Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS)

This paper describes informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography (GCxGC) and high-resolution mass spectrometry (HRMS). GCxGC-HRMS analysis produces large data sets that are rich with information, but highly complex. The size of the data and volume of information requires automated processing for comprehensive cross-sample analysis, but the complexity poses a challenge for developing robust methods. The approach developed here analyzes GCxGC-HRMS data from multiple samples to extract a feature template that comprehensively captures the pattern of peaks detected in the retention-times plane. Then, for each sample chromatogram, the template is geometrically transformed to align with the detected peak pattern and generate a set of feature measurements for cross-sample analyses such as sample classification and biomarker discovery. The approach avoids the intractable problem of comprehensive peak matching by using a few reliable peaks for alignment and peak-based retention-plane windows to define comprehensive features that can be reliably matched for cross-sample analysis. The informatics are demonstrated with a set of 18 samples from breast-cancer tumors, each from different individuals, six each for Grades 1-3. The features allow classification that matches grading by a cancer pathologist with 78% success in leave-one-out cross-validation experiments. The HRMS signatures of the features of interest can be examined for determining elemental compositions and identifying compounds.

Clinicopathologic features and long-term outcomes of NUT midline carcinoma

NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.

An unmatched case controlled study of clinicopathologic abnormalities in dogs with Bartonella infection

We compared clinicopathologic findings in dogs with Bartonella infection to Bartonella spp. negative dogs suspected of a vector-borne disease. Cases (n=47) and controls (n=93) were selected on the basis of positive or negative enrichment culture PCR results, respectively. Signalment, clinicopathologic findings and treatments were extracted from medical records. DNA sequencing identified Bartonella henselae (n=28, 59.6%), Bartonella vinsonii subsp. berkhoffii (n=20, 42.6%), Bartonella koehlerae (n=3, 6.4%), Bartonella volans-like (n=3, 6.4%) and Bartonella bovis (n=1, 2.1%). There were no significant differences in age, breed, size, sex or neuter status between cases and controls. Dogs infected with Bartonella sp. often had a history of weight loss [OR=2.82; 95% CI: 1.08-7.56] and were hypoglobulinemic [OR=4.26; 95% CI: 1.31-14.41]. With the exception of weight loss and hypoglobulinemia, clinicopathologic abnormalities in Bartonella-infected dogs in this study were similar to dogs suspected of other vector-borne infections.

Spontaneous onset of complex regional pain syndrome Type I in a woman infected with Bartonella koehlerae

After a short-term fever, complex regional pain syndrome, characterized by hyperalgesia, intermittent swelling, erythema and cyanosis of both feet, was diagnosed in a female veterinarian. The woman was infected with Bartonella koehlerae and she was also Bartonella vinsonii subsp. berkhoffii seroreactive. Having failed other treatments, symptoms resolved following initiation of antibiotics.

Successful treatment of Bartonella henselae endocarditis in a cat

This report describes the clinical presentation, diagnosis and treatment of a cat with vegetative valvular endocarditis temporally associated with natural infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the main clinical signs that resulted in referral for diagnostic evaluation. Using a novel and sensitive culture approach, B henselae was isolated from the blood. Following antibiotic therapy there was total resolution of clinical signs, the heart murmur, the valvular lesion by echocardiography, and no Bartonella species was isolated or amplified from a post-treatment blood culture. In conjunction with previous case reports, infective endocarditis can be associated with natural B henselae infection in cats; however, early diagnosis and treatment may result in a better prognosis than previously reported.

Unilateral epididymitis associated with salmonella bacteremia in a dog

This report describes the clinical features, diagnosis and treatment of a dog with unilateral epididymitis associated with Salmonella spp. bacteremia. Fever and an enlarged and painful testicle were the main clinical signs that resulted in referral for diagnostic evaluation. Unilateral septic epididymitis was diagnosed via ultrasonography of the genitourinary tract and aerobic culture of scrotal fluid, urine and blood, which yielded heavy growth of Salmonella spp. Pulsed-field gel electrophoresis (PFGE) confirmed the presence of Salmonella javiana. Following antibiotic therapy there was total resolution of clinical signs, and no Salmonella was isolated from a post-treatment urine culture. The source of infection was unknown, however an environmental exposure was suspected. Although infrequent, infection with Salmonella spp. should be included in the differential diagnosis of canine epididymitis. Given the major zoonotic importance of salmonellosis, and to prevent re-infection after treatment, the source of the infection should be investigated and eliminated, if possible.

Climate refugia: joint inference from fossil records, species distribution models and phylogeography

Climate refugia, locations where taxa survive periods of regionally adverse climate, are thought to be critical for maintaining biodiversity through the glacial–interglacial climate changes of the Quaternary. A critical research need is to better integrate and reconcile the three major lines of evidence used to infer the existence of past refugia – fossil records, species distribution models and phylogeographic surveys – in order to characterize the complex spatiotemporal trajectories of species and populations in and out of refugia. Here we review the complementary strengths, limitations and new advances for these three approaches. We provide case studies to illustrate their combined application, and point the way towards new opportunities for synthesizing these disparate lines of evidence. Case studies with European beech, Qinghai spruce and Douglas-fir illustrate how the combination of these three approaches successfully resolves complex species histories not attainable from any one approach. Promising new statistical techniques can capitalize on the strengths of each method and provide a robust quantitative reconstruction of species history. Studying past refugia can help identify contemporary refugia and clarify their conservation significance, in particular by elucidating the fine-scale processes and the particular geographic locations that buffer species against rapidly changing climate.