Discordant Patterns Research Articles

Chronic intermittent hypoxia creates the perfect storm with calamitous consequences for respiratory control.

Obstructive sleep apnoea syndrome (OSAS) is a common respiratory disorder with devastating consequences for integrative body systems. A picture is emerging to illustrate wide-ranging deleterious consequences of disordered breathing during sleep for major homeostatic control systems, with considerable interest in cardiorespiratory and autonomic morbidity underpinning the development of hypertension. The vista is bleak when one also considers the link between OSAS and a host of other maladies. Exposure to chronic intermittent hypoxia (CIH), resulting from repeated obstructions of the pharyngeal airway, is a hallmark feature of OSAS that appears, in animal models, to drive the development and maintenance of several key morbidities. A growing body of evidence now points to aberrant respiratory plasticity at multiple levels following exposure to CIH. Herein, we review the experimental data revealing that CIH causes: respiratory muscle weakness and fatigue; impaired motor control of the upper airway; and, discordant respiratory rhythm and pattern generation. This multifaceted conspiracy creates the perfect storm with the potential to exacerbate OSAS—serving to establish an inescapable cycle of respiratory morbidity. Several pharmacological interventions in animal models appear wholly effective in preventing the calamitous consequences of CIH and may have application as adjunctive therapies in the treatment of OSAS.

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children.

The colonization pattern of intestinal microbiota during childhood may impact health later in life, but children older than 1 year are poorly studied. We followed healthy children aged 1-4 years (n=28) for up to 12 months, during which a synbiotic intervention and occasional antibiotics intake occurred, and compared them with adults from the same region. Microbiota was quantified with the HITChip phylogenetic microarray and analyzed with linear mixed effects model and other statistical approaches. Synbiotic administration increased the stability of Actinobacteria and antibiotics decreased Clostridium cluster XIVa abundance. Bacterial diversity did not increase in 1- to 5-year-old children and remained significantly lower than in adults. Actinobacteria, Bacilli and Clostridium cluster IV retained child-like abundances, whereas some other groups were converting to adult-like profiles. Microbiota stability increased, with Bacteroidetes being the main contributor. The common core of microbiota in children increased with age from 18 to 25 highly abundant genus-level taxa, including several butyrate-producing organisms, and developed toward an adult-like composition. In conclusion, intestinal microbiota is not established before 5 years of age and diversity, core microbiota and different taxa are still developing toward adult-type configuration. Discordant development patterns of bacterial phyla may reflect physiological development steps in children.

TCT-267 Agreement Between Pre-Hospital and Emergency Department ECG in the Diagnosis of STEMI – Patterns of Concordance and Discordance

Pre-hospital (PH) ECG enables field diagnosis and triage of STEMI patients to specialized STEMI receiving centers. Despite the proven benefits of early identification, false-positive ECG interpretations and unnecessary cardiac catheterization laboratory activations remain a common, challenging

High phylogeographical complexity within Mediterranean islands: insights from the Corsican fire salamander

AbstractAimMediterranean islands have been the subject of intense phylogeographical investigation. While most studies have focused on the processes of colonization and dispersal between landmasses, the phylogeographical structures within islands have received less attention. Here, we investigate the Pleistocene evolutionary history of the fire salamander Salamandra corsica. Our main aim is to shed more light on the importance of intra‐island micro‐evolutionary processes in structuring the patterns of biodiversity on Mediterranean islands.LocationCorsica Island.MethodsWe sampled 165 individuals across the entire range of S. corsica, and we sequenced two mitochondrial (cytb and cox1) and one nuclear (ßfib) gene fragments. We used Bayesian phylogeographical and historical demographic analyses based on DNA sequence data, together with species distribution modelling (SDM) under the present and past bioclimatic envelopes.ResultsBayesian phylogeographical analyses indicated that S. corsica (re)colonized its northern range during the Last Interglacial period from an ancestral area located in central‐southern Corsica. According to these analyses and the SDM, S. corsica was already established throughout the island during the last glacial phase, although likely with a fragmented distribution. Historical demographic analyses suggested a post‐glacial demographic expansion, probably associated with the climate‐driven spatial and temporal dynamics of forested habitats.Main conclusionsDespite its restricted and insular distribution, S. corsica showed past demographic and range dynamics that are comparable to those of wide‐ranging species on the continent. These dynamics are not consistent with temporal, spatial, and demographic patterns previously seen for other Corsican endemics. Such patterns of complex Pleistocene evolutionary histories and extensive phylogeographical discordance are also emerging from other insular systems. We conclude that island endemics should not be considered, a priori, as single populations and conservation units, and that the use of co‐occurrence patterns of island populations as inferential tools in historical biogeography should also be carefully reconsidered.

Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.

The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization.

Trends in Type of Health Insurance Coverage for US Children and Their Parents, 1998–2011

ObjectiveTo examine trends in health insurance type among US children and their parents. MethodsUsing the Medical Expenditure Panel Survey (1998–2011), we linked each child (n = 120,521; weighted n ≈ 70 million) with his or her parent or parents and assessed patterns of full-year health insurance type, stratified by income. We examined longitudinal insurance trends using joinpoint regression and further explored these trends with adjusted regression models. ResultsWhen comparing 1998 to 2011, the percentage of low-income families with both child and parent or parents privately insured decreased from 29.2% to 19.1%, with an estimated decline of −0.86 (95% confidence interval, −1.10, −0.63) unadjusted percentage points per year; middle-income families experienced a drop from 74.5% to 66.3%, a yearly unadjusted percentage point decrease of −0.73 (95% confidence interval, −0.98, −0.48). The discordant pattern of publicly insured children with uninsured parents increased from 10.4% to 27.2% among low-income families and from 1.4% to 6.7% among middle-income families. Results from adjusted models were similar to joinpoint regression findings. ConclusionsDuring the past decade, low- and middle-income US families experienced a decrease in the percentage of child–parent pairs with private health insurance and pairs without insurance. Concurrently, there was a rise in discordant coverage patterns—mainly publicly insured children with uninsured parents.

Collective dynamics in two populations of noisy oscillators with asymmetric interactions.

We study two intertwined globally coupled networks of noisy Kuramoto phase oscillators that have the same natural frequency but differ in their perception of the mean field and their contribution to it. Such a give-and-take mechanism is given by asymmetric in- and out-coupling strengths which can be both positive and negative. We uncover in this minimal network of networks intriguing patterns of discordance, where the ensemble splits into two clusters separated by a constant phase lag. If it differs from π, then traveling wave solutions emerge. We observe a second route to traveling waves via traditional one-cluster states. Bistability is found between the various collective states. Analytical results and bifurcation diagrams are derived with a reduced system.

Positive and purifying selection in mitochondrial genomes of a bird with mitonuclear discordance.

Diversifying selection on metabolic pathways can reduce intraspecific gene flow and promote population divergence. An opportunity to explore this arises from mitonuclear discordance observed in an Australian bird Eopsaltria australis. Across >1500km, nuclear differentiation is low and latitudinally structured by isolation by distance, whereas two highly divergent, parapatric mitochondrial lineages (>6.6% in ND2) show a discordant longitudinal geographic pattern and experience different climates. Vicariance, incomplete lineage sorting and sex-biased dispersal were shown earlier to be unlikely drivers of the mitonuclear discordance; instead, natural selection on a female-linked trait was the preferred hypothesis. Accordingly, here we tested for signals of positive, divergent selection on mitochondrial genes in E.australis. We used codon models and physicochemical profiles of amino acid replacements to analyse complete mitochondrial genomes of the two mitochondrial lineages in E.australis, its sister species Eopsaltria griseogularis, and outgroups. We found evidence of positive selection on at least five amino acids, encoded by genes of two oxidative phosphorylation pathway complexes NADH dehydrogenase (ND4 and ND4L) and cytochrome bc1 (cyt-b) against a background of widespread purifying selection on all mitochondrial genes. Three of these amino acid replacements were fixed in ND4 of the geographically most widespread E.australis lineage. The other two replacements were fixed in ND4L and cyt-b of the geographically more restricted E.australis lineage. We discuss whether this selection may reflect local environmental adaptation, a by-product of other selective processes, or genetic incompatibilities, and propose how these hypotheses can be tested in future.

Multicentric occurrence of multiple papillary thyroid carcinomas--HUMARA and BRAF mutation analysis.

