Are there leaks in your product pipeline?

Jump Starting Technologies, Patent Issues, and Translational Medicine Poster SessionSuccessful businesses move new products through the development pipeline swiftly and efficiently. An integral part of this process is the research design and execution. The field of statistics can provide knowledge and guidance that aides a successful flow through the developmental pipeline. The involvement of a professional statistician as a team member can help plug potential leaks and increase your probability of success. It pays to consider all sources of measurement variation in the design of an experiment and to account for them in the data analysis. Randomly assigning subjects to treatments reduces bias and controls for important, but unknown, factors. Various randomization strategies differ in their time and cost. More powerful analyses are possible when subjects are matched so that when different treatments are compared, other sources of variation are controlled. More powerful experiments are more sensitive at the same cost as less powerful experiments. When baseline measurements are incorporated into data analysis, treatment effects beyond baseline can be identified. Sample sizes should be large enough to detect real differences, yet small enough to be manageable and cost effective. New technology allows the measurement of many variables at many time points. The skills of a statistician can be useful in collaboration with the scientist to find the best way to transform large amounts of data into useful information. Finally, the presentation of study results needs to include the relevant statistical methods. Potential investors want to see data and be confident it has been subjected to the appropriate analysis. Meeting the requirements of regulatory agencies (FDA and EPA) will proceed more quickly if the analysis has been conducted by a professional statistician. The University of Missouri System has statisticians on several campuses. There are graduate programs at the University of Missouri, UMKC and Missouri University of Science and Technology. Graduate students are available for internships and/or summer employment. Graduate student support often leads to long term collaborations with statistics faculty

Differential transcript expression between the microfilariae of the filarial nematodes, Brugia malayi and B. pahangi

<p>Abstract</p> <p>Background</p> <p><it>Brugia malayi </it>and <it>B. pahangi </it>are two closely related nematodes that cause filariasis in humans and animals. However, <it>B. pahangi </it>microfilariae are able to develop in and be transmitted by the mosquito, <it>Armigeres subalbatus</it>, whereas most <it>B. malayi </it>are rapidly melanized and destroyed within the mosquito hemocoel. A cross-species microarray analysis employing the <it>B. malayi </it>V2 array was carried out to determine the transcriptional differences between <it>B. malayi </it>and <it>B. pahangi </it>microfilariae with similar age distribution.</p> <p>Results</p> <p>Following microarray data analysis, a list of preferentially expressed genes in both microfilariae species was generated with a false discovery rate estimate of 5% and a signal intensity ratio of 2 or higher in either species. A total of 308 probes were preferentially expressed in both species with 149 probes, representing 123 genes, in <it>B. pahangi </it>microfilariae and 159 probes, representing 107 genes, in <it>B. malayi </it>microfilariae. In <it>B. pahangi</it>, there were 76 (62%) up-regulated transcripts that coded for known proteins that mapped into the KEGG pathway compared to 61 (57%) transcripts in <it>B. malayi </it>microfilariae. The remaining 47 (38%) transcripts in <it>B. pahangi </it>and 46 (43%) transcripts in <it>B. malayi </it>microfilariae were comprised almost entirely of hypothetical genes of unknown function. Twenty-seven of the transcripts in <it>B. pahangi </it>microfilariae coded for proteins that associate with the secretory pathway compared to thirty-nine in <it>B. malayi </it>microfilariae. The data obtained from real-time PCR analysis of ten genes selected from the microarray list of preferentially expressed genes showed good concordance with the microarray data, indicating that the microarray data were reproducible.</p> <p>Conclusion</p> <p>In this study, we identified gene transcripts that were preferentially expressed in the microfilariae of <it>B. pahangi </it>and <it>B. malayi</it>, some of which coded for known immunomodulatory proteins. These comparative transcriptome data will be of interest to researchers keen on understanding the inherent differences, at the molecular level, between <it>B. malayi </it>and <it>B. pahangi </it>microfilariae especially because these microfilariae are capable of surviving in the same vertebrate host but elicit different immune response outcomes in the mosquito, <it>Ar. subalbatus</it>.</p

