cssi/SciSciGPT-SciSciNet huggingface dataset:
Whitney towers and the Kontsevich integral

We continue to develop an obstruction theory for embedding 2-spheres into 4-manifolds in terms of Whitney towers. The proposed intersection invariants take values in certain graded abelian groups gener- ated by labelled trivalent trees, and with relations well known from the 3-dimensional theory of finite type invariants. Surprisingly, the same exact relations arise in 4 dimensions, for example the Jacobi (or IHX) relation comes in our context from the freedom of choosing Whitney arcs. We use the finite type theory to show that our invariants agree with the (leading term of the tree part of the) Kontsevich integral in the case where the 4- manifold is obtained from the 4-ball by attaching handles along a link in the 3-sphere. AMS Classification 57M99; 57M25
Enhanced myocardial salvage by maintenance of microvascular patency following initial thrombolysis with recombinant tissue plasminogen activator.

Study objective – The aim was to examine the value of a subthrombolytic maintenance infusion of recombinant double chain tissue plasminogen activator (BW t-PA, Duteplase) in preserving microvascular coronary flow following initial thrombolysis. Design – Coronary arterial thrombi were induced by a copper coil (placed under fluoroscopic control) in the canine left anterior descending coronary artery. Complete vessel occlusion occurred within 10–15 min of coil placement. Following 90 min of thrombotic occlusion, animals received one of three treatments: group 1, vehicle 0.9% saline; group 2, t-PA 1.0 × 106 IU·kg−1·h−1 for 1 h; group 3, t-PA l.0 × 106 IU·kg−1·h−1 for 1 h followed by 0.12 × 106 IU·kg−1·h−1 throughout the 2 h reperfusion period. Radiolabelled microspheres were administered to assess microvascular coronary flow at various time points throughout the experimental period. Subjects – Experimental subjects were beagle dogs of either sex (n = 30), weight 8.9-14.3 kg. Measurements and main results – Main vessel patency (assessed fluoroscopically) was achieved within 40.0(SEM 4.0) min and 37.0(3.1) min for group 2 and group 3 animals respectively. Group 1 animals did not reperfuse. Full microvascular coronary flow was achieved following the lytic infusion of t-PA. However, microvascular flow to the ischaemic zone was significantly reduced at the end of the 2 h reperfusion phase in group 2 animals despite ‘aggressive’ anticoagulation with heparin throughout the reperfusion period: subendocardial flow decreased from 0.74(0.14) to 0.24(0.08) ml·min−1·g−1; subepicardial flow decreased from 0.82(0.13) to 0.36(0.09) ml·min−1·g−1, p<0.05. Microvascular coronary flow to the ischaemic zone was better preserved following the maintenance infusion of t-PA given throughout the reperfusion phase: subendocardial flow decreased from 0.95(0.07) to 0.50(0.10) ml·min−1·g−1; subepicardial flow decreased from 0.73(0.04) to 0.52(0.08) ml·min−1·g−1. Thrombolytic reperfusion led to salvage of the ischaemic myocardium, with infarct/risk ratio decreasing from 75.0(10.0)% in group 1 to 46.3(11.0)% in group 2, p<0.05. Further salvage of the ischaemic myocardium followed a lytic plus maintenance infusion of t-PA, with infarct/risk ratio decreasing to 35.5(6.7)% but this did not reach statistical significance. Conclusions – t-PA consistently achieved main vessel reperfusion within 40 min (mean) of instituting therapy in our model, leading to marked salvage of ischaemic myocardium. The data also suggest that maintenance infusion of t-PA helps preserve microvascular coronary flow throughout reperfusion and tends to reduce infarct size further.
Pharmaceutical use of mouse models humanized for the xenobiotic receptor.