Papillary thyroid carcinomas (PTCs) occasionally form multiple tumor foci in different sites of the same thyroid gland. However, it is controversial whether discrete nodules of PTC arise independently (multicentric occurrence) or are seeded from a single tumor via lymphatic channels (intraglandular metastasis). In order to determine the clonal origin of multiple PTCs, we examined X-chromosome inactivation patterns using a human androgen receptor gene-based assay (HUMARA) and the BRAF mutation using allele-specific PCR (AS-PCR) in 32 microdissected cancerous tissues from 14 Japanese women with multifocal PTC. All tumor foci were greater than 3 mm in size and met the criteria for microscopic classical PTC. Samples from 13 of the 14 patients were informative based on HUMARA. Tumor foci from two cases (15.4%) displayed a discordant X-chromosome inactivation pattern. Foci from the other 11 cases (84.6%) showed a concordant inactivation pattern of the X-chromosome. AS-PCR indicated that BRAF mutational status between the tumor foci was discordant in three (25%) and concordant in nine (75%) of 12 available cases. When the results of these two molecular analyses were combined, 28.6% of the cases were discordant in X-chromosome inactivation pattern and/or BRAF mutation, suggesting multicentric origin. Some of the remaining concordant cases also may be of multicentric origin. These results support a hypothesis that multicentric occurrence in multiple PTCs may be common, possibly greater than 30%. Although the exact mechanism of multicentric occurrence is still unclear, our findings contribute to the understanding the histogenesis of papillary thyroid carcinoma.

Canadian practice patterns for pancreaticoduodenectomy.

Discordant practice patterns may be a consequence of evidence-practice gaps or deficiencies in knowledge translation. We examined the current strategies used by hepato-pancreatico-biliary (HPB) surgeons in Canada for the perioperative management of pancreaticoduodenectomy (PD). We generated a web-based survey that focused on the perioperative measures surrounding PD. The survey was distributed to all members of the Canadian Hepato-Pancreatico-Biliary Association. The survey was distributed to 74 surgeons and received a response rate of 50%. Many similarities in surgical techniques were reported; for example, most surgeons (86.5%) reconstruct the pancreas with pancreaticojejunostomy rather than pancreaticogastrostomy. In contrast, variable techniques regarding the use of peritoneal drainage tubes, anastomotic stents, octreotide and other intraoperative modalities were reported. Most surgeons (75.7%) reported that their patients frequently required preoperative biliary drainage, yet there was minimal agreement with the designated criteria. There was variability in postoperative care, including the use of epidural analgesia and timing of postoperative oral nutrition. We identified heterogeneity among Canadian HPB surgeons, suggesting a number of evidence-practice gaps within specific domains of pancreatic resections. Focused research in these areas may facilitate technical agreement and improve patient outcomes following PD.

Anti–Factor Xa and Activated Partial Thromboplastin Time Measurements for Heparin Monitoring in Mechanical Circulatory Support

ObjectivesThis study investigated the relationship between anti–factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs). BackgroundCF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events. MethodsA prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels. ResultsA total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r2 = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001). ConclusionsLevels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

P40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations: A Comparative Immunohistochemical Study with 34betaE12.

Immunohistochemistry is important for the accurate diagnosis of basal cells in atypical glandular proliferations of the prostate. p40, an isoform of p63, may be an adjunct to a marker panel in this setting. Biopsies of 68 patients were analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal cell staining was classified as negative, partial (<60%), or diffuse (≥60%); irregular staining was defined as discordant staining patterns. In acinar proliferations (N = 41), partial staining for both markers was seen in 42%, and diffuse staining in 46% of reactive cases. An irregular reactivity was noted in one case only (2%). Finally, these lesions were signed out as benign. Acinar proliferations negative for both markers and limited amount of glands (≤4) were termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two cases showed partial, three cases showed diffuse reactivity for both markers, and one case was stained irregular. All cases diagnosed as prostate carcinomas (N = 20) had no evidence of basal cell staining for neither of the markers. p40 expression is closely correlated to 34betaE12 with respect to demonstration of basal cells of prostate glands and may provide further information on the dignity of glandular proliferations of the prostate.

Adapted Bland–Altman method was used to compare measurement methods with unequal observations per case

ObjectivesTo describe an adjustment of the Bland–Altman approach to evaluate possible patterns of discord between two measurement methods with an unequal number of observations per case. Study Design and SettingTwo methods of adaptation were compared using self-assessed general well-being scores (one individual rater) and scores given by multiple external raters for illustration. Both empirical data derived from the Older Person's Relevant Outcome of Care Score study and simulated data were used. ResultsWhen the mean of a number of assessments [X¯] is compared with a single assessment [Y], the variation [X¯ − Y] (vertical axis) will be correlated with the mean of X¯ and Y (horizontal axis) because the means of scores given by a larger group of raters tend to be less extreme than the scores given by individual raters. In contrast, in the absence of discord patterns, the variation [X¯ − Y] will not be correlated with the mean of all observations Xi and Yj made irrespective of who made them as denominator in the Bland–Altman plot. Thus, the second approach should be used for the valuation. ConclusionThe Bland–Altman approach needs correct adaptations, else artificial biases may occur.

