Comparison of Post-injection Site Pain Between Technetium Sulfur Colloid and Technetium Tilmanocept in Breast Cancer Patients Undergoing Sentinel Lymph Node Biopsy.

BackgroundNo prior studies have examined injection pain associated with Technetium-99m Tilmanocept (TcTM).MethodsThis was a randomized, double-blinded study comparing postinjection site pain between filtered Technetium Sulfur Colloid (fTcSC) and TcTM in breast cancer lymphoscintigraphy. Pain was evaluated with a visual analogue scale (VAS) (0-100 mm) and the short-form McGill Pain Questionnaire (SF-MPQ). The primary endpoint was mean difference in VAS scores at 1-min postinjection between fTcSC and TcTM. Secondary endpoints included a comparison of SF-MPQ scores between the groups at 5 min postinjection and construction of a linear mixed effects model to evaluate the changes in pain during the 5-min postinjection period.ResultsFifty-two patients underwent injection (27-fTcSC, 25-TcTM). At 1-min postinjection, patients who received fTcSC experienced a mean change in pain of 16.8 mm (standard deviation (SD) 19.5) compared with 0.2 mm (SD 7.3) in TcTM (p = 0.0002). At 5 min postinjection, the mean total score on the SF-MPQ was 2.8 (SD 3.0) for fTcSC versus 2.1 (SD 2.5) for TcTM (p = 0.36). In the mixed effects model, injection agent (p < 0.001), time (p < 0.001) and their interaction (p < 0.001) were associated with change in pain during the 5-min postinjection period. The model found fTcSC resulted in significantly more pain of 15.2 mm (p < 0.001), 11.3 mm (p = 0.001), and 7.5 mm (p = 0.013) at 1, 2, and 3 min postinjection, respectively.ConclusionsInjection with fTcSC causes significantly more pain during the first 3 min postinjection compared with TcTM in women undergoing lymphoscintigraphy for breast cancer

cis-Acting and trans-acting modulation of equine infectious anemia virus alternative RNA splicing

AbstractEquine infectious anemia virus (EIAV), a lentivirus distantly related to HIV-1, encodes regulatory proteins, EIAV Tat (ETat) and Rev (ERev), from a four-exon mRNA. Exon 3 of the tat/rev mRNA contains a 30-nucleotide purine-rich element (PRE) which binds both ERev and SF2/ASF, a member of the SR family of RNA splicing factors. To better understand the role of this element in the regulation of EIAV pre-mRNA splicing, we quantified the effects of mutation or deletion of the PRE on exon 3 splicing in vitro and on alternative splicing in vivo. We also determined the branch point elements upstream of exons 3 and 4. In vitro splicing of exon 3 to exon 4 was not affected by mutation of the PRE, and addition of purified SR proteins enhanced splicing independently of the PRE. In vitro splicing of exon 2 to exon 3 was dependent on the PRE; under conditions of excess SR proteins, either the PRE or the 5′ splice site of exon 3 was sufficient to activate splicing. We applied isoform-specific primers in real-time RT-PCR reactions to quantitatively analyze alternative splicing in cells transfected with rev-minus EIAV provirus constructs. In the context of provirus with wild-type exon 3, greater than 80% of the viral mRNAs were multiply spliced, and of these, less than 1% excluded exon 3. Deletion of the PRE resulted in a decrease in the relative amount of multiply spliced mRNA to about 40% of the total and approximately 39% of the viral mRNA excluded exon 3. Ectopic expression of ERev caused a decrease in the relative amount of multiply spliced mRNA to approximately 50% of the total and increased mRNAs that excluded exon 3 to about 4%. Over-expression of SF2/ASF in cells transfected with wild-type provirus constructs inhibited splicing but did not significantly alter exon 3 skipping

Fertilizer and Swine Manure Management Systems: Impacts on Crop Production and Nitrate-Nitrogen Leaching with Subsurface Drainage

Nutrient losses from row-crop land can cause nonpoint source water quality problems and “impaired waters.” Nitrogen (N) losses due to nitrate (NO3) leaching cause drinking water problems and possibly increase hypoxia (low oxygen) problems in the Gulf of Mexico. Phosphorus (P) losses can cause eutrophication problems in surface waters (lakes, streams, and reservoirs) in Iowa where algal blooms decrease oxygen, kill fish, and result in murky and bad tasting water. The U.S. EPA and the Iowa Department of Natural Resources are developing nutrient criteria/standards and implementation plans to address TMDL’s (Total Maximum Daily Load) and to improve the quality of impaired waters. These plans need to be based on sound information. To address the need for information about water quality impacts from the use of swine manure as a source of nutrients (N and P), a field study was funded by the Leopold Center for Sustainable Agriculture in 1999. Properly managed, swine manure can supply N and P needed by corn and soybeans. This study is being conducted at the Northeast Research Farm on 36 one-acre plots that are instrumented to monitor subsurface drainage for continuous water quality assessment

