intervention prior to cancer therapy. This paper will be limited to a discussion of the detrimental effects of radiation therapy on the oral cavity and salivary glands and appropriate dental management.

Villous trophoblast: morphometric perspectives on growth, differentiation, turnover and deposition of fibrin-type fibrinoid during gestation.

Villous trophoblast growth and deposition of perivillous fibrin-type fibrinoid were examined in human placentas from 10-41 weeks of gestation. The main aims were: (1) to study growth of different trophoblast domains implicated in epithelial turnover (proliferation, differentiation, extrusion, denudation); (2) to test predictions about relationships between fibrinoid deposits and intervillous volume or villous surface area; and (3) to derive baseline data for future studies on complicated pregnancies. Microscopical fields on trichrome-stained paraffin sections were selected by systematic random sampling. Volumes were estimated stereologically by point counting and surface areas by intersection counting. Apparent differences were tested by analyses of variance and relationships by regression and contingency table analyses. All compartments increased in absolute volume and/or surface area although not at the same rates. Relative volumes of cytotrophoblast were greater at earlier stages (10-20 weeks) but, due to differential growth, syncytiotrophoblast nuclear aggregation sites (syncytial knots and 'bridges') occupied greater proportions of trophoblast volume and surface near term (37-41 weeks). Fibrinoid volume correlated positively with intervillous volume and villous surface area but, relative to intervillous volume, seemed to increase near term. Findings confirm that the incidence of syncytial knots increases during gestation and contributes to trophoblast thickness variability. Greater relative volumes and surfaces of syncytial 'bridges' are consistent with increased incidences of true intervillous bridges and/or villous branching points. These findings support the notion that fibrinoid deposition during normal gestation is influenced by the quality of vascular perfusion but also emphasize that the villous surface is another important factor. Haemostatic events operate at the maternal surface of trophoblastic epithelium and influence the steady state between coagulation and fibrinolysis. Fibrinoid is deposited at sites of trophoblast de-epithelialization and these arise following trauma (e.g. abruption of intervillous bridges) or during the extrusion phase of normal epithelial turnover. Like knots and bridges, sites of de-epithelialization also expand at a faster rate than overall villous surface area. These and other events in villous development can be interpreted in terms of a coherent concept of epithelial turnover in which proliferation early in gestation is mainly for growth whilst that at later stages is mainly for renewal and repair.

The correlation between colposcopically directed cervical biopsy and loop electrosurgical excision procedure pathology and the effect of time on that agreement.

OBJECTIVE: The goal of this study was to evaluate whether colposcopically directed cervical biopsy accurately predicts histopathology found on loop electrosurgical excision procedure specimen and to assess whether this correlation was affected by a delay in treatment of greater than 12 weeks. METHODS: A retrospective review was performed of all cervical biopsy and loop electrosurgical excision procedure pairs performed at University of Arizona Medical Center between March 1992 and March 2000. Agreement was assessed by kappa statistics and Spearman rho coefficients. A subgroup analysis was performed to assess the effect of a delay greater than 12 weeks between cervical biopsy and loop excision on the histopathologic correlation. RESULTS: An 84% agreement was found between cervical biopsy histopathology and loop electrosurgical excision procedure histopathology when compared to within 1 degree (kappa = 0.78, P < 0.0001; Spearman rho = 0.40, P < 0.0001). This agreement remained strong (87%) even when loop electrosurgical excision procedure was delayed greater than 12 weeks (kappa = 0.81, P = 0.01). CONCLUSION: Colposcopically directed cervical biopsy correlated strongly with loop specimen histopathology. A delay in loop electrosurgical excision procedure greater than 12 weeks does not negatively affect this correlation. This delay of 12 weeks may be used safely in the future to test chemotherapeutic dysplasia treatments.

Volume and enthalpy profiles of CO binding to Fe(II) tetrakis-(4-sulfonatophenyl)porphyrin.

The focus of this study is to examine volume and enthalpy profiles of ligand binding associated with CO-Fe(II) tetrakis-(4-sulfonato phenyl)-porphyrin (COFe(II)4SP) in aqueous solution. Temperature dependent photothermal beam deflection was employed to probe the overall enthalpy and volume changes associated with CO-photolysis and recombination. The analysis demonstrates that ligand recombination occurs with a pseudo first order rate constant of (2.5+/-0.2)x10(4) s(-1) (at 25 degrees C) with a corresponding volume decrease of 6+/-1 ml/mol. The activation enthalpy (DeltaH(double dagger)) and volume (DeltaV(double dagger)) change for CO recombination (determined from temperature/pressure dependent transient absorption spectroscopy) are found to be 3.9 kcal/mol and 8.2 ml/mol, respectively. These data are consistent with a mechanism in which photolysis yields a five-coordinate high spin (H(2)O)Fe(II)4SP complex that recombines in a single step to form the low spin (CO)(H(2)O)Fe(II)4SP complex. Base elimination, often associated with CO photolysis from hemes, is not observed in this system. The overall volume changes suggest a transition state with significant high spin character. Furthermore, these results demonstrate the utility of coupling photothermal techniques with variable pressure/temperature transient absorption spectroscopy to probe heme reaction dynamics.

The Filshie clip for laparoscopic adnexal surgery.

BACKGROUND: Gynecologic endoscopic procedures are increasingly common and require the ability to control large vascular structures. METHOD: The Filshie clip is a silicone-lined, titanium occlusive device, originally designed and Food and Drug Administration (FDA) approved for surgical contraception. This device also has the potential for occluding vascular structures during laparoscopic surgery. EXPERIENCE AND RESULTS: We describe a salpingectomy, an excision of bilateral hydrosalpinges, and a salpingo-oopherectomy. We performed all procedures laparoscopically using this device as the primary modality for assuring hemostasis. CONCLUSION: The Filshie clip is a useful and economical device for assuring hemostasis during gynecologic endoscopic surgery.