cssi/SciSciGPT-SciSciNet huggingface dataset:
Late Relapses Following High Dose Chemotherapy and Autologous Stem Cell Transplant in Patients with Diffuse Large B Cell Lymphoma in the Rituximab Era

Introduction: For patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), salvage treatment followed by consolidation with high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is the standard of care for those with chemosensitive disease, as established by the PARMA and CORAL trials. In the pre-rituximab era, patients with DLBCL experiencing disease progression following HD-ASCT had a dismal prognosis with a median overall survival of 3 months. These early studies demonstrate that early progression following HD-ASCT is the most important predictor of poor outcome. In the rituximab era, there is very little data examining incidence and outcomes of patients with late relapses following HD-ASCT for relapsed/refractory DLCBCL. Therefore, we sought to evaluate survival outcomes in a cohort population of patients relapsing late after HD-ASCT for DLBCL. Methods: We reviewed consecutive patients who underwent HD-ASCT for biopsy confirmed relapsed or refractory DLBCL between 2001 and 2010 at the University of Rochester James P. Wilmot Cancer Institute. Eligible patients were required to have received rituximab as part of their therapeutic regimen. Survival probability was estimated by the Kaplan-Meier method. Comparisons were made using the X2 test and Fisher's exact test, where appropriate. Results: A total of 88 patients were identified. Median age was 55 (range 20-74). Eighty percent of patients received a BEAM – like conditioning regimen (Carmustine, Etoposide, Cytarabine, and Melphalan). Thirty-five patients were in complete remission at the time of transplant. Median follow up for surviving patient was 5.8 years (range 139 days -12.5 years). The median overall survival for all patients was 5.2 years (range of 15 days-12.5 years). In total, 51 patients died (58%); 31 of these deaths were related to DLBCL (61%). Median progression free survival was not reached. Thirty-five patients relapsed following ASCT. Of these, 89% relapsed < 3 years from ASCT (early relapse), 2 of whom remain alive. Only 4 patients (11%) relapsed ≥ 3 years from ASCT (late relapse), 2 of whom died, and 2 of whom remain alive. Of the deaths, 1 was lymphoma-related, and 1 was death from graft versus host disease in a patient undergoing subsequent allogeneic transplant. Median time to progression in the entire cohort was 167 days. Consistent with early studies, the presence of disease status prior to ASCT was associated with shorter time to progression, p=0.0028 by Fisher's exact test. Conclusions: Ours is one of few series examining late relapses following ASCT performed for relapsed and refractory DLBCL in the rituximab era. In this cohort, late relapses following ASCT for relapsed and refractory DLBCL occurred infrequently. Our data indicate that for the few patients relapsing beyond 3 years, there is a suggestion of long-term disease control. ![Figure 1:][1] Figure 1: Disclosures No relevant conflicts of interest to declare. [1]: pending:yes
Guiding Moral Behavior Through a Reflective Learning Practice

Reflective learning practice embedded across the business curriculum is a powerful way to equip students with intentionally formed moral habits of the mind and heart. This article explores why and ...
Student Perceptions: The Test of Spatial Contiguity and Gestures for Robot Instructors

Multimedia lessons have the potential to foster deeper understanding and knowledge. The way a robot instructor presents material and uses gestures likely impacts the perception students have toward the robot. We present preliminary data of students' (N=30) perceptions (i.e., social presence, personality, and method of instruction) of a robot instructor that applies spatial contiguity through the use of gestures. We conducted a between-subjects study with three conditions (no robot, robot without gestures, and robot with gestures). Students had the more positive perceptions of the robot with gestures and the less positive perceptions of the robot without gestures. Future work will include a larger sample size and investigate the impact on learning and retention.
Extraterritorial Prosecution, the Late Capitulations, and the New International Lawyers

This contribution considers the international debate among legal specialists on the status of the so-called ‘capitulations’ sparked by the ‘Joris affair’. Joris’s trial and incarceration revealed the inconsistencies and ambiguities of the legal system governing the status of foreign subjects in the Ottoman domains. The influential Belgian expert on international law Alberic Rolin argued for the extradition of Joris to the Belgian judiciary based on the Belgian-Ottoman treaty of 1838. The fact that Belgium was a small and relatively ‘powerless’ nation encouraged Ottoman legal scholars to respond without risking entrapment in major political or diplomatic incidents. Rolin’s position met with serious criticism from the Ottoman Gabriel Noradounghian and others in the growing community of international lawyers. The Joris affair incited debate about the access of ‘non-Christian’ states to the civilized international community of nations. The chapter situates this episode in two broader, interlocking legal histories: that of the capitulations, which were drawing to a close at the beginning of the 20th century, and that of international law in the modern state system, which was in the midst of its precipitous ascent.
Review: In primary prevention, BP-lowering treatment reduces major CV events in patients with SBP ≥ 140 mm Hg.

