cssi/SciSciGPT-SciSciNet huggingface dataset:
Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4

A series of combretastatin A-4 (CA-4) analogues have been prepared from (Z)-substituted diarylacrylonitriles (1a-1p) obtained in a two-step synthesis from appropriate arylaldehydes and acrylonitriles. The resulting 4,5-disubstituted 2H-1,2,3-triazoles were evaluated for their anti-cancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogue 2l exhibited the most potent anti-cancer activity in the screening studies, with GI₅₀ values of <10 nM against almost all the cell lines in the human cancer cell panel and TGI values of <10 nM against cancer cell lines SF-539, MDA-MB-435, OVCAR-3 and A498. Furthermore, in silico docking studies of compounds 2l, 2e and 2h within the active site of tubulin were carried out in order to rationalize the mechanism of the anti-cancer properties of these compounds. From the in silico studies, compound 2e was predicted to have better affinity for the colchicine binding site on tubulin compared to compounds 2l and 2h. Analogue 2e was also evaluated for its anti-cancer activity by colony formation assay against 9LSF rat gliosarcoma cells and afforded an LD₅₀ of 7.5 nM. A cell cycle redistribution assay using analogue 2e was conducted to further understand the mechanism of action of these CA-4 analogues. From this study, analogues 2e and 2l were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.
Inherited focal, episodic neuropathies

Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or “sausage-like” formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often triggered by infections, immunizations, the puerperium, and stress. Electrophysiological studies show normal or mildly prolonged motor nerve conduction velocities distal to the affected brachial plexus. Pathological studies have found axonal degeneration in nerves examined distal to the plexus abnormality. In some HNA pedigrees there are characteristic facial features, including hypotelorism. The prognosis for recovery of normal function of affected limbs in HNA is good, although recurrent episodes may cause residual deficits. HNA is genetically linked to chromosome 17q25, where mutations in the septin-9 (SEPT9) gene have been found.
Agency Law as Asset Partitioning

This article suggests a shift in how we think about agency. The essential function of agency law lies not in enabling the delegation of authority, as is widely suggested, but more significantly in its effect on creditors’ rights through asset partitioning. Most of what agency law does in commerce could be accomplished through standard-form contracts, providing default terms for the relationships among firms, their managers, and third parties. Even agency’s much-vaunted fiduciary duties are easily altered or waived by contract. This article identifies the role agency law plays that parties could not contractually replicate. This role is asset partitioning: Just as limited liability and organizational law partition off the assets of a firm’s owners from the assets of the firm itself, agency law partitions off the assets and liabilities of a firm’s managers from the firm’s own assets. Asset partitioning shows that whether owners or managers should be liable for a firm’s unpaid contracts is not a win-lose distributional question, but can be socially efficient. Through simplifying and specializing asset pools, asset partitioning lowers the cost of monitoring the firm’s assets and thus the cost of credit. More generally, legal personality enables the parties that control a firm (its owners and managers) to contribute financial and human capital to the firm, while maintaining a separation between their assets and liabilities and the assets and liabilities of the firm itself.
Science traceability

Any comprehensive science mission proposal must be able to simply explain why it is important to accomplish the goals of the mission and how it will be implemented. This can be accomplished through use of a Science traceability matrix, a construct that is becoming a required component of all NASA science mission proposals. The science traceability matrix (STM) provides the overview of what a Mission will accomplish relative to high-level objectives suggested through Academy of science surveys, NASA roadmaps, or program objectives. It provides a logical flow from these high level objectives through mission objectives, science objectives, measurement objectives, measurement requirements, instrument requirements and spacecraft and system requirements to data products and eventual publications. It is the one document that shows the relationship between all these key elements and the one document that provides the breadth needed to perform and document high level trades effecting science outcome and overall design. The STM can be used as a gauge to determine the completeness of the definition of a proposed mission. If the matrix flows effortlessly from high level objective to publishable science result then it has been carefully laid out. If the logic that ties one aspect to another is not clear then there is more work to be done prior to any proposal preparation. The science matrix provides a basis for negotiating lower level requirements (typically tracked with tools such as Telelogic's DOORS/spl reg/ requirements tracking tool) and evaluating affects of the results of those negotiations on the ability to achieve objectives originating at higher levels. It also provides a succinct snapshot of those high level objectives particularly important for high-level goals since there is often no objective algorithm to quantify the relative merits of the conflicting high-level goals. For this case, the matrix provides a convenient notation for assessing and arbitrating the impact on equal-valued objects caused by changes in available mission resources.
Higgs boson production and decay: Effects from light third generation and vectorlike matter