Abstract The regulation of hepatic cytochrome P450 (CYP) enzymes is implicated in both drug metabolism and drug–drug interactions. The CYP genes are induced by numerous xenobiotics, yet the inducibility shows clear species specificity. Recently, the rodent nuclear receptor PXR and its human homolog, SXR or hPXR, have been established as species-specific xeno-sensors that regulate CYP3A enzymes. By knocking-out the rodent gene and replacing it with the human receptor, a ‘humanized’ mouse model has been established. Displaying a human drug-response profile, this mouse represents a unique tool to dissect the drug-induced xenobiotic response and should aid the development of safer drugs.
Inflation Rate Variability and the Phillips Curve

This paper studies the relationship between inflation and unemployment by focusing on the effect of inflation rate uncertainty on real wages, employment and output. The effect of inflation on employment is shown to depend on the relationship between the mean rate of inflation and the variability of its forecasts. This can explain why the Phillips curve is negatively slopped in some periods and undetermined or positively slopped in others.
Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population

A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. Among gout patients, before Colcrys’ market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011–1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992–0.999) (p < 0.001). Similarly, among FMF patients, odds of initiating colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p < 0.001) and health care costs ($3,406 vs. $3,534, p < 0.001). Incidence rates of colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [−0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p < 0.001]. The FDA’s actions were associated with a reduction in colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.
Cooperative energy spanners: Energy-efficient topology control in cooperative ad hoc networks

Cooperative communication (CC) allows multiple nodes to simultaneously transmit the same packet to the receiver so that the combined signal at the receiver can be correctly decoded. Since CC can reduce the transmission power and extend the transmission coverage, it has been considered in topology control protocols [1], [2]. However, prior research on topology control with CC only focuses on maintaining the network connectivity, minimizing the transmission power of each node, whereas ignores the energy-efficiency of paths in constructed topologies. This may cause inefficient routes and hurt the overall network performance. In this paper, to address this problem, we introduce a new topology control problem: energy-efficient topology control problem with cooperative communication, and propose two topology control algorithms to build cooperative energy spanners in which the energy efficiency of individual paths are guaranteed. Simulation results confirm the nice performance of the proposed algorithms.
Separation of nucleotide oligomers by unitary anion-exchange.

This paper is the first report on the retention behavior of synthetic oligonucleotides and nucleotide oligomers on a continuous-bedmatrix, strong-anion-exchange column. The separation mechanism is predominantly an anion-exchange process, but hydrophobic interaction plays a role as well. The separation is based on the chain length of the oligonucleotide. Both the addition of organic mobile phase modifiers and changes in column temperature affect the retention of oligomers significantly. A volatile buffer system (e.g., triethylamine acetate) could be employed to purify oligonucleotides, and no desalting procedure would be required after the column separation step. The recoveries from the separation are 70% or higher. The maximum loading capacity of an analytical column (35 ￻ 7-mm i.d.) was found to be more than 366 µg.
Intermittent patterns of synchronous activity in human basal ganglia

Introduction Basal ganglia (BG) are involved in control of movement and are impacted in Parkinson's disease (PD). This impact is believed to be responsible for the symptoms. Recent studies provided evidence for the significance of oscillatory activity in beta and gamma bands for BG physiology in both health and disease, such as PD and dystonia [1,2]. The dynamics of the oscillations and their mechanisms are the subjects of this study. Methods We record intraoperatively from subthalamic nucleus (STN) of patients undergoing stereotactic surgery in PD. We use the network of conductance based models of excitatory subthalamic and inhibitory pallidal cells (following [3]) to study intermittent activity in the model of BG circuits. We rely on the approach of detection of statistically significant episodes of phase-locking activity developed by us and colleagues [4] to characterize intermittent from Seventeenth Annual Computational Neuroscience Meeting: CNS*2008 Portland, OR, USA. 19–24 July 2008
Beyond Culture: A Proposal for Agent-Based Content Analyses of International Advertisements

Abstract This paper argues for a paradigmatic shift away from the current cultural framework that dominates content analyses of international advertisements. It proposes a new framework that recognizes the direct influence of agents such as the advertiser/agency, the consumer, and the regulator on international advertising. This agent-based approach aims to link content analysis to other areas of advertising and consumer research, and investigate the interaction between the characteristics of these agents and international advertising content. This way, content analysis serves as an exploratory tool to generate hypotheses and facilitate other forms of analysis so that more actionable results can be obtained.
Phylogenomic approaches to common problems encountered in the analysis of low copy repeats: The sulfotransferase 1A gene family example