Source Citation Brunstrom M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA I...
Roles of Vitamin Metabolizing Genes in Multidrug-Resistant Plasmids of Superbugs

Superbug crisis has rocked this world with million deaths due to failure of potent antibiotics. Thousands mdr genes with hundreds of mutant isomers are generated. Small integrons and R-plasmids have combined with F9-plasmids creating a space for >10-20 of mdr genes that inactivate antibiotics in different mechanisms. Mdr genes are created to save bacteria from antibiotics because gut microbiota synthesize >20 vitamins and complex bio-molecules needed for >30000 biochemical reactions of human metabolosome. In other words, mdr gene creation is protected from both sides, intestinal luminal cells and gut bacteria in a tight symbiotic signalling system. We have proposed, to avert the crisis all vitamin metabolizing genes will be acquired in MDR-plasmids if we continue oral antibiotics therapy. Therefore, we have checked the plasmid databases and have detected thiamine, riboflavin, folate, cobalamine and biotin metabolizing enzymes in MDR plasmids. Thus vit genes may mobilise recently into MDR-plasmids and are likely essential for gut microbiota protection. Analysis found that cob and thi genes are abundant and likely very essential than other vit genes.
In Search of Mobile Applications for Urogynecology Providers.

INTRODUCTION Thousands of medical applications (apps) are available for mobile devices. Finding accurate, health care provider-centered apps may be time consuming and frustrating for urogynecologists. The objective of this study was to identify and evaluate urogynecology (urogyn) apps using a modified APPLICATIONS scoring system. MATERIALS AND METHODS Urogyn apps were identified from the Apple iTunes and Google Play Stores using the following 10 MeSH terms: urogynecology, incontinence, prolapse, urinary tract infection, pelvic surgery, fecal incontinence, defecation disorder, voiding disorder, urethral diverticulum, and fistula. Patient-centered and inaccurate apps were excluded. The remaining apps were evaluated with a modified APPLICATIONS scoring system, which included both objective and subjective criteria to determine each app's ability to aid in clinical decision making and to provide informational data. Objective rating components were price, paid subscription, literature referenced, in-app purchases, Internet connectivity, advertisements, text search field, interplatform compatibility and incorporated images, figures, videos, and special features. Subjective rating components were ease of navigation and presentation. RESULTS Our search yielded 133 and 235 apps in the Apple iTunes and Google Play Stores, respectively. Only 8 apps (4 of which were in both stores) were determined to be accurate and useful; these were evaluated using the modified APPLICATIONS scoring system. The top-rated app was Practical Urology. CONCLUSION Few accurate clinical decision-making and informational apps exist for urogynecologists. Apps varied by comprehensiveness and quality. This study highlights the importance of systematically reviewing and rating medical apps. It also emphasizes the need for developing accurate apps for urogynecologists that improve health care provider performance and patient outcomes.
Real-Time case-based reasoning for interactive digital entertainment

User-generated content is everywhere: photos, videos, news, blogs, art, music, and every other type of digital media on the Social Web. Games are no exception. From strategy games to immersive virtual worlds, game players are increasingly engaged in creating and sharing nearly all aspects of the gaming experience: maps, quests, artifacts, avatars, clothing, even games themselves. Yet, there is one aspect of computer games that is not created and shared by game players: the AI. Building sophisticated personalities, behaviors, and strategies requires expertise in both AI and programming, and remains outside the purview of the end user. To understand why authoring Game AI is hard, we need to understand how it works. AI can take digital entertainment beyond scripted interactions into the arena of truly interactive systems that are responsive, adaptive, and intelligent. I will discuss examples of AI techniques for character-level AI (in embedded NPCs, for example) and game-level AI (in the drama manager, for example). These types of AI enhance the player experience in different ways. The techniques are complicated and are usually implemented by expert game designers. I propose an alternative approach to designing Game AI: Real-Time CBR. This approach extends CBR to real-time systems that operate asynchronously during game play, planning, adapting, and learning in an online manner. Originally developed for robotic control, Real-Time CBR can be used for interactive games ranging from multiplayer strategy games to interactive believable avatars in virtual worlds. As with any CBR technique, Real-Time CBR integrates problem solving with learning. This property can be used to address the authoring problem. I will show the first Web 2.0 application that allows average users to create AIs and challenge their friends to play them—without programming. I conclude with some thoughts about the role of CBR in AI-based Interactive Digital Entertainment.
Synchrotron X-ray Scanning Tunneling Microscopy: A Novel Approach for the Nanoscale Characterization of Functional Magnetic Materials with Chemical Contrast

The real-space observation of magnetic structure using scanning probe microscopy (SPM) methods or synchrotron-based microscopy continues to have a tremendous impact on our understanding of functional magnetic materials. However, although SPM methods provide high spatial resolution, they lack direct chemical contrast and the ability to quantify magnetic moments. X-ray microscopy, on the other hand, can provide chemical as well as magnetic sensitivity, but the spatial resolution is limited.
A National Evaluation of Scholarly Activity Requirement in Osteopathic EM Residency Programs: Survey of EM Program Directors.

OBJECTIVES The objectives of the study were to determine the percentage of osteopathic emergency medicine (EM) residencies that require an original research project to meet the American Osteopathic Association requirement, describe the resources available to the residents and faculty members to complete their projects, and determine resident and faculty research productivity. METHODS This was a cross-sectional online survey of program directors from osteopathic EM residency programs. Participants were asked about demographics and specifics related to their program's research curriculum, which included resources, outcomes, and challenges. RESULTS The response rate was 48.21% (27/56) of program directors from EM residencies. The majority (82.77%) of respondents were from a community-based EM program, had a requirement that a research project be completed before graduation from residency (87.5%), and did not have a research associate program to assist in recruiting patients (83.33%). A physician research director was noted to lead the department in 53.57% of respondents, whereas 70.83% noted having a statistician on staff. A total of 2.91% of program faculty had received federal grant funding, and 13.88% had a research study indexed in PubMed. EM programs that had a physician-led research director were more likely to have core faculty with federal funding, articles indexed in PubMed, residents who submit their research for publication, and residents with competitive grants, as compared with programs without a research director. Program directors noted that analyzing data, designing a study, and generating a hypothesis were the biggest challenges to conducting research in the residency. CONCLUSIONS Osteopathic EM residencies significantly differ from their allopathic counterparts in their research curriculum, capabilities, and outcomes.
CRISPR genomic screening informs gene–environment interactions

Abstract Gene–environment interactions impact the adverse health effects of environmental exposure to toxicants. Identification of genetic factors modulating organismal and cellular response to environmental toxicants can inform risk assessment. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)–based genetic perturbation screening has recently emerged as a powerful approach to illuminate complex cellular processes including mechanisms modulating chemical toxicity. Here, we review key studies that demonstrate the utility of CRISPR screens in deciphering the molecular determinants of sensitivity and tolerance to toxic substances. We reflect on key considerations for implementing a CRISPR screen in toxicology. We also discuss computational methods used for analyzing CRISPR screens and strategies for validating screening results. Finally, we highlight potential future directions to address limitations in CRISPR screening approaches as applied to toxicology.
Fungal Enzymes, Plant Cell Wall Fragments, and Plant Cell Death — A Possible Mechanism for Hypersensitivity in the Rice Blast System

The hypersensitive response is a commonly observed phenomenon in plant pathology (Tomiyama et al 1979). A plant, when challenged by a microbe that is either a species that is not a pathogen of that plant or an incompatible race of a species that is a pathogen of other cultivars of the plant, commonly exhibits a hypersensitive resistance response, which is phenotypically observed as the rapid necrosis of one or a few plant cells at the site of attempted infection. This necrosis is presumed to result in processes that limit the spread of the pathogen.
Sexual and Reproductive Health and Rights

This chapter follows the arguments of women’s health movements surrounding the conflicts between the sexual and reproductive rights of individual women and the social groups to which they belong, on the one hand, and religious dogma and national and international population policies, on the other hand. Provocative aspects discussed are population dynamics, birth control and contraception, and sterilization and abortion. The second part of the chapter takes up issues of infertility and surrogacy. With the advent of new reproductive technologies, women’s groups are questioning the commercialization of the field and their rights in relation to gender and biology and the commodification of body parts. These conflicts are playing out against a backdrop of dramatic economic, social, political, climatic, and demographic changes worldwide.
Palliative care knowledge, information sources, and beliefs: Results of a national survey of adults in the USA.

OBJECTIVE Despite its established benefits, palliative care (PC) is not well known among patients and family/caregivers. From a nationally representative survey, we sought to assess the following associated with PC: knowledge, knowledge sources, and beliefs. METHODS Data were drawn from the Health Information National Trends Study (HINTS 5 Cycle 2), a cross-sectional, survey of non-institutionalized adults aged 18+ years in the USA. Data were weighted and assessed by proportional comparison and multivariable logistic regression. RESULTS A total of 3504 respondents were identified, and approximately 29% knew about PC. In the adjusted model, less PC knowledge was associated with: lower age (those aged <50), male gender, lower education (<high school graduation or high school graduate), and non-internet users. A little over half (55%) of respondents accessed healthcare providers first for PC information, and 80% considered providers the most trusted source of PC information. Most of the participants strongly/somewhat agreed that the goal of PC is to help friends and family cope with a patient's illness (90.6%), offer social and emotional support (93.4%), and manage pain and other physical symptoms (95.1%). Similarly, a majority (83.3%) strongly/somewhat agreed that it is a doctor's obligation to inform all patients with cancer about the option of PC. SIGNIFICANCE OF RESULTS PC knowledge was generally low (1-in-3 respondents knew of PC), with significant differences according to age, gender, education, and internet use. These data provide a baseline from which PC education policies and interventions may be measured.
Impacts of interest rate caps on the payday loan market: Evidence from Rhode Island

