Cross-validated Linear Discriminant Analysis Research Articles

Real Time Tissue Identification From Diathermy Smoke by Differential Mobility Spectrometry

Current methods for intraoperative surgical margin assessment are inadequate in terms of diagnostic accuracy, ease-of-use, and speed of analysis. Molecular analysis of tissues could potentially overcome these issues. A system based on differential ion mobility spectrometry (DMS) analysis of surgical smoke has been proposed as one potential method, but to date, it has been able to function in a relatively slow and heavily controlled manner that is inadequate for clinical use. In this study, we present an integrated sensor system that can measure a surgical smoke sample in seconds and relay the information of the tissue type to the user in near real time in simulated surgical use. The system was validated by operating porcine adipose tissue and muscle tissue. The differentiation of these tissues based on their surgical smoke profile with a cross-validated linear discriminant analysis model produced a classification accuracy of 93.1% (N = 1059). The measurements were also classified with a convolutional neural network model, resulting in a classification accuracy of 93.2%. These results indicate that the DMS-based smoke analysis system is capable of rapid tissue identification from surgical smoke produced in freehand surgery.

The Smell of Hypoxia: using an electronic nose at altitude and proof of concept of its role in the prediction and diagnosis of acute mountain sickness.

† Electronic nose (e‐nose) devices may be used to identify volatile organic compounds (VOCs) in exhaled breath. VOCs generated via metabolic processes are candidate biomarkers of (patho)physiological pathways. We explored the feasibility of using an e‐nose to generate human “breathprints” at high altitude. Furthermore, we explored the hypothesis that pathophysiological processes involved in the development of acute mountain sickness (AMS) would manifest as altered VOC profiles. Breath analysis was performed on Sherpa and lowlander trekkers at high altitude (3500 m). The Lake Louise Scoring (LLS) system was used to diagnose AMS. Raw data were reduced by principal component (PC) analysis (PCA). Cross validated linear discriminant analysis (CV‐LDA) and receiver‐operating characteristic area under curve (ROC‐AUC) assessed discriminative function. Breathprints suitable for analysis were obtained from 58% (37/64) of samples. PCA showed significant differences between breathprints from participants with, and without, AMS; CV‐LDA showed correct classification of 83.8%, ROC‐AUC 0.86; PC 1 correlated with AMS severity. There were significant differences between breathprints of participants who remained AMS negative and those whom later developed AMS (CV‐LDA 68.8%, ROC‐AUC 0.76). PCA demonstrated discrimination between Sherpas and lowlanders (CV‐LDA 89.2%, ROC‐AUC 0.936). This study demonstrated the feasibility of breath analysis for VOCs using an e‐nose at high altitude. Furthermore, it provided proof‐of‐concept data supporting e‐nose utility as an objective tool in the prediction and diagnosis of AMS. E‐nose technology may have substantial utility both in altitude medicine and under other circumstances where (mal)adaptation to hypoxia may be important (e.g., critically ill patients).

A new multivariate method for determining sex of immature human remains using the maxillary first molar.

This study investigated the use of sexually dimorphic metrics of the first permanent maxillary molar (M1 ) to determine sex in adult and immature individuals within and between populations. Ten M1 dimensions were measured in 91 adults (19-55 years) and 58 immatures (5-18 years) from two English populations, one of documented sex (Spitalfields crypt) and another of morphologically-assigned sex (Black Gate). Preliminary statistical analysis was undertaken to explore bilateral differences and variation by age and sex, followed by multivariate analyses to predict sex from dental metrics. Both cross-validated linear discriminant analysis and binary logistic regression predicted biological sex consistent with known sex in 94.6% of adults and 90.9% of immatures. When functions extracted from the Spitalfields data were used to assign sex to Black Gate adults, consistency with morphological sex varied from 83.3% to 57.7%. A new function developed on Black Gate resulted in only a 4.8% increase in maximum accuracy but reduced bias. The immature cohort comprised 19 (52.8%) males and 17 (47.2%) females. This study demonstrates substantial sexual dimorphism in a single tooth which is commonly preserved in archaeological and forensic contexts. It successfully assigns biological sex to immatures from 5 years of age with substantially greater accuracy than any other morphological or metric method. We suggest that accurate cross-population functions based on dentition require a trade-off between accuracy and applicability, and that functions extracted from populations of documented sex can be used to assign sex to other archaeological and forensic remains.

