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There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. This study was a case series. This study was performed at a single institution in a University setting. Patients requiring prolonged VA-ECMO were included. No interventions were done. This was an observational study. Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss. ALS is now associated with mutations in numerous genes, many of which cause disease in part through toxic gain-of-function mechanisms. Antisense oligonucleotides (ASOs) are small sequences of DNA that can reduce expression of a target gene at the post-transcriptional level, making them attractive for neutralizing mutant or toxic gene products. Advancements in the medicinal chemistries of ASOs have improved their pharmacodynamic profile to allow safe and effective delivery to the central nervous system. ASO therapies for ALS have rapidly developed over the last two decades, and ASOs that target SOD1, C9orf72, FUS, and ATXN2 are now in clinical trials for familial or sporadic forms of ALS. This review discusses the current state of ASO therapies for ALS, outlining their successes from preclinical development to early clinical trials. [ABSTRACT FROM AUTHOR]

While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60–69 years, 2 points: 70–79 years, 3 points: 80–84 years, 4 points: 85 years or older), NIHSS (2 points: 13–17, 3 points: 18–22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76–0.85) in our training cohort and 0.78 (95 %CI 0.70–0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity. [ABSTRACT FROM AUTHOR]

Natural language processing (NLP), which aims to convert human language into expressions that can be analyzed by computers, is one of the most rapidly developing and widely used technologies in the field of artificial intelligence. Natural language processing algorithms convert unstructured free text data into structured data that can be extracted and analyzed at scale. In medicine, this unlocking of the rich, expressive data within clinical free text in electronic medical records will help untap the full potential of big data for research and clinical purposes. Recent major NLP algorithmic advances have significantly improved the performance of these algorithms, leading to a surge in academic and industry interest in developing tools to automate information extraction and phenotyping from clinical texts. Thus, these technologies are poised to transform medical research and alter clinical practices in the future. Radiation oncology stands to benefit from NLP algorithms if they are appropriately developed and deployed, as they may enable advances such as automated inclusion of radiation therapy details into cancer registries, discovery of novel insights about cancer care, and improved patient data curation and presentation at the point of care. However, challenges remain before the full value of NLP is realized, such as the plethora of jargon specific to radiation oncology, nonstandard nomenclature, a lack of publicly available labeled data for model development, and interoperability limitations between radiation oncology data silos. Successful development and implementation of high quality and high value NLP models for radiation oncology will require close collaboration between computer scientists and the radiation oncology community. Here, we present a primer on artificial intelligence algorithms in general and NLP algorithms in particular; provide guidance on how to assess the performance of such algorithms; review prior research on NLP algorithms for oncology; and describe future avenues for NLP in radiation oncology research and clinics. [ABSTRACT FROM AUTHOR]

Background: Postoperative complications increase hospital length of stay and patient mortality. Optimal perioperative fluid management should decrease patient complications. This study examined associations between fluid volume and noncardiac surgery patient outcomes within a large multicentre US surgical cohort.Methods: Adults undergoing noncardiac procedures from January 1, 2012 to December 31, 2017, with a postoperative length of stay ≥24 h, were extracted from a large US electronic health record database. Patients were segmented into quintiles based on recorded perioperative fluid volumes with Quintile 3 (Q3) serving as the reference. The primary outcome was defined as a composite of any complications during the surgical admission and a postoperative length of stay ≥7 days. Secondary outcomes included in-hospital mortality, respiratory complications, and acute kidney injury.Results: A total of 35 736 patients met the study criteria. There was a U-shaped pattern with highest (Q5) and lowest (Q1) quintiles of fluid volumes having increased odds of complications and a postoperative length of stay ≥7 days (Q5: odds ratio [OR] 1.51 [95% confidence interval {CI}: 1.30-1.74], P<0.001; Q1: OR 1.20 [95% CI: 1.04-1.38], P=0.011) compared with Q3. Patients in Q5 had greater odds of more severe acute kidney injury compared with Q3 (OR 1.52 [95% CI: 1.22-1.90]; P<0.001) and respiratory complications (OR 1.44 [95% CI: 1.17-1.77]; P<0.001).Conclusions: Both very high and very low perioperative fluid volumes were associated with an increase in complications after noncardiac surgery. [ABSTRACT FROM AUTHOR]

