Wind Symphony

Center for the Performing Arts November 29, 2017 Wednesday Evening 8:00p.m

Feigned Consensus: Usurping the Law in Shaken Baby Syndrome/Abusive Head Trauma Prosecutions

Few medico-legal matters have generated as much controversy--both in the medical literature and in the courtroom--as Shaken Baby Syndrome (SBS), now known more broadly as Abusive Head Trauma (AHT). The controversies are of enormous significance in the law because child abuse pediatricians claim, on the basis of a few non-specific medical findings supported by a weak and methodologically flawed research base, to be able to “diagnose” child abuse, and thereby to provide all of the evidence necessary to satisfy all of the legal elements for criminal prosecution (or removal of children from their parents). It is a matter, therefore, in which medical opinion claims to fully occupy the legal field. As controversies flare up increasingly in the legal arena, child abuse pediatricians and prosecutors now respond by claiming both that there is actually no real controversy about SBS/AHT, and that it is a purely medical “diagnosis” and not a legal conclusion, so testimony in support of the SBS hypothesis should not be challenged in court. This article, coauthored by four law professors, two physicians, and a physicist, demonstrates that there is very much a live controversy about the SBS/AHT hypothesis and maintains that, under traditional principles of evidence law, physicians should not be permitted to “diagnose” abuse in court (as opposed to identifying specific symptoms or medical findings)

Expectation Modulates Human Brain Responses to Acute Cocaine: A Functional Magnetic Resonance Imaging Study

Background Human expectation of psychoactive drugs significantly alters drug effects and behavioral responses. However, their neurophysiological mechanisms are not clear. This study investigates how cocaine expectation modulates human brain responses to acute cocaine administration. Methods Twenty-six right-handed non–treatment-seeking regular cocaine abusers participated in this study. Changes in blood oxygenation level-dependent (BOLD) signals were measured, and online behavioral ratings during cocaine expectation and acute cocaine administration were recorded. Results Distinct regional characteristics in BOLD responses to expected and unexpected cocaine infusions were observed in the medial orbitofrontal gyrus (Brodmann area [BA] 11), frontal pole (BA 10), and anterior cingulate gyrus regions. Active engagement in the amygdala and the lateral orbitofrontal cortex (OFC; BA 47) by unexpected but not expected cocaine infusion was discovered. Cocaine expectation did not change BOLD responses to acute cocaine administration in a set of subcortical substrates, the nucleus accumbens, ventral putamen, ventral tegmental area, and thalamus. Conclusions These results suggest that cocaine expectation modulates neural-sensitivity adaptation between the expected events and the actual outcomes but did not modulate the pharmacological characteristics of cocaine. In addition, the amygdala–lateral OFC circuitry plays an important role in mediating stimulus-outcome relations and contextual factors of drug abuse

Bayes Wars Redivivus - An Exchange

An electronic exchange among 10 evidence scholars that began with a discussion of the restyled Federal Rules and grew into a significant restatement of debates in evidentiary scholarship over the last 50 years, touching on relevance, probative value, inference, Bayesianism and the foundations of evidence, with an introduction by Michael Risinger

A hPMS2 Mutant Cell Line Is Defective in Strand-specific Mismatch Repair

Human cells contain several homologs of the bacterial mutL gene required for mismatch repair, including a gene on chromosome 7 designated hPMS2. We have identified an endometrial carcinoma cell line, HEC-1-A, that has a C-->T mutation in hPMS2 that generates a nonsense codon and yields a protein truncated at the C terminus. No wild-type gene or gene product was detected. The missing amino acids in hPMS2 are highly conserved among PMS homologs, suggesting that they may be critical for function. In support of this, extracts of HEC-1-A cells are defective in repairing a variety of mismatched substrates. Moreover, di-, tri-, and tetranucleotide repeated sequences are highly unstable in single cell clones of HEC-1-A cells, and HEC-1-A cells are resistant to killing by N-methyl-N'-nitro-N-nitrosoguanidine. The results provide strong experimental support for the involvement of the hPMS2 gene product in mismatch repair in human cells and support the concept that a defective hPMS2 gene may lead to predisposition to certain forms of cancer

Peripheral Blood Pressure Changes Induced by Dobutamine Do Not Alter BOLD Signals in The Human Brain

