Pro Se Perils: The Eighth Circuit’s Approach to Sixth Amendment Challenges After Guilty Pleas

On August 27, 2019, in United States v. Dewberry, the U.S. Court of Appeals for the Eighth Circuit held that defendants who have pleaded guilty waive their right to challenge a lower court’s decision precluding them from exercising their Sixth Amendment right to self-representation. In doing so, the Eighth Circuit joined the circuit split about whether the constitutional requirements for a valid guilty plea are met when defendants are denied these pro se rights. The Fourth, Sixth, Seventh, Ninth, and Tenth Circuits had previously addressed this issue, with only the Ninth Circuit holding that a defendant may challenge the lower court’s denial of his Sixth Amendment right after pleading guilty. This Comment argues that the Ninth Circuit’s approach is preferable to that of the other circuits because it expands Sixth Amendment rights

Diode-side-pumped Alexandrite slab lasers

We present the investigation of diode-side-pumping of Alexandrite slab lasers in a range of designs using linear cavity and grazing-incidence bounce cavity configurations. An Alexandrite slab laser cavity with double-pass side pumping produces 23.4 mJ free-running energy at 100 Hz rate with slope efficiency ~40% with respect to absorbed pump energy. In a slab laser with single-bounce geometry output power of 12.2 W is produced, and in a double-bounce configuration 6.5 W multimode and 4.5 W output in TEM00 mode is produced. These first results of slab laser and amplifier designs in this paper highlight some of the potential strategies for power and energy scaling of Alexandrite using diode-side-pumped Alexandrite slab architectures with future availability of higher power red diode pumping

Lafora disease offers a unique window into neuronal glycogen metabolism

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase

Effect of methamphetamine dependence on inhibitory deficits in a novel human open-field paradigm.

RationaleMethamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions.ObjectivesIn the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology.ResultsMA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year.ConclusionsAbstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Cardiac autophagic vacuolation in severe X-linked myopathy with excessive autophagy

X-linked myopathy with excessive autophagy (XMEA), caused by mutations of the VMA21 gene, is a strictly skeletal muscle disease. Extensive studies in yeast established VMA21 as the master assembly chaperone of V-ATPase, the complex multisubunit proton pump that acidifies organelles and that is vital to all mammalian tissues. As such, skeletal muscle disease exclusivity in XMEA is highly surprising. We now show that the severest VMA21 mutation, c.164-6t>g, does result in XMEA-typical pathology with autophagic vacuolar changes outside skeletal muscle, namely in the heart. However, even patients with this mutation do not exhibit clinical extramuscular disease, including cardiac disease, despite extreme skeletal muscle wasting to the extent of ventilation dependence. Uncovering the unique skeletal muscle vulnerability to defective organellar acidification, and resultant tissue-destructive excessive autophagy, will be informative to the understanding of muscle physiology. Alternatively, understanding extramuscular resistance to VMA21 mutation might disclose heretofore unknown mammalian V-ATPase assembly chaperones other than VMA21. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Ariel - Volume 8 Number 3

Executive Editor James W. Lockard, Jr. Business Manager Neeraj K. Kanwal University News Richard J . Perry World News Doug Hiller Opinions Elizabeth A. McGuire Features Patrick P. Sokas Sports Desk Shahab S. Minassian Managing Editor Edward H. Jasper Managing Associate Brenda Peterson Photography Editor Robert D. Lehman. Jr. Graphics Christine M. Kuhnl

Dissociating anticipation from perception: Acute pain activates default mode network.

Few studies have explored the effect of acute pain on attentional networks and on the default mode network. Moreover, these studies convey conflicting results, seemingly caused by design. To reassess this issue, we studied 20 healthy subjects with functional magnetic resonance imaging while delivering painful electric shocks. The design was purposely constructed to separate rest, anticipation, and pain perception. We found that default mode network activity in response to pain was biphasic. It deactivated during anticipation when the dorsal attentional network was activated. During pain perception, the default mode network was activated, as were attentional networks. The left posterior fusiform gyrus showed the same dynamics as the default mode network, and its activity was negatively correlated to the subject\u27s pain intensity rating. The associative pregenual anterior cingulate cortex seemed to play a key role in these coactivations. These results concur with data from the literature showing that enhanced pain perception results in greater default mode network activity and that the anticorrelation between the default mode network and the dorsal attentional network disappears in chronic pain patients