An MRI-Derived Definition of MCI-to-AD Conversion for Long-Term, Automati c Prognosis of MCI Patients

Alzheimer's disease (AD) and mild cognitive impairment (MCI), continue to be widely studied. While there is no consensus on whether MCIs actually "convert" to AD, the more important question is not whether MCIs convert, but what is the best such definition. We focus on automatic prognostication, nominally using only a baseline image brain scan, of whether an MCI individual will convert to AD within a multi-year period following the initial clinical visit. This is in fact not a traditional supervised learning problem since, in ADNI, there are no definitive labeled examples of MCI conversion. Prior works have defined MCI subclasses based on whether or not clinical/cognitive scores such as CDR significantly change from baseline. There are concerns with these definitions, however, since e.g. most MCIs (and ADs) do not change from a baseline CDR=0.5, even while physiological changes may be occurring. These works ignore rich phenotypical information in an MCI patient's brain scan and labeled AD and Control examples, in defining conversion. We propose an innovative conversion definition, wherein an MCI patient is declared to be a converter if any of the patient's brain scans (at follow-up visits) are classified "AD" by an (accurately-designed) Control-AD classifier. This novel definition bootstraps the design of a second classifier, specifically trained to predict whether or not MCIs will convert. This second classifier thus predicts whether an AD-Control classifier will predict that a patient has AD. Our results demonstrate this new definition leads not only to much higher prognostic accuracy than by-CDR conversion, but also to subpopulations much more consistent with known AD brain region biomarkers. We also identify key prognostic region biomarkers, essential for accurately discriminating the converter and nonconverter groups

Void or Voidable? — Curing Defects in Stock Issuances Under Delaware Law

It is not unusual for a Delaware corporation’s stock records to have omissions or procedural defects raising questions as to the valid authorization of some of the outstanding stock. Confronted with such irregularities, most corporate lawyers would likely attempt to cure the defect through board and, if necessary, stockholder ratification. However, in a number of leading cases, the Delaware Supreme Court has treated the statutory formalities for the issuance of stock as substantive prerequisites to the validity of the stock being issued, and the court has determined that failure to comply with such formalities renders the stock in question void, i.e., not curable by ratification. Unfortunately, the decisions issued by the Delaware courts have not afforded the necessary certainty to allow practitioners to decide whether a particular defect in stock issuance is a substantive defect that renders stock void or a mere technical defect that renders stock voidable. This Article analyzes the cases giving rise to this lack of clarity and proposes that the Delaware courts apply the policy underlying Article 8 of the Delaware Uniform Commercial Code to validate stock in the hands of innocent purchasers for value in determining whether stock is void or voidable