Abstract Interest rate caps are the most common form of payday loan regulation, yet little academic research has examined their consequences. I investigate the impacts of tightening the cap from 15% to 10% in Rhode Island, using a difference-in-difference framework and a unique proprietary dataset of payday loans issued by major nationwide lenders between 2009 and 2013. Lenders always charge the prevailing cap, creating a sharp and clean variation in interest rate. I show that loan usage increases at the extensive and intensive margins, amounting to elasticity estimates in the range of 0.7–1.0. I also find that loan sequences become longer and more likely to end with default. No lenders exit the market, implying that market power existed. Furthermore, I find no evidence of credit rationing as a result of the lower cap. These changes imply an upper bound of $3.3 million per year for neoclassical consumer surplus. However, I show that behavioral consumers can be worse off by the policy if more than half of the increase in demand is due to overborrowing.
A Contrarian View of Ownership Concentration in the United States and Around the World

This paper offers evidence on the ownership concentration at a representative sample of U.S. firms. 96% of these firms have blockholders who in aggregate own 39% of the common stock. The ownership of U.S. firms is at least as concentrated, and by some measures more concentrated, than the ownership of firms in other countries. Such concentrated ownership is consistent with a fundamental property right of a market economy, which is that owners are active. These findings challenge current thinking on a number of issues.
High-Performance, Bio-Based, Jet Fuel Blends Containing Hydrogenated Monoterpenes and Synthetic Paraffinic Kerosenes

Three biorenewable monoterpenes, α-pinene, limonene, and sabinene, were hydrogenated to generate cycloalkane blendstocks. The saturated terpenes, along with the high density multicyclic fuels JP-10...
Thermal Debugging Tool for Servers

Among the different possible random causes of failure in server clusters, temperature variability inside the server's chassis is the most common/relevant variable. Random failures are difficult to isolate, which makes it difficult to find the root cause and debug it. At the silicon level, the experience shows that process, voltage, and temperature (PVT) variations are the most relevant variables that are used to replicate issues, since such variables increase the failure probability, which allows to understand and speed up the failure mechanism of a given problem. When random problems happen in server cluster environments at a customer data center, the debug in the validation laboratory becomes a challenging task since it is difficult to reproduce the conditions that triggers the problem. With this in mind, this paper shows a methodology that focus in one of these variables, temperature, to apply controlled and located variations at the system level to expedite the replication of thermal issues and to perform validation for commercial platforms.
Beclin 1–ATG14L Protein–Protein Interaction Inhibitor Selectively Inhibits Autophagy through Disruption of VPS34 Complex I

Autophagy, a catabolic recycling process, has been implicated as a critical pathway in cancer. Its role in maintaining cellular homeostasis helps to nourish hypoxic, nutrient-starved tumors and protects them from chemotherapy-induced death. Recent efforts to target autophagy in cancer have focused on kinase inhibition, which has led to molecules that lack specificity due to the multiple roles of key kinases in this pathway. For example, the lipid kinase VPS34 is present in two multiprotein complexes responsible for the generation of phosphatidylinositol-3-phosphate. Complex I generates the autophagosome, and Complex II is crucial for endosomal trafficking. Molecules targeting VPS34 inhibit both complexes, which inhibits autophagy but causes undesirable defects in vesicle trafficking. The lack of specific autophagy modulators has limited the utility of autophagy inhibition as a therapeutic strategy. We hypothesize that disruption of the Beclin 1-ATG14L protein-protein interaction, which is required for the formation, proper localization, and function of VPS34 Complex I but not Complex II, will disrupt Complex I formation and selectively inhibit autophagy. To this end, a high-throughput, cellular NanoBRET assay was developed targeting this interaction. An initial screen of 2560 molecules yielded 19 hits that effectively disrupted the interaction, and it was confirmed that one hit disrupted VPS34 Complex I formation and inhibited autophagy. In addition, the molecule did not disrupt the Beclin 1-UVRAG interaction, critical for VPS34 Complex II, and thus had little impact on vesicle trafficking. This molecule is a promising new tool that is critical for understanding how modulation of the Beclin 1-ATG14L interaction affects autophagy. More broadly, its discovery demonstrates that targeting protein-protein interactions found within the autophagy pathway is a viable strategy for the discovery of autophagy-specific probes and therapeutics.
Radiographic patterns of first disease recurrence after neoadjuvant therapy and surgery for patients with resectable and borderline resectable pancreatic cancer

