cssi/SciSciGPT-SciSciNet huggingface dataset:
OHM3597: A novel fentanyl derivative with morphine‐like behavioral effects in rhesus monkeys

OHM3597, a fentanyl-like piperidine with a thalidomide-like moiety, was studied in rhesus monkeys for its behavioral effects and for its effects on lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)-α, OHM3597 had morphine-like discriminative stimulus effects that were antagonized by naltrexone in a manner that was consistent with μ receptor mediation. OHM3597 also had antinociceptive effects, producing a maximal (20 sec) antinociceptive effect in a tail withdrawal procedure with a 50°C stimulus. This effect of OHM3597 also was antagonized by naltrexone in a dose-related manner. Behavioral effects of this fentanyl derivative had a rapid onset and a relatively short duration of action; discriminative stimulus effects were evident 3 min after subcutaneous (sc) administration of 0.32 mg (0.58 μM)/kg of OHM3597 and the duration of antinociceptive effects produced by 1.0 mg (1.6 μM)/kg (sc) was less than 90 min. OHM3597 also was compared to thalidomide for its effects on LPS-induced TNF-α production in peripheral blood mononuclear cells that were obtained from drug-naive rhesus monkeys. Thalidomide suppressed the production of TNF-α in a concentration-dependent manner with concentrations of 10 nM and 1 μM of thalidomide decreasing TNF-α levels to 81 and 65%, respectively, of control (saline) values. In contrast, up to a concentration of 1 μM, OHM3597 failed to suppress LPS-induced TNF-α production. These results demonstrate OHM3597 to be a potent, morphine-like opioid with a relatively short duration of action. Although OHM3597 did not alter TNF-α production, a compound with both antinociceptive and immunomodulatory effects might be available within this chemical series and could provide a unique approach to the concurrent treatment of pain and infectious disease. © 1995 Wiley-Liss, Inc.
Erratum to:Mass spectrometry and natural variations of iron isotopes

The original article to which this Erratum refers was published in Mass Spectrometry Reviews 25:515–550, 2006. No Abstract.
On the correlation between polarizabilities and molecular dimensions

Abstract A correlation between electric polarizabihty and the mean linear electronic charge density is proposed and shown to exist for some homologous electrically neutral atomic and molecular species. The correlation implies an inverse relationship between molecular dimensions in these species and the charge distortion induced in them by a uniform electric field.
Muscle tension induced after learning enhances long-term narrative and visual memory in healthy older adults

Arousing events are better remembered than mundane events. Indeed, manipulation of arousal, such as by muscle tension, can influence memory even when it occurs shortly after learning. Indeed, our founding study showed this approach can raise delayed memory performance in older adults to a level comparable to that of unaided young adults. Yet, systematic studies, especially those investigating different modalities or types of memory, have not been done. This study investigated the effects of a brief bout of isometric exercise via handgrip on narrative and visuospatial episodic memory in healthy elders. Forty-seven participants completed the Logical Memory subtest of the Wechsler Memory Scales III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no treatment and by moderately squeezing a sand-filled latex ball for 1-min (counterbalanced order and test forms). Isometric exercise significantly increased both positive and negative affect ratings. Retention was tested 2 weeks later. Delayed recall and recognition of LM was enhanced by arousal relative to control, as was recognition of the BVRT. The results extend past findings that muscle tension induced after learning modulates memory consolidation, extending findings in elders to suggest that a simple form of isometric exercise can have practical effects, such as aiding memory for stories and images.
A twin and adoption study of reading achievement: Exploration of shared-environmental and gene–environment-interaction effects

Existing behavior-genetic research implicates substantial influence of heredity and modest influence of shared environment on reading achievement and reading disability. Applying DeFries-Fulker analysis to a combined sample of twins and adoptees (N = 4,886, including 266 reading-disabled probands), the present study replicates prior findings of considerable heritability for both reading achievement and reading disability. A simple biometric model adequately described parent and offspring data (combined N = 9,430 parents and offspring) across differing types of families present in the sample Analyses yielded a high heritability estimate (around 0.70) and a negligible shared-environmentality estimate for both reading achievement and reading disability. No evidence of gene × environment interaction was found for parental reading ability and parental educational attainment, the two moderators analyzed.
MULTIPION PRODUCTION IN DEUTERON--DEUTERON INTERACTIONS AT 7.9 GeV/c.

