Mirage of Defense: Reexamining Article Five of the North Atlantic Treaty After the Terrorist Attacks on the United States

In 1949, twelve nations formed a regional alliance in an effort to counter perceived Soviet expansion, creating the North Atlantic Treaty Organization (NATO). Collective defense-assisting member states under attack by an outside country, as articulated in Article Five of the North Atlantic Treaty-has historically been its core function. Following fifty years of dormancy, Article Five was invoked after the September 11, 2001 terrorist attacks on the United States. This Note discusses the expanding role of Article Five, increasing regionalization challenges, and whether the Treaty\u27s obligations compel affirmative actions from its members

An Empirical Biomarker-based Calculator for Autosomal Recessive Polycystic Kidney Disease - The Nieto-Narayan Formula

Autosomal polycystic kidney disease (ARPKD) is associated with progressive enlargement of the kidneys fuelled by the formation and expansion of fluid-filled cysts. The disease is congenital and children that do not succumb to it during the neonatal period will, by age 10 years, more often than not, require nephrectomy+renal replacement therapy for management of both pain and renal insufficiency. Since increasing cystic index (CI; percent of kidney occupied by cysts) drives both renal expansion and organ dysfunction, management of these patients, including decisions such as elective nephrectomy and prioritization on the transplant waitlist, could clearly benefit from serial determination of CI. So also, clinical trials in ARPKD evaluating the efficacy of novel drug candidates could benefit from serial determination of CI. Although ultrasound is currently the imaging modality of choice for diagnosis of ARPKD, its utilization for assessing disease progression is highly limited. Magnetic resonance imaging or computed tomography, although more reliable for determination of CI, are expensive, time-consuming and somewhat impractical in the pediatric population. Using a well-established mammalian model of ARPKD, we undertook a big data-like analysis of minimally- or non-invasive serum and urine biomarkers of renal injury/dysfunction to derive a family of equations for estimating CI. We then applied a signal averaging protocol to distill these equations to a single empirical formula for calculation of CI. Such a formula will eventually find use in identifying and monitoring patients at high risk for progressing to end-stage renal disease and aid in the conduct of clinical trials.Comment: 3 tables and 8 figure

Paroxysmal eye–head movements in Glut1 deficiency syndrome

Objective:To describe a characteristic paroxysmal eye–head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS).Methods:We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients.Results:A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seizures in 10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented long-term course. Episodes were brief (usually &lt;5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200 to 800 ms. The movements were consistent with eye–head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement.Conclusions:Paroxysmal eye–head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder.</jats:sec

Horizontal compressive stress regime on the northern Cascadia margin inferred from borehole breakouts

During Integrated Ocean Drilling Program Expedition 311 five boreholes were drilled across the accretionary prism of the northern Cascadia subduction zone. Logging-while-drilling borehole images are utilized to determine breakout orientations to define maximum horizontal compressive stress orientations. Additionally, wireline logging data at two of these sites and from Site 889 of Ocean Drilling Program Leg 146 are used to define breakouts from differences in the aperture of caliper arms. At most sites, the maximum horizontal compressive stress SHmax is margin-normal, consistent with plate convergence. Deviations from this trend reflect local structural perturbations. Our results do not constrain stress magnitudes. If the margin-normal compressional stress is greater than the vertical stress, the margin-normal SHmax direction we observe may reflect current locking of a velocity-weakening shallow megathrust and thus potential for trench-breaching, tsunamigenic rupture in a future megathrust earthquake

Application Of The Domestic Production Activities Tax Deduction (Relating To A Wide Range Of Industries)

Internal Revenue Code Section 199 is the domestic production activities deduction, which was enacted under the American Jobs Creation Act of 2004. This new deduction was to help compensate the repeal of the exterritorial income exclusion. Section 199 was intended to lower the tax burden on domestic manufacturers as well as to attract new investments in domestic manufacturing facilities.&nbsp; The deduction would yield tax breaks for certain types of businesses ranging large to small that predominately manufacture, produce, grow, or extract tangible personal property entirely or partially within the United States. &nbsp;The types of businesses, specifically, that will have an impact from Section 199 would be those in the film and sound recordings industries, companies in the construction business, and those in the field of architectural and engineering.&nbsp; In addition, those that qualified as doing business in any of the specific industries falling under Section 199 must be located and providing services in the United States. The Section 199 tax break will also benefit those in the business of producing electricity, natural gas, and water in the United States. The deduction is allowed to be taken for taxable years beginning after 2004, which creates many challenges. First, Section 199 establishes detailed tax concepts conditions, de minimis rules, exceptions, and safe harbors. Second, the deduction forces many businesses to implement new accounting systems to classify between qualifying and non-qualifying activities. &nbsp;All in all, this report explains how Section 199 works as well as benefits specific industries. However, important production eligibility issues remain in determining the production deduction for tangible property, which are the central items focused throughout this article. Furthermore, the research contain within, covers the guidance in Notice 2005-14, along with the proposed and final regulations to the rules under Section 199.&nbsp;&nbsp; An understanding of these rules will provide additional opportunities to qualify property and take advantage of tax breaks, yielding a better financial result to the taxpayer

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Determination of the Baryon Density from Large Scale Galaxy Redshift Surveys

We estimate the degree to which the baryon density, $\Omega_{b}$, can be determined from the galaxy power spectrum measured from large scale galaxy redshift surveys, and in particular, the Sloan Digital Sky Survey. A high baryon density will cause wiggles to appear in the power spectrum, which should be observable at the current epoch. We assume linear theory on scales $\geq 20h^{-1}Mpc$ and do not include the effects of redshift distortions, evolution, or biasing. With an optimum estimate of $P(k)$ to $k\sim 2\pi/(20 h^{-1} Mpc)$, the $1 \sigma$ uncertainties in $\Omega_{b}$ are roughly 0.07 and 0.016 in flat and open ($\Omega_{0}=0.3$) cosmological models, respectively. This result suggests that it should be possible to test for consistency with big bang nucleosynthesis estimates of $\Omega_{b}$ if we live in an open universe.Comment: 23 Pages, 10 Postscript figure

Determination of the baryon density from large scale galaxy redshift surveys

The Astrophysical Journal. 495, pp. 29.We estimate the degree to which the baryon density, b, can be determined from the galaxy power spectrum measured from large scale galaxy redshift surveys, and in particular, the Sloan Digital Sky Survey. A high baryon density will cause wiggles to appear in the power spectrum, which should be observable at the current epoch. We assume linear theory on scales ≥ 20h−1Mpc and do not include the effects of redshift distortions, evolution, or biasing. With an optimum estimate of P(k) to k ∼ 2 /(20h−1Mpc), the 1 uncertainties in b are roughly 0.07 and 0.016 in flat and open ( 0 = 0.3) cosmological models, respectively. This result suggests that it should be possible to test for consistency with big bang nucleosynthesis estimates of b if we live in an open universe