Abstract Background More than 70% of patients with localized pancreatic cancer treated with upfront surgery develop disease recurrence. Herein we describe the radiographic patterns and timing of disease recurrence after neoadjuvant therapy and surgery in patients with pancreatic cancer. Methods Radiographic patterns of first disease recurrence were examined in patients with localized pancreatic cancer who completed neoadjuvant therapy and surgery. Disease recurrence was classified as local (pancreas, resection bed, or peripancreatic vasculature); regional (peritoneum or abdominal wall); or distant (liver, lung, bone). Progression-free survival was calculated from the date of diagnosis to the date of recurrence. Results Of 306 consecutive patients who completed neoadjuvant therapy and surgery, 149 (49%) had resectable pancreatic cancer and 157 (51%) had borderline resectable disease. Neoadjuvant therapy consisted of chemoradiation (32%), chemotherapy (14%), or both therapies (54%). Overall, primary therapy (including preoperative and postoperative therapy) consisted of chemoradiation alone in 29 (9%), chemotherapy alone in 14 (5%), and both therapies in 263 (86%) patients. At a median follow-up of 27 months, 186 (61%) of the 306 patients had recurrent pancreatic cancer. Sites of first recurrence were local-only in 29 (9%), regional-only in 19 (6%), distant-only in 87 (28%), and multisite in 51 (17%). The overall median progression-free survival for all patients was 24 months. Neoadjuvant chemoradiation reduced the odds of local-only recurrence (odds ratio: 0.21; 95% confidence interval: 0.06–0.77; P = .02). Conclusion After neoadjuvant therapy and surgery, 9% of patients were found to have local-only recurrence. Treatment sequencing that incorporates neoadjuvant chemoradiation may improve local disease control.
Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes

Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple HH/Gli mouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is required to support Sox9+ chondrocyte progenitors and 2) a dramatic reduction in Rspo2, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal a HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.
Accelerating ophthalmic artificial intelligence research: the role of an open access data repository.

Purpose of review Artificial intelligence has already provided multiple clinically relevant applications in ophthalmology. Yet, the explosion of nonstandardized reporting of high-performing algorithms are rendered useless without robust and streamlined implementation guidelines. The development of protocols and checklists will accelerate the translation of research publications to impact on patient care. Recent findings Beyond technological scepticism, we lack uniformity in analysing algorithmic performance generalizability, and benchmarking impacts across clinical settings. No regulatory guardrails have been set to minimize bias or optimize interpretability; no consensus clinical acceptability thresholds or systematized postdeployment monitoring has been set. Moreover, stakeholders with misaligned incentives deepen the landscape complexity especially when it comes to the requisite data integration and harmonization to advance the field. Therefore, despite increasing algorithmic accuracy and commoditization, the infamous 'implementation gap' persists. Open clinical data repositories have been shown to rapidly accelerate research, minimize redundancies and disseminate the expertise and knowledge required to overcome existing barriers. Drawing upon the longstanding success of existing governance frameworks and robust data use and sharing agreements, the ophthalmic community has tremendous opportunity in ushering artificial intelligence into medicine. By collaboratively building a powerful resource of open, anonymized multimodal ophthalmic data, the next generation of clinicians can advance data-driven eye care in unprecedented ways. Summary This piece demonstrates that with readily accessible data, immense progress can be achieved clinically and methodologically to realize artificial intelligence's impact on clinical care. Exponentially progressive network effects can be seen by consolidating, curating and distributing data amongst both clinicians and data scientists.
A Redescription of Eriphostoma microdon Broom, 1911 (Therapsida, Gorgonopsia) from the Tapinocephalus Assemblage Zone of South Africa and a Review of Middle Permian Gorgonopsians

The problematic Tapinocephalus Assemblage Zone (AZ) theriodont Eriphostoma microdon Broom, 1911 is redescribed based on computed tomographic images of the type and only known specimen. Eriphostoma is identified as a gorgonopsian, one of the few representatives of this clade known from the Middle Permian. Eriphostoma microdon represents a valid taxon diagnosed by the combination of elongate delta-shaped palatine bosses with numerous small teeth and a short, downward-sloping snout. Among gorgonopsians, Eriphostoma is most similar to Gorgonops torvus, but can be distinguished from that taxon by a trough separating the palatal bosses, relatively larger fossa for the lower canine, relatively shorter, taller snout, and mediolaterally thinner premaxilla at its posterior alveolar margin. Other nominal gorgonopsian taxa from the Tapinocephalus AZ exhibit the same general cranial morphology as Eriphostoma, suggesting that most are synonymous. Additional preparation and study of these other taxa will be necessary before their synonymy can be confirmed, however.
Application of Cooperative Game Theory Principles to Interpret Machine Learning Models of Nonhome Discharge Following Spine Surgery.