Void or Voidable?—Curing Defects in Stock Issuances Under Delaware Law

It is not unusual for practitioners reviewing a Delaware corporation's stock records to find omissions or procedural defects raising questions as to the valid authorization of some of the outstanding stock. Examples of such omissions and defects are limitless, but not infrequently found examples include the absence of board resolutions authorizing the issuance of stock shown by the transfer books as having been issued, the absence of evidence that issuances were properly authorized by the requisite votes of the board or, if required, by the stockholders, the absence of evidence that the consideration to have been received by the corporation in exchange for the stock was in fact received, the issuance of more shares than were authorized by the certificate of incorporation at the time, the issuance of stock prior to the filing of the charter amendment or certificate of designations authorizing or creating the stock, and similar procedural and substantive irregularities. Not infrequently, these defects occurred some time ago, and the stock in question may have changed hands multiple times since issuance. Confronted with such irregularities, most corporate lawyers' first instinct would be to attempt to correct the defect through board and, if necessary, stockholder, ratification of the defective issuance, with the intent of putting the parties in the positions they thought they were in prior to discovering the irregularity. However, Delaware courts have not always viewed defects in stock issuances as being curable by ratification. In a number of leading cases, the Delaware Supreme Court has treated the statutory formalities for the issuance of stock as substantive prerequisites to the validity of the stock being issued, and has determined that failure to comply with such formalities renders the stock in question void. A finding that stock is void means that defects in it cannot be cured, whether by ratification or otherwise. Thus, practitioners finding defects in stock issuances are put in the uncomfortable position of having to make a judgment whether the defect is one that renders the stock void, in which case ratification is not an option, or voidable, in which case ratification is an option. Unfortunately, the decisions issued by the Delaware courts have not afforded certainty in this critical area. Indeed, a recent decision of the Court of Chancery acknowledges that although "Delaware law is replete with cases" discussing the void-voidable distinction, the law as to when and whether a defective stock issuance can be cured "is not as clear as it could be." This article analyzes the reasons for this lack of clarity, and proposes some solutions which would benefit buyers and sellers of corporate stock. We begin by examining the legal requirements applicable to stock issuances. Next, we discuss the foundation of the doctrinal distinction between void and voidable stock. We then discuss the cases where courts have found stock to have not been issued in accordance with these legal requirements, and whether such finding has resulted in the stock being found void or voidable. We also consider the purposes, principles and policies of certain provisions of Article 8 of the Uniform Commercial Code, designed to validate, in most circumstances, certain defects in stock in the hands of innocent purchasers for value. Interestingly, these provisions of the UCC have not been frequently discussed in the court cases that have considered whether stock is void or voidable, and the cases that have discussed them refer to them as setting forth an equitable rather than a legal principle - which is ultimately not helpful to corporate lawyers who opine on legal, not equitable, matters. In conclusion, we suggest that the policy underlying Article 8 of the Uniform Commercial Code to validate stock in the hands of innocent purchasers for value, notwithstanding technical defects in its issuance, should be recognized as a principle of law, not solely as a principle of equity, and should be applied by the Delaware courts as such. As a result, technical defects relating to statutory formalities should not lead to a finding of void stock, but at worst to voidable stock. Cure or ratification should be permitted except in cases where the issuance violates the directors' duty of loyalty or otherwise would be inequitable. Such a rule would allow practitioners to opine as to the validity of a corporation's outstanding stock where the stock was issued defectively but the defect cured, subject to a standard exception for fiduciary duties and other equitable matters, and would eliminate the risk that stock held in the trading markets or otherwise held by innocent purchasers for value might be deemed void

Ultra-low phase noise all-optical microwave generation setup based on commercial devices

In this paper, we present a very simple design based on commercial devices for the all-optical generation of ultra-low phase noise microwave signals. A commercial, fibered femtosecond laser is locked to a laser that is stabilized to a commercial ULE Fabry-Perot cavity. The 10 GHz microwave signal extracted from the femtosecond laser output exhibits a single sideband phase noise $\mathcal{L}(f)=-104 \ \mathrm{dBc}/\mathrm{Hz}$ at 1 Hz Fourier frequency, at the level of the best value obtained with such "microwave photonics" laboratory experiments \cite{Fortier2011}. Close-to-the-carrier ultra-low phase noise microwave signals will now be available in laboratories outside the frequency metrology field, opening up new possibilities in various domains.Comment: 8 pages, 3 figures. To be published in Applied Optics, early posting version available at http://www.opticsinfobase.org/ao/upcoming_pdf.cfm?id=23114

Acute transverse myelitis in Lyme neuroborreliosis

Introduction: Acute transverse myelitis (ATM) is a rare disorder (1-8 new cases per million of population per year), with 20% of all cases occurring in patients younger than 18years of age. Diagnosis requires clinical symptoms and evidence of inflammation within the spinal cord (cerebrospinal fluid and/or magnetic resonance imaging). ATM due to neuroborreliosis typically presents with impressive clinical manifestations. Case presentation: Here we present a case of Lyme neuroborreliosis-associated ATM with severe MRI and CSF findings, but surprisingly few clinical manifestations and late conversion of the immunoglobulin G CSF/blood index of Borrelia burgdorferi sensu lato. Conclusion: Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosi

Acute transverse myelitis in Lyme neuroborreliosis

Introduction: Acute transverse myelitis (ATM) is a rare disorder (1-8 new cases per million of population per year), with 20% of all cases occurring in patients younger than 18years of age. Diagnosis requires clinical symptoms and evidence of inflammation within the spinal cord (cerebrospinal fluid and/or magnetic resonance imaging). ATM due to neuroborreliosis typically presents with impressive clinical manifestations. Case presentation: Here we present a case of Lyme neuroborreliosis-associated ATM with severe MRI and CSF findings, but surprisingly few clinical manifestations and late conversion of the immunoglobulin G CSF/blood index of Borrelia burgdorferi sensu lato. Conclusion: Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosi

Working with Traumatic Brain Injury in Schools: Transition, Assessment, and Intervention

Every day, children and adolescents worldwide return to the educational setting having sustained a traumatic brain injury (TBI). The possible negative consequences of TBI range from mild to severe and include neurological, cognitive, emotional, social, and behavioral difficulties. Within the school setting, the negative effects of TBI tend to persist or worsen over time, often resulting in academic and social difficulties that require formal and informal educational assistance and support. School psychologists and other educational professionals are well-positioned to help ensure students with TBI receive this assistance and support

Vr 2: a new apple scab resistance gene

Reports from several European countries of the breakdown of the Vf resistance, the most frequently used source of resistance in breeding programs against apple scab, emphasize the urgency of diversifying the basis of apple scab resistance and pyramiding different apple scab resistances with the use of their associated molecular markers. GMAL 2473 is an apple scab resistant selection thought to carry the resistance gene Vr. We report the identification by BSA of three AFLP markers and one RAPD marker associated with the GMAL 2473 resistance gene. SSRs associated with the resistance gene were found by (1) identifying the linkage group carrying the apple scab resistance and (2) testing the SSRs previously mapped in the same region. One such SSR, CH02c02a, mapped on linkage group 2, co-segregates with the resistance gene. GMAL 2473 was tested with molecular markers associated with other apple scab resistance genes, and accessions carrying known apple scab resistance genes were tested with the SSR linked to the resistance gene found in GMAL 2473. The results indicate that GMAL 2473 does not carry Vr, and that a new apple scab resistance gene, named Vr 2, has been identifie

Seasonal Home Ranges of Raccoons, Procyon lotor, Using a Common Feeding Site in Rural Eastern Ontario: Rabies Management Implications

Thirteen adult Raccoons (Procyon lotor) (six females, seven males) that fed at a garbage dump north of Kingston, Ontario were radio-tracked from 21 June to 16 October 1995 to assess their seasonal home ranges and movements. Average Minimum Convex Polygon (MCP) summer and fall home ranges for the collared Raccoons were 78.4 ha (SD=46.2 ha) and 45.6 ha (SD=29.7 ha), respectively. Average grid cell summer and fall home ranges for the collared Raccoons were 143.3 ha (SD=40.0 ha) and 116.9 ha (SD=24.9 ha), respectively. Summer ranges of the Raccoons were significantly larger than fall ranges using both the MCP method (P=0.05) and the grid cell method (P=0.073). Yearling Raccoons travelled an average summer maximum distance from the dump of 2608 m (SD=1964, n=3), more than double the distance of adults (≥2 yr) at 1239 m (SD=547, n=10). The population density for the study area in late August 1995 was estimated at 1 Raccoon/12 ha based on an effective area surrounding the dump of 234 ha. Home range and movement data may be useful to design a strategy to control Raccoon rabies in Ontario

Rotwein unter Hochspannung: Mehrjährige Qualitäts- Untersuchung mit Gas-Discharge-Visualisation (GDV)

We investigated whether we can detect any differences in red wines produced either by bio-dynamic or by standard organic agriculture. We used standard methods to investigate the quality of the wines and Gas-Discharge-Visualisation (GDV) method to investigate a holistic quality of the wines. With the GDV-method, samples are exposed to high voltage. The halo-like gas discharge caused by a burst of electron emission of the sample is captured by a digital camera underneath a transparent, dielectric surface. The wine samples measured originate from an On-Farm experiment in South of France with two separately managed but neighbouring blocks (same soil and climate conditions): bio-organic and bio-dynamic. Apart from the use of bio-dynamic preparations, plant protection and fertilization was the same in both blocks. The vinification of the sampled grapes was made in two replicates which were analysed separately. During the three years of examination, the bio-dynamic samples did not reveal significant differences when assessed with standard methods (sensory triangle test, polyphenol analysis etc.). However, with GDV measurements the values for the imageparameter “mean intensity” were mostly higher for the wines from bio-dynamically produced grapes. In a „mixed effect model“ (GDV-parameter „mean intensity“ as dependent variable, replication und cultivation-system as fix and year as random effect) the difference was statistically significant. We conclude that the GDV-method has an interesting potential to detect very sensitively differences in food attributes. However, in order to interpret the results in terms of consumer-relevant quality further research is needed