Metastatic Squamous Cell Carcinoma in a Northern Brown Bandicoot (<i>Isoodon macrourus</i>)

Aside from a handful of notable exceptions, neoplasia is not reported as a major cause of mortality in wild animal populations and often goes undetected. For northern brown bandicoots specifically, there are few reported tumors in the literature and on file in the Australian Registry of Wildlife Health. This report describes a case of squamous cell carcinoma in a northern brown bandicoot (Isoodon macrourus), with metastases to the draining lymph nodes and lung. This neoplasm consisted predominantly of well-differentiated squamous cells and multifocal keratin pearls, with areas possibly consistent with epithelial to mesenchymal transition, as identified by positive immunohistochemical staining by both pancytokeratin (AE1/AE3) and vimentin. Additional investigations were negative for bandicoot papillomatosis carcinomatosis viruses

Laboratory and tentative interstellar detection of trans-methyl formate using the publicly available Green Bank Telescope PRIMOS survey

The rotational spectrum of the higher-energy trans conformational isomer of methyl formate has been assigned for the first time using several pulsed-jet Fourier transform microwave spectrometers in the 6-60 GHz frequency range. This species has also been sought toward the Sagittarius B2(N) molecular cloud using the publicly available PRIMOS survey from the Green Bank Telescope. We detect seven absorption features in the survey that coincide with laboratory transitions of trans-methyl formate, from which we derive a column density of 3.1 (+2.6, -1.2) \times 10^13 cm-2 and a rotational temperature of 7.6 \pm 1.5 K. This excitation temperature is significantly lower than that of the more stable cis conformer in the same source but is consistent with that of other complex molecular species recently detected in Sgr B2(N). The difference in the rotational temperatures of the two conformers suggests that they have different spatial distributions in this source. As the abundance of trans-methyl formate is far higher than would be expected if the cis and trans conformers are in thermodynamic equilibrium, processes that could preferentially form trans-methyl formate in this region are discussed. We also discuss measurements that could be performed to make this detection more certain. This manuscript demonstrates how publicly available broadband radio astronomical surveys of chemically rich molecular clouds can be used in conjunction with laboratory rotational spectroscopy to search for new molecules in the interstellar medium.Comment: 40 pages, 7 figures, 4 tables; accepted for publication in Ap

Cost-saving opportunities with appropriate utilization of cardiac telemetry

A third of healthcare spending in the United States is considered waste, and costs are growing at an unsustainable rate. Reducing unnecessary cardiac telemetry, a costly intervention with a high potential for overuse, may be an opportunity to reduce waste. We performed a review of 250 consecutive patients admitted to telemetry capable beds on the general medical-surgical, noncritical care units. Based on the American Heart Association Practice Standards for Electrocardiographic Monitoring in Hospital Settings, appropriateness of telemetric monitoring during each inpatient day was assessed, with identification of significant new arrhythmias, code calls, and clinical decisions resulting from telemetry. Cost of a telemetry day was calculated using a time-driven activity-based cost model. Patients (63 ± 19 years, 54% male) spent a total of 1,640 days hospitalized, 1,399 (85%) of which were on telemetry. Average length of stay was 6.6 days, and average telemetry time was 5.6 days. Only 334 (24%) telemetry days were deemed appropriate based on Practice Standards. During telemetric monitoring, 16 new significant arrhythmias were detected, 4 code calls were made, and 19 significant clinical decisions were prompted by telemetry. No cardiac code call occurred on a nontelemetry day. The cost of telemetry was calculated as $34.28 more per day than a nontelemetry hospital day. Elimination of inappropriate telemetry days would result in a minimum estimated savings of$37,007 in these 250 patients, and an annual savings of $528,241 overall. Telemetric monitoring is frequently overused. In conclusion, our findings propose that a reduction in inappropriate telemetry days in accordance with the American Heart Association Practice Standards could result in significant cost savings