STUDY DESIGN Retrospective analysis of prospectively acquired data. OBJECTIVE The aim of this study was to identify interaction effects that modulate nonhome discharge (NHD) risk by applying coalitional game theory principles to interpret machine learning models and understand variable interaction effects underlying NHD risk. SUMMARY OF BACKGROUND DATA NHD may predispose patients to adverse outcomes during their care. Previous studies identified potential factors implicated in NHD; however, it is unclear how interaction effects between these factors contribute to overall NHD risk. METHODS Of the 11,150 reviewed cases involving procedures for degenerative spine conditions, 1764 cases (15.8%) involved NHD. Gradient boosting classifiers were used to construct predictive models for NHD for each patient. Shapley values, which assign a unique distribution of the total NHD risk to each model variable using an optimal cost-sharing rule, quantified feature importance and examined interaction effects between variables. RESULTS Models constructed from features identified by Shapley values were highly predictive of patient-level NHD risk (mean C-statistic = 0.91). Supervised clustering identified distinct patient subgroups with variable NHD risk and their shared characteristics. Focused interaction analysis of surgical invasiveness, age, and comorbidity burden suggested age as a worse risk factor than comorbidity burden due to stronger positive interaction effects. Additionally, negative interaction effects were found between age and low blood loss, indicating that intraoperative hemostasis may be critical for reducing NHD risk in the elderly. CONCLUSION This strategy provides novel insights into feature interactions that contribute to NHD risk after spine surgery. Patients with positively interacting risk factors may require special attention during their hospitalization to control NHD risk.Level of Evidence: 3.
Epidemiology and Diagnosis of Neuroendocrine Tumors

Neuroendocrine tumors (NETs) constitute a group of malignancies arising from neuroendocrine precursor cells that can arise anywhere in the body. The incidence and prevalence of NETs have steadily increased over the past four decades. Given their heterogeneous and often indolent presentation, the initial diagnosis of NETs can be challenging. In this chapter, we provide a comprehensive overview on the epidemiology and diagnosis of NETs.
Anger, Emotional Expressivity and Psychological Well-Being in Sports Players

The objective of the present study is to observe whether there is a difference between boys and girls engaged in Instrumental Aggression Sports and those engaged in Hostile Aggression Sports with respect to anger, emotional expressivity and psychological well-being and to observe whether there is a relationship between these variables. A non-probability purposive sampling method was used to select a sample of 160 sports players, among whom 80 (40 boys and 40 girls) were engaged in instrumental aggression sports and 80 (40 boys and 40 girls) were engaged in hostile aggression sports. The Multidimensional Anger Inventory (Siegel, 1986), Berkeley Expressivity Questionnaire (Gross, & John, 1998) and Psychological Well Being Scale (Ryff& Keyes, 1995) were administered to the participants. The results showed significant gender differences with respect to the dimension of anger arousal (p
A mutational gradient drives somatic mutation accumulation in mitochondrial DNA and influences germline polymorphisms and genome composition

Abstract Background Mutations in the mitochondrial genome (mtDNA) can cause devastating maternally inherited diseases, while the accumulation of somatic mtDNA mutations is linked to common diseases of aging. Although mtDNA mutations impact human health, the process(es) that give rise to these mutations are unclear and are under considerable debate. We analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing to provide clues to the mechanism by which de novo mutations arise as well as how the genome is replicated. Results We observe two distinct mutational gradients in G→A and T→C transitions, but not their complements, that are delimited by the light-strand origin and the control region (CR). The gradients increase with age and are lost in the absence of DNA polymerase γ proofreading activity. A nearly identical pattern is present in human mtDNA somatic mutations. The distribution of mtDNA single nucleotide polymorphisms (SNPs) in the human population and genome base composition across >3,000 vertebrate species mirror this gradient pattern, pointing to evolutionary conservation of this phenomenon. Lastly, high-resolution analysis of the mtDNA control region highlights mutational ‘hot-spots’ and ‘cold-spots’ that strongly align with important regulatory regions. Conclusions Collectively, these patterns support an asymmetric strand-displacement mechanism with key regulatory structures in the CR and argue against alternative replication models. The mutational gradient is a fundamental consequence of mtDNA replication that drives somatic mutation accumulation and influences inherited polymorphisms and, over evolutionary timescales, genome composition.
The Gym Membership Purchase Task: Early Evidence Towards Establishment of a Novel Hypothetical Purchase Task

Hypothetical purchase tasks are a widely used tool to determine the reinforcing value of commodities, especially commodities which are difficult to deliver experimentally. Amazon Mechanical Turk users (N = 375) completed two novel hypothetical purchase tasks (quantity of purchase and probability of purchase) and other measures to estimate how much an individual values the opportunity to exercise in a gym. We examined correlations between demand indices generated by each task and measures related to physical activity. In addition, we compared rates of systematic and nonsystematic responding between the two tasks. Exploratory analyses of demand indices and measures of physical activity suggest initial evidence of construct validity for each task. When accounting for an order effect, the probability of purchase task generated significantly lower rates of nonsystematic responding compared to the quantity of purchase task (2.87% vs. 14.6%, respectively). We discuss how these results may inform improved construction of future hypothetical purchase tasks and implications for using likelihood and quantity purchase tasks.
The spectrum of clinical sequelae associated with alpha-1 antitrypsin deficiency:

Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of lung disease, primarily emphysema. Emphysema results from the breakdown of lung matrix elastin by proteases, including neutrophil elastase, a protease normally inhibited by AAT. AATD also predisposes to liver (cirrhosis) and skin (panniculitis) disease, and to vasculitis. The prevalence of AATD is estimated to be approximately 1 in 3,500 individuals in the United States. However, lack of awareness of AATD among some physicians, misperceptions regarding the absence of effective therapy, and the close overlap in symptoms with asthma and non-AATD chronic obstructive pulmonary disease are thought to contribute to under-recognition of the disease. In patients with AATD, treatment with intravenous AAT augmentation therapy is the only currently available treatment known to slow the progression of emphysema. Moreover, smoking cessation and other lifestyle interventions also help improve outcomes. Early diagnosis and intervention are of key importance due to the irreversible nature of the resultant emphysema. Liver disease is the second leading cause of death among patients with AATD and a minority of patients present with panniculitis or antineutrophil cytoplasmic antibody-associated vasculitis, thought to be directly related to AATD. Though no randomized trial has assessed the effectiveness of augmentation therapy for AATD-associated panniculitis, clinical experience and case series suggest there is a benefit. Other diseases putatively linked to AATD include aneurysmal disease and multiple neurological conditions, although these associations remain speculative in nature.
Energy in Focus

Editor-in-Chief Sean Shaheen reflects on the role of JPE in advancing critical technologies toward rapid realization of large-scale change in global energy systems.
Elaborated thermochemical treatment of HF, CO, N2, and H2O: Insight into HEAT and its extensions

Empirical, highly accurate non-relativistic electronic total atomization energies (eTAEs) are established by combining experimental or computationally converged treatments of the nuclear motion and relativistic contributions with the total atomization energies of HF, CO, N2, and H2O obtained from the Active Thermochemical Tables. These eTAEs, which have estimated (2σ) uncertainties of less than 10 cm−1 (0.12 kJ mol−1), form the basis for an analysis of high-level ab initio quantum chemical calculations that aim at reproducing these eTAEs for the title molecules. The results are then employed to analyze the performance of the high-accuracy extrapolated ab initio thermochemistry, or High-Accuracy Extrapolated Ab Initio Thermochemistry (HEAT), family of theoretical methods. The method known as HEAT-345(Q), in particular, is found to benefit from fortuitous error cancellation between its treatment of the zero-point energy, extrapolation errors in the Hartree-Fock and coupled cluster contributions, neglect of post-(T) core-correlation, and the basis-set error involved in higher-level correlation corrections. In addition to shedding light on a longstanding curiosity of the HEAT protocol—where the cheapest HEAT-345(Q) performs comparably to the theoretically more complete HEAT-456QP procedure—this study lays the foundation for extended HEAT variants that offer substantial improvements in accuracy relative to the established approaches.
Risk factors for wound morbidity after open retromuscular (sublay) hernia repair

Background Retrorectus repairs (RR) of abdominal wall hernias are growing in popularity, yet wound morbidity and predictors in this context have been characterized poorly. Models aimed at predicting wound morbidity typically do not control for technique and/or location of mesh. Our aim was to describe wound morbidity and risk factors specifically in the context of RR hernia repair. Our hypothesis was that the incidence of wound morbidity with mesh sublay would be less than predicted by a model that does not control for mesh position. Methods Consecutive RR hernia repairs with at least a 90-day follow-up were identified in our prospective database and analyzed. The primary outcome measures were the incidence of surgical-site occurrence (SSO) and surgical-site infection (SSI) via modern, standardized definitions. For predictors of SSO, statistical analysis was performed with univariate analysis, χ2, and logistic regression as well as multivariate regression. Results A total of 306 patients met the inclusion criteria. Eighty-four SSOs identified in 72 (23.5%) patients included 48 (15.7%) SSIs, 14 (4.6%) instances of wound cellulitis, 12 (3.9%) skin dehiscences, 6 (2.0%) seromas, and 4 (1.3%) hematomas but no instances of mesh excision or fistula formation. Treatment entailed antibiotics alone in 30 patients, 14 bedside drainage procedures, 9 radiographically assisted drainage procedures, and 10 returns to the operating room for debridement. After multivariate analysis, diabetes (OR 2.41), hernia width >20 cm (OR 2.49), and use of biologic mesh (OR 2.93) were statistically associated with the development of a SSO (P Conclusion Based on a large cohort of patients, we identified factors contributing to SSOs specifically for RR hernia repairs. Paradoxically, biologic mesh was an independent predictor of wound morbidity. The development of clinically important mesh complications and rates of wound morbidity less than anticipated by recent predictive models suggest that the retromuscular (sublay) mesh position may be more advantageous.
Parenteral Infusion of a Lactating Woman with Intralipid

A nursing woman afflicted with short bowel syndrome received parenteral infusions of Intralipid. In the morning following 2 nights of infusion, samples of milk and blood were taken; additional samples were taken the morning after 1 and 2 nights of no infusion. The fatty acid composition of these samples was determined by gas chromatography. The Intralipid infusion contained 51.5% linoleic acid (C18:2). The C18:2 content of the milk was highest (14%) after each infusion and dropped to about 10% on days 1 and 2. Inverse changes were seen in stearic acid (C18:0). The C18:2 content of the plasma showed little change, remaining at about 23%. These results provide further direct evidence that the composition of milk fatty acids can be influenced by changes in the composition of external sources of fatty acids to the lactating mother.
A Characterization of Minimalist Languages