In extending the use of functional MRI to neuropharmacology, a primary area of concern is that peripheral blood pressure changes induced by pharmacological agents could independently produce a change in the blood oxygenation level-dependent (BOLD) signal, resulting in difficulties distinguishing or interpreting drug-induced neural activations. In the present study, we utilized intravenous dobutamine, a beta-adrenergic receptor agonist, to increase the mean arterial blood pressure (MABP), while examining the effects of MABP changes on the BOLD signal in cocaine-dependent participants. Dobutamine infusion significantly increased the MABP from 93 ± 8 mm Hg to 106 ± 12 mm Hg (P \u3c 0.0005), but did not produce a significant global BOLD signal. Yet, a few voxels in the anterior cingulate showed BOLD signal changes that paralleled the changes in blood pressure (BP). Our observations support the conclusion that following the infusion of psychoactive agents, brain BOLD signals accurately reflect neuronal activity, even in the face of relatively large peripheral cardiovascular effects that transiently increase systemic BP

The Daubert/Kumho Implications of Observer Effects in Forensic Science: Hidden Problems of Expectation and Suggestion

After the Supreme Court's decision in Kumho Tire v. Carmichael and the recent amendment of Federal Rule of Evidence 702, proffers of expert testimony will have to be found reliable for the particular application of the asserted expertise to the "task at hand." That is, expertise which is reliable in some global sense, which might apply to other cases but not to the particular application before the court, does not satisfy the requirements for admission. With that in mind, this article examines the phenomoenon of "observer effects" and the vulnerability of forensic science examinations to such observer effects. Observer effects occur when the results of an examination are distorted by the context and state of the observer, including the observer's expectations and desires. The article reviews the findings and practices of a range of scientific fields concerning such observer effects and their control, with special attention to the relevant research and theory from cognative and social psychology. This literature establishes that in virtually every area of human judgment, such observer effects have a relentless and sometimes dramatic effect on the accuracy of results. The article then examines current forensic science practice in light of that research, concluding that forensic science practice is far behind most scientific fields in controlling for such effects, leaving the reliability and accuracy of many forensic science results in doubt. The article then suggests practical ways in which forensic science practice can be changed to reduce such problems, such as the adoption of blind testing regimes. Finally, the article analyzes the current state of the law under Kumho Tire and Rule 702, concluding that the results of forensic science examinations are in danger of being excluded if their reliability continues to be undermined by the failure to control observer effects.Psycholog

Re-evaluation of the Fijianolide/Laulimalide Chemotype Suggests an Alternate Mechanism of Action for C-15/C-20 Analogs.

Herein, we report on naturally derived microtubule stabilizers with activity against triple negative breast cancer (TNBC) cell lines, including paclitaxel, fijianolide B/laulimalide (3), fijianolide B di-acetate (4), and two new semisynthetic analogs of 3, which include fijianolide J (5) and fijianolide L (6). Similar to paclitaxel, compound 3 demonstrated classic microtubule stabilizing activity with potent (GI50 = 0.7–17 nM) antiproliferative efficacy among the five molecularly distinct TNBC cell lines. Alternatively, compounds 5 or 6, generated from oxidation of C-20 or C-15 and C-20 respectively, resulted in a unique profile with reduced potency (GI50 = 4–9 μM), but improved efficacy in some lines, suggesting a distinct mechanism of action. The C-15, C-20 di-acetate, and dioxo modifications on 4 and 6 resulted in compounds devoid of classic microtubule stabilizing activity in biochemical assays. While 4 also had no detectable effect on cellular microtubules, 6 promoted a reorganization of the cytoskeleton resulting in an accumulation of microtubules at the cell periphery. Compound 5, with a single C-20 oxo substitution, displayed a mixed phenotype, sharing properties of 3 and 6. These results demonstrate the importance of the C-15/C-20 chiral centers, which appear to be required for the potent microtubule stabilizing activity of this chemotype and that oxidation of these sites promotes unanticipated cytoskeletal alterations that are distinct from classic microtubule stabilization, likely through a distinct mechanism of action

Interictal cerebral metabolism in partial epilepsies of neocortical origin

We performed interietal [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in 24 patients with partial epilepsy of neocortical origin. Two-thirds of patients had regions of hypometabolism. The zone of intracranially recorded electrographic ictal onset was always located in a region of hypometabolism, in those with hypometabolism. Hypometabolic regions in partial epilepsies of neocortical origin were usually associated with structural imaging abnormalities. Regional hypometabolism occasionally occurred without localizing ictal scalp EEG and cerebral magnetic resonance imaging findings, however. FDG PET may be useful in directing placement of intracranial electrodes for presurgical evaluation of refractory neocortical seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29049/1/0000082.pd