Premotor Gray Matter Volume is Associated with Clinical Findings in Idiopathic and Genetically Determined Parkinson’s Disease

In the present voxel-based morphometric study, we investigated whether the severity and duration of disease are associated with alterations in gray matter volume (GMV) in symptomatic Parkin mutation carriers (sPARKIN-MC) and patients with idiopathic Parkinson’s disease (iPD). Regression analyses revealed different negative correlations between GMV in cortical motor areas and the severity as well as the disease duration in sPARKIN-MC and iPD patients. SPARKIN-MC showed a less involvement of cortical motor areas, in particular in the supplementary motor area (SMA) than iPD patients. Specifically, in iPD patients, but not in sPARKIN-MC, there was a negative correlation between the SMA degeneration and the UPDRS-II item freezing. The different degeneration patterns may mirror diverse kinetics of the disease progress in these two groups of PD patients with different underlying etiologies

Spin fluctuations in the quasi-two dimensional Heisenberg ferromagnet GdI_2 studied by Electron Spin Resonance

The spin dynamics of GdI_2 have been investigated by ESR spectroscopy. The temperature dependences of the resonance field and ESR intensity are well described by the model for the spin susceptibility proposed by Eremin et al. [Phys. Rev. B 64, 064425 (2001)]. The temperature dependence of the resonance linewidth shows a maximum similar to the electrical resistance and is discussed in terms of scattering processes between conduction electrons and localized spins.Comment: to be published in PR

Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests

The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells.</p

A new high-speed IR camera system

A multi-organizational team at the Goddard Space Flight Center is developing a new far infrared (FIR) camera system which furthers the state of the art for this type of instrument by the incorporating recent advances in several technological disciplines. All aspects of the camera system are optimized for operation at the high data rates required for astronomical observations in the far infrared. The instrument is built around a Blocked Impurity Band (BIB) detector array which exhibits responsivity over a broad wavelength band and which is capable of operating at 1000 frames/sec, and consists of a focal plane dewar, a compact camera head electronics package, and a Digital Signal Processor (DSP)-based data system residing in a standard 486 personal computer. In this paper we discuss the overall system architecture, the focal plane dewar, and advanced features and design considerations for the electronics. This system, or one derived from it, may prove useful for many commercial and/or industrial infrared imaging or spectroscopic applications, including thermal machine vision for robotic manufacturing, photographic observation of short-duration thermal events such as combustion or chemical reactions, and high-resolution surveillance imaging

Bartonella spp. isolated from wild and domestic ruminants in North America.

Bartonella species were isolated from 49% of 128 cattle from California and Oklahoma, 90% of 42 mule deer from California, and 15% of 100 elk from California and Oregon. Isolates from all 63 cattle, 14 deer, and 1 elk had the same polymerase chain reaction/restriction fragment length polymorphism profiles. Our findings indicate potential for inter- and intraspecies transmission among ruminants, as well as risk that these Bartonella spp. could act as zoonotic agents

Optimizing the post-graduate institutional program evaluation process

Abstract Background Reviewing program educational efforts is an important component of postgraduate medical education program accreditation. The post-graduate review process has evolved over time to include centralized oversight based on accreditation standards. The institutional review process and the impact on participating faculty are topics not well described in the literature. Methods We conducted multiple Plan-Do-Study-Act (PDSA) cycles to identify and implement areas for change to improve productivity in our institutional program review committee. We also conducted one focus group and six in-person interviews with 18 committee members to explore their perspectives on the committee’s evolution. One author (MLL) reviewed the transcripts and performed the initial thematic coding with a PhD level research associate and identified and categorized themes. These themes were confirmed by all participating committee members upon review of a detailed summary. Emergent themes were triangulated with the University of Michigan Medical School’s Admissions Executive Committee (AEC). Results We present an overview of adopted new practices to the educational program evaluation process at the University of Michigan Health System that includes standardization of meetings, inclusion of resident members, development of area content experts, solicitation of committed committee members, transition from paper to electronic committee materials, and focus on continuous improvement. Faculty and resident committee members identified multiple improvement areas including the ability to provide high quality reviews of training programs, personal and professional development, and improved feedback from program trainees. Conclusions A standing committee that utilizes the expertise of a group of committed faculty members and which includes formal resident membership has significant advantages over ad hoc or other organizational structures for program evaluation committees.http://deepblue.lib.umich.edu/bitstream/2027.42/117363/1/12909_2016_Article_586.pd