In this paper we will fix the position of Minimalist Grammars as defined in Stabler (1997) in the hierarchy of formal languages. Michaelis (1998) has shown that the set of languages generated by Minimalist Grammars is a subset of the set of languages generated by Multiple Context-Free Grammars (Seki et al., 1991). In this paper we will present a proof showing the reverse. We thus conclude that Minimalist Grammars are weakly equivalent to Multiple Context-Free Grammars.
Food habits of pumas in northwestern Sonora, Mexico

It is questionable whether food-habits studies of pumas conducted in the southwestern United States can be extrapolated to northwestern Mexico, because of differences in management, distribution, and abundance of wildlife. We determined food habits of pumas (Puma concolor) in the Sonoran Desert of northwestern Sonora, Mexico. Based on studies in the western United States, we hypothesized that desert mule deer (Odocoileus hemionus) were the major food source of pumas in Sonoran Desert habitats of Mexico. The study area supports populations of desert mule deer, white-tailed deer (Odocoileus virginianus), Iagomorphs (Lepus spp. and Sylvilagus audubonii), collared peccary (Pecari tajacu), and the largest population (∼300 individuals) of desert bighorn sheep (Ovis canadensis) in Sonora. Based on pugmark characteristics, we recorded 3 different adult resident pumas in approximately 90 km 2 . We analyzed 60 puma fecal samples collected September 1996-November 1998. Primary prey items based on frequency of occurrence and estimated biomass consumed were desert bighorn sheep (40% and 45%, respectively), lagomorphs (33%, 19%), deer (17%, 17%), and collared peccary (15%, 11%). The high percentage of desert bighorn sheep in puma diets may be due to high abundance relative to mule deer, which declined in number during our study. No differences were found in puma diets between seasons (Χ 2 2=2.4526, P=0.2934). Fluctuations in mule deer populations in northwestern Sonora may influence prey selection by pumas.
The Streptomyces glaucescens TcmR protein represses transcription of the divergently oriented tcmR and tcmA genes by binding to an intergenic operator region.

Abstract Preliminary evidence has been presented by Guilfoile and Hutchinson (J. Bacteriol. 174:3651-3658, 1992) suggesting that the Streptomyces glaucescens TcmR protein is a transcriptional repressor. Here, we extend that work by showing that transcription of the S. glaucescens tcmA gene is inducible by tetracenomycin C and that inactivation of the tcmR gene results in constitutive transcription of the tcmA gene. Gel retardation studies show that the TcmR protein binds to the tcmA-tcmR intergenic region in vitro and that this binding is inhibited by tetracenomycin C. Footprinting experiments demonstrate that the TcmR protein binds to an operator region that encompasses both the tcmA and the tcmR promoters. This genetic and biochemical evidence strongly supports the model of the TcmR protein acting as a repressor in inhibiting transcription of both the tcmA and the tcmR genes, in much the same way that TetR from Tn10 inhibits transcription of tetA and tetR.
Real-time seismic monitoring and functionality assesment of a building

This paper presents recent developments and approaches (using GPS technology and real-time double-integration) to obtain displacements and, in turn, drift ratios, in real-time or near real-time to meet the needs of the engineering and user community in seismic monitoring and assessing the functionality and damage condition of structures. Drift ratios computed in near real-time allow technical assessment of the damage condition of a building. Relevant parameters, such as the type of connections and story structural characteristics (including geometry) are used in computing drifts corresponding to several pre-selected threshold stages of damage. Thus, drift ratios determined from real-time monitoring can be compared to pre-computed threshold drift ratios. The approaches described herein can be used for performance evaluation of structures and can be considered as building health-monitoring applications.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
An H 2 O flare in W49N

We monitored the 22-GHz water vapor emission from W49N using a single VLBA antenna on intervals of a few days to about a week from December 1989 through May 1990. During this period, a strong flare occurred in one of the spectral features. This feature increased in flux density by a factor of ≳20 over a period of approximately 30 days. Line narrowing accompanied the rise in flux density; the decrease in linewidth with flux density follows the power law ΔV ∝ F−0.22
The GDB™ Human Genome Database Anno 1997

The value of the Genome Database (GDB) for the human genome research community has been greatly increased since the release of version 6. 0 last year. Thanks to the introduction of significant technical improvements, GDB has seen dramatic growth in the type and volume of information stored in the database. This article summarizes the types of data that are now available in the Genome Database, demonstrates how the database is interconnected with other biomedical resources on the World Wide Web, discusses how researchers can contribute new or updated information to the database, and describes our current efforts as well as planned improvements for the future.