Pion pair production is studied in the pure state of isospin $T=0$ using the reaction $\mathrm{dd}\ensuremath{\rightarrow}\mathrm{dd}\ensuremath{\pi}\ensuremath{\pi}$ in a bubble chamber experiment. The data are compared in detail with a one-pion-exchange and a Reggeized one-pion-exchange model including proper Bose symmetrization and the effects of the deuteron spin. No additional $\ensuremath{\pi}\ensuremath{\pi}$ interaction is necessary to explain our data. A $\ensuremath{\pi}\ensuremath{\pi}$ mass plot in bins close to our experimental resolution is presented as an incentive for bump hunters.
Sequence-specific Interactions in the Tus-Ter Complex and the Effect of Base Pair Substitutions on Arrest of DNA Replication in Escherichia coli

Arrest of DNA replication in Escherichia coli is mediated by specific interactions between the Tus protein and terminator (Ter) sequences. Binding of Tus to aTer site forms a asymmetric protein-DNA complex that arrests DNA replication in an orientation-dependent fashion. In this study, mutant Ter sites carrying single base pair substitutions at 16 different positions were examined for their ability to bind purified Tus protein and arrest DNA replication.In vitro competition assays demonstrated that base pair substitutions at positions 8–19 had significant effects on the free energy of Tus binding (ΔΔG 0 of 1.5 to >4.0 kcal/mol). Concomitant with loss of binding affinity, mutations at these positions also showed significantly lower or undetectable replication arrest activities in vivo. Substitutions at positions 6, 20, and 21 had moderate effects on Tus-Terinteractions, suggesting that these base pairs contribute to, but are not absolutely critical for, Tus binding. Even though the effects on binding were minimal, these Ter mutants were not as efficient as wild type Tus-TerB complexes at arresting replication forks. Three new potential Ter sites, referred to as TerH, TerI, and TerJ, were identified by searching the E. coli genome for sequence similarity to a consensus Ter site sequence.
Fradicin, an Antifungal Agent Produced by Streptomyces fradiae.∗

SummaryAn antibiotic, designated as fradicin and active only upon fungi, was isolated from the culture filtrate of the neomyein producing Streptomyces fradiae. Fradicin is characterized by an antifungal spectrum, which includes saprophytes as well as plant and animal pathogens. It is stable to 100°C for 30 minutes at pH 7.0. At more acid reactions, it is gradually destroyed. It is soluble in a number of organic solvents and has a characteristic absorption spectrum which differentiates it from other antibiotics.
Haemolymph proteins of Ostrinia nubilalis during diapause and prepupal differentiation

Metabolism during diapause and prepupal differentiation of the European corn borer, Ostrinia nubilalis (Hubner), was evaluated on the basis of changes in fat body proteins. The protein concentration results showed that, although the prepupal titre of about 75 mg/g dry fat body remained fairly constant throughout diapause, an increase and sex difference were detected in postdiapause pharate pupae. In these latter forms the males had a protein titre of 253 ± 14 mg/g dry fat body as compared to the 393 ± 20 mg/g titre of the females. The disk electrophoretic results showed that 10- to 14-day-old larvae had protein patterns composed of about ten anionically migrating bands. By the fifteenth day, however, the larvae were reaching maturity, and a sex difference was apparent. The females developed a high titre of another protein, Rf 13, which was not detectable in males. To determine whether changes occurred during diapause, fat body proteins from short-day and long-day exposed prepupae were compared. The pattern data indicated that, in both sexes, only minor changes occurred during this period. Dramatic changes were not detected until the pupal moulting cycle, characterized by the existence of only two major bands (Rf 12 and 19) in the pharate pupae. Circumstantial evidence suggested that in the female one of these bands (Rf 12) eventually was translocated to the ovary. A study of glucose-6-phosphate and malic dehydrogenase activity of prepupal fat body revealed one and two major bands, respectively, without an ostensible sex difference. These bands appeared in both short-day and long-day exposed prepupae, showing no apparent changes during diapause. The implications of the results are discussed in relation to the metabolic role of the fat body during this period of metamorphosis.
The bowel prep conundrum.

