Pediatric intracranial dural arteriovenous fistulas: age-related differences in clinical features, angioarchitecture, and treatment outcomes.

OBJECTIVE Intracranial dural arteriovenous fistulas (DAVFs) are rare in children. This study sought to better characterize DAVF presentation, angioarchitecture, and treatment outcomes. METHODS Children with intracranial DAVFs between 1986 and 2013 were retrospectively identified from the neurointerventional database at the authors' institution. Demographics, clinical presentation, lesion angioarchitecture, treatment approaches, angiographic outcomes, and clinical outcomes were assessed. RESULTS DAVFs constituted 5.7% (22/423) of pediatric intracranial arteriovenous shunting lesions. Twelve boys and 10 girls presented between 1 day and 18 years of age; boys presented at a median of 1.3 years and girls presented at a median of 4.9 years. Four of 8 patients ≤ 1 year of age presented with congestive heart failure compared with 0/14 patients > 1 year of age (p = 0.01). Five of 8 patients ≤ 1 year old presented with respiratory distress compared with 0/14 patients > 1 year old (p = 0.0021). Ten of 14 patients > 1 year old presented with focal neurological deficits compared with 0/8 patients ≤ 1 year old (p = 0.0017). At initial angiography, 16 patients harbored a single intracranial DAVF and 6 patients had 2-6 DAVFs. Eight patients (38%) experienced DAVF obliteration by the end of treatment. Good clinical outcome (modified Rankin Scale score 0-2) was documented in 77% of patients > 1 year old at presentation compared with 57% of patients ≤ 1 year old at presentation. Six patients (27%) died. CONCLUSIONS Young children with DAVFs presented predominantly with cardiopulmonary symptoms, while older children presented with focal neurological deficits. Compared with other pediatric vascular shunts, DAVFs had lower rates of angiographic obliteration and poorer clinical outcomes

Radiological and clinical features of vein of Galen malformations.

BackgroundVein of Galen malformations (VOGMs) are rare and complex congenital arteriovenous fistulas. The clinical and radiological features of VOGMs and their relation to clinical outcomes are not fully characterized.ObjectiveTo examine the clinical and radiological features of VOGMs and the predictors of outcome in patients.MethodsWe retrospectively reviewed the available imaging and medical records of all patients with VOGMs treated at the University of California, San Francisco between 1986 and 2013. Radiological and clinical features were identified. We applied the modified Rankin Scale to determine functional outcome by chart review. Predictors of outcome were assessed by χ(2) analyses.ResultsForty-one cases were confirmed as VOGM. Most patients (78%) had been diagnosed with VOGM in the first year of life. Age at treatment was bimodally distributed, with predominantly urgent embolization at <10 days of age and elective embolization after 1 year of age. Patients commonly presented with hydrocephalus (65.9%) and congestive heart failure (61.0%). Mixed-type (31.7%) VOGM was more common in our cohort than purely mural (29.3%) or choroidal (26.8%) types. The most common feeding arteries were the choroidal and posterior cerebral arteries. Transarterial embolization with coils was the most common technique used to treat VOGMs at our institution. Functional outcome was normal or only mildly disabled in 50% of the cases at last follow-up (median=3 years, range=0-23 years). Younger age at first diagnosis, congestive heart failure, and seizures were predictive of adverse clinical outcome. The survival rate in our sample was 78.0% and complete thrombosis of the VOGM was achieved in 62.5% of patients.ConclusionsVOGMs continue to be challenging to treat and manage. Nonetheless, endovascular approaches to treatment are continuing to be refined and improved, with increasing success. The neurodevelopmental outcomes of affected children whose VOGMs are treated may be good in many cases

Going Solo: Discovery of the First Parthenogenetic Gordiid (Nematomorpha: Gordiida)

Despite the severe fitness costs associated with sexual reproduction, its persistence and pervasiveness among multicellular organisms testifies to its intrinsic, short-term advantages. However, the reproductive assurance hypothesis predicts selection favoring asexual reproduction in sparse populations and when mate finding is difficult. Difficulties in finding mates is especially common in parasites, whose life cycles involve multiple hosts, or being released from the host into the external environment where the parasite can find itself trapped without a sexual partner. To solve this problem and guarantee reproduction, parasites in numerous phyla have evolved reproductive strategies, as predicted by the reproductive assurance hypothesis, such as hermaphroditism or parthenogenesis. However, this type of strategy has not been reported from species in the phylum Nematomorpha, whose populations have often been described as sparse. A new Nematomorpha species, Paragordius obamai n. sp., was discovered from Kenya, Africa, and appears to have solved the problem of being trapped without a mate by eliminating the need for males. Paragordius obamai n. sp. represents the first and only known species within this phylum to reproduce asexually. To determine the mechanism of this mating strategy, we ruled out the involvement of reproduction manipulating endosymbionts by use of next generation sequencing data, thus suggesting that parthenogenesis is determined genetically and may have evolved as a means to assure reproduction. Since this new parthenogenetic species and a closely related gonochoristic North American congener, P. varius, are easy to propagate in the laboratory, these gordiids can be used as model systems to test hypotheses on the genetic advantages and disadvantages of asexual reproduction and the genetic determinants of reproductive strategies in parasites