Tissue Identification in a Porcine Model by Differential Ion Mobility Spectrometry Analysis of Surgical Smoke.

Electrosurgery is widely used in various surgical operations. When tissue is cut with high-frequency current, the cell contents at the incision area evaporate and together with water and possible soot particles, form surgical smoke. The smoke contains cell metabolites, and therefore, possible biomarkers for cancer or bacterial infection. Thus, the analysis of surgical smoke could be used in intraoperative medical diagnostics. We present a method that can be used to detect the characteristics of various tissue types by means of differential ion mobility spectrometry (DMS) analysis of surgical smoke. We used our method to test tissue identification with ten different porcine tissues. We classified the DMS responses with cross-validated linear discriminant analysis models. The classification accuracy in a measurement set with ten tissue types was 95%. The presented tissue identification by DMS analysis of surgical smoke is a proof-of-concept, which opens the possibility to research the method in diagnosing human tissues and diseases in the future.

Taxonomic revision of imitating carpenter ants, Camponotus subgenus Myrmopytia (Hymenoptera, Formicidae) of Madagascar, using morphometry and qualitative traits.

The ant genus Camponotus (Mayr, 1861) is one of the most abundant and species rich ant genera in the Malagasy zoogeographical region. Although this group is commonly encountered, its taxonomy is far from complete. Here, we clarify the taxonomy of the Malagasy-endemic Camponotus subgenus Myrmopytia (Emery, 1920). Species delimitation was based on traditional morphological characters and multivariate morphometric analyses, including exploratory Nest Centroid clustering and confirmatory cross-validated Linear Discriminant Analysis. Four species are recognized: Camponotus imitator (Forel, 1891), Camponotus jodina sp. n., Camponotus karaha sp. n., and Camponotus longicollis sp. n. All four species appear to mimic co-occurring Aphaenogaster species. A diagnosis of the subgenus Myrmopytia, species descriptions, an identification key based on minor and major subcastes of workers, and the known geographical distribution of each species are provided.

Taxonomic revision of the Malagasy Camponotus grandidieri and niveosetosus species groups (Hymenoptera, Formicidae) using qualitative and quantitative morphology.

The Camponotus grandidieri species group and Camponotus niveosetosus species group of the Malagasy region are revised. Species delimitation was inferred from the evidence of both qualitative morphological analysis and multivariate morphometry. The multivariate method combined the Nest Centroid (NC)-clustering method and Partitioning Algorithm based on Recursive Thresholding (PART) function to generate hypotheses about species boundaries (clusters) based on 19 continuous morphological traits of minor workers. The proposed species hypotheses were tested by cumulative cross-validated Linear Discriminant Analysis (LOOCV-LDA) and Principal Component Analysis in a shape space (shape PCA). Morphometric ratios for the subsets of minor and major workers were used in species descriptions and redefinitions. Here, eight species are recognized, of which three are newly described and five are redescribed. Four species belong to the Camponotus grandidieri species group: auropubens Forel, efitra n. sp., grandidieri Forel, and maintikibo n. sp.; and four species belong to the Camponotus niveosetosus species group: descarpentriesi Santschi, madagascarensis Forel stat. rev., mita n. sp., and voeltzkowii Forel. Camponotus auropubens aldabrensis Forel and C. olivieri freyeri Santschi are synonymized under C. auropubens. Camponotus grandidieri atrabilis Santschi and C. grandidieri comorensis Santschi are synonymized under C. grandidieri. Illustrated species identification keys for both minor and major castes, taxonomic discussions, images, and distribution maps for each species superimposed on the ecoregions of Madagascar are also provided.

Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study.

1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5–8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5–4.5 Hz and 4.5–6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo-controlled study.