Blocks of duplicated genomic DNA sequence longer than 1000 base pairs are known as low copy repeats (LCRs). Identified by their sequence similarity, LCRs are abundant in the human genome, and are interesting because they may represent recent adaptive events, or potential future adaptive opportunities within the human lineage. Sequence analysis tools are needed, however, to decide whether these interpretations are likely, whether a particular set of LCRs represents nearly neutral drift creating junk DNA, or whether the appearance of LCRs reflects assembly error. Here we investigate an LCR family containing the sulfotransferase (SULT) 1A genes involved in drug metabolism, cancer, hormone regulation, and neurotransmitter biology as a first step for defining the problems that those tools must manage. Sequence analysis here identified a fourth sulfotransferase gene, which may be transcriptionally active, located on human chromosome 16. Four regions of genomic sequence containing the four human SULT1A paralogs defined a new LCR family. The stem hominoid SULT1A progenitor locus was identified by comparative genomics involving complete human and rodent genomes, and a draft chimpanzee genome. SULT1A expansion in hominoid genomes was followed by positive selection acting on specific protein sites. This episode of adaptive evolution appears to be responsible for the dopamine sulfonation function of some SULT enzymes. Each of the conclusions that this bioinformatic analysis generated using data that has uncertain reliability (such as that from the chimpanzee genome sequencing project) has been confirmed experimentally or by a "finished" chromosome 16 assembly, both of which were published after the submission of this manuscript. SULT1A genes expanded from one to four copies in hominoids during intra-chromosomal LCR duplications, including (apparently) one after the divergence of chimpanzees and humans. Thus, LCRs may provide a means for amplifying genes (and other genetic elements) that are adaptively useful. Being located on and among LCRs, however, could make the human SULT1A genes susceptible to further duplications or deletions resulting in 'genomic diseases' for some individuals. Pharmacogenomic studies of SULT1Asingle nucleotide polymorphisms, therefore, should also consider examining SULT1A copy number variability when searching for genotype-phenotype associations. The latest duplication is, however, only a substantiated hypothesis; an alternative explanation, disfavored by the majority of evidence, is that the duplication is an artifact of incorrect genome assembly.
Mutations and the age pattern of death

The age pattern of death is what biologists and demographers think about when they consider mortality (or immortality). As everyone knows, human lives on average have nearly doubled in length over the past century (1), yet human mortality still increases exponentially fast (Fig. 1) as people age past 40. Not surprisingly, the health of older people is now a major concern (2), often focused on proximate factors, biological, economic and social, that affect health (3⇓–5). However, a deeper question is, how did evolution shape the age pattern of mortality? In particular, is the rise in old-age mortality driven by an increase in the number and frequency of deleterious (i.e., bad for you) alleles? In PNAS, Wachter et al. (6) show how to compute the equilibrium distribution of deleterious mutant alleles in a large, age-structured, and genetically heterogeneous population. Their analysis is a significant advance over previous work on this question (7, 8).
Acute Respiratory Failure in Infants with Bronchiolitis

Bronchiolitis, an acute pulmonary infection of infants, is reported to result in acute respiratory failure and death in approximately 5 per cent of hospitalized cases. Sequential arterial pH, Pco and Po2 levels, determined in 30 infants with bronchiolitis, revealed an uncompensated respiratory acido
Privacy, security and interoperability of mobile health applications

This paper will discuss the security, privacy and interoperability of mobile health applications (MHAs) and how these issues must be reconciled in order for MHA devices to be implemented in the most robust fashion. Balance is needed between privacy and accessibility, between security and interoperability and between flexibility and standardization. The interoperability of diverse MHA devices must be a goal for the future in order to realize portability, true continuity and quality of care across a wide spectrum of health services. A pilot project to determine potential threats to the privacy of personal health information on an iPad will be described.
A simultaneous regression model for double stimulation tasks

Reaction time in double stimulation tasks was investigated, and a simultaneous regression model was proposed within the concept of variable capacity allocation theory. The model was tested using a double stimulation task paradigm. In the experiment, six levels of inter-stimulus interval (ISI) and three levels of stimulus complexity were employed. The regression analysis showed that the effects of stimulus complexity and ISI were significant. From the simultaneous regression model, reaction times to the first and to the second stimulus were predicted for the different experimental conditions.
Controlling Institutions: Access to IMF resources