24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex

Circadian rhythms modulate the biology of many human tissues, including brain tissues, and are driven by a near 24-hour transcriptional feedback loop. These rhythms are paralleled by 24-hour rhythms of large portions of the transcriptome. The role of dynamic DNA methylation in influencing these rhythms is uncertain. While recent work in Neurospora suggests that dynamic site-specific circadian rhythms of DNA methylation may play a role in modulating the fungal molecular clock, such rhythms and their relationship to RNA expression have not, to our knowledge, been elucidated in mammalian tissues, including human brain tissues. We hypothesized that 24-hour rhythms of DNA methylation exist in the human brain, and play a role in driving 24-hour rhythms of RNA expression. We analyzed DNA methylation levels in post-mortem human dorsolateral prefrontal cortex samples from 738 subjects. We assessed for 24-hour rhythmicity of 420,132 DNA methylation sites throughout the genome by considering methylation levels as a function of clock time of death and parameterizing these data using cosine functions. We determined global statistical significance by permutation. We then related rhythms of DNA methylation with rhythms of RNA expression determined by RNA sequencing. We found evidence of significant 24-hour rhythmicity of DNA methylation. Regions near transcription start sites were enriched for high-amplitude rhythmic DNA methylation sites, which were in turn time locked to 24-hour rhythms of RNA expression of nearby genes, with the nadir of methylation preceding peak transcript expression by 1–3 hours. Weak ante-mortem rest-activity rhythms were associated with lower amplitude DNA methylation rhythms as were older age and the presence of Alzheimer's disease. These findings support the hypothesis that 24-hour rhythms of DNA methylation, particularly near transcription start sites, may play a role in driving 24-hour rhythms of gene expression in the human dorsolateral prefrontal cortex, and may be affected by age and Alzheimer's disease

Predictive response-relevant clustering of expression data provides insights into disease processes

This article describes and illustrates a novel method of microarray data analysis that couples model-based clustering and binary classification to form clusters of ;response-relevant' genes; that is, genes that are informative when discriminating between the different values of the response. Predictions are subsequently made using an appropriate statistical summary of each gene cluster, which we call the ;meta-covariate' representation of the cluster, in a probit regression model. We first illustrate this method by analysing a leukaemia expression dataset, before focusing closely on the meta-covariate analysis of a renal gene expression dataset in a rat model of salt-sensitive hypertension. We explore the biological insights provided by our analysis of these data. In particular, we identify a highly influential cluster of 13 genes-including three transcription factors (Arntl, Bhlhe41 and Npas2)-that is implicated as being protective against hypertension in response to increased dietary sodium. Functional and canonical pathway analysis of this cluster using Ingenuity Pathway Analysis implicated transcriptional activation and circadian rhythm signalling, respectively. Although we illustrate our method using only expression data, the method is applicable to any high-dimensional datasets

Impact of shortened crop rotation of oilseed rape on soil and rhizosphere microbial diversity in relation to yield decline

Oilseed rape (OSR) grown in monoculture shows a decline in yield relative to virgin OSR of up to 25%, but the mechanisms responsible are unknown. A long term field experiment of OSR grown in a range of rotations with wheat was used to determine whether shifts in fungal and bacterial populations of the rhizosphere and bulk soil were associated with the development of OSR yield decline. The communities of fungi and bacteria in the rhizosphere and bulk soil from the field experiment were profiled using terminal restriction fragment length polymorphism (TRFLP) and sequencing of cloned internal transcribed spacer regions and 16S rRNA genes, respectively. OSR cropping frequency had no effect on rhizosphere bacterial communities. However, the rhizosphere fungal communities from continuously grown OSR were significantly different to those from other rotations. This was due primarily to an increase in abundance of two fungi which showed 100% and 95% DNA identity to the plant pathogens Olpidium brassicae and Pyrenochaeta lycopersici, respectively. Real-time PCR confirmed that there was significantly more of these fungi in the continuously grown OSR than the other rotations. These two fungi were isolated from the field and used to inoculate OSR and Brassica oleracea grown under controlled conditions in a glasshouse to determine their effect on yield. At high doses, Olpidium brassicae reduced top growth and root biomass in seedlings and reduced branching and subsequent pod and seed production. Pyrenochaeta sp. formed lesions on the roots of seedlings, and at high doses delayed flowering and had a negative impact on seed quantity and quality

Sample selection and reasons for non-participation in the PRedictors and Outcomes of incident FRACtures (PROFRAC) study

