The Scientific Evaluation of New Claims

In the scientific world, the burden of proof for new claims is on the claimant. This is consistent with probabilities, because most new suggestions do turn out to be false. There is no single path from claim to proof This article illustrates four typical stages of the process, using the example of a claim for effectiveness of a new treatment. They are labeled "Tentative or Suggestive Evidence, " "Promising or Interesting, " "Probably Effective, " and "Established Effectiveness. " Each is based on characteristic levels of evidence. A few clues for identifying naive enthusiasts or outright frauds who try to shortcut these stages include claims of being ignored or rejected by an "establishment" that is too self-interested or set in its ways to consider new approaches; claims of special skills that others lack; vagueness about how the treatment has been evaluated and tested; and expressions such as "amazing, " "unique, " "special, " and "never dreamed of. "Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68962/2/10.1177_104973159600600111.pd

Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks

Endothelial cells line all major blood vessels and serve as integral regulators of many functions including vessel diameter, cellular trafficking, and transport of soluble mediators. Despite similar functions, the phenotype of endothelial cells is highly organ-specific, yet our understanding of the mechanisms leading to organ-level differentiation is incomplete. We generated 3D microvessel networks by combining a common naïve endothelial cell with six different stromal cells derived from the lung, skin, heart, bone marrow, pancreas, and pancreatic cancer. Single cell RNA-Seq analysis of the microvessel networks reveals five distinct endothelial cell populations, for which the relative proportion depends on the stromal cell population. Morphologic features of the organotypic vessel networks inversely correlate with a cluster of endothelial cells associated with protein synthesis. The organotypic stromal cells were each characterized by a unique subpopulation of cells dedicated to extracellular matrix organization and assembly. Finally, compared to cells in 2D monolayer, the endothelial cell transcriptome from the 3D in vitro heart, skin, lung, and pancreas microvessel networks are more similar to the in vivo endothelial cells from the respective organs. We conclude that stromal cells contribute to endothelial cell and microvessel network organ tropism, and create an endothelial cell phenotype that more closely resembles that present in vivo

The effects of ethanol intoxication on phobic anxiety

Behavioral conceptions of alcohol abuse often include the hypothesis that drinking behavior is a negatively reinforced operant, with ethanol intoxication viewed as alleviating aversive environmental and internal states. This hypothesis has not been confirmed or refuted by previous studies which employed mild stressors and limited assessment methodology. In the present experiment, 22 patients with severe phobias approached their phobic animal under two consecutive conditions--first while sober and second after drinking either a placebo or an intoxicating dose of ethanol. The severe anxiety induced was assessed behaviorally, physiologically and by the patient's self-report of fear. The intoxicated patients did not experience decreased anxiety, tachycardia or avoidance, compared to the placebo group. These results have clinical implications and suggest the need to reconsider tension-reduction theories of alcohol abuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25019/1/0000446.pd

The repeated pretest-posttest single-subject experiment: A new design for empirical clinical practice

The logic of a new design for empirical clinical practice, the repeated pretest-posttest experiment, is described. This design is readily applicable by individual practitioners in the human services, possesses high internal validity, and presents minimal intrusiveness into the delivery of service. A single-case study is used to illustrate the application of the repeated pretest-posttest experiment in clinical research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25047/1/0000475.pd

Discontinuation of Alprazolam after successful treatment of panic disorder: a naturalistic follow-up study

Low rates of benzodiazepine discontinuation have been seen in long-term outcome studies of alprazolam-treated panic disorder. Discontinuation studies reveal high rates of relapse when alprazolam is stopped. Available data may lack relevance to clinical practice, however, because drug taper rates are often more rapid than those used in many clinical settings. In order to obtain naturalistic data on the long-term course of alprazolam treatment of panic, we obtained follow-up data on 18 of 20 patients who had been enrolled one to two years earlier in a study of alprazolam effects on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA protocol provided measures of symptom severity, biological markers, and short-term treatment response (12 weeks). Routine clinical care was then provided, with dosage adjustments dictated by individual clinical needs. The follow-up study repeated clinical measures at a mean of 21 months after initiation of treatment. Alprazolam was discontinued in 78% of patients. Relapse occured in 36% of these. At follow-up, 61% were medication-free. Only 28% were on a benzodiazepine. The four patients remaining on alprazolam were on reduced doses and had maintained clinical gains. HPA axis activity did not predict dose or outcome. Factors related to successful alprazolam discontinuation are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30929/1/0000599.pd

Categorization of species as native or nonnative using DNA sequence signatures without a complete reference library.

New genetic diagnostic approaches have greatly aided efforts to document global biodiversity and improve biosecurity. This is especially true for organismal groups in which species diversity has been underestimated historically due to difficulties associated with sampling, the lack of clear morphological characteristics, and/or limited availability of taxonomic expertise. Among these methods, DNA sequence barcoding (also known as "DNA barcoding") and by extension, meta-barcoding for biological communities, has emerged as one of the most frequently utilized methods for DNA-based species identifications. Unfortunately, the use of DNA barcoding is limited by the availability of complete reference libraries (i.e., a collection of DNA sequences from morphologically identified species), and by the fact that the vast majority of species do not have sequences present in reference databases. Such conditions are critical especially in tropical locations that are simultaneously biodiversity rich and suffer from a lack of exploration and DNA characterization by trained taxonomic specialists. To facilitate efforts to document biodiversity in regions lacking complete reference libraries, we developed a novel statistical approach that categorizes unidentified species as being either likely native or likely nonnative based solely on measures of nucleotide diversity. We demonstrate the utility of this approach by categorizing a large sample of specimens of terrestrial insects and spiders (collected as part of the Moorea BioCode project) using a generalized linear mixed model (GLMM). Using a training data set of known endemic (n = 45) and known introduced species (n = 102), we then estimated the likely native/nonnative status for 4,663 specimens representing an estimated 1,288 species (412 identified species), including both those specimens that were either unidentified or whose endemic/introduced status was uncertain. Using this approach, we were able to increase the number of categorized specimens by a factor of 4.4 (from 794 to 3,497), and the number of categorized species by a factor of 4.8 from (147 to 707) at a rate much greater than chance (77.6% accuracy). The study identifies phylogenetic signatures of both native and nonnative species and suggests several practical applications for this approach including monitoring biodiversity and facilitating biosecurity

Hepatocellular carcinoma survival in uninsured and underinsured patients.

BACKGROUND: The incidence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) is increasing. The purpose of this study is to establish baseline survival in a medically-underserved population and to evaluate the effect of HCV seropositivity on our patient population. MATERIALS AND METHODS: We reviewed clinicopathologic parameters from a prospective tumor registry and medical records from the Harris County Hospital District (HCHD). Outcomes were compared using Kaplan-Meier survival analysis and log-rank tests. RESULTS: A total of 298 HCC patients were identified. The median survival for the entire cohort was 3.4 mo. There was no difference in survival between the HCV seropositive and the HCV seronegative groups (3.6 mo versus 2.6 mo, P = 0.7). Patients with a survival \u3c1 mo had a significant increase in\u3eαfetoprotein (AFP), international normalized ratio (INR), model for end-stage liver disease (MELD) score, and total bilirubin and decrease in albumin compared with patients with a survival ≥ 1 mo. CONCLUSIONS: Survival for HCC patients in the HCHD is extremely poor compared with an anticipated median survival of 7 mo reported in other studies. HCV seropositive patients have no survival advantage over HCV seronegative patients. Poorer liver function at diagnosis appears to be related to shorter survival. Further analysis into variables contributing to decreased survival is needed