Inconvenient hyperdiversity - the traditional concept of "PheIdole pallIdula" includes four cryptic species (Hymenoptera: Formicidae)

Results of a pilot study are presented suggesting that Edward Wilson’s guess of some 1500 species in the hyperdiverse genus Pheidole Westwood, 1839 is likely to turn out as rather moderate estimate. Investigation of 112 nest samples containing 287 major workers of Westpalaearctic ants currently named Pheidole pallidula (Nylander, 1849) was performed by the explorative data analyses NC-Ward and NC-k-means clustering in combination with cross-validated linear discriminant analysis. Seventeen primary morphometric data were recorded by high-resolution stereomicroscopy. Allometric variance of shape variables was removed. Four cryptic species, forming the Ph. pallidula complex, were resolved: Ph. pallidula, Ph. balcanica nov. sp., Ph. koshewnikovi Ruzsky, 1905 and Ph. cicatricosa Stitz, 1917. The classification error varied between 0 and 2.8 % in NC clustering of nest samples and between 1.6 and 3.7 % in cross-validated linear discriminant analysis of individuals. Ph. cicatricosa has a North African distribution whereas Ph. pallidula, Ph. balcanica nov. sp. and Ph. koshewnikovi are Eurasian species with large sympatric ranges in the Balkans and Asia Minor. Colonization of urban regions north of the Alps and of offshore islands in the Mediterranean Sea indicates an invasive potential of the supercolonial social type of Ph. pallidula. There are no indications that any of these four taxa might represent an intraspecific polymorphism and signals for putative interspecific hybridization are not significant. The following synonymies were established: Ph. subdentata Mayr, 1853, Ph. pallidula var. obscura Santschi, 1936 and Xenoaphaenogaster inquilina Baroni Urbani, 1964 are junior synonyms of Ph. pallidula, Ph. pallidula var. arenarum Ruzsky, 1905 and Ph. pallidula ssp. orientalis Muller, 1923 are junior synonyms of Ph. koshewnikovi and Ph. pallidula var. recticeps Menozzi, 1932 is a junior synonym of Ph. cicatricosa. The senior synonymy of the following seven Westpalaearctic taxa with any member of the Ph. pallidula complex was excluded by type investigation and diagostic statements in the original descriptions: Ph. sinaitica Mayr, 1862, Ph. jordanica Saulcy, 1874, Ph. teneriffana Forel, 1893, Ph. laticeps Mayr, 1904, Ph. schmitzi Forel, 1911, Ph. obtusa Stitz, 1917 and Ph. pallidula selenia Ozdikmen, 2010. Species delimitation in the less differentiated caste of minor workers was not tested but seems possible when accessory morphological characters are included.

Taxonomic revision of the Malagasy members of the Nesomyrmex angulatus species group using the automated morphological species delineation protocol NC-PART-clustering.

Background. Applying quantitative morphological approaches in systematics research is a promising way to discover cryptic biological diversity. Information obtained through twenty-first century science poses new challenges to taxonomy by offering the possibility of increased objectivity in independent and automated hypothesis formation. In recent years a number of promising new algorithmic approaches have been developed to recognize morphological diversity among insects based on multivariate morphometric analyses. These algorithms objectively delimit components in the data by automatically assigning objects into clusters.Method. In this paper, hypotheses on the diversity of the Malagasy Nesomyrmex angulatus group are formulated via a highly automated protocol involving a fusion of two algorithms, (1) Nest Centroid clustering (NC clustering) and (2) Partitioning Algorithm based on Recursive Thresholding (PART). Both algorithms assign samples into clusters, making the class assignment results of different algorithms readily inferable. The results were tested by confirmatory cross-validated Linear Discriminant Analysis (LOOCV-LDA).Results. Here we reveal the diversity of a unique and largely unexplored fragment of the Malagasy ant fauna using NC-PART-clustering on continuous morphological data, an approach that brings increased objectivity to taxonomy. We describe eight morphologically distinct species, including seven new species: Nesomyrmex angulatus (Mayr, 1862), N. bidentatus sp. n., N. clypeatus sp. n., N. devius sp. n., N. exiguus sp. n., N. fragilis sp. n., N. gracilis sp. n., and N. hirtellus sp. n.. An identification key for their worker castes using morphometric data is provided.Conclusions. Combining the dimensionality reduction feature of NC clustering with the assignment of samples into clusters by PART advances the automatization of morphometry-based alpha taxonomy.

Quantitative inferences on the locomotor behaviour of extinct species applied to Simocyon batalleri (Ailuridae, Late Miocene, Spain).

Inferences of function and ecology in extinct taxa have long been a subject of interest because it is fundamental to understand the evolutionary history of species. In this study, we use a quantitative approach to investigate the locomotor behaviour of Simocyon batalleri, a key taxon related to the ailurid family. To do so, we use 3D surface geometric morphometric approaches on the three long bones of the forelimb of an extant reference sample. Next, we test the locomotor strategy of S. batalleri using a leave-one-out cross-validated linear discriminant analysis. Our results show that S. batalleri is included in the morphospace of the living species of musteloids. However, each bone of the forelimb appears to show a different functional signal suggesting that inferring the lifestyle or locomotor behaviour of fossils can be difficult and dependent on the bone investigated. This highlights the importance of studying, where possible, a maximum of skeletal elements to be able to make robust inferences on the lifestyle of extinct species. Finally, our results suggest that S. batalleri may be more arboreal than previously suggested.

Improving Sex Estimation from Crania Using a Novel Three‐dimensional Quantitative Method,,

This study utilizes an innovative 3D approach to discover metric variables that obtain the highest classification rates for sex estimation from the cranium. Models were constructed from 222 cranial CT scans of U.S. Whites from the Bass Donated Collection. These models were used to create a statistical bone atlas that captures the primary shape variation in the skull and facilitates rapid computer-automated analyses. The bone atlas showed that important size-related sex variables are bizygomatic breadth, maximum cranial length, cranial base length, and mastoid height. Shape-related variables capture sex differences in the projection of the glabellar region, inclination of the frontal, and cranial base flexion. In addition, vault thickness is highly dimorphic, with females having on average thicker vaults in the frontal region, and males having thicker vaults in the occipital region. Cross-validated linear discriminant analysis obtained >95% accuracy (97.5% with 11 variables and 95.5% with eight variables).

Efficacy of fatty acids and terpenoids and weakness of electronic nose response as tracers of Asiago d’Allevo PDO cheese produced in different seasons

The goal of this study was to verify the suitability of using fatty acids (FAs), terpenoids, and electronic nose response as potential tracers of the seasonal variations in Asiago d’Allevo PDO cheese. Cheese samples produced during the early and late summer grazing and the autumn/winter indoor seasons were compared. Based on their FA composition, the early and late summer cheeses were almost completely indistinguishable from each other. However, they both demonstrated higher quality when compared to the autumn/winter cheeses, showing lower levels of hypercholesterolemic saturated FAs (C12, C14, and C16) and higher levels of total mono- and polyunsaturated FAs, oleic (C18:1 c9), trans-vaccenic (C18:1 t11), rumenic (C18:2 c9t11), and α-linolenic (C18:3 c9c12c15) acids. Among terpenoids, camphene, cedrane, and total sesquiterpenoids were able to differentiate the cheeses manufactured during the three periods of production. Moreover, α-pinene, α-thujene, β-pinene, δ-3-carene, myrtenol, dihydrocarveol isomer 1, and unidentified sesquiterpene 1 distinguished the late summer cheeses from those obtained in the other two seasons. Principal component analysis of electronic nose data showed that the Asiago cheese samples were widely dispersed in the score plot and no clear clusters appeared evident. Furthermore, cross-validated linear discriminant analysis of the electronic nose data showed unsatisfactory classification performance (53.8%) regarding the period of production. Our results showed that coupling FAs and terpenoids information could be a suitable method for tracing Asiago d’Allevo PDO cheeses according to their season of production. However, no reliable information at this level seemed to be obtainable from the electronic nose response.

Pathology of Barrett’s esophagus by proton magnetic resonance spectroscopy and a statistical classification strategy

Background Barrett’s esophagus is thought to be a precursor of adenocarcinoma. The incidence of adenocarcinoma of the lower esophagus in the Western world is rising and accounts for more than 40% of esophageal carcinomas in males. It is not possible to identify which Barrett’s patients are at high risk of developing malignancy. Here we applied a statistical classification strategy to the analysis of magnetic resonance spectroscopy and histopathological data from esophageal biopsies to ascertain whether this risk could be identified in Barrett’s patients. Methods Tissue specimens from 72 patients (29 noncancer-bearing and 43 cancer-bearing) were analyzed by one-dimensional proton magnetic resonance spectroscopy at 8.5 Tesla. Diagnostic correlation was performed between the magnetic resonance spectra and histopathology. The magnetic resonance magnitude spectra were preprocessed, followed by identification of optimal spectral regions, and were then classified by cross-validated linear discriminant analysis of rank orders of the first derivative of magnetic resonance spectra. Results Magnetic resonance spectroscopy combined with a statistical classification strategy analysis distinguished normal esophagus from adenocarcinoma and Barrett’s epithelium with an accuracy of 100%. Barrett’s epithelium and adenocarcinoma were distinguished with an accuracy of 98.6% but only when 4 of the Barrett’s specimens and 7 of the carcinoma specimens, determined to be “fuzzy” (ie, unable to be accurately assigned to either class) were withdrawn. The 7 cancer and 4 Barrett’s specimens, determined to be “fuzzy” using the Barrett’s versus cancer (B versus C) classifier, were submitted to the other two classifiers (Barrett’s versus normal [B versus N] and normal versus cancer [N versus C], respectively). The 4 Barrett’s specimens were assigned to Barrett’s by the N versus B classifier and to normal (n = 2) or cancer (n = 2) classes by the N versus C classifer. The 7 cancer specimens were crisply assigned to the cancer class (N versus C), or for the B versus N classifier, to the Barrett’s class (ie, more similar to Barrett’s than to normal tissue). Visual inspection of the spectra from histologically identified Barrett’s epithelium showed a gradation from normal to carcinoma. Conclusions Proton magnetic resonance spectroscopy of esophageal biopsies combined with a statistical classification strategy data analysis provides a robust diagnosis with a high degree of accuracy for discriminating normal epithelium from esophageal adenocarcinoma and Barrett’s esophagus. Different spectral categories of Barrett’s epithelium were identified both by visual inspection and by statistical classification strategy, possibly reflecting the risk of future malignant transformation.

Pathology of hepatocellular carcinoma and its precursors using proton magnetic resonance spectroscopy and a statistical classification strategy

Apply the statistical classification strategy (SCS) to magnetic resonance spectroscopy (MRS) data from liver biopsies and test its potential to discriminate between normal liver, cirrhotic nodules and nodules of hepatocellular carcinoma with a high degree of accuracy. Liver tissue specimens from 54 patients undergoing either partial (hemi) or total hepatectomy were analysed by one-dimensional proton MRS at 8.5 Tesla. Histologically, these specimens were confirmed as normal (n=31), cirrhotic (n=59), and hepatocellular carcinoma (HCC, n=32). Diagnostic correlation was performed between the MR spectra and histopathology. An SCS was applied consisting of pre-processing MR magnitude spectra to identify spectral regions of maximal discriminatory value, and cross-validated linear discriminant analysis. SCS applied to MRS data distinguished normal liver tissue from HCC with an accuracy of 100%. Normal liver tissue was distinguished from cirrhotic liver with an accuracy of 92% and cirrhotic liver was distinguished from HCC with an accuracy of 98%. SCS applied to proton MRS of liver biopsies provides a robust method to distinguish, with a high degree of accuracy, HCC from both cirrhotic and normal liver.

Distinct Human T Cell Repertoires Mediate Immediate and Delayed-Type Hypersensitivity to theTrichophytonAntigen, Tri r 2

The 29-kDa subtilase homologue, Tri r 2, derived from the dermatophyte fungus Trichophyton rubrum, exhibits unique immunologic characteristics in its ability to elicit immediate (IH) and delayed-type (DTH) hypersensitivity skin tests in different individuals. Thus, Tri r 2 provides a model for comparing the T cell repertoire in subjects with distinct immune responses to a single Ag. Recombinant Tri r 2 produced as a GST fusion protein in Escherichia coli stimulated strong in vitro lymphoproliferative responses in 10 IH and 10 DTH responders. Patterns of T cell epitope recognition were compared between skin test groups using 28 overlapping peptides (each in 12 replicate wells) derived from Tri r 2 to stimulate T lymphocyte proliferation in vitro. Peptide 5 (P5; aa 41-60) induced the strongest response in DTH subjects and showed the largest difference between DTH and IH responders in proliferation (mean standardized index, 2.22 and 0.82, respectively; p = 0.0047) and number of positive wells (81 vs 12). Responses to P5 were associated with diverse HLA haplotypes. These results showed that P5 contains an immunodominant epitope specifically associated with DTH and that this peptide is recognized in a permissive manner. Cross-validated linear discriminant analysis using T cell proliferative responses to two regions of Tri r 2 (aa 51-90 and 231-270) gave a 95% predictive accuracy for classification of subjects into IH or DTH groups. We conclude that different immune responses to Trichophyton are mediated by distinct T cell repertoires between individuals with IH and DTH reactions to Tri r 2.