Use of a polyphasic approach including MALDI-TOF MS for identification of Aspergillus section Flavi strains isolated from food commodities in Brazil

Brazil is one the largest producers and exporters of food commodities in the world. The evaluation of fungi capable of spoilage and the production mycotoxins in these commodities is an important issue that can be of help in bioeconomic development. The present work aimed to identify fungi of the genus Aspergillus section Flavi isolated from different food commodities in Brazil. Thirty-five fungal isolates belonging to the section Flavi were identified and characterised. Different classic phenotypic and genotypic methodologies were used, as well as a novel approach based on proteomic profiles produced by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Type or reference strains for each taxonomic group were included in this study. Three isolates that presented discordant identification patterns were further analysed using the internal transcribed spacer (ITS) region and calmodulin gene sequences. The data obtained from the phenotypic and spectral analyses divide the isolates into three groups, corresponding to taxa closely related to Aspergillus flavus, Aspergillus parasiticus, and Aspergillus tamarii. Final polyphasic fungal identification was achieved by joining data from molecular analyses, classical morphology, and biochemical and proteomic profiles generated by MALDI-TOF MS.

An Exploration of Decision-Making Processes on Infant Delivery Site from the Perspective of Pregnant Women, New Mothers, and Their Families in Northern Karnataka, India.

This study was conducted to explore the decision-making processes regarding sites for delivery of infants among women, their husbands, and mothers-in-law in a rural area of northern Karnataka state, south India. Qualitative semi-structured, individual in-depth interviews were conducted in 2010 among 110 pregnant women, new mothers, husbands and mothers-in-law. Interviews were conducted by trained local researchers in participants' languages and then translated into English. Decisions were made relationally, as family members weighed their collective attitudes and experiences towards a home, private or public delivery. Patterns of both concordance and discordance between women and their families' preferences for delivery site were present. The voice of pregnant women and new mothers was not always subordinate to that of other family members. Still, the involvement of husbands and mothers-in-law was important in decision-making, indicating the need to consider the influence of household gender and power dynamics. All respondent types also expressed shifts in social context and cultural attitudes towards increasing preference for hospital delivery. An appreciation of the interdependence of family members' roles in delivery site decision-making, and how they are influenced by the socio-cultural context, must be considered in frameworks used to guide the development of relevant interventions to improve the utilization and quality of maternal, neonatal and child health services.

Orogenic paleofluid flow recorded by discordant detrital zircons in the Caledonian foreland basin of northern Greenland

Concordant detrital zircon dates from Neoproterozoic to Paleozoic continental slope and trough deposits in northern Greenland indicate Late Archean and Paleoproterozoic sediment sources. Significant numbers of dates are, however, discordant and, together with a few apparently concordant dates, give ages younger than the depositional ages of overlying fossiliferous sediments. The discordance pattern implies partial or total radiogenic-Pb loss during the Middle Devonian, possibly facilitated by postdepositional fluid movement. Such timing of radiogenic-Pb loss is supported by results from a novel modeling method, which indicate that the greatest statistical similarity between concordant and discordant detrital populations occurs when Pb loss is constrained to the interval of 380-390 Ma, i.e., long after deposition. This radiogenic-Pb loss event is interpreted to reflect fluid flow associated with Caledonian orogenic uplift to the east.

The Gondwanan legacy in South American biogeography

AbstractThe tropical conservatism hypothesis (TCH) suggests that phylogenetic niche conservatism (the tendency for traits to be maintained during diversification) should be the main driver of latitudinal diversity gradients. For example, the tropical–temperate diversity gradient for woody angiosperms should reflect the tropical, older origin of most clades, the constrained evolution of cold tolerance, and the fact that few clades were able to persist in temperate zones after the beginning of the global cooling in the Eocene. Evidence for this explanation has been discussed primarily from a Northern Hemisphere perspective. Recently, two studies have presented diversity and clade–age relationships in South American forests that are inconsistent with the TCH, with older woody families being more frequent at higher latitudes and higher elevations in the Andes. We argue that a broader framework considering the ancient history of the Southern Hemisphere flora and the recent history of the Andean flora can help explain these discordant patterns. Here, we provide an initial discussion of this new perspective, emphasizing the historical development of a unique and rich palaeoflora of Gondwanan ancestry at mid‐ to high latitudes of South America and Antarctica. We suggest that the idea of Austral niche conservatism (ANC) of a warm‐temperate Antarctic–South American biota should be explored further to improve our understanding of biogeographical patterns in the Southern Hemisphere.