We study the implications of light third generation sparticles on the production cross section and decay widths of a light $CP$-even Higgs boson. For simplicity, we consider scenarios in which only one of the sfermions from the third generation is light. For each case, we attempt to explain the apparently large enhancement in the Higgs production and decay in the diphoton channel with small deviations in the $ZZ$ channel. In the minimal supersymmetric standard model (MSSM) framework we find that only a light stau can explain these observations while keeping the lightest $CP$-even Higgs boson mass in the interval $123\text{ }\text{ }\mathrm{GeV}\ensuremath{\lesssim}{m}_{h}\ensuremath{\lesssim}127\text{ }\text{ }\mathrm{GeV}$. For the light stop scenario, the observations related to the diphoton and $ZZ$ channel can be accommodated but, in order to satisfy the Higgs mass bound, one needs to go beyond the MSSM. In particular, we invoke vectorlike particles with masses around a TeV. These new particles preserve gauge coupling unification and provide additional contributions to the Higgs mass. With these new contributions a 126 GeV Higgs mass is easily achieved. We also find that with only a light sbottom quark, the above mentioned excess is hard to accommodate.
Poland: Gender Discrimination Unrecognized:

Les AA. mettent en evidence l'existence en Pologne d'un systeme ideologique qui desavantage les femmes. En examinant les tendances nationales de l'emploi et du chomage, ils montrent que non seulement cet heritage est anterieur au regime communiste de 1945 a 1989, mais qu'il perdure aujourd'hui alors que le gouvernement travaille a etablir une democratie liberale et une economie de marche capitaliste. Ce modele durable d'inegalite sexuelle est donc ancre structurellement.
Speaker recognition using matched filters

Nowadays state-of-the-art speaker recognition systems obtain quite accurate results for both text-independent and text-dependent tasks as long as they are trained on a fair amount of development data from the target domain, and as long as the target data is clean. In this work we investigate the use of matched filters for speaker recognition in the framework of a small in-domain development data. We show how a matched filter can be optimized to maximize SNR (signal to noise ratio) when the noise component includes both intra-speaker variability and center/mean hyper-parameter variability. The proposed method generalizes our previous method named score stabilization and obtains significant speaker recognition error reductions.
Manifold warping: manifold alignment over time

Knowledge transfer is computationally challenging, due in part to the curse of dimensionality, compounded by source and target domains expressed using different features (e.g., documents written in different languages). Recent work on manifold learning has shown that data collected in real-world settings often have high-dimensional representations, but lie on low-dimensional manifolds. Furthermore, data sets collected from similar generating processes often present different high-dimensional views, even though their underlying manifolds are similar. The ability to align these data sets and extract this common structure is critical for many transfer learning tasks. In this paper, we present a novel framework for aligning two sequentially-ordered data sets, taking advantage of a shared low-dimensional manifold representation. Our approach combines traditional manifold alignment and dynamic time warping algorithms using alternating projections. We also show that the previously-proposed canonical time warping algorithm is a special case of our approach. We provide a theoretical formulation as well as experimental results on synthetic and real-world data, comparing manifold warping to other alignment methods.
The Response of Tree Squirrels to Conspecific and Heterospecific Alarm Calls

Publisher Summary This chapter focuses on whether tree squirrels respond more strongly (or even exclusively) to the alarm calls of their own species, or whether they also attend to the alarm calls of other species within their environment though a lab experiment. The hypothesis might be that squirrels respond more strongly to alarm calls of their own species than to alarm calls of other species, because natural selection has presumably favored squirrels' communicating clearly with others of their species. Alternatively, squirrels might respond just as strongly to the alarm calls of other species within their environment, such as bluejays and chipmunks, because the squirrels are likely to be threatened by the same predators, such as hawks and house cats. There should, therefore, be strong selective pressure for animals to respond quickly and appropriately to conspecific alarm calls. Different species within the same environment may be threatened by the same predators and thus may also benefit from listening for and responding to the alarm calls of other species
Factors Modifying Drug Action

The specific effect which drugs exert on certain organs may be altered in both intensity and rate of appearance and disappearance. This variance of drug action may be due to a number of factors not inherent in the drug itself. This chapter, therefore, deals with the following factors which modify drug action: (1) route of administration, (2) rate and degree of absorption, (3) rate of elimination, (4) effect of other drugs, (5) tolerance, (6) idiosyncrasy and allergy, (7) disease.
Efficient pointer management of stack data for software managed multicores