Opioid-based anesthesia and analgesia is a traditional component of perioperative care for the cardiac surgery patient. Growing enthusiasm for Enhanced Recovery Programs (ERPs) coupled with evidence of potential harm associated with high-dose opioids suggests that we reconsider the role of opioids in cardiac surgery. An interdisciplinary North American panel of experts, using a structured appraisal of the literature and a modified Delphi method, derived consensus recommendations for optimal pain management and opioid stewardship for cardiac surgery patients. Individual recommendations are graded based on the strength and level of evidence. The panel addressed 4 main topics: the harms associated with historical opioid use, the benefits of more targeted opioid administration, the use of nonopioid medications and techniques, and patient and provider education. A key principle that emerged is that opioid stewardship should apply to all cardiac surgery patients, entailing judicious and targeted use of opioids to achieve optimal analgesia with the fewest potential side effects. The process resulted in the promulgation of 6 recommendations regarding pain management and opioid stewardship in cardiac surgery, focused on avoiding the use of high-dose opioids, as well as encouraging more widespread application of foundational aspects of ERPs, such as the use of multimodal nonopioid medications and regional anesthesia techniques, formal patient and provider education, and structured system-level opioid prescription practices. Based on the available literature and expert consensus, there is an opportunity to optimize anesthesia and analgesia for cardiac surgery patients. Although additional research is needed to establish specific strategies, core principles of pain management and opioid stewardship apply to the cardiac surgery population. [Display omitted] [ABSTRACT FROM AUTHOR]

We sought to determine the early range of motion, complication rates, and 1-year patient-reported outcomes following Achilles tendon repair, using a modified gift-box suture loop technique. Sixty consecutive patients (49 males, mean age 36.2 ± 9.9 years) who underwent Achilles tendon repair with a modified gift-box suture loop technique performed by a single surgeon were prospectively enrolled. The range of motion at the final follow-up visit (mean 6 months) and the Achilles tendon rupture score (ATRS) and the complication rates at 1 year were obtained with 83% follow-up. The predictors of complications and ATRS were assessed. The mean operative time was 63.1 ± 10.8 minutes, which decreased throughout the case series (r = 0.46, p <.001). The mean plantarflexion at the final office evaluation was 31.7° ± 6.2°, dorsiflexion was 11.7° ± 6.3°, and total ankle arc of motion was 43.6° ± 9.7°; longer length of follow-up was associated with greater dorsiflexion (p =.008) and the total arc of motion (p =.008) but not with plantarflexion (p =.16). The overall rerupture rate was 1.7% (1 patient), wound complication rate was 1.7% (1 patient), and the overall complication rate was 6.7% (4 patients). No predictors of complications were identified. Complication rates did not differ between the first 30 (6.7%) cases and second 30 (6.7%) cases. The mean ATRS at 1 year was 81.8 ± 16.8 points. The rerupture and overall complication rates by 1 year were low. The range of motion, particularly dorsiflexion, improved through at least 6 months. Diabetic patients had lower 1-year ATRS than nondiabetic patients using this technique. [ABSTRACT FROM AUTHOR]

Background: Patellar or quadriceps tendon ruptures after total knee arthroplasty constitute a devastating complication with historically poor outcomes. With advances in soft tissue reconstruction and repair techniques, treatment has become more nuanced. Numerous graft options for reconstruction and suture techniques for repair have been described but there is no consensus regarding optimal treatment.Methods: A search of PubMed, MEDLINE, Embase, and Scopus was conducted. Articles meeting inclusion criteria were reviewed. Type of intervention performed, type of injury studied, outcome measures, and complications were recorded. Quantitative and qualitative analyses were performed.Results: Twenty-eight articles met inclusion criteria. The complication rate after repair of patellar tendon (63.16%) was higher than the complication rate after repair of quadriceps tendon (25.37%). However, the complication rate for patellar and quadriceps tendon tears after autograft, allograft, or mesh reconstruction was similar (18.8% vs 19.2%, respectively). The most common complication after extensor mechanism repair or reconstruction was extension lag of 30° or greater (45.33%). This was followed by re-rupture and infection (25.33% and 22.67%, respectively). Early ruptures had a higher overall complication rate than late injuries.Conclusion: Extensor mechanism disruption after total knee arthroplasty is a complication with high morbidity. Reconstruction of patellar tendon rupture has a much lower complication rate than repair. Our findings support the recommendation of patellar tendon reconstruction in both the early and late presentation stages. Quadriceps rupture can be treated with repair in early ruptures or with reconstruction in the late rupture or in the case of revision surgery. [ABSTRACT FROM AUTHOR]