My prior essay in this section dissected recent European work that claimed an amazing surgical-site infection (SSI) prevention benefit of giving patients 80% oxygen by mask for a few hours perioperatively. Its authors proposed that using this simple adjunct halves SSI risk in colorectal operations. Besides addressing some specific methodology concerns, I asserted that the article had dubious impact on me because its authors had not used the “standard of care” in their control and treatment groups. The patients in both arms received no oral nonabsorbed antibiotic agents during preoperative preparation of the colon, but only systemic prophylactic agents. Local comments about my exegesis of the article were sparse. One of our research residents volunteered only that “mentioning your two dogs at the start of the article was cute”. A local surgeon, who casts a rather large shadow both literally and politically, displayed astonishing naivete when he told me that “even if that oxygen work is valid, we will have to do the same number of operations that the article reported before any benefit could occur for our patients.”
Accelerated Ovarian Aging in the Absence of the Transcription Regulator TAF4B in Mice

The mammalian ovary is unique in that its reproductive life span is limited by oocyte quantity and quality. Oocytes are recruited from a finite pool of primordial follicles that are usually exhausted from the ovary during midadult life. If regulation of this pool is perturbed, the reproductive capacity of the ovary is compromised. TAF4B is a gonad-enriched subunit of the TFIID complex required for female fertility in mice. Previous characterization of TAF4B-deficient ovaries revealed several reproductive deficits that collectively result in infertility. However, the etiology of such fertility defects remains unknown. By assaying estrous cycle, ovarian pathology, and gene expression changes in young Taf4b-null female mice, we show that TAF4B-deficient female mice exhibit premature reproductive senescence. The rapid decline of ovarian function in Taf4b-null mice begins in early postnatal life, and follicle depletion is completed by 16 wk of age. To uncover differences in gene expression that may underlie accelerated ovarian aging, we compared genome-wide expression profiles of 3-wk-old, prepubescent Taf4b-null and wild-type ovaries. At 3 wk of age, decreased gene expression in Taf4b-null ovaries is similar to that seen in aged ovaries, revealing several molecular signatures of premature reproductive senescence, including reduced Smc1b. One significantly reduced transcript in the young TAF4B-null ovary codes for MOV10L1, a putative germline-specific RNA helicase that is related to the Drosophila RNA interference protein, armitage. We show here that Mov10l1 is expressed in mouse oocytes and that its expression is sensitive to TAF4B level, linking TAF4B to the posttranscriptional control of ovarian gene expression.
Haplotype-specific suppression of cytotoxic t cell induction by antigen inappropriately presented on t cells.

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.
Environmental Toxins and α-Synuclein in Parkinson's Disease

In recent years, environmental influences have been thought to play an important role in Parkinson’s disease (PD). Evidence from epidemiological investigations suggests that environmental factors might take part in the disease process. Intriguingly, most of environmental toxins share the common mechanism of causing mitochondria dysfunction by inhibiting complex I and promoting α-synuclein aggregation, a key factor in PD. Therefore, understanding the mechanism of interactions between α-synuclein and environmental factors could lead to new therapeutic approaches to PD.
Transporting Lazarus: Physicians, the State, and the Creation of the Modern Paramedic and Ambulance, 1955-73

In 1966, morticians provided 50 percent of ambulance services in the United States; today advanced care by trained medical professionals en route to the hospital is considered a basic standard of care. The creation of emergency medical services (EMS) provides an important case study for how physicians acting as "experts" helped to shape the creation of federal policy in the post-World War II years. This paper challenges a narrative of the development of EMS that has emphasized technology, individual agency, and the role of fortuitous chance as the prime movers of EMS development. Instead it argues that a key factor in EMS development was the National Academy of Science-National Research Council's Committee on Emergency Medical Services. Using the examples of paramedic training and ambulance design, this paper argues that members of the committee utilized complex mix of local experimentation and professional networking to suggest directions for the federal government's efforts to create national standards and guidelines for EMS. The NAS-NRC Committee retained a prominent role in EMS development until the passage of the Emergency Medical Services Systems Act of 1973, when federal interest in EMS largely shifted from prehospital transport to an emphasis on in hospital care and regional trauma systems planning.
On Research-Minded Practitioners: A Response to McBeath and Austin.

McBeath and Austin define the concept of research-minded practitioners, describe the organizational contexts, structures, and strategies for supporting this type of practitioner. Further, the authors propose a research agenda to establish effective organizational development strategies to support research-minded practitioners, align their efforts with organizational improvement processes, and culminate in new directions for practice research. This response to McBeath and Austin disagrees with their characterization of evidence-based practice, their definition of practice research, and their conceptualization of the research-minded practitioner as something different from an evidence-based practitioner. While McBeath and Austin are commended on their analysis of organizational barriers to research-minded practice, the redundancy of the concept of research-minded practice is questioned by reiterating commonly held definitions of evidence-based practice.
Seismotectonic Model of the Kraljevo 3 November 2010 Mw 5.4 Earthquake Sequence