Assessment of Olfactory Function in MAPTAssociated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson’s disease, Lewy body disease and Alzheimer’s disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson’s disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more “error-prone” than other sensory systems

Selective preservation of organic matter in marine environments; processes and impact on the sedimentary record

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Biogeosciences 7 (2010): 483-511, doi: 10.5194/bg-7-483-2010The present paper is the result of a workshop sponsored by the DFG Research Center/Cluster of Excellence MARUM "The Ocean in the Earth System", the International Graduate College EUROPROX, and the Alfred Wegener Institute for Polar and Marine Research. The workshop brought together specialists on organic matter degradation and on proxy-based environmental reconstruction. The paper deals with the main theme of the workshop, understanding the impact of selective degradation/preservation of organic matter (OM) in marine sediments on the interpretation of the fossil record. Special attention is paid to (A) the influence of the molecular composition of OM in relation to the biological and physical depositional environment, including new methods for determining complex organic biomolecules, (B) the impact of selective OM preservation on the interpretation of proxies for marine palaeoceanographic and palaeoclimatic reconstruction, and (C) past marine productivity and selective preservation in sediments. It appears that most of the factors influencing OM preservation have been identified, but many of the mechanisms by which they operate are partly, or even fragmentarily, understood. Some factors have not even been taken carefully into consideration. This incomplete understanding of OM breakdown hampers proper assessment of the present and past carbon cycle as well as the interpretation of OM based proxies and proxies affected by OM breakdown. To arrive at better proxy-based reconstructions "deformation functions" are needed, taking into account the transport and diagenesis-related molecular and atomic modifications following proxy formation. Some emerging proxies for OM degradation may shed light on such deformation functions. The use of palynomorph concentrations and selective changes in assemblage composition as models for production and preservation of OM may correct for bias due to selective degradation. Such quantitative assessment of OM degradation may lead to more accurate reconstruction of past productivity and bottom water oxygenation. Given the cost and effort associated with programs to recover sediment cores for paleoclimatological studies, as well as with generating proxy records, it would seem wise to develop a detailed sedimentological and diagenetic context for interpretation of these records. With respect to the latter, parallel acquisition of data that inform on the fidelity of the proxy signatures and reveal potential diagenetic biases would be of clear value.We acknowledge generous financial support by the DFG Research Center/Cluster of Excellence MARUM “The Ocean in the Earth System”, the International Graduate College EUROPROX and the Alfred Wegener Institute for Polar and Marine Research enabling the realisation of the “Workshop on Selective Preservation of Organic Matter: Processes and Impact on the Fossil Record” which formed the basis of this paper. GJMV acknowledges support by the German Science Foundation (DFG grant VE486/2)

Recovery of visual fields in brain-lesioned patients by reaction perimetry treatment

<p>Abstract</p> <p>Background</p> <p>The efficacy of treatment in hemianopic patients to restore missing vision is controversial. So far, successful techniques require laborious stimulus presentation or restrict improvements to selected visual field areas. Due to the large number of brain-damaged patients suffering from visual field defects, there is a need for an efficient automated treatment of the total visual field.</p> <p>Methods</p> <p>A customized treatment was developed for the reaction perimeter, permitting a time-saving adaptive-stimulus presentation under conditions of maximum attention. Twenty hemianopic patients, without visual neglect, were treated twice weekly for an average of 8.2 months starting 24.2 months after the insult. Each treatment session averaged 45 min in duration.</p> <p>Results</p> <p>In 17 out of 20 patients a significant and stable increase of the visual field size (average 11.3° ± 8.1) was observed as well as improvement of the detection rate in the defective visual field (average 18.6% ± 13.5). A two-factor cluster analysis demonstrated that binocular treatment was in general more effective in augmenting the visual detection rate than monocular. Four out of five patients with a visual field increase larger than 10° suffered from hemorrhage, whereas all seven patients with an increase of 5° or less suffered from infarction. Most patients reported that visual field restoration correlated with improvement of visual-related activities of daily living.</p> <p>Conclusion</p> <p>Rehabilitation treatment with the Lubeck Reaction Perimeter is a new and efficient method to restore part of the visual field in hemianopia. Since successful transfer of treatment effects to the occluded eye is achieved under monocular treatment conditions, it is hypothesized that the damaged visual cortex itself is the structure in which recovery takes place.</p