Marine animals have been the bio-inspirational source for some novel concepts for locomotion, sensing, and the intelligent control of undersea vehicles. There has been little (if any) research in the area of bio-inspired energy utilization strategies applied to undersea vehicles. For example, there are reasons why some fish swim at a specific cruise speed; why some fish move by burst acceleration to higher speeds followed by coasting; and why some negatively buoyant fish alternately glide downwards, and then swim upward. The goal of this study is to develop the theory and models of the climb and glide form of autonomous undersea vehicle transit in a form that can permit assessment of future practical technology insertions (such as drag reduction and wing design). In addition, existing theory was expanded to address vehicles with significant wet weight and the effect of hotel load (equivalent to the basal metabolic rate of animals). Several observations from this preliminary analysis for climb/glide operation of practical vehicles were made. Over a practical and useful range of hotel loads and net vehicle lift-to-drag ratios, energy savings benefits relative to level flight transit from 10% to excess of 40% can be expected. This translates directly into a 10–40% increase in range if a climb/glide strategy is employed instead of level flight transit under the right operating conditions. [ABSTRACT FROM AUTHOR]

The presence of retrospective patterns in stock assessments is problematic for determining stock and harvest status because current estimates of stock size or fishing mortality are consistently lower or higher than those when the assessment model is updated with new data. A statistical measure of evidence for retrospective patterns is needed, but a requisite method to estimate variance of retrospective patterns is lacking. We evaluated the statistical behavior of a parametric bootstrap-based variance estimator for retrospective patterns that arise due to a change in natural mortality using a simulation experiment patterned after an assessment of yellowtail flounder on Georges Bank. We also evaluated effects of retrospective patterns on accuracy of stock assessment results and adjustments to terminal stock attributes intended to correct for retrospective patterns. We focused our analyses on Mohn's ρ , but the bootstrap approach could be used with any measure of retrospective pattern. We found that coverage for confidence intervals of Mohn's ρ were adequate, particularly for commonly specified percentage levels near 95%. We also found increased statistical efficiency of terminal year stock attributes that are adjusted for estimated retrospective patterns when the model structures used to simulate observations and estimate the parameters were inconsistent. Furthermore, this increase in efficiency was generally greater than the decrease in efficiency of adjusted stock attributes when models for simulated data and parameter estimation were consistent. However, the utility of adjustments for estimating stock and harvest status depended on our expectation for future productivity of the stock and using confidence interval coverage of Mohn's ρ to determine whether to adjust terminal stock attributes provided no greater benefit than simply always adjusting. [ABSTRACT FROM AUTHOR]

Fishery-independent surveys provide valuable information about trends in population abundance for management of commercially important fish stocks. A critical component of the relationship of the catches of the survey to the size of a fish stock is the catch efficiency of the survey gear. Using a general hierarchical model we estimated the relative efficiency of a chain sweep to the rockhopper sweep used by the Northeast Fisheries Science Center bottom trawl survey from paired-gear experimental tows carried out between 2015 and 2017 using a twin-trawl vessel. For 10 commercially important species, we fitted and compared a set of models with alternative assumptions about variation of relative efficiency between paired gear tows, size and diel effects on the relative efficiency, and extra-binomial variation of observations within paired gear tows. These analyses provided evidence of changes in relative efficiency with size for all species and diel effects were important for all but one species. We then used the bottom trawl survey data from surveys between 2009 and 2019 with the relative catch efficiency estimates from the best performing models to estimate annual and seasonal chain sweep-based swept area biomass for 17 managed stocks. We estimated uncertainty in all results using bootstrap procedures for each data component. We also assessed the effect of calibration on uncertainty and correlation of the annual biomass estimates. [ABSTRACT FROM AUTHOR]

The National Research Council has identified in situ exploration of Venus as an important mission for the coming decade of NASA's exploration of our solar system (Squyers, 2013 [1] ). Heavy cloud cover makes the use of solar photovoltaics extremely problematic for power generation for Venus surface missions. In this paper, we propose a class of planetary exploration missions (for use on Venus and elsewhere) in solar-deprived situations where photovoltaics cannot be used, batteries do not provide sufficient specific energy and mission duration, and nuclear systems may be too costly or complex to justify or simply unavailable. Metal-fueled, combustion-based powerplants have been demonstrated for application in the terrestrial undersea environment. Modified or extended versions of the undersea-based systems may be appropriate for these sunless missions. We describe systems carrying lithium fuel and sulfur-hexafluoride oxidizer that have the potential for many days of operation in the sunless craters of the moon. On Venus a system level specific energy of 240 to 370 W e -hr/kg should be possible if the oxidizer is brought from earth. By using either lithium or a magnesium-based alloy fuel, it may be possible to operate a similar system with CO 2 derived directly from the Venus atmosphere, thus providing an estimated system specific energy of 1100 W e+PV -hr/kg (the subscript refers to both electrical and mechanical power), thereby providing mission durations that enable useful scientific investigation. The results of an analysis performed by the NASA Glenn COMPASS team describe a mission operating at 2.3 kW e+PV for 5 days (120 h), with less than 260 kg power/energy system mass total. This lander would be of a size and cost suitable for a New Frontiers class of mission. [ABSTRACT FROM AUTHOR]