Online Material: Additional Kraljevo sequence data, details. An M w 5.4 earthquake occurred on 3 November 2010 (Fig. 1) near the city of Kraljevo, Serbia, the population of which is more than 100,000 people. By the end of March 2011, the earthquake had been followed by a sequence of more than 650 aftershocks of magnitude greater than 1.0. Despite the moderate magnitude of the event, two people were killed, many others were injured, and the total damage to the city has been evaluated as more than 100 million EUR (United Nations, Kraljevo Earthquakes Report, 2010). Liquefaction and rockslides occurred in several places (Serbian Seismological Survey (SSS) Report, 2011). The earthquake also caused changes in groundwater circulation: some existing wells have totally dried out and new geothermal springs have appeared. Figure 1. Geodynamics of the Central Mediterranean region: Major plates (Africa, Eurasia, and Anatolia) and their boundaries, important fault systems, and orogenic belts (after Dilek, 2010). Thick black arrows, plate convergence directions; white star, the location of the 3 November 2010 Kraljevo earthquake. Symbols, seismological station networks from which data were used in this study. Virtual Regional Seismic Network includes data from the following networks: Italy, Romania, Croatia, Former Yugoslav Republic of Macedonia, Republic of Serbia, and Albania. The Kraljevo 3 November 2010 earthquake was recorded by seismological stations worldwide. Although different seismological agencies show consistency in determination of magnitude ( M w 5.3 or 5.4), proposed locations for the mainshock vary greatly. In particular, proposed depths vary from 2 to 30 km. In this article, we jointly determine the location of the mainshock and aftershocks that occurred between 3 November and 31 December 2010, along with a new P ‐ and S ‐wave 1D velocity model for that area. Focal mechanism solutions are obtained for selected events using both local and regional data. The …
Comparison of the Allo-Kramer Shear and Texture Profile Methods of Broiler Breast Meat Texture Analysis

Abstract Two experiments were conducted to compare the Allo-Kramer shear (AK) and the texture profile analysis (TPA) methods of determining objective texture using broiler breast meat. In one experiment broilers obtained from a commercial processing plant were killed by cervical dislocation and one half of the breast muscles, pectoralis (p.) major and p. minor, were either removed immediately (hot boned, HB) or left on the carcass for 24 h prior to removal (chill-boned, CB). The breast meat samples were cooked in steam, and one half of the samples from each treatment were sliced to a constant thickness. Samples from the anterior, middle, and posterior sections were analyzed by Allo-Kramer shear or TPA. A second experiment was conducted identical to the first except that all birds were obtained in the form of ready-to-cook carcasses (conventional processed) from a commercial processing plant, aged 24 h, and effects of the AK and TPA methods on breast halves were compared. Processing treatment (HB vs. CB) was found to significantly affect AK and TPA values, except for values of springiness and cohesiveness. Slicing the p. major appeared to affect the results of the TPA method more than the AK method in both experiments. Both the AK and TPA methods detected differences across muscle locations.
The essence of command injection attacks in web applications

Web applications typically interact with a back-end database to retrieve persistent data and then present the data to the user as dynamically generated output, such as HTML web pages. However, this interaction is commonly done through a low-level API by dynamically constructing query strings within a general-purpose programming language, such as Java. This low-level interaction is ad hoc because it does not take into account the structure of the output language. Accordingly, user inputs are treated as isolated lexical entities which, if not properly sanitized, can cause the web application to generate unintended output. This is called a command injection attack, which poses a serious threat to web application security. This paper presents the first formal definition of command injection attacks in the context of web applications, and gives a sound and complete algorithm for preventing them based on context-free grammars and compiler parsing techniques. Our key observation is that, for an attack to succeed, the input that gets propagated into the database query or the output document must change the intended syntactic structure of the query or document. Our definition and algorithm are general and apply to many forms of command injection attacks. We validate our approach with SqlCheckS, an implementation for the setting of SQL command injection attacks. We evaluated SqlCheckS on real-world web applications with systematically compiled real-world attack data as input. SqlCheckS produced no false positives or false negatives, incurred low runtime overhead, and applied straightforwardly to web applications written in different languages.
Optimizing communication for Charm++ applications by reducing network contention