Scratchpad-memory (SPM) based memory hierarchy is a promising alternative to cache-based memory hierarchies, due to the difficulty in scaling caches to processors with high core count. However, explicit data management in software is required on SPM-based memory hierarchies. This paper focuses on optimizing the stack data management on SPM-based multicore processors, as memory accesses to call stack present in most applications. While previous works have developed techniques to enable correct stack pointer management, they have not optimized it. As a result, existing techniques still incur high overhead. This paper proposes an automated compiler-based scheme for efficient pointer management. Our experiments on MiBench benchmarks demonstrate that our scheme almost completely eliminates pointer management overhead. As a result, as compared to the state-of-the-art approach, our approach reduces the average execution time of the benchmarks by 52%. Furthermore, with our approach, the performance of stack management on SPM becomes better than hardware caches on average even with conservative estimates.
Efficient Efficiencies Analysis: False Dichotomies, Modeling, and Applications to Health Care

Efficiencies analysis is both an important area and one where research efforts can be particularly productive. Thinking of efficiencies and competitive effects together as components of a unified analysis is a productive conceptual framework and one that may yield methodological advances. The increased availability of detailed data, combined with increased attention to methods for analyzing efficiencies, have the potential for increasing insights and advancing enforcement.
Dislocations—Their origin and multiplication

Impurity particles, grain boundaries, and localized nonequilibrium vacancy concentrations are discussed as the most probable sites of dislocation nucleation in crystals. Thermal stresses during cooling may be responsible for operating such sources. The operation of grain-boundary sources is indicated to be one of the significant factors controlling the effect of grain size upon strength.
Can noninvasive follicular thyroid neoplasm with papillary-like nuclear features be distinguished from classic papillary thyroid carcinoma and follicular adenomas by fine-needle aspiration?

BACKGROUND Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has recently been reclassified to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical pathology. Due to the effects of such a recategorization on rate of malignancy and clinical management algorithms, it is imperative that we explore whether presurgical fine-needle aspiration can differentiate NIFTP from PTC and follicular adenoma (FA). METHODS Cytology slides from subjects with final surgical pathology resection diagnoses of NIFTP/encapsulated follicular variant of papillary thyroid carcinoma, classic PTC, and FA made between January 2013 and August 2016 were assessed. The Bethesda System diagnoses were tabulated and cytomorphologic features were analyzed for an association with surgical pathology diagnoses. RESULTS A total of 56 NIFTP, 67 classic PTC, and 30 FA cases were included. The presurgical NIFTP diagnosis according to The Bethesda System was most often atypia of undetermined significance (37.5%) followed by suspicious for follicular neoplasm/follicular neoplasm (26.8%), suspicious for malignancy (17.9%), benign (10.7%), and positive for malignancy (7.1%). The most common NIFTP cytomorphologic features were nuclear enlargement (83.9%), nuclear crowding (82.1%), nuclear clearing (69.6%), and microfollicles (73.2%). All cytomorphologic features demonstrated statistically significant associations (P value range, <.001-.002) between NIFTP and PTC, whereas select cytomorphologic features demonstrated significant associations between NIFTP and FA. CONCLUSIONS Several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC, and FA on fine-needle aspiration. Although diagnostic confirmation of NIFTP must occur at the time of excision, similar to follicular neoplasms, the possibility of NIFTP may be raised preoperatively on cytology. Cancer Cytopathol 2017;125:378–88. © 2017 American Cancer Society.
Clinical chemoproteomics—Opportunities and obstacles

Chemoproteomics is the large-scale study of proteins using chemical methods. Although chemoproteomic techniques are becoming commonplace in preclinical research, few examples have found clinical utility. We explore the prospects for advancing chemoproteomics into the clinical setting to understand drug-target interactions and to identify new therapeutically relevant targets.
SAT0376 ANTI-NT5C1A autoantibodies are frequent in juvenile myositis and associated with increased illness severity