Preplant soil fumigation is commonly used to control soilborne pathogens and weeds in forest seedling nurseries of Oregon and Washington. However, lower chemical inputs are desired to meet state and federal application regulations, to minimize buffer zone size requirements, and to help protect the environment. Therefore, the objectives of this research were to evaluate the efficacy of three reduced rate soil fumigants under totally impermeable film (TIF) in managing soilborne diseases and weeds, and to determine if combined applications of up to four biocontrol agents improved soilborne disease control. Reduced rates of methyl bromide, metam sodium, and 1,3-dichloropropene, all applied in combination with chloropicrin, were effective in decreasing soil populations of Pythium and Fusarium as well as the presence of Pythium in root debris from the previous crop. The roots of Douglas-fir ( Pseudotsuga menziesii ) seedlings transplanted into each fumigant treatment were also colonized less by Pythium and Fusarium than those transplanted into nonfumigated control plots. However, biocontrol treatments were not effective against either pathogen. Weed biomass and weeding times were also significantly reduced by fumigation. Application costs were similar for all three fumigant treatments, but seedling size was largest from the methyl bromide and metam sodium treatments followed by the 1,3-dichloropropene treatment. Based on the results of this study, reduced rates of methyl bromide, metam sodium, and 1,3-dichloropropene show promise in managing soilborne diseases and weeds in forest nurseries. [ABSTRACT FROM AUTHOR]

Penalties are widely used for a range of parameters while fitting fish stock assessment models. Penalizing annual recruitments for deviating from an underlying mean recruitment is probably the most common. Assuming that recruits are log-normally distributed for the purposes of this penalty is theoretically justifiable. In practice, however, bias may be induced because this distributional assumption includes a term equal to the summation of the log observed data, which in the case of recruitment equals the summation of the log recruitment parameters that are not data. Using simulation, the potential for bias caused by assuming that recruits were log-normally distributed was explored, and results were contrasted with the assumption that log-recruitment was normally distributed, an alternative that avoids the potentially troublesome summation term. Spawning stock biomass ( SSB ) and recruitment were negatively biased, while fishing mortality ( F ) was positively biased under the assumption of log-normally distributed recruitments, and the bias worsened closer to the terminal year. The bias also worsened when the true underlying F was low relative to natural mortality, and with domed fishery selectivity. Bias in SSB , recruitment, and F was nonexistent or relatively small under the assumption that log-recruitment was normally distributed. Distributional assumptions for penalties used in assessment models should be reviewed to reduce the potential for biased estimation. These results also provide further support for simulation testing to evaluate statistical behavior of assessment models. [ABSTRACT FROM AUTHOR]

The effect of surface treatment on the properties of fine aluminum powders was investigated using both chemical and rheological characterization techniques. Four different particle size distributions (PSD) were surface treated with methyltriethoxysilane and subsequently evaluated through classic density measurements and by using an FT4 powder rheometer (Freeman Technologies, UK). The chemical surface properties were analyzed using diffuse reflectance infrared spectroscopy (DRIFTs) and X-ray photoelectron spectroscopy (XPS) which confirmed retention of the silane and production of a siloxane-like layer on all PSD samples. The results of the bulk measurements, both direct and empirical, showed enhanced flowability and easier fluidization, indicating reduction of intrinsic cohesion for all samples. Fluidization testing showed decrease in total energy of the uniformly fluidized bed by ~ 80–90% in all cases. Shear stress values as a function of applied normal stress were collected to produce Mohr diagrams which generated extrapolated cohesion and unconfined yield strength values using the Mohr–Coulomb criteria. Cohesion and unconfined yield strength were reduced in all surface treated powders which indicated easier flowability and an increase in the flow function at 6 kPa. The compressibility of the treated powders at 8 kPa was decreased by > 60% in all cases, indicating significant reduction in entrained air and improvement in packing density. Classical density measurements showed small improvements in the Hausner Ratio and little to no improvement in the Carr index, whereas directly measured properties using powder rheology showed substantial changes in the flow and fluidization properties. Overall, fluidization behavior and flowability properties were enhanced in all PSDs and showed the increased potential for the use of fine aluminum powders after surface treatment in delivery applications. [ABSTRACT FROM AUTHOR]

