A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient’s physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.

The preconception, pregnancy and immediate postpartum and newborn periods are times for mothers and their offspring when they are especially vulnerable to major stressors – those that are sudden and unexpected and those that are chronic. Their adverse effects can transcend generations. Stressors can include natural disasters or political stressors such as conflict and/or migration. Considerable evidence has accumulated demonstrating the adverse effects of natural disasters on pregnancy outcomes and developmental trajectories. However, beyond tracking outcomes, the time has arrived for gathering more information related to identifying mechanisms, predicting risk and developing stress-reducing and resilience-building interventions to improve outcomes. Further, we need to learn how to encapsulate both the quantitative and qualitative information available and share it with communities and authorities to mitigate the adverse developmental effects of future disasters, conflicts and migrations. This article briefly reviews prenatal maternal stress and identifies three contemporary situations (wildfire in Fort McMurray, Alberta, Canada; hurricane Harvey in Houston, USA and transgenerational and migrant stress in Pforzheim, Germany) where current studies are being established by Canadian investigators to test an intervention. The experiences from these efforts are related along with attempts to involve communities in the studies and share the new knowledge to plan for future disasters or tragedies.

Carbon-14 (radiocarbon, 14C) is a long-lived radionuclide (5730 yr) of interest regarding the safety for the management of intermediate level wastes (ILW). The present study gives an overview of the release of 14C from irradiated Zircaloy cladding in alkaline media. 14C is found either in the alloy part of Zircaloy cladding due to the neutron activation of 14N impurities by 14N(n,p)14C reaction, or in the oxide layer (ZrO2) formed at the metal surface by the neutron activation of 17O from UO2 or (U-Pu)O2 fuel and water from the primary circuit in the reactor by 17O(n,α)14C reaction. Various irradiated and unirradiated Zircaloys have been studied. The total 14C inventory has been determined both experimentally and by calculations. The results seem to be in good agreement. Leaching experiments were conducted in alkaline media for several time durations. 14C was mainly released as carboxylic acids. Further, corrosion measurements were performed by using both hydrogen measurements and electrochemical measurements. The corrosion rate (CR) ranges from a few nm/yr to 100 nm/yr depending on the surface conditions and the method used for measurement. From a safety assessment point of view, the instant release fraction (IRF) was determined on irradiated Zircaloy-2. The results showed that the 14C inventory in the oxide was significantly below the 20% commonly used in safety case assessments.

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

Direct ink writing of silicone elastomers enables printing with precise control of porosity and mechanical properties of ordered cellular solids, suitable for shock absorption and stress mitigation applications. With the ability to manipulate structure and feedstock stiffness, the design space becomes challenging to parse to obtain a solution producing a desired mechanical response. Here, we derive an analytical design approach for a specific architecture. Results from finite element simulations and quasi-static mechanical tests of two different parallel strand architectures were analyzed to understand the structure-property relationships under uniaxial compression. Combining effective stiffness-density scaling with least squares optimization of the stress responses yielded general response curves parameterized by resin modulus and strand spacing. An analytical expression of these curves serves as a reduced order model, which, when optimized, provides a rapid design capability for filament-based 3D printed structures. As a demonstration, the optimal design of a face-centered tetragonal architecture is computed that satisfies prescribed minimum and maximum load constraints.

Abundant tubular macrofossils occur in finely laminated siltstones and shales of the 548–542 Ma Schwarzrand Subgroup, Nama Group, Namibia. The Nama tubes occur in both the Vingerbreek and Feldschuhhorn members commonly in dense populations and always in fine-grained, lower shore-face lithologies deposited below fair-weather wave base. The tubes are preserved mostly as compressed casts and molds that range in width from 0.6 to 2.1 mm; apparently incomplete specimens reach lengths up to 10 cm. All specimens show sinuous bending and occasional brittle fracture, indicating an original construction of strong but flexible organic matter. Feldschuhhorn specimens preserve fine longitudinal pleats or folds that record pliant organic walls, but the older Vingerbreek populations do not. Similarly, some specimens in the Feldschuhhorn Member display branching, while Vingerbreek tubes do not. The abundant Feldschuhhorn tubes are assigned to the widespread Ediacaran problematicum Vendotaenia antiqua; however, the distinctive Vingerbreek population remains in open nomenclature. The most abundant fossils in Nama rocks, these tubes resemble populations in Ediacaran successions from Russia, China, Spain, and elsewhere. Beyond their local importance, then, such tubes may turn out to be the most abundant record of Ediacaran life.

Background: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non–evidence-based medical tourism for CCSVI procedures. Methods: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. Results: In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. Conclusions: Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.

The long-term behavior of the UO2 fuel matrix under conditions of the Belgian “Supercontainer design” was investigated by dissolution tests of high burn-up spent nuclear fuel (SNF) in high alkaline solution under 40 bar of (Ar + 8%H2) atmosphere. Four fragments of SNF, obtained from a pellet previously leached during two years, were exposed to young cement water with Ca (YCWCa) under 3.2 bar H2 partial pressure in four single/independent autoclave experiments for a period of 59, 182, 252 and 341 days, respectively. After a decrease of the concentration of dissolved 238U, which is associated with a reduction of U(VI) to U(IV), the concentration of 238U in solution is constant in the experiments running for 252 and 341 days. These observations indicate an inhibition of the matrix dissolution due to the presence of H2. A slight increase in the concentration of 90Sr and 137Cs in the aqueous solution indicates that there is still dissolution of the grain boundaries. These findings are similar to those reported for spent nuclear fuel corrosion in synthetic near neutral pH solutions.

Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.

Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.