Optimal network performance is critical for efficient parallel scaling of communication-bound applications on large machines. No-load latencies do not increase significantly with the number of hops traveled when wormhole routing is deployed. Yet, we and others have recently shown that in the presence of contention, message latencies can grow substantially large. Hence, task mapping strategies should take the topology of the machine into account on large machines. In this paper, we present topology aware mapping as a technique to optimize communication on three-dimensional mesh interconnects and hence improve the performance. Our methodology is facilitated by the idea of object-based decomposition used in Charm++ which separates the processes of decomposition from mapping of computation to processors and allows a more flexible mapping based on communication patterns between objects. Exploiting this and the topology of the allocated job partition, we present mapping strategies for a production code, OpenAtom to improve the overall performance and scaling. OpenAtom presents complex communication scenarios of interaction involving multiple groups of objects and makes the mapping task a challenge. Results are presented for OpenAtom on up to 16 384 processors of Blue Gene/L, 8192 processors of Blue Gene/P and 2048 processors of Cray XT3. Copyright © 2010 John Wiley & Sons, Ltd.
Defining the Optimal Treatment for Clinical Stage I Nonseminomatous Germ Cell Testicular Cancer Using Decision Analysis

Purpose There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. Methods Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. Conclusion A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.
On the Rate Versus ML-Decoding Complexity Tradeoff of Square LDSTBCs with Unitary Weight Matrices

The low decoding complexity structure of Linear Dispersion Space Time Block Codes (LDSTBCs) with unitary weight matrices is analyzed. It is shown that given n = 2alpha, the maximum number of groups in which the information symbols can be separated and decoded independently is (2a + 2), and as we lower the number of different groups to (2k + 2), 0 les k les alpha, we get higher rate codes. We also find the analytic expression for rates that such codes can achieve for any chosen group number, thus completely characterizing the rate-ML-decoding-complexity tradeoff for this class of codes. The proof of the result also includes a method for constructing such optimal rate achieving codes. Interestingly, this analysis produces some low decoding complexity codes with rate greater than one.
A Reexamination of Glenwood Locality Ceramic Variation and Vessel Forms

AbstractGlenwood locality in Mills County, Iowa has been intensively researched in the last century. Many of the excavated assemblages, however, have not been analyzed in great detail including the sites 13ML79 and 13ML235, the focus of this study. A descriptive analysis of the ceramic assemblages was conducted to determine what information they could provide regarding Glenwood vessel form and function. Data were then compared to models proposed by Billeck (1993) and Blakeslee and Caldwell (1979) to test their validity in light of new ceramic analyses. A sample of sherds from both sites and 18 reconstructed Glenwood vessels from other sites were examined, with afocus on rim form, orientation, and vessel orifice constriction. Most of the sherds from 13ML79 and 13ML235 likely came from straight-rimmed, medium-sized vessels used for cooking or short-term storage for a small group of people. When 13ML79 and 13ML235 were compared to the models, they supported Billeck’s expectations for geographic variability a...
Inequality and infection in China

In their Letter to the Editor, Zhang et al. suggest that increasing income inequalities may be associated with increases in notifiable infectious diseases in China, highlighting the need for epidemiological investigation. We would like to enrich this discussion with two important points about income inequalities and health. First, the influence of unequal economic status on health outcomes has been described in many contexts beyond China. Other research has demonstrated that more than poverty alone, economic inequalities contribute to illness and premature mortality. Within China, the unequal allocation of government planned medical services between urban and rural populations has contributed to large differences in health outcomes. Service demand is still the greatest at the village level, where there are fewer resources to confront diseases. Second, the relationship between reported syphilis cases and economic growth in China has already been described at municipal and district levels. Such ecological analyses should be interpreted with some caution, since economically developed areas are likely to have more accessible and developed reporting infrastructure, resulting in greater diagnostic coverage and higher reported cases. This is supported by the trend of more latent syphilis cases – cases without symptoms – reported in higher GDP municipalities where routine syphilis screening programs are likely to be more robust. Understanding the impact of China’s rapid economic development on infectious diseases is critical, but must be understood in the context of broader arguments surrounding economic inequalities, health, and the limitations of available data. Funding: This study was supported by an NIH Fogarty K01 Award (US NIH 1K01TW008200-01A1).
An analysis of heavy utilizers of opioids for chronic noncancer pain in the TROUP study.

Abstract Context Although opioids are increasingly used for chronic noncancer pain (CNCP), we know little about opioid dosing patterns among individuals with CNCP in usual care settings, and how these are changing over time. Objectives To investigate the distribution of mean daily dose and mean days supply among patients with CNCP in two disparate populations, one national and commercially insured population (HealthCore) and one state based and publicly insured (Arkansas Medicaid), for years 2000 and 2005. Methods For individuals with any opioid use, we calculated the distribution of mean daily dose (in milligram morphine equivalents), mean days supply in a year, mean annual dose, and patient characteristics associated with heavy utilizers of opioids. Results Between 2000 and 2005, across all percentiles, there was little change in the mean daily opioid dose. In HealthCore, mean days supply increased most rapidly at the top end of the days supply distribution, whereas in Arkansas Medicaid, the greatest increases were near the median of days supply. In HealthCore, the top 5% of users accounted for 70% of total use (measured in milligram morphine equivalents), and the top 5% of Arkansas Medicaid users accounted for 48% of total use. The likelihood of heavy opioid utilization was increased among individuals with multiple pain conditions, and in HealthCore, among those with mental health and substance use disorders. Conclusion Opioid use is heavily concentrated among a small percent of patients. The characteristics of these high utilizers need to be further established, and the benefits and risks of their treatment evaluated.
Prenatal Exposure to Parents' Smoking and Childhood Cancer