Background. Fragility fractures, associated with osteoporosis, are an escalating public health problem. We aim to describe sample selection, recruitment methods and reasons for non-participation in The PRedictors and Outcomes of incident FRACtures (PROFRAC) study. Design and Methods. Barwon Statistical Division residents aged 20+ years, with a radiologically-confirmed fracture between June 1st 2012 and May 31st 2013, were eligible. Individuals identified as fracture cases were invited by mail to complete a questionnaire. Reasons for non-participation were documented. Logistic regression techniques were used to determine odds ratios for participation and non-participation reasons. Results. A total of 1,458 of 2,155 (67.7%) adults with fracture (48.7% men) participated. Individuals were excluded due to inability to give informed consent, death, no knowledge of fracture, or inability to be contacted. The odds of participation decreased with age (OR 0.99, 95%CI 0.99-0.99, P=0.011) and increased among specific fracture groups [clavicle/scapula (OR 2.50, 1.30-4.68, P=0.006), forearm/humerus (OR 2.00, 1.22-3.27, P=0.006), wrist (OR 2.08, 1.31-0.32, P=0.002), hip (OR 2.12, 1.20-3.75, P=0.009), ankle (OR 1.85, 1.20-2.87, P=0.001), compared to face/skull fractures]. The odds of reporting disinterest, time constraints or personal reasons as the reason for non-participation decreased with age, whereas the odds of reporting frailty, language-related issues or illness as the reason for non-participation increased with of age [disinterest (OR 0.98, 0.97-0.98, P<0.001), time constraints (OR 0.97, 0.96-0.98, P<0.001), personal reasons (OR 0.98, 0.97-0.99, P=0.007), frailty (OR 1.12, 1.09- 1.15, P<0.001), language-related issues (OR 1.02, 1.01-1.04, P<0.001), illness (OR 1.03, 1.02-1.05, P<0.001)]. Conclusions. Understanding drivers of research participation can inform study design to achieve optimal participation in health research

The development, usability, and reliability of the Electronic Patient Visit Assessment (ePVA) for head and neck cancer

Background: Annually, over 65,000 persons are diagnosed with head and neck cancer in the United States. During treatment, up to 50% of patients become severely symptomatic with pain, fatigue, mouth sores, and inability to eat. Long term complications are lymphedema, fibrosis, dysphagia, and musculoskeletal impairment. Patients’ ability to perform daily activities and to interact socially may be impaired, resulting in poor quality of life. A pragmatic, clinically useful assessment is needed to ensure early detection and intervention for patients to report symptoms and functional limitations over time. We developed the Electronic Patient Visit Assessment (ePVA) that enables patients to report 42 symptoms related to head and neck cancer and 17 limitations of functional status. This manuscript reports (I) the development of the ePVA, (II) the content validity of the ePVA, and (III) the usability and reliability of the ePVA. Methods: Usability was evaluated using the “Think Aloud” technique to guide the iterative process to refine the ePVA based on participants’ evaluations. After signing the informed consent, 30 participants with head and neck cancer completed the ePVA using digital tablet devices while thinking aloud about ease of use. All patient conversations were recorded and professionally transcribed. Reliability of the ePVA symptom and functional limitation measures was estimated using the Kuder-Richardson test. Convergent validity of the ePVA was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global QoL/health scale. Transcribed qualitative data were analyzed using directed content analysis approach. Quantitative analyses consisted of descriptive statistics and correlation analyses. Results: Among participants, 90% strongly agreed or agreed that the ePVA system was easy to use and 80% were very satisfied. Only minor usability problems were reported due to formatting and software “bugs”. Reporting of usability problems decreased in frequency over the study period and no usability problems were reported by the last 3 participants who completed the ePVA. Based on participants’ suggestions during the iterative process, refinement of the ePVA included increased touch sensitivity of the touch screen technology and customized error messages to improve ease of use. The ePVA also recorded patient reported symptoms (mouth symptoms: 93%, fibrosis: 60%, fatigue: 60%). The ePVA demonstrated acceptable reliability (alpha =0.82–0.85) and convergent validity (ePVA total number of reported symptoms and function limitations was negatively correlated with EORTC QLQ-C30 global QOL/health scale: r=−0.55038, P<0.01). Conclusions: The ePVA was rigorously developed, accepted by patients with satisfaction, and demonstrated acceptable reliability and convergent validity. Future research will use data generated by the ePVA to determine the impact of symptom trajectories on functional status, treatment interruptions and terminations, and health resource use in head and neck cancer