Morphing or adaptive structures may be of interest in underwater vehicle design due to their potential for optimizing the operational envelopes of complex vehicles. Adaptive structures have been researched heavily and put to use extensively in the aerospace industry. This paper examines a possible use and benefit associated with morphing structures with unmanned underwater vehicles (UUVs). The growing résumé of applications associated with UUVs as well as their unique abilities make them an excellent subject of study for morphing concepts. This paper focuses on possible uses of flexible hull morphing, specifically the benefits associated with such adaptability in terms of range, endurance, and speed. This research proposes a UUV system which has a flexible hull wrapped around a standard pressure hull. The annulus created between the pressure hull and the flexible hull is used for the storage of expendable energetics, in this case diesel fuel. Storing fuel in the newly created annulus also eliminates the need to waste space within the pressure hull storing fuel and thus the pressure hull may also be shrunk. This paper focuses on the benefits of morphing where the shape of the flexible hull remains the same but the diameter of the outer hull is shrunk in concert with the consumption of fuel thus decreasing the drag profile of the vehicle, resulting in increased vehicle range. Two different UUV missions were outlined: (1) constant speed survey and (2) slow speed survey with high speed excursion. For the slow speed survey mission, semi-submersible heavy vehicles carrying in the range of 50,000 kg of fuel could realize increases of range close to 40% when compared to a similarly sized vehicle without the adaptive capabilities. Small vehicles on the other hand, show limited benefits of diameter morphing, gaining less than 5% in range over the non-adaptive system. Excursion missions during which a surveying operation must be augmented with some sort of high speed maneuver show more significant benefits with a morphing system. The results show that diameter morphing is not viable in all situations, yet the concept shows promise for certain long range/long endurance UUV missions, as well as missions that require occasional high speed operation. [ABSTRACT FROM AUTHOR]

Purpose To study the relationship between intracranial thrombus length and number of stent retrievals, revascularization rates, and functional outcomes in stroke. Materials and Methods Retrospective data were collected from consecutive cases of stroke treated with endovascular procedures at a single institution from April 2012–September 2013. Thrombus length was measured in the anterior cerebral circulation. Demographic and clinical details; involved vessels; and procedural details, including the number of devices used and number of retrievals used for each device, were recorded. Revascularization rates and 90-day functional outcomes were recorded. Results Data regarding the length of thrombus in the anterior cerebral circulation were available for 28 patients. There was no significant association between thrombus length and number of stent retrievals ( P = .3780), final thrombolysis in cerebral infarction (TICI) score ( P = .4835), or 90-day modified Rankin Scale score ( P = .4146). There was a significant difference ( P = .0280) between number of retrievals and final TICI score, with lower number of retrieval passes corresponding to higher final TICI scores. Conclusions The data suggest no relationship between thrombus length and number of stent retrievals, final TICI score, or functional neurologic outcomes at 90 days in stent retrieval thrombectomy for acute ischemic stroke. These results do not support a predictive value for thrombus length quantification in the evaluation of stroke. [ABSTRACT FROM AUTHOR]

Abstract: Stereotactic radiosurgery is generally accepted as one of the best treatment options for vestibular schwannomas. We question whether growth control is an accurate measure of success in vestibular schwannoma treatment. We aim to clarify the success rate of stereotactic radiosurgery and adjust the reported results to the benign natural history of untreated tumors. All articles were taken from a PubMed search of the English literature from the years 2000–2011. Inclusion criteria were articles containing the number of patients treated, radiation technique, average tumor size, follow-up time, and percentage of tumors growing during follow-up. Data were extracted from 19 articles. Success rates were adjusted using published data that 17% to 30% of vestibular schwannomas grow. The average reported success rate for stereotactic radiosurgery across all articles was 95.5%. When considering 17% or 30% natural growth without intervention, the adjusted success rates became 78.2% and 86.9% respectively. These rates were obtained by applying the natural history growth percentages to any tumors not reported to be growing before radiosurgical intervention. Success in the treatment of vestibular schwannomas with stereotactic radiosurgery is often defined as lack of further growth. Recent data on the natural growth history of vestibular schwannomas raise the question of whether this is the best definition of success. We have identified a lack of continuity regarding the reporting of success and emphasize the importance of the clarification of the success of radiosurgery to make informed decisions regarding the best treatment options for vestibular schwannoma. [Copyright &y& Elsevier]