The relation between parents' tobacco smoking prior to birth and cancer in the offspring was investigated with the use of data from a case-control study. Incident cases included all children (aged 0-14 years) diagnosed in Denver, Colorado from 1976 to 1983. Controls were selected through random digit dialing, and matched to cases on age, sex, and geographic area. Information on smoking by parents and other household members was obtained by personal interview for 223 cases and 196 controls. After adjustment for father's education, mother's smoking during the first trimester of pregnancy was associated with an increased risk for all cancers combined (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.7-2.1), acute lymphocytic leukemia (OR = 1.9, 95% CI 0.9-4.1), and lymphomas (OR = 2.3, 95% CI 0.8-7.1). Adjusting for father's education, associations with father's smoking in the absence of mother's smoking were found for all cancers combined (OR = 1.2, 95% CI 0.8-2.1), acute lymphocytic leukemia (OR = 1.4, 95% CI 0.6-3.1), lymphomas (OR = 1.6, 95% 0.5-5.4), and brain cancer (OR = 1.6, 95% CI 0.7-3.5). In spite of imprecision resulting from small numbers of cases in diagnostic subgroups, these results are suggestive of a possible influence of parents' smoking on childhood cancer.
Noncoding RNAs: Regulators of the Mammalian Transcription Machinery

Transcription by RNA polymerase II (Pol II) is required to produce mRNAs and some noncoding RNAs (ncRNAs) within mammalian cells. This coordinated process is precisely regulated by multiple factors, including many recently discovered ncRNAs. In this perspective, we will discuss newly identified ncRNAs that facilitate DNA looping, regulate transcription factor binding, mediate promoter-proximal pausing of Pol II, and/or interact with Pol II to modulate transcription. Moreover, we will discuss new roles for ncRNAs, as well as a novel Pol II RNA-dependent RNA polymerase activity that regulates an ncRNA inhibitor of transcription. As the multifaceted nature of ncRNAs continues to be revealed, we believe that many more ncRNA species and functions will be discovered.
Cognitive Complexity: Construct Descriptive Terms vs Cognitive Process

Summary.-It was hypothesized that cognitive complexity (CC) scores derived from own and provided constructs may be equivalent because of the limited relevance of specific construct descriptive terms to the actual underlying cognitive dimensions used by the judge. Sixry-three Ss, assigned to three levels of abstracrness, were administered the Interpersonal Discrimination Test from which werc derived 2 CC type scores: differentiarion, based on the number of non-repeated constructs generated, and over-all discrimination, based on the extent to which functionally independent construct dimensions were broken down. The groups were not significantly different on mean differentiarion scores, but were significantly different on mean discrimination scores. The results were inrerpretecl as supporting the original hypothesis and further implications were discussecl. Tripodi and Bieri ( 1963) have recently argued that cognitive complexiry scores (CC) obtained with provided constructs are not significantly different from those obcained with the judge's own conscmcn. For research purposes there are definite advantages in using provided constructs. Test-retest reliabiliry coefficients are generally more respectable and the researcher can assert that one more source of extraneous variance has been controlled. While Tripodi and Bieri resolve a methodological difficulry, they raise an interesting theoretical problem. Their results suggest that there may be no difference in CC scores provided by the two methods because of the limited relevance of specific construct descriptive terms to the actual underlying cognitive dimensions used by the judge. Evidence bearing on this problem was sought by re-analysis of data from a previous study (Carr, in press). Sixty-three Ss were assigned to one of three levels of abstractness according to criteria set forth by Harvey, Hunt, and Schroder (1961). These groups were designated Systems I, 11, and 111, with System 111 being most abstract. Ss were then administered the Interpersonal Discrimination Test (IDT), an inscn~menc similar to Kelly's Role Rep Test. Ss generated 24 constnlcts from descriptions of thelnselves and six other persons meeting specific role titles, then attempted to delineate among all seven persons on each construct dimension. Two CC rype scores were derived. The first, called differentiation, was based upon the number of unique independent constructs generated, defined as the total number of non-repeated conscnlct descriptive terms. The second measure, called over-all discrimination, was based upon the extent to which functicnally independent conscn~ct dimensions were broken down. The rationale and mechanics of scoring have been described in detail elsewhere (Carr, in press) but can be briefly s~~mmarized here. In order to provide a basis for its independence from differentiation, over-all discrimination was defined in terms of the mean number of interpersonal discriminations made on
Consumer Satisfaction with Foreign and Domestic Products: A Cross-Cultural Comparison