Parallel Genome-Wide Expression Profiling of Host and Pathogen During Soybean Cyst Nematode Infection of Soybean

Global analysis of gene expression changes in soybean (Glycine max) and Heterodera glycines (soybean cyst nematode [SCN]) during the course of infection in a compatible interaction was performed using the Affymetrix GeneChip soybean genome array. Among 35,611 soybean transcripts monitored, we identified 429 genes that showed statistically significant differential expression between uninfected and nematode-infected root tissues. These included genes encoding enzymes involved in primary metabolism; biosynthesis of phenolic compounds, lignin, and flavonoids; genes related to stress and defense responses; cell wall modification; cellular signaling; and transcriptional regulation. Among 7,431 SCN transcripts monitored, 1,850 genes showed statistically significant differential expression across different stages of nematode parasitism and development. Differentially expressed SCN genes were grouped into nine different clusters based on their expression profiles during parasitism of soybean roots. The patterns of gene expression we observed in SCN suggest coordinated regulation of genes involved in parasitism. Quantitative real-time reverse-transcription polymerase chain reaction confirmed the results of our microarray analysis. The simultaneous genome-wide analysis of gene expression changes in the host and pathogen during a compatible interaction provides new insights into soybean responses to nematode infection and the first profile of transcript abundance changes occurring in the nematode as it infects and establishes a permanent feeding site within a host plant root

The impact of supportive nursing care on the needs of men with prostate cancer: a study across seven European countries

Background: prostate cancer is for many men a chronic disease with a long life expectancy after treatment. The impact of prostate cancer therapy on men has been well defined, however, explanation of the consequences of cancer treatment has not been modelled against the wider variables of long-term health-care provision. The aim of this study was to explore the parameters of unmet supportive care needs in men with prostate cancer in relation to the experience of nursing care. Methods: a survey was conducted among a volunteer sample of 1001 men with prostate cancer living in seven European countries. Results: at the time of the survey, 81% of the men had some unmet supportive care needs including psychological, sexual and health system and information needs. Logistic regression indicated that lack of post-treatment nursing care significantly predicted unmet need. Critically, men's contact with nurses and/or receipt of advice and support from nurses, for several different aspects of nursing care significantly had an impact on men's outcomes. Conclusion: Unmet need is related not only to disease and treatment factors but is also associated with the supportive care men received. Imperative to improving men's treatment outcomes is to also consider the access to nursing and the components of supportive care provided, especially after therapy

Microbial Symbionts in Insects Influence Down-Regulation of Defense Genes in Maize

Diabrotica virgifera virgifera larvae are root-feeding insects and significant pests to maize in North America and Europe. Little is known regarding how plants respond to insect attack of roots, thus complicating the selection for plant defense targets. Diabrotica virgifera virgifera is the most successful species in its genus and is the only Diabrotica beetle harboring an almost species-wide Wolbachia infection. Diabrotica virgifera virgifera are infected with Wolbachia and the typical gut flora found in soil-living, phytophagous insects. Diabrotica virgifera virgifera larvae cannot be reared aseptically and thus, it is not possible to observe the response of maize to effects of insect gut flora or other transient microbes. Because Wolbachia are heritable, it is possible to investigate whether Wolbachia infection affects the regulation of maize defenses. To answer if the success of Diabrotica virgifera virgifera is the result of microbial infection, Diabrotica virgifera virgifera were treated with antibiotics to eliminate Wolbachia and a microarray experiment was performed. Direct comparisons made between the response of maize root tissue to the feeding of antibiotic treated and untreated Diabrotica virgifera virgifera show down-regulation of plant defenses in the untreated insects compared to the antibiotic treated and control treatments. Results were confirmed via QRT-PCR. Biological and behavioral assays indicate that microbes have integrated into Diabrotica virgifera virgifera physiology without inducing negative effects and that antibiotic treatment did not affect the behavior or biology of the insect. The expression data and suggest that the pressure of microbes, which are most likely Wolbachia, mediate the down-regulation of many maize defenses via their insect hosts. This is the first report of a potential link between a microbial symbiont of an insect and a silencing effect in the insect host plant. This is also the first expression profile for a plant attacked by a root-feeding insect

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation