Novel insertional presenilin 1 mutation causing Alzheimer disease with spastic paraparesis.

Journal ArticleA four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6-nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is described. Serial examinations, PET scans, and autopsy revealed that the mutation in this highly conserved portion of PS1 causes an aggressive dementia that maintains the usual regional hierarchy of disease pathology while extending abnormalities into more widespread brain areas than typically seen in AD

Justifying reimbursement for Alzheimers diagnostics and treatments: Seeking alignment on evidence

pre-printThe increasing cost of health care combined with expensive new drugs and diagnostics is leading to more frequent gaps between regulatory and reimbursement approval decisions. As a result, persons with Alzheimer's disease may have difficulty accessing the benefits of medical advances. In contrast to the long history and established structure for drug approval, payer decision-making is dispersed, not standardized and perspectives on necessary evidence differ and often poorly defined. Particularly challenging is how to demonstrate the value of drugs and diagnostics for patients who do not yet have significant functional decline. While discussions to develop consensus continue, clinical trials should begin to incorporate health system and patient-oriented outcomes. In some situations additional studies designed to demonstrate value and comparative effectiveness will be needed. Such studies should examine outcomes of representative populations in community settings. To assure scientific advances in diagnosis and treatment benefit patients, developing evidence to support reimbursement will become as important as obtaining regulatory approval

Ursinus College Alumni Journal, Spring 1940

Current comment: In memoriam, Matthew Beardwood • President\u27s page • On the campus: Founder\u27s Day; Temple University confers LL.D. upon President McClure; Former Metropolitan soprano added to Ursinus faculty; Speakers; State associations re-elect Ursinus executives; Meistersingers present musical programs in churches • Review of the Letters of John Chamberlain, edited by President McClure • Alumni Association nominees • Winter sports • Radiologists honor Dr. Pfahler • About ourselves • 70th annual Commencementhttps://digitalcommons.ursinus.edu/alumnijournal/1008/thumbnail.jp

Posterior cingulate cortex in Alzheimer's disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31318/1/0000227.pd

Standard methods for Apis mellifera anatomy and dissection

An understanding of the anatomy and functions of internal and external structures is fundamental to many studies on the honey bee Apis mellifera. Similarly, proficiency in dissection techniques is vital for many more complex procedures. In this paper, which is a prelude to the other papers of the COLOSS BEEBOOK, we outline basic honey bee anatomy and basic dissection techniques

EFFECTS OF TERNARY ADDITIONS OF ALUMINUM-35 w/o URANIUM ALLOYS

The effects of a number of ternary additions on the constitution, casting, and fabricating characteristics and the physical properties of aluminum- 35 wt.% uranium were investigated. Initial investigations were concerned with the effects of 3 at.% ternary additions on the microstructure and press-forging characteristics of the alloy. It was found that additions of this magnitude often introduced extrinsic phases in the alloy. At the 3 wt% level, additions of germanium, silicon, tin, or zirconium inhibited the formation of UAl/sub 4/ and thereby increased the extent of the aluminum matrix in the alloy. It was also noted that these additions decreased the pressures required for extruding, and the tin addition also improved the homogeneity of cast shapes. Lead and palladium also improved the homogeneity of the cast material; however, neither of these was an effective inhibitor of UAl/sub 4/ and free lead was detected in the alloy to which lead had been added as the ternary. From these studies it appears that tin and zirconium are as effective as silicon in enhancing the fabricating characteristics of rior when evaluated on the bases of casting qualities and recycling characteristics. (auth

Multivariate and Univariate Neuroimaging Biomarkers of Alzheimer's Disease

We performed univariate and multivariate discriminant analysis of FDG-PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG-PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures

A human-centered design methodology to enhance the usability, human factors, and user experience of connected health systems: a three-phase methodology.

peer-reviewedDesign processes such as human-centered design, which involve the end user throughout the product development and testing process, can be crucial in ensuring that the product meets the needs and capabilities of the user, particularly in terms of safety and user experience. The structured and iterative nature of human-centered design can often present a challenge when design teams are faced with the necessary, rapid, product development life cycles associated with the competitive connected health industry. We wanted to derive a structured methodology that followed the principles of human-centered design that would allow designers and developers to ensure that the needs of the user are taken into account throughout the design process, while maintaining a rapid pace of development. In this paper, we present the methodology and its rationale before outlining how it was applied to assess and enhance the usability, human factors, and user experience of a connected health system known as the Wireless Insole for Independent and Safe Elderly Living (WIISEL) system, a system designed to continuously assess fall risk by measuring gait and balance parameters associated with fall risk. We derived a three-phase methodology. In Phase 1 we emphasized the construction of a use case document. This document can be used to detail the context of use of the system by utilizing storyboarding, paper prototypes, and mock-ups in conjunction with user interviews to gather insightful user feedback on different proposed concepts. In Phase 2 we emphasized the use of expert usability inspections such as heuristic evaluations and cognitive walkthroughs with small multidisciplinary groups to review the prototypes born out of the Phase 1 feedback. Finally, in Phase 3 we emphasized classical user testing with target end users, using various metrics to measure the user experience and improve the final prototypes. We report a successful implementation of the methodology for the design and development of a system for detecting and predicting falls in older adults. We describe in detail what testing and evaluation activities we carried out to effectively test the system and overcome usability and human factors problems. We feel this methodology can be applied to a wide variety of connected health devices and systems. We consider this a methodology that can be scaled to different-sized projects accordingly.PUBLISHEDpeer-reviewe

In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [ 123 I]iodoben-zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [ 18 F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50361/1/410400309_ftp.pd

IC‐P2‐074: Differentiating amnestic MCI converting to probable AD from stable amnestic MCI using FDG‐PET and an AD‐related hypometabolism overlap index

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152594/1/alzjjalz200805067.pd