The Future Role of Strategic Landpower

Recent Russian aggression in Ukraine has reenergized military strategists and senior leaders to evaluate the role of strategic Landpower. American leadership in the European theater has mobilized allies and partners to reconsider force postures for responding to possible aggression against NATO members. Although Russian revisionist activity remains a threat in Europe, the challenges in the Pacific for strategic Landpower must also be considered. At the same time, the homeland, the Arctic, climate change, and the results of new and emerging technology also challenge the application of strategic Landpower. This publication serves as part of an enduring effort to evaluate strategic Landpower’s role, authorities, and resources for accomplishing the national strategic goals the Joint Force may face in the next conflict. This study considers multinational partners, allies, and senior leaders that can contribute to overcoming these enduring challenges. The insights derived from this study, which can be applied to both the European and Indo-Pacific theaters, should help leaders to consider these challenges, which may last a generation. Deterrence demands credible strategic response options integrated across warfighting functions. This valuable edition will continue the dialogue about addressing these issues as well as other emerging ones.https://press.armywarcollege.edu/monographs/1959/thumbnail.jp

The Incremental Garbage Collection of Processes

Key Words and Phrases: garbage collection, multiprocessing systems, processor scheduling. "lazy evaluation, "eager" evaluation. CR Categories: 3.60, 3.80, 4.13, 4.22, 4.32. This report describes research done at the Artificial Intelligence Laboratory of the Massachusetts Institute of Technology. Support for the laboratory's artificial intelligence research is provided in part by the Advanced Research Projects Agency of the Department of Defense under Office of Naval Research contract N00014-75-C-0522. This paper was presented at the AI*PL Conference at Rochester, N.Y. in August, 1977.This paper investigates some problems associated with an argument evaluation order that we call "future" order, which is different from both call-by-name and call-by-value. In call-by-future, each formal parameter of a function is bound to a separate process (called a "future") dedicated to the evaluation of the corresponding argument. This mechanism allows the fully parallel evaluation of arguments to a function, and has been shown to augment the expressive power of a language. We discuss an approach to a problem that arises in this context: futures which were thought to be relevant when they were created become irrelevant through being ignored in the body of the expression where they were bound. The problem of irrelevant processes also appears in multiprocessing problem-solving systems which start several processors working on the same problem but with different methods, and return with the solution which finishes first. This parallel method strategy has the drawback that the processes which are investigating the losing methods must be identified, stopped, and re-assigned to more useful tasks. The solution we propose is that of garbage collection. We propose that the goal structure of the solution plan be explicitly represented in memory as part of the graph memory (like Lisp's heap) so that a garbage collection algorithm can discover which processes are performing useful work, and which can be recycled for a new task. An incremental algorithm for the unified garbage collection of storage and processes is described.MIT Artificial Intelligence Laboratory Department of Defense Advanced Research Projects Agenc

Global increases in both common and rare copy number load associated with autism.

Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism

Biliary reconstructive techniques and associated anatomic variants in adult living donor liver transplantations: The adult‐to‐adult living donor liver transplantation cohort study experience

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140020/1/lt24872.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140020/2/lt24872_am.pd

Use of a liquid nicotine delivery product to promote smoking cessation

<p>Abstract</p> <p>Background</p> <p>Despite access to various pharmacotherapies and counseling support to aid cessation, smokers typically demonstrate quit rates below 50%. This report describes the results of a Phase 2a study exploring the efficacy of a liquid nicotine delivery system as an aid to smoking cessation assessed after 12 weeks of therapy.</p> <p>Methods</p> <p>A single-arm Phase 2a study was conducted. Community-based smokers (ages 18+ years, smoking at least 10 cigarettes daily for the past year and interested in making a quit attempt) were recruited and completed clinic visits at 2 week intervals over the 12 week study period where carbon monoxide levels were assessed and the Smoke-Break product was rated on taste and overall satisfaction. Participants were provided with a supply of liquid nicotine cigarettes (e.g., Smoke-Break) at each clinic visit. A total of 69 smokers were enrolled and received the intervention product (intention to treat group, ITT) and 52 smokers verified participation (according to protocol group, ATP).</p> <p>Results</p> <p>The cessation rate at 12 weeks after the baseline visit, assessed as the bioverified point prevalence of abstinence, was 71.1% (95% confidence interval [CI] 58.8%-83.5%) in the ATP group and 53.6% (41.8%-65.4%) in the ITT group. Participants rated the liquid nicotine delivery system highly and also expressed general satisfaction. Few adverse events were identified with no serious adverse events.</p> <p>Conclusions</p> <p>These results support the efficacy of the liquid nicotine delivery system in smoking cessation. If this nicotine delivery product proves to be effective in larger trials, it could represent an inexpensive, readily accessible and well-tolerated agent to promote smoking cessation.</p> <p>Trial Registration</p> <p>This trial is registered at clinicaltrials.gov as study NCT00715871.</p