Abstract: Introduction: High resolution MRI findings suggestive of mesial temporal sclerosis (MRI-MTS) correlate with good outcome after surgery. However, a large group of patients present with normal brain MRI (N-MRI) and temporal lobe epilepsy (TLE). We aim to compare pre-operative ictal EEG patterns in predicting surgical outcomes in the population with MRI-MTS vs. N-MRI after selective anterior-mesial temporal lobe (AMTL) resection. Methods: 241 patients with unilateral anterior ictal EEG findings underwent selective AMTL resection. 143 MRI-MTS and 98 N-MRI patients were identified. Outcome was based on the modified Engel classification, ictal EEG pattern at seizure onset, demographics and MRI findings. Results: Seizure-free outcome was seen in the MRI-MTS in 79% of patients, compared to 59.1% (p <.005) of the N-MRI group. No significant difference was identified in ictal EEG patterns at presentation between groups. Class I outcome was achieved in 78.9% of patients that had theta rhythm and MRI-MTS compared to 57.9% of patients that had theta rhythm and N-MRI (p <0.05). Discussion and conclusion: Surgical treatment for mesial TLE is effective. Positive MRI suggestive of mesial temporal sclerosis (MTS) predicts better seizure control after surgery. Theta rhythm is the most common ictal pattern and seems to carry the best prognosis for TLE. However, a well-selected group of patients with N-MRI will benefit from surgical intervention, and similar outcome to MRI-MTS patients can be achieved if delta ictal EEG pattern is presented at initial onset. Early referral to an epilepsy center cannot be emphasized enough, even in situations when high-resolution brain MRI is normal. [Copyright &y& Elsevier]

The article describes three cases of intravascular papillary endothelial hyperplasia of the skull base and intracranial compartment. The first case involves a 56-year-old woman who presented with chronic, recurrent sinus infections. The second case involves a 39-year-old woman who presented with multiple syncopal episodes and chose surgical removal of the lesion. The third case involves a 73-year-old man who presented with intractable seizures.

Summary: Background: Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the SOD1 Gly93Ala rat model of amyotrophic lateral sclerosis, the antisense oligonucleotide ISIS 333611 delivered to CSF decreased SOD1 mRNA and protein concentrations in spinal cord tissue and prolonged survival. We aimed to assess the safety, tolerability, and pharmacokinetics of ISIS 333611 after intrathecal administration in patients with SOD1-related familial amyotrophic lateral sclerosis. Methods: In this randomised, placebo-controlled, phase 1 trial, we delivered ISIS 333611 by intrathecal infusion using an external pump over 11·5 h at increasing doses (0·15 mg, 0·50 mg, 1·50 mg, 3·00 mg) to four cohorts of eight patients with SOD1-positive amyotrophic lateral sclerosis (six patients assigned to ISIS 333611, two to placebo in each cohort). We did the randomisation with a web-based system, assigning patients in blocks of four. Patients and investigators were masked to treatment assignment. Participants were allowed to re-enrol in subsequent cohorts. Our primary objective was to assess the safety and tolerability of ISIS 333611. Assessments were done during infusion and over 28 days after infusion. This study was registered with Clinicaltrials.gov, number NCT01041222. Findings: Seven of eight (88%) patients in the placebo group versus 20 of 24 (83%) in the ISIS 333611 group had adverse events. The most common events were post-lumbar puncture syndrome (3/8 [38%] vs 8/24 [33%]), back pain (4/8 [50%] vs 4/24 [17%]), and nausea (0/8 [0%] vs 3/24 [13%]). We recorded no dose-limiting toxic effects or any safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611. Re-enrolment and re-treatment were also well tolerated. Interpretation: This trial is the first clinical study of intrathecal delivery of an antisense oligonucleotide. ISIS 333611 was well tolerated when administered as an intrathecal infusion. Antisense oligonucleotides delivered to the CNS might be a feasible treatment for neurological disorders. Funding: The ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals. [Copyright &y& Elsevier]