Asymmetric Introgression in a Spotted Salamander Hybrid Zone.

Before the establishment of reproductive isolation, deeply diverged intraspecific lineages can experience complex genetic and behavioral interactions as they come into secondary contact. Divergent selective and demographic processes mediate gene flow among lineages, resulting in hybrid zones with complex biogeographic structure. Discordance in the biogeographic patterns of autosomal and maternally inherited loci provides a useful window to infer the processes mediating admixture and introgression across hybrid zones. Here, we sampled 489 genotypes across a hybrid zone between 2 phylogeographic lineages of the spotted salamander, Ambystoma maculatum, and characterize discordant patterns of nuclear and mitochondrial introgression across the contact boundary. Our results indicate asymmetric introgression of nuclear DNA beyond the contact boundary from the western to eastern lineage, with introgression of eastern mitochondrial DNA into the western lineage. We discuss alternative mechanisms for this pattern and attribute this result to neutral patterns of population expansion of the western lineage into the east in combination with female mate choice for larger-bodied western males. Our results underscore the complexity of interacting mechanisms that give rise to reproductive asymmetries in the earliest stages of the speciation process.

Multi-character approach reveals a discordant pattern of phenotypic variation during ontogeny in Culex pipiens biotypes (Diptera: Culicidae).

Culex (Culex) pipiens s.l. (Diptera: Culicidae) comprises two distinct biotypes, pipiens ('rural') and molestus ('urban'), both of which are thought to have differing capacities due to different host preferences. To better understand West Nile encephalitis epidemiology and improve risk assessment, local distinction between these forms is essential. This study assesses phenotypic variation at larval and adult stages of 'urban' and 'rural' biotypes of the species by complementary use of meristic, univariate and multivariate traits analyzed by traditional and geometric morphometrics. Third- and fourth-instar larvae from a broad area of the city of Novi Sad (Serbia) were collected and reared in the laboratory. After adult eclosion, the sex of each larva was recorded based on the sex of the corresponding adult. Examination of the association between variations of larval traits revealed contrasting variations regarding pecten spines vs. siphonal size and siphonal shape in the 'rural' biotype. Siphons of larvae collected in marshes and forest ecosystems outside urban areas were found to be the largest, but possessed the smallest number of pecten spines. In addition, statistically significant female-biased sexual dimorphism was observed in siphonal size, wing size and wing shape. Finally, we propose that an integrative approach is essential in delimitation of Cx. pipiens s.l. biotypes, since their differentiation was not possible based solely on larval and adult traits. Our findings shed light on the phenotypic plasticity important for population persistence in the changing environment of these medically important taxa.

Enhanced detection of viral diversity using partial and near full-length genomes of human immunodeficiency virus Type 1 provirus deep sequencing data from recently infected donors at four blood centers in Brazil.

Here, we report application of high-throughput near full-length genome (NFLG) and partial human immunodeficiency virus Type 1 (HIV-1) proviral genome deep sequencing to characterize HIV in recently infected blood donors at four major blood centers in Brazil. From 2007 to 2011, a total of 341 HIV+ blood donors from four blood centers were recruited to participate in a case-control study to identify HIV risk factors and motivations to donate. Forty-seven (17 from São Paulo, eight from Minas Gerais, 11 from Pernambuco, and 11 from Rio de Janeiro) were classified as recently infected based on testing by less-sensitive enzyme immunoassays. Five overlapping amplicons spanning the HIV genome were polymerase chain reaction amplified from peripheral blood mononuclear cells. The amplicons were molecularly barcoded, pooled, and sequenced by a paired-end protocol (Illumina). Of the 47 recently infected donor samples studied, 39 (82.9%) NFLGs and six (12.7%) partial fragments were de novo assembled into contiguous sequences and successfully subtyped. Subtype B was the only nonrecombinant virus identified in this study and accounted for 62.2% (28/45) of samples. The remaining 37.8% (17/45) of samples showed various patterns of subtype discordance in different regions of HIV-1 genomes, indicating two to four circulating recombinant subtypes derived from Clades B, F, and C. Fourteen samples (31.1%) from this study harbored drug resistance mutations, indicating higher rate of drug resistance among Brazilian blood donors. Our findings revealed a high proportion of HIV-1 recombinants among recently infected blood donors in Brazil, which has implications for future blood screening, diagnosis, therapy, and vaccine development.