This study deals with the satisfaction of US and Indian consumers of foreign and domestic products. The purpose of the investigation is to explore attitudinal differences between the citizens of both countries, and to determine whether male and female consumers hold different attitudes within each country sample. The findings were that in general US consumers are more satisfied with imported products than are Indian consumers. There were differences along gender lines as well. The results suggest that familiarity with foreign products appears to influence the level of satisfaction with these products.
Nucleotide and Mg2+ induced conformational changes in GroEL can be detected by sulfhydryl labeling.

The accessibility of fluorescein-5-maleimide to sulfhydryl groups in the molecular chaperone GroEL was used to follow structural rearrangements in the protein triggered by binding Mg2+ and/or adenine nucleotides. Three peptides, each containing one of the cysteines of GroEL (C138, C458 and C519) were identified. GroEL labeled in 50mM TrisHCl, pH 7.8, incorporated ~0.3 labels each on C138 and C458. With 10mM MgCl2, the labeling increased to ~0.8 labels each on C138 and C458. The increase was partially due to a conformational change which occurred upon Mg2+ binding as well as to an increase in ionic strength. When ADP, ATP, or AMP-PNP were added to a solution of GroEL and Mg2+, C138 incorporated ~0.8 labels, while C458 incorporated ~0.1 labels. These results suggest that the binding of adenine nucleotides changed the conformation of GroEL and made a previously highly exposed sulfhydryl group inaccessible. GroEL slowly dissociated into monomers when it was extensively labeled at C458. GroEL labeled with fluorescein-5-maleimide, under any of the conditions examined, was able to bind but not release active rhodanese. The observed variations in sulfhydryl accessibility are consistent with mechanisms that suggest binding of GroES to GroEL differs from the binding of substrate protein to GroEL, and that the binding of Mg2+ or Mg-adenine nucleotides results in conformational changes in GroEL.
Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T.

Purpose To determine the reproducibility of a comprehensive single-session measurement of glutathione (GSH), γ-aminobutyric acid (GABA), glutamate, and other biochemicals implicated in the pathophysiology of multiple sclerosis (MS) in the human brain with 1 H magnetic resonance spectroscopy (MRS). Materials and methods Five healthy subjects were studied twice in separate 1-hour sessions at 7T. One MS patient was also scanned once. GSH and GABA were measured with J-difference editing using a semilocalized by adiabatic selective refocusing sequence (semi-LASER, TE = 72 msec). A stimulated echo acquisition mode sequence (STEAM, TE = 10 msec) was used to detect glutamate along with the overall biochemical profile. Spectra were quantified with LCModel. Quantification accuracy was assessed through Cramer-Rao lower bounds (CRLB). Reproducibility of the metabolite quantification was tested using coefficients of variation (CoV). Results CRLB were ≤7% for GSH, GABA, and glutamate and average CoV of 7.8 ± 3.2%, 9.5 ± 7.0%, and 3.2 ± 1.7% were achieved, respectively. The average test/retest concentration differences at this measurement reproducibility and quantification accuracy were smaller for GABA and glutamate than intersubject variations in metabolite content with CoV ratios of 0.6 and 0.8, respectively. As proof of principle, GSH, GABA, and glutamate were also detected in an MS patient. Conclusion GSH, GABA, glutamate, and other metabolites relevant in MS can be quantified at 7T with high accuracy and reproducibility in a single 1-hour session. This methodology might serve as a clinical research tool to investigate biochemical markers associated with MS. Level of evidence 2 J. Magn. Reson. Imaging 2017;45:187-198.
A Cadaveric Investigation of the Dorsal Scapular Nerve.