Abstract: Background: Simvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. However, the effect of simvastatin on cholangiocarcinoma has not been evaluated. Aim: The aim of our study was to determine the effect of simvastatin on cholangiocarcinoma proliferation. Methods: The effect of simvastatin was evaluated in five human cholangiocarcinoma cell lines (Mz-ChA-1, HuH-28, TFK-1, SG231, and HuCCT1) and normal cholangiocyte cell line (HiBEpiC). Results: We found that simvastatin stimulates a reduction in cell viability and apoptosis of cholangiocarcinoma cell lines, whilst in normal human cholangiocytes, HiBEpiC, simvastatin inhibits proliferation with no effect on apoptosis. Simvastatin-induced reduction of cell viability was partially blocked by pre-treatment with metabolites of the mevalonate pathway. In Mz-ChA-1 cells, pre-treatment with cholesterol alone stimulated an increase in the number of viable cells and fully restored cell viability following simvastatin treatment. Treatment with simvastatin triggered the loss of lipid raft localised Rac1 and reduction of Rac1 activity in Mz-ChA-1 cells. This effect was prevented by pre-treatment with cholesterol. Conclusion: Collectively, our results demonstrate that simvastatin induces cholangiocarcinoma cancer cell death by disrupting Rac1/lipid raft colocalisation and depression of Rac1 activity. [Copyright &y& Elsevier]

Objective: To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. Study design: The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. Results: Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. Conclusions: There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay. [Copyright &y& Elsevier]

Major surgery is associated with significant trauma and is a potential cause of multiple system organ failure and death. Measurement of cardiac output using a variety of techniques during the perioperative period has enabled practitioners to proactively optimise stroke volume and cardiac output in an attempt to reduce postoperative complications. Although pulmonary artery catheter has been widely used and considered as the gold standard for measuring cardiac output, recent advancement of technology has seen the development of a number of less-invasive haemodynamic monitors. Oesophageal Doppler ultrasonography is a minimally invasive method for measuring stroke volume and cardiac output. It is user-friendly and is one of the few low-invasive technologies to date, which has been used successfully to guide intra-operative fluid administration, resulting in improvement in outcome and significant reduction in duration of hospital stay. [ABSTRACT FROM AUTHOR]

The northeast US fishing industry and other stakeholders have considerable interest in the quality of bottom trawl survey results because of their importance in the setting of quotas, especially those directly derived from bottom trawl indices measured in catch per area swept by the survey net. Net spread (also referred to as wing spread) impacts catches and thus indices and, for the federal northeast bottom trawl survey, it is correlated with the depth at which a tow is performed. As part of an ongoing partnership between the Northeast Fisheries Science Center, the New England and Mid-Atlantic Fisheries Management Councils, members of the fishing industry, and academics in the region, an experiment to evaluate the impact of wing spread on the catchability of a number of species was conducted in the Fall of 2019 on the F/V Karen Elizabeth. The experiment targeted four species of flatfishes using a twin trawl rigging to collect simultaneous observations of catch and wing spread relative to a controlled optimal net spread. We analyzed these data to estimate the effect of net spread on relative catch efficiency and to evaluate the hypothesis that relative catch efficiency decreases as net spread departs from the optimal configuration. We found that, while the total catch was impacted by net wing spread (catches increased with increasing swept-area), there was no evidence of a wing spread effect on relative catch efficiency for any of the flatfish species. These results suggest that bottom trawl surveys should account for swept-area of individual tows, but that it is not necessary to incorporate species- or length-specific efficiency conversions based on the width of the net. • An extensive field study was conducted to assess the impact of trawl net wings spread on relative catch efficiency. • This experiment was designed in collaboration with industry members to address concerns about federal survey performance. • Results indicated wingspread impacted total weight of catches because a larger area was sampled. • However results suggested no significant impact of wing spread on the relative catch efficiency of the survey net. • Similar experiments conducted with industry may be helpful in exploring the impact of other conditions on survey performance. [ABSTRACT FROM AUTHOR]