Background Autoantibodies (Abs) against 59-Nucleotidase, Cytosolic 1A (NT5C1A) have been portrayed as a potential diagnostic aide in distinguishing inclusion body myositis (IBM) and polymyositis (PM) in adults. However, 4–21% of dermatomyositis (DM) patients also have Abs to NT5C1A. Objectives The prevalence and clinical features of anti-NT5C1A Abs in juvenile-onset myositis (IIM) patients is unknown, so we sought to examine this in a large cohort. Methods We screened 384 juvenile IIM patients meeting probable or definite Bohan and Peter criteria for anti-NT5C1A Abs by immunoblotting for the full length NT5C1A protein in transfected and non-transfected lysates. Clinical characteristics and HLA typing were compared between juvenile IIM patients who were anti-NT5C1A positive (Ab+) and those who were anti-NT5C1A negative (Ab-). Results In this cohort, 29% (103) of juvenile DM, 15% (3) of juvenile PM, and 37% (15) of juvenile overlap myositis patients tested positive for anti-NT5C1A Abs. Compared with anti-NT5C1A Ab- patients, anti-NT5C1A Ab+ juvenile IIM patients showed a similar distribution of race, gender, and association with myositis-specific Abs. However, NT5C1A Ab was associated with anti-p155/140 Abs (p=0.05). The only observed clinical difference was an increased frequency of V- or shawl-sign rashes ever present (44% vs. 26%, p=0.002). Disease severity was increased in anti-NT5C1A Ab+ patients, based on more frequent hospitalizations (p=0.02), more medications used (p Conclusions Anti-NT5C1A Abs are commonly present in juvenile DM and juvenile overlap myositis patients, and are present more frequently in patients with anti-p155/140 Abs, but are also seen in association with other myositis specific Abs. Consistent with data in adult IIM patients, anti-NT5C1A Abs have few distinguishing clinical features in juvenile myositis, but are associated with increased illness severity marked by increased hospitalizations and receipt of additional therapy. Disclosure of Interest R. Yeker: None declared, I. Pinal-Fernandez Grant/research support from: The Myositis Association, T. Kishi Grant/research support from: The Myositis Association, I. Targoff Consultant for: Oklahoma Medical Research Foundation Clinical Immunology Laboratory regarding myositis autoantibody testing, F. Miller: None declared, L. Rider: None declared, A. Mammen: None declared
Why hospitals adopt patient engagement functionalities at different speeds? A moderated trend analysis.

Abstract Objective To investigate acute care hospitals’ adoption speed of patient engagement health information technology (HIT) functionalities from 2008 to 2013 and how this speed is contingent on environmental factors and hospital characteristics. Methods Data on non-government acute care hospitals located in the United States was obtained from merging three databases: the American Hospital Association’s (AHA) annual survey information technology supplement, AHA annual survey, and the Area Health Resource File (AHRF). The variables obtained from these datasets were the amount of annually adopted patient engagement HIT functionalities and environmental and organizational characteristics. Environmental factors included were uncertainty, munificence, and complexity. Hospital characteristics included size, system membership, ownership, and teaching status. Results A regression analysis of 4176 hospital-year observations revealed a positive trend in the adoption of HIT functionalities for patient engagement (β= 1.109, p Discussion From 2008 to 2013, there was a significant acceleration in the speed of adopting patient engagement HIT functionalities. Further efforts should be made to ensure proper adoption and consistent use by patients in order to reap the benefits of these IT investments. Conclusion Hospitals adopted at least one HIT functionality for patient engagement per year. The adoption speed varied across hospitals, depending on both environmental and organizational factors.
Do Gold Humanism Honor Society Inductees Differ From Their Peers in Empathy, Patient-Centeredness, Tolerance of Ambiguity, Coping Style, and Perception of the Learning Environment?

ABSTRACTConstruct: Induction into the Gold Humanism Honor Society (GHHS) during medical school is recognized as an indicator of humanistic orientation and behavior. Various attitudes and interpersonal orientations including empathy and patient-centeredness have been posited to translate into behaviors constituting humanistic care. Background: To our knowledge there has never been a longitudinal, multi-institutional empirical study of the attitudinal and interpersonal orientations correlated with GHHS membership status. Approach: We used the American Medical Association Learning Environment Study (LES) data set to explore attitudinal correlates associated with students whose behaviors are recognized by their peers as being exceptionally humanistic. Specifically, we examined whether empathy, patient-centeredness, tolerance of ambiguity, coping style, and perceptions of the learning environment are associated with GHHS membership status. We further considered to what extent GHHS members arrive in medical sch...
Treatment of distal iliotibial band syndrome in a long distance runner with gait re-training emphasizing step rate manipulation.

Background & Purpose: Iliotibial band syndrome (ITBS) is a common injury associated with long distance running. Researchers have previously described biomechanical factors associated with ITBS. The purpose of this case report is to present the treatment outcomes in a runner with distal ITBS utilizing running gait re‐training to increase step rate above the runner's preferred or self‐chosen step rate.
Prediction of early-onset esotropia from components of the infantile squint syndrome