Compression of the dorsal scapular nerve (DSN) is associated with pain in the upper extremity and back. Even though entrapment of the DSN within the middle scalene muscle is typically the primary cause of pain, it is still easily missed during diagnosis. The purpose of this study was to document the DSN’s anatomy and measure the oblique course it takes with regard to the middle scalene muscle. From 20 embalmed adult cadavers, 23 DSNs were documented regarding the nerve’s spinal root origin, anatomical route, and muscular innervations. A transverse plane through the laryngeal prominence was established to measure the distance of the DSN from this plane as it enters, crosses, and exits the middle scalene muscle. Approximately 70% of the DSNs originated from C5, with 74% piercing the middle scalene muscle. About 48% of the DSNs supplied the levator scapulae muscle only and 52% innervated both the levator scapulae and rhomboid muscles. The average distances from a transverse plane at the laryngeal prominence where the DSN entered, crossed, and exited the middle scalene muscle were 1.50 cm, 1.79 cm, and 2.08 cm, respectively. Our goal is to help improve clinicians’ ability to locate the site of DSN entrapment so that appropriate management can be implemented.
The Dynamic Effect of Incentives on Post-Reward Task Engagement

Although incentives can be a powerful motivator of behavior when they are available, an influential body of research has suggested that rewards can persistently reduce engagement after they end. This research has resulted in widespread skepticism among practitioners and academics alike about using incentives to motivate behavior change. However, recent field studies looking at the longer-term effects of temporary incentives have not found such detrimental behavior. We design an experimental framework to study dynamic behavior under temporary rewards, and find that although there is a robust decrease in engagement immediately after the incentive ends, engagement returns to a post-reward baseline that is equal to or exceeds the initial baseline. As a result, the net effect of temporary incentives on behavior is strongly positive. The decrease in post-reward engagement is not on account of a reduction in intrinsic motivation, but is instead driven by a desire to take a ‘break’, consistent with maintaining a balance between goals with primarily immediate and primarily delayed benefits. Further supporting this interpretation, the initial decrease in post-reward engagement is reduced by contextual factors (such as less task difficulty and higher magnitude incentives) that reduce the imbalance between effort and leisure. These findings are contrary to the predictions of major established accounts and have important implications for designing effective incentive policies to motivate behavior change.
Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications

Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation. The unopposed activation of Wnt/β-catenin pathways, either due to loss of APC function or up-regulation of related stimulatory pathways, results in unopposed hyperproliferation of colonic crypts, considered the single most important risk factor for colon carcinogenesis. Hypermethylation of CpG islands within the promoters of specific genes can potentially inactivate DNA repair genes and/or critical tumor suppressor genes. Recently, CpG methylation of the 5’ promoter of human (h) DCLK1 gene was reported in many human epithelial cancers, including colorectal cancers (CRCs), resulting in the loss of expression of the canonical long isoform of DCLK1 (DCLK1-L) in hCRCs. Instead, a shorter isoform of DCLK1 (DCLK1-S) was discovered to be expressed in hCRCs, from an alternate β promoter of DCLKL1 -gene; the clinical and biological implications of these novel findings, in relation to recent publications is discussed.
Growth and Customer Loyalty: Evidence from the App Economy

The burgeoning app economy increasingly drives growth in today's service sector. We study a dataset encompassing apps' daily, weekly, and monthly usership time series and show how its nested-echelon structure allows researchers to reliably infer how and when an app's customers adopt, use, and leave its services. Thereby gaining novel visibility into these services' customer flows, we study how firms should prioritize the acquisition of customers and market share via viral effects against cultivating customer loyalty. Contrary to common wisdom in the app economy, our findings reinforce the central role and effects of customer loyalty, as theorized by the Service Profit Chain. While loyalty bolsters customers' retention and repeat business (i.e., usage), a natural experiment that suppressed viral customer acquisition across the Facebook platform demonstrates the power of a more subtle benefit: improved customer loyalty actually amplifies the rate of word-of-mouth acquisition. A potent experience curve that rewards firms' experience with loyal customers dismantles a classic trade-off between customer loyalty and market share in services.
TSmap3D: Browser visualization of high dimensional time series data

Large volumes of high dimensional time series data are increasingly becoming commonplace, and the ability to project such data into three dimensional space to visually inspect them is an important capability for scientific exploration. Algorithms such as Multidimensional Scaling (MDS) and Principal Component Analysis (PCA) can be used to reduce high dimensional data into a lower dimensional space. The time sensitive nature of such data requires continuous processing in time windows and visualizations to be shown as moving plots. In this paper we present: 1. an MDS-based approach to project high dimensional time series data to 3D with automatic transformation to align successive data segments; 2. an open source commodity visualization of three-dimensional time series in web browser based on Three.js; and 3. An example based on stock market data. The paper discusses various options available when producing the visualizations and how one optimizes the heuristic methods based on experimental results.