An osteocalcin-deficient mouse strain without endocrine abnormalities

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc– ) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, μCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc− allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/ 2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution

Rule 36 Decisions at the Federal Circuit: Statutory Authority

Recent commentary has questioned the validity of the US Court of Appeals for the Federal Circuit\u27s use of Rule 36 affirmances in deciding appeals from the US Patent and Trademark Office (USPTO). One article in particular posits that 35 U.S.C. § 144 and 15 U.S.C.§ 1071(a)(4) require the Federal Circuit to write an opinion in every appeal from the USPTO and therefore the court\u27s use of Rule 36 affirmances, particularly with appeals of cases from the America Invents Act, is improper. This Article presents a reasoned counterpoint to that argument. A complete analysis of the statutory text, the legislative history, the historical context of the statutes, and other considerations, including other applicable Federal Rules of Appellate Procedure, the delegation of authority under the Rules Enabling Act, and traditional deference afforded the judiciary in how it applies procedural rules, support the conclusion that Rule 36 affirmances are entirely within the authority and discretion of the court. A contrary conclusion would rest on a slender reed of statutory text and would create a rare situation--perhaps the only instance--in which Congress has directly dictated procedure for the federal courts of appeal since the enactment of the Rules Enabling Act

A New Leader in the World of Legalized Gambling: What the Illinois General Assembly Should do to Protect Pathological Gamblers from the Rapidly Expanding Industry

This Comment addresses the increasingly recognized disorder of pathological gambling and the lack of consideration it receives from the Illinois General Assembly as gambling in Illinois continues its trend of rapid decriminalization. The Comment first analyzes the well-documented individual and communal problems that are associated with pathological gambling and then examines the historical movement toward dependence on gambling revenues in Illinois. A close examination of gambling legislation in Illinois, Indiana, and New Jersey, and the interpretation of that legislation within those respective courts, reveals that pathological gamblers receive very little statutory protection from the abusive and negligent conduct of casinos. Ultimately, this Comment argues that the Illinois General Assembly should amend, and thereby revive, the Illinois Loss Recovery Act and create a cause of action by pathological gamblers against casinos when casinos engage in extreme behavior designed to entice pathological gamblers to relapse

FINITE SIZE SCALING ANALYSIS OF THE ANDERSON TRANSITION

The America Invents Act of 2011 created three administrative patent review regimes that have flooded the rechristened Patent Trial and Appeal Board with almost 7,000 new matters in just under five years. The flood of matters—primarily, inter partes reviews (IPRs)—has led to more than 1,000 appeals to the U.S. Court of Appeals for Federal Circuit from administrative proceedings, eclipsing any other forum of origin. With the flood of administrative appeals, questions of first instance on appellate standing have arisen, resulting in a handful of important panel decisions. While the other regional Courts of Appeals have largely adopted legal tests, standards, and local procedural rules for addressing appellant, appellee, and even intervenor and amici standing, the Federal Circuit has only recently begun to address it. We review cases from the Supreme Court, the other circuits, and recent Federal Circuit panel decisions deciding issues in the first instance. We conclude that two schools of thought dominate standing on appeal, that one is the more sensible and appropriate approach in line with Supreme Court precedent, and that the Federal Circuit has already signaled it will—as it should—adopt that approach

Technical factors affecting outcomes following endovascular treatment of posterior circulation atherosclerotic lesions

Atherosclerotic disease of the vertebrobasilar system causes significant morbidity and mortality. All lesions require aggressive medical management, but the role of endovascular interventions remains unsettled. This study examines such endovascular interventions for vertebrobasilar atherosclerosis.Retrospective review was performed of prospectively maintained procedure logs at three hospitals with comprehensive neurointerventional services. Patients with angiographically-proven stenosis undergoing elective stent placement were selected for analysis of demographic factors, lesion characteristics, and treatment details. Multivariate analysis was performed to evaluate for associations with ischemic stroke, death, and functional status as measured by modified Rankin scale at multiple intervals.One hundred and twenty-three lesions were treated in 110 patients. A total of 43 (58.1%) lesions caused stroke, while 66 (89.2%) caused transient ischemic attacks (TIAs). Forty lesions (32.5%) were at the vertebral origin; 97 (60.2%) were intracranial. A total of 112 (91.1%) were treated successfully. 4 (3.3%) of 10 (8.1%) procedural complications were symptomatic. Intracranial lesions were associated with death at 1 and 2 years (OR 24.91, P 2 at last contact (OR 12.83, P 2 at last contact (OR 0.234, P = 0.018) when angioplasty was performed with a device other than that packaged with the stent.Endovascular treatment of vertebrobasilar atherosclerosis can be performed safely, particularly for vertebral origin lesions. Higher rates of technical failure and complication may be acceptable for certain intracranial lesions due to their refractory nature and the morbidity caused by such lesions. Treatment should be tailored to features of each individual lesion