Nine quick tips for efficient bioinformatics curriculum development and training.

Biomedical research is becoming increasingly data driven. New technologies that generate large-scale, complex data are continually emerging and evolving. As a result, there is a concurrent need for training researchers to use and understand new computational tools. Here we describe an efficient and effective approach to developing curriculum materials that can be deployed in a research environment to meet this need

Use of case reports and the Adverse Event Reporting System in systematic reviews: overcoming barriers to assess the link between Crohn’s disease medications and hepatosplenic T-cell lymphoma

BACKGROUND: To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn’s disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn’s disease. METHODS: We identified cases of HSTCL in Crohn’s disease in studies included in a comparative effectiveness review of Crohn’s disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL. RESULTS: We found 37 unique cases of HSTCL in patients with Crohn’s disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn’s disease based on the data contained in the case reports. CONCLUSION: Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than ‘possible’ between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication

Dissolved organic carbon export in a small, disturbed peat catchment: insights from long-term, high-resolution, sensor-based monitoring

Understanding dissolved organic carbon (DOC) export dynamics from carbon-rich environments is critical. Peatlands act as terrestrial carbon stores, and consequently supply substantial amounts of DOC to drainage. This DOC flux is temporally heterogeneous and subject to long- and short-term variability. Ultrahigh temporal resolution sampling (&lt; hourly) is still in-frequent in peatland catchments. We used a field-deployable —ultraviolet–visible light spectrometer (Spectro::lyser™) and monitored DOC flux from a temperate peatland over 31 months to examine seasonal and event dynamics. DOC concentration varied from 6.8 to 63.5 mg L−1, in the higher reported range for peatlands and showed clear seasonal (high-summer, low-winter) variability coinciding with elevated biological productivity in the peatland. Discharge was an unreliable predictor of instantaneous DOC concentration overall, with antecedent water temperatures proving the most reliable predictor overall. Discharge drove total DOC export in the catchment, where the top 10% of flow events, accounted for 41.3% of all DOC exported—increasing to 84.6% in the top 50% of flow events. Total estimated catchment DOC flux was sensitive to measurement frequency: increasing from every 30 min to daily altered export estimates by &lt; 1%, increasing to &gt; 10% at 1-week intervals. The variation in estimated flux increased approximately linearly with reduced sampling frequency, reaching &gt; 40% at monthly intervals. High-resolution data reveal the large amount of within-site complexity of DOC export dynamics in a temperate peatland and provide evidence on the subsequently recommended sampling frequency for the future elucidation of detailed DOC budgets in these environments

Developing models of good practice in meeting the needs of homeless young people in rural areas

Andrew Beer, Paul Delfabbro, Susan Oakley, Fiona Verity, Kristin Natalier, Jasmin Packer and Alice Bas

3D Collagen Alignment Limits Protrusions to Enhance Breast Cancer Cell Persistence

Patients with mammographically dense breast tissue have a greatly increased risk of developing breast cancer. Dense breast tissue contains more stromal collagen, which contributes to increased matrix stiffness and alters normal cellular responses. Stromal collagen within and surrounding mammary tumors is frequently aligned and reoriented perpendicular to the tumor boundary. We have shown that aligned collagen predicts poor outcome in breast cancer patients, and postulate this is because it facilitates invasion by providing tracks on which cells migrate out of the tumor. However, the mechanisms by which alignment may promote migration are not understood. Here, we investigated the contribution of matrix stiffness and alignment to cell migration speed and persistence. Mechanical measurements of the stiffness of collagen matrices with varying density and alignment were compared with the results of a 3D microchannel alignment assay to quantify cell migration. We further interpreted the experimental results using a computational model of cell migration. We find that collagen alignment confers an increase in stiffness, but does not increase the speed of migrating cells. Instead, alignment enhances the efficiency of migration by increasing directional persistence and restricting protrusions along aligned fibers, resulting in a greater distance traveled. These results suggest that matrix topography, rather than stiffness, is the dominant feature by which an aligned matrix can enhance invasion through 3D collagen matrices

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers’ narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers

Clinical applicability of current pharmacokinetic models: Splanchnic elimination of 5-fluorouracil in cancer patients

What can be inferred from limited clinical data by using current models of hepatic elimination? We examined this question by analyzing previously published data on the steady-state uptake of the anticancer agent 5-fluorouracil (5-FU) in seven cancer patients in terms of the venous equilibration model, the undistributed and distributed forms of the sinusoidal perfusion model, and the convection-dispersion model. Because of appreciable extrasplanchnic removal of 5-FU, the value of the steady infusion rate was not used in our analysis. When the data from all patients were pooled by plotting the measured hepatic venous concentration against the measured hepatic arterial concentration, the high concentration data fell on a limiting straight line of slope 1, indicating that at high dose rates elimination of 5-FU in both the liver and gastrointestinal tract was close to saturation. The intercept of this line gave a model-independent estimate of V max /Q= 48.0± 11.6 (SD) μM for the pooled data set, where V max is the maximum splanchnic elimination rate of 5-FU, and Q is the hepatic blood flow. The low concentration data points fell on a limiting straight line through the origin, from which model-dependent values of the Michaelis constant were determined. The venous equilibration model gave K m =9.4 μM , while the undistributed sinusoidal perfusion model gave K m * =26,5 μM. With these values of K m , both models fit the pooled data equally well. These methods were applied to analyses of the five individual data sets which contained sufficiently high concentration data points. The resulting mean values were V max /Q=41.0±5.1 (sem) μM, K m =8.4±1.3μM and K m * =23.2±3.2 μM. However, the splanchnic region is a highly heterogeneous organ system, for which an undistributed analysis provides no more than an upper bound on the Michaelis constant K m + ( K m + ⩽ K m * ). A perfusion model distributed to represent total splanchnic elimination is developed in the Appendix. Using previous estimates of the degree of functional heterogeneity in the liver alone, this model yields K m + values for individual patients which have a mean of 20.3±2.8 μM .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45038/1/10928_2005_Article_BF01062135.pd