Purpose. To examine the association between components of the infantile squint syndrome (ISS) and age of onset of esotropia among subjects in the Cooperative Amblyopia Classification Study (CACS). Methods. Fifty subjects were classified retrospectively as having early-onset esotropia (EOE) and 150 subjects were classified as having late-onset esotropia (LOE), depending on whether symptoms of (or treatment for) strabismus occured before the first birthday or between the first and ninth birthdays, respectively. The authors compared the degree to which latent nystagmus (LN), dissociated vertical deviation (DVD), monocular asymmetry of optokinetic nystagmus (MOKN), monocular asymmetry of smooth pursuit (MSP), and perceived monocular speed bias (MSB) predicted EOE. Results. Slow-phase velocity of MOKN and MSP were faster in response to nasal than to temporal target motion. In contrast, MSB revealed that targets of equal velocity were perceived as moving faster temporally than nasally. The authors evaluated MOKN, MSP, and MSB as dichotomous and as continuous predictors. Dichotomous analysis showed significant associations between DVD and asymmetries of MOKN in the preferred eye of subjects with EOE. Univariate logistic regression models, based on DVD and LN as well as on continuous measures of MOKN, MSP, and MSB, revealed predictive power for all ISS components except I.N. In the preferred eye, MSP asymmetry was the strongest single predictor of EOE; multivariate analysis revealed that prediction of EOE improved with the inclusion of DVD. Conclusions. Multivariate analysis indicated that dichotomous measures of DVD and continuous measures of MSP were independent predictors of EOE in a population of 8- to 40-year-old subjects with strabismus. In the preferred eye, MOKN asymmetry was predictive of EOE in the absence of information about MSP. Predictive values of all ISS components depended heavily on the baseline prevalence of EOE in the target population.
Repairable Damage in DNA: Overview

Due to the central functional role of DNA and the fact that each cell contains only one or at the most a few copies of each chromosome, damage to DNA has more severe implications for the functional integrity of the cell than does damage to most other cellular components. The chemical makeup and the large target size of chromosomal DNA make it particularly susceptible to attack by exogenous chemical and physical agents. Most, if not all, reactions of exogenous agents with the sugar residues of the DNA backbone result in strand breakage. While the continuity of the sugar-phosphate backbone usually remains intact for reactions involving the heterocyclic bases, such reactions may cause local distortion of the DNA conformation and of the native structure of eukaryotic chromatin. The preservation of the unique three-dimensional structure of the double-stranded DNA helix appears to be a prerequisite for its unimpaired biological activity. DNA base damage and concomitant helix distortion may lead to inhibition of replication and transcription and to a deterioration of the fidelity and a breakdown of the regulation of these processes. Restoration of the structural integrity of the DNA by repair processes is, therefore, a vital function of every cell.
Large Bowel Obstruction: Current Techniques and Trends in Management

The treatment of a large bowel obstruction remains a complex surgical decision-making process. The presentation of this condition is quite variable, with multiple treatment strategies both endoscopically and operatively. Furthermore, with the advent of self-expanding metallic stents, patients may now be converted from an emergent to semi-elective operation, potentially avoiding a permanent stoma. However, there is still a role for a segmental or extended resection and the need for a diverting or end colostomy. Maintaining an algorithmic approach to the management of this condition is critical, and patients should be individualized based on their clinical status, as well as the location and etiology of the obstruction.
End user software engineering: CHI 2010 special interest group meeting

End users create software whenever they create, for instance, interactive web pages, games, educational simulations, or spreadsheets. Researchers are working to bring the benefits of rigorous software engineering methodologies to these end users to try to make their software more reliable. Unfortunately, errors are pervasive in end-user software, and the resulting impact is sometimes enormous. This special interest group meeting will bring together the community of researchers who are addressing this topic with the companies that are creating and using end-user programming tools.
A 17-gene genomic prostate score as a predictor of adverse pathology for men on active surveillance.

97Background: The OncotypeDX Genomic Prostate Score (GPS) test is a RNA expression assay that can be performed on needle-core biopsies from men with prostate cancer (PCa). GPS has previously been v...
Discrete Wigner functions from informationally complete quantum measurements

Wigner functions provide a way to do quantum physics using quasiprobabilities, that is, ``probability'' distributions that can go negative. Informationally complete positive operator-valued measures, a much younger subject than phase-space formulations of quantum mechanics, are less familiar but provide wholly probabilistic representations of quantum theory. In this paper, we show that the Born rule links these two classes of structure and discuss the art of interconverting between them. In particular, we demonstrate that the operator bases corresponding to minimal discrete Wigner functions (Wigner bases) are orthogonalizations of minimal informationally complete measurements (MICs). By not imposing a particular discrete phase-space structure at the outset, we push Wigner functions to their limits in a suitably quantified sense, revealing an extremality condition satisfied by the symmetric informationally complete measurements (SICs). This contributes another member to the set of optimality criteria that SICs are known to satisfy. Finally, we speculate that astute choices of MICs from the orthogonalization preimages of Wigner bases may in general give quantum measurements that are conceptually illuminating for the quasiprobability representations defined by those Wigner bases.
Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes

INTRODUCTION The Food and Drug Administration may set a maximum nicotine content in cigarettes to minimize smoking's addictiveness. Our recent research may indirectly support setting levels applicable to the population of dependent smokers below 1 mg/g (mg nicotine/g of tobacco filler). METHODS Using a within-subjects design in laboratory-based studies totaling 61 nontreatment seeking adult dependent smokers, Spectrum research cigarettes with nicotine contents ranging from 1.3 to 17 mg/g (just one per session) were compared with the lowest content available, 0.4 mg/g. Identified for each participant was the smallest difference in nicotine content, or "threshold," between cigarettes that still supported behavioral discrimination (ie, ability to objectively distinguish their difference). The next lower nicotine content cigarette, not discriminated (by definition), was labeled their "subthreshold." Subjective perceptions and choice behavior were also assessed. RESULTS Thresholds varied widely among all 61 smokers but, importantly, fewer than 7% of smokers could discriminate the two lowest, 1.3 versus 0.4 mg/g nicotine, meaning more than 90% could not do so. Moreover, we found a consistent association between their nicotine discrimination threshold and their subjective perceptions and subsequent reinforcement behavior later in the session. Specifically, a participant's discrimination threshold cigarette was also more highly rated and preferred (ie, self-administered), whereas their subthreshold cigarette was rated similarly to the 0.4 mg/g and not preferred. CONCLUSIONS Cigarette nicotine content below the threshold for perceiving nicotine's effects (ie, its discriminability) in nearly all smokers from a no nicotine comparison is likely below 1.0 mg/g, or less than or equal to 10% of that in typical commercial cigarettes. IMPLICATIONS Cigarettes with nicotine contents able to be discriminated (threshold) are also reinforcing, and those unable to be discriminated are not reinforcing, as anticipated. Yet, research explicitly comparing cigarettes with contents below 1.0 mg/g versus no nicotine (ie, a "placebo") is needed with larger samples. Results may confirm what nicotine content lower than 1.0 mg/g is below the threshold for discrimination (and self-administration) in the vast majority (>95%) of adult dependent smokers as well as teens beginning to smoke. Identifying that content would strongly support the Food and Drug Administration policy to establish a maximum nicotine content in cigarettes that will not maintain dependence.
BETWEEN A ROCK AND A HARD PLACE: SIMULTANEOUS RIGHT VENTRICULAR FAILURE AND RECURRENT SUSTAINED VENTRICULAR TACHYCARDIA IN A PATIENT WITH LVAD

Retrospective studies and meta-analyses have shown that there is no survival benefit associated with the use of implantable cardioverter-defibrillators (ICDs) in patients with continuous-flow left ventricular assist devices (LVADs). There are case reports of patients kept alive by LVADs for hours or
Viral Hepatitis Other than A, B, and C: Evaluation and Management

Viral hepatitis can cause a wide spectrum of clinical presentations from a benign form with minimal or no symptoms to acute liver failure or death. Hepatitis D coinfection and superinfection have distinct clinical courses, with the latter more likely leading to chronic infection. Management of chronic hepatitis D virus is individualized because of the paucity of treatment options and significant side effect profile of currently available treatments. Sporadic cases of hepatitis E caused by contaminated meats are becoming increasingly prevalent in immunocompromised hosts. Human herpesviruses are an important cause of disease also in immunocompromised individuals.
Midterm outcomes and durability of sinus segment preservation compared with root replacement for acute type A aortic dissection.

Abstract Objective The durability of root repair for acute type A aortic dissection is not well studied in the context of aortic insufficiency and stability of the sinuses of Valsalva. We compared clinical and functional outcomes in patients undergoing root repair and replacement for acute type A aortic dissection. Methods Of 716 patients undergoing surgery for acute type A aortic dissection, 585 (81.7%) underwent root repair and 131 (18.3%) underwent root replacement. Survival, cumulative incidence of reoperation, aortic insufficiency, and sinuses of Valsalva dilation were compared between the 2 groups. Results Survival at 1, 5, and 10 years was 84.1% versus 77.3%, 70.8% versus 69.2%, 57.6% versus 58.0% in the root repair and replacement groups, respectively (P = .69). Cumulative incidence of reoperation at 1, 5, and 10 years was 0.0% versus 0.8%, 1.4% versus 3.8%, and 3.4% versus 8.6% in the root repair and root replacement groups, respectively (P = .011). Multivariable Cox regression identified sinuses of Valsalva diameter 45 mm or more as a risk factor for proximal aortic reoperation (hazard ratio, 9.06; 95% confidence interval, 1.26-65.24). In a repeated-measures, linear, mixed-effects model, root replacement was associated with smaller follow-up of sinuses of Valsalva dimensions (β = −0.66, P Conclusions Survival is similar, but the incidence of aortic insufficiency and root dilation may be greater after root repair compared with root replacement for acute type A aortic dissection.
Chapter e29 – Firewalls