The Johnson Thermoelectric Converter (JTEC) operates as an approximation of an Ericsson cycle thermodynamic heat engine with no moving parts. During operation, hydrogen flows from a high-temperature high-pressure region to a low-pressure region by way of a membrane-electrode assembly. In passing through the assembly, the hydrogen is stripped of its electrons which flow through the circuit and reform with protons to the recover hydrogen on the low-pressure side. Some of the electrical power extracted is used to electrochemically "pump" the hydrogen back to the low-temperature high-pressure side and sustain the pressure differential. The objective of the work presented here was to mathematically characterize a JTEC system and to develop the coupled relationships between design goals like efficiency, net power production, and power density; and design parameters like high versus low operating temperatures and pressures, device geometry, and thermophysical properties of the device materials and working fluid. Power production is related to the operating pressure ratio, the ratio of high to low device operating temperatures, the high operating temperature, and the effective heat transfer area of the hot end. The efficiency is related to several non-dimensional and dimensional number groups (especially the recuperator effectiveness). The power density or volume of the device is related to a different recuperator parameter, the high temperature of the heat addition source, the cold temperature of the thermal rejection source, and the internal device geometry. Even with reasonable simplifications and assumptions, the design space contains a large number of variable parameters. The model equations were exercised over the large parametric trade space. • Parametric study of a solid state Ericsson heat engine was performed. • Good recuperator design was the greatest contributor to cycle efficiency. • Power was most impacted by ratio of device surface area to ion exchange thickness. [ABSTRACT FROM AUTHOR]

The rapid changes observed in many marine ecosystems that support fisheries pose a challenge to stock assessment and management predicated on time-invariant productivity and considering species in isolation. In single-species assessments, two main approaches have been used to account for productivity changes: allowing biological parameters to vary stochastically over time (empirical), or explicitly linking population processes such as recruitment (R) or natural mortality (M) to environmental covariates (mechanistic). Here, we describe the Woods Hole Assessment Model (WHAM) framework and software package, which combines these two approaches. WHAM can estimate time- and age-varying random effects on annual transitions in numbers at age (NAA), M , and selectivity, as well as fit environmental time-series with process and observation errors, missing data, and nonlinear links to R and M. WHAM can also be configured as a traditional statistical catch-at-age (SCAA) model in order to easily bridge from status quo models and test them against models with state-space and environmental effects, all within a single framework. We fit models with and without (independent or autocorrelated) random effects on NAA, M , and selectivity to data from five stocks with a broad range of life history, fishing pressure, number of ages, and time-series length. Models that included random effects performed well across stocks and processes, especially random effects models with a two dimensional (2D) first-order autoregressive, AR(1), covariance structure over age and year. We conducted simulation tests and found negligible or no bias in estimation of important assessment outputs (SSB, F , stock status, and catch) when the operating and estimation models matched. However, bias in SSB and F was often non-trivial when the estimation model was less complex than the operating model, especially when models without random effects were fit to data simulated from models with random effects. Bias of the variance and correlation parameters controlling random effects was also negligible or slightly negative as expected. Our results suggest that WHAM can be a useful tool for stock assessment when environmental effects on R or M , or stochastic variation in NAA transitions, M , or selectivity are of interest. In the U.S. Northeast, where the productivity of several groundfish stocks has declined, conducting assessments in WHAM with time-varying processes via random effects or environment-productivity links may account for these trends and potentially reduce retrospective bias. [ABSTRACT FROM AUTHOR]

The optimal recanalization goal and number of endovascular thrombectomy (EVT) passes for elderly patients with large vessel occlusion strokes is unclear. Consecutive patients 80 years or older undergoing EVT were identified from 2016 to 2022 at a single center. Clinical information, procedural details, and modified treatment in cerebral ischemia (mTICI) scores were collected. Primary outcome was modified Rankin scale (mRS) at 90 days. Bivariate and multivariable analyses were conducted to assess associations between mTICI scores, EVT passes, and 90-day outcomes. One hundred twenty-six patients were identified. At 90 days, mTICI 2b recanalization resulted in high rates of poor outcomes (8.7% functional independence and 60.9% mortality) not significantly different from mTICI 0, 1 or 2a (median mRS 6 vs. 6, P = 0.61). Complete recanalization (mTICI 2c or 3) led to significantly better mRS outcomes at 90 days compared to mTICI 2b (median mRS 4 vs. 6, adjusted P = 0.038), with 26.8% functional independence and 37.8% mortality. In multivariable analysis, complete recanalization was significantly associated with better 90-day outcomes than mTICI 2b or lower recanalization (odds ratio 4.24 [95% Confidence interval 1.46–12.3]; P = 0.002), while the number of passes was not independently associated with worse outcomes (P = 0.98). For octogenarians, mTICI 2b recanalization yields limited clinical benefit and results in poor 90-day outcomes. In contrast, complete recanalization is independently associated with significantly better outcomes. Thus, once the decision is made to pursue EVT in the elderly, mTICI 2c or better recanalization should be the angiographic goal. Providers should not withhold thrombectomy passes based on age alone. [ABSTRACT FROM AUTHOR]