The purpose of the firewall and its location is to have network connections traverse the firewall, which can then stop any unauthorized packets. A simple firewall will filter packets based on IP addresses and ports. A useful analogy is filtering your postal mail based only on the information on the envelope. You typically accept any letter addressed to you and return any letter addressed to someone else. This act of filtering is essentially the same for firewalls. This chapter refers to the secure network as the internal network; the insecure network is the external network. The remainder of this chapter provides an overview of firewall policies, designs, features, and configurations. Of course, technology is always changing, and network firewalls are no exception. However, the intent of this chapter is to describe aspects of network firewalls that tend to endure over time.
Keeping the family home: Reproducing gentrifiers in two Boston neighborhoods

The migration patterns of middle-class families in urban landscapes has been a point of discussion in studies of gentrification since the 1980s; however, most studies focus on the movements of fami...
Food web fuel differs across habitats and seasons of a tidal freshwater estuary

Estuarine food webs are fueled by multiple different primary producers. However, identifying the relative importance of each producer to consumers is difficult, particularly for fishes that utilize multiple food sources due to both their mobility and their generally high trophic levels. Previous studies have documented broad spatial differences in the importance of primary producers to fishes within the Upper San Francisco Estuary, California, including separation between pelagic and littoral food webs. In this study, we evaluated the importance of primary producers to adult fishes in three closely spaced subregions that represented disparate habitat types (a tidal wetland channel, a turbid backwater channel, and a deep open-water channel), each a potential outcome of local restoration projects. Using stable isotope analysis coupled with a Bayesian mixing model, we identified significant differences in primary-producer contribution to fishes and invertebrates across habitats and seasons, especially in the relative contribution of submersed aquatic vegetation and phytoplankton. Most fishes utilized multiple primary producers and showed little segregation between pelagic and littoral food webs among habitats. Availability of primary producers differs seasonally and across multiple spatial scales, helping to buffer environmental variability and thus enhancing food web resilience. Ecosystem restoration may improve with emphasis on restoring a wide variety of primary producers to support consumers.
P147 Cost-offset Community-Supported Agriculture plus Nutrition Education Improves Household Food Security and Nutrition Attitudes and Self-efficacy: A Randomized Controlled Trial

Background Subsidized or ‘cost-offset’ Community-Supported Agriculture (CO-CSA) has the potential to improve food security in low-income households. Furthermore, CO-CSA coupled with tailored nutrition education may affect nutrition knowledge, attitudes, and self-efficacy. To date, many studies of CO-CSA had small samples and no comparison group; few studies incorporated formal nutrition education into CO-CSA. Objective To understand the effect of CO-CSA plus education on nutrition knowledge, attitudes, self-efficacy, and food security among low-income families; whether any observed effects are durable beyond the CO-CSA season; and whether intervention dose mediated net effect. Study Design, Setting, Participants Farm Fresh Foods for Healthy Kids (F3HK), a randomized controlled trial in New York, North Carolina, Vermont, and Washington (2016-2018) that assigned caregiver-child dyads (n = 305) from low-income households into intervention or control. The F3HK intervention included a cost-offset (50% subsidy) CSA, weekly payments (including SNAP-EBT), kitchen equipment, and 9 CSA-tailored education classes. Measureable Outcome/Analysis Household food security was measured using the 6-item Short Form of the US Department of Agriculture Food Security Survey Module (FSSM). Caregiver knowledge was assessed by asking recommended cups of fruit and vegetables (FV) per day and FV as a fraction of a dinner plate. The 4-item Negative Cooking Attitude Scale measured caregiver's attitudes towards cooking. The 4-item Self-Efficacy for Eating/Cooking Fruits and Vegetables Scale measured FV self-efficacy. Results Significant net effects were observed for outcomes related to household food security as well as caregiver nutrition attitudes and self-efficacy. Improvements in caregiver attitudes and self-efficacy remained 6 months post-intervention. Weeks of CSA pick-up mediated changes household food security. Conclusions CO-CSA plus nutrition education for low-income caregivers and their children improved household food security and caregiver attitudes and self-efficacy. Attitude and self-efficacy but not food security effects were maintained post-intervention, indicating both the promise and limitations of seasonal food access interventions. Funding USDA.
Adult Learning and Development Goals for Female Veterans' Career Transitions Amid Cultural Adaptation and Identity Formation.

Differences between military culture and civilian culture can affect the postmilitary experience for transitioning veterans. Adult educators should acquire and maintain a high level of military cultural competence to effectively serve female veterans as they transition out of the military. For women, the military-to-veteran transition also includes unique challenges related to identity formation, including occupational gender identity formation, which is not a salient concern for male veterans. Six learning and development goals are presented to guide adult educators in successfully facilitating the cultural adaptation and identity formation process for new female veterans.
Health care options and factors influencing health seeking behavior in a rural community in Nigeria: A cross-sectional study

Introduction: Healthcare resources are disproportionately distributed between urban and rural areas in many developing countries including Nigeria. Barriers to healthcare like cultural beliefs, poor education, and financial constraints make many rural dwellers seek other options of healthcare available to them. This paper aimed to determine healthcare options and sociodemographic factors associated with health-seeking practices in a rural community setting. Methods: A sample of 380 rural community dwellers in southern Nigeria was recruited in a cross-sectional study. An interviewer-administered questionnaire was used to collect socio-demographic, healthcare access and utilization data. Data were analyzed with SPSS version 25.0 software. A chi-square test was used to find the association between sociodemographic characteristics and their health-seeking practices. Results: Equal proportions (43.4%, 42.9%) of the respondents fell within the younger age categories of 10-29 and 30-49 years. Self-reported factors influencing the choice of health care were: Promptness of care (41.8%), cost (22.4%), professionalism (16.8%), distance (15.8%), and cultural belief (3.2%). The patent medicine store was the most utilized source of health care (42.1%). 140 (36.8%) respondents sought health care in the hospital. The hospital was utilized by 41.8% of respondents with secondary education; 34.9% with tertiary education; 31.7% primary and 26.1% with no formal education, respectively. Females tended to seek health care from hospitals (40.2%) and patent medicine store (43.7%) compared to males (33.3% and 41.0%). There was a statistically significant association between education and health care options utilized (P<0.05). Conclusion: Less than half of rural dwellers make minimal use of standard health care mainly due to cost and perception of promptness. The health authority should, therefore, prioritize community health education and expand healthcare access to enable rural dwellers to optimize the minimum standard healthcare available within their various communities.
Does More Intense Competition Lead to Higher Growth

The relationship between the intensity of competition in an economy and its long-run growth is an open question in economics. Theoretically, there is no clear-cut answer. Empirical evidence exists, however, that in some sectors more competition leads to more innovation, and accelerates productivity growth. To complement those findings, and capture economy-wide effects, the authors conduct a cross-country study. They examine the impact on growth of various measures having to do with intensity of domestic competition - beyond the effects of trade liberalization. Their results indicate a strong correlation between long-run growth, and effective enforcement of antitrust, and competition policy.
Characteristics and growth rate of lung metastases in patients with primary gastrointestinal malignancies: A retrospective cohort analysis.

442Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course than metastati...
A Physician Assistant Entry-Level Doctoral Degree: More Harm Than Good?

As most health professions in the United States have adopted clinical or practice doctorates, there has been an ongoing debate on whether physician assistants (PAs) should transition from a master’s to a doctorate as the terminal degree. The authors examined perceived risks, benefits and impact of transitioning to an entry-level PA doctoral degree. A multi-prong, mixed-methods approach was used that included a literature review and collecting quantitative and qualitative data using a survey and interviews. Bivariate analysis and binomial logistic regression were performed to evaluate relationships between perceptions/perspectives on an entry-level PA doctoral degree and the anticipated impact of it causing more harm than good to the PA profession. Deductive content analysis was used to analyze the qualitative data. Of 636 PA clinicians and students (46% response rate), 457 (72%) disagreed that an entry-level PA doctoral degree should be required. More than half of the respondents (54%) agreed that it should be offered but not required and 380 respondents (60%) agreed that an entry-level doctoral degree would cause more harm than good. Race, educational attainment, occupation, and length of practice as a PA were significantly associated with having a perception of causing more harm. There was strong positive association between the perception of a doctoral degree causing more harm with expectations of having a negative impact on the availability of clinical training sites (OR = 4.39, p < .05). The most commonly cited benefits were parity with other professions and competitive advantage, whereas the perceived risks were increased cost for education, decreased diversity in the profession, and negative impact on the PA/physician relationship. The major takeaway of our study was that perceived benefits and risks are strongly influenced by the lens of the stakeholder. While the majority of PAs and students appear to be not in favor mainly due to the potential harm, the proportion of those in favor is not insignificant and their views should not be ignored. Addressing concerns with key stakeholders could help the PA profession to transition to a doctoral degree with minimal adverse impact.
Environmental Aspects of Oxide Nanoparticles: Probing Oxide Nanoparticle Surface Processes Under Different Environmental Conditions.

Surface chemistry affects the physiochemical properties of nanoparticles in a variety of ways. Therefore, there is great interest in understanding how nanoparticle surfaces evolve under different e...