Part Two presented three international organizations as case studies to illustrate the logic of the model of informal governance and to assess its broad applicability. Part Three is more rigorous, and turns to empirical hypothesis testing. This is the first of three chapters that turn up the power on the microscope and study the behavior of the IMF quantitatively. The empirical strategy is to investigate the stages of the IMF product cycle in detail, moving from the initiation of IMF programs to their design and ultimate implementation. The current chapter focuses on the initiation stage, in which countries request to participate in an IMF program, and the Fund makes a portion of its resources available to support the country's adjustment plans. The key dependent variable in this chapter will be the degree of access granted to Fund resources. In this chapter and the ones that follow, the quantitative analysis will be supplemented with illustrations drawn from five prominent financial crises that I have studied in detail: Mexico (1994–5), Korea (1997), Indonesia (1997), Russia (1998) and Argentina (2001). The cases were selected for their systemic importance, and there is no intention to claim that they are a representative sample of IMF lending or of financial crises; the generality of the results rests on the quantitative analysis, not on the cases. However, the cases perform two important functions that the quantitative analysis alone could not.
Some Explanations of Dobinski's Formula

The geometric, algebraic, and combinatorial explanations of Dobinski's formula are presented by mixed volumes of compact convex sets, Mobius inversion, difference operator, and species. The employed method may be useful in proving some other combinatorial identities.
27.1 A 12b 2GS/s dual-rate hybrid DAC with pulsed timing-error pre-distortion and in-band noise Cancellation Achieving >74dBc SFDR up to 1GHz in 65nm CMOS

A dual-rate hybrid DAC is proposed in [1] that shows a path toward high speed/linearity in scaled technology. In this hybrid architecture, the resolution of the DAC is achieved through an oversampled LSB path, while its output power is mostly delivered by a Nyquist MSB path, resulting in a reduced number of current-steering cells and relaxed amplitude-matching requirement via digital pre-distortion in the LSB path. To further extend the DAC bandwidth, this architecture incurs high cost, such as higher oversampling ratio in the LSB path and an increasing number of MSB bits. Both cases can increase the complexity of the analog circuit. Moreover, when the DAC output frequency is higher, timing error effects (including delay and duty-cycle errors) become more important than that of the amplitude error. In this work, we propose: a) an in-band noise-cancellation scheme that extends the overall bandwidth with less overhead, and b) a pulsed timing-error pre-distortion scheme to achieve high linearity at higher frequencies. A proof-of-concept 12b 2GS/s hybrid DAC is implemented in 65nm CMOS that achieves 96 to 74dBc SFDR from DC to 1GHz Nyquist band, which is higher than that of the state-of-the-art high-speed (>1GS/s) CMOS DACs reported in [2–4], compared at the same output frequencies. The proposed pulsed timing error pre-distortion scheme also improves the SFDR from 68 to 74dBc at 949MHz, which confirms its effectiveness when the signal frequency is high.
Facile Synthesis of a Platinum Nanoflower Monolayer on a Single-Walled Carbon Nanotube Membrane and Its Application in Glucose Detection

Platinum nanomaterials have shown to be highly attractive due to their superior catalytic ability with high utilization efficiency. Electrodeposition is a flexible technique to produce nanostructures with controllable morphology and high purity. In this study, platinum nanoparticles with tunable structure were synthesized on a single-walled carbon nanotube membrane via cyclic voltammetry. Specifically, a Pt nanoflower monolayer consisting of numerous petal-like nanosheets with a high specific surface area was obtained under the optimized condition. The Pt nanosheet grew anisotropically along the ⟨111⟩ direction and showed a typical face-centered cubic crystal structure. Moreover, the as-prepared free-standing Pt nanoflower membrane exhibited excellent catalytic ability toward amperometric detection of glucose at neutral pH with a low detection limit and a wide linear range.
Defining the Focus in Solution-Focused Brief Therapy

This paper explores an often underrepresented aspect of solution-focused brief therapy (SFBT): the notion of focus. The view that the focus in SFBT is on solution development is often overrepresented, and it seems that the evolving relational focus of SFBT needs to be put in the foreground. That is, there is a recursive relationship between the client’s focus and the therapist’s focus. In the beginning of therapy, the therapist pays attention to the client’s focus—usually problem discussion. Once the therapist acknowledges the client’s current position, the client is better able to pay attention to the therapist’s alternative focus—solution development. In this paper, we utilize a case transcript of Insoo Kim Berg, one of the developers of SFBT, to demonstrate how the relational focus moves the session forward toward client change. We conclude by suggesting that future SFBT treatment manuals and textbooks include the importance of having a relational focus when using SFBT in order to uphold the integrity and quality of the SFBT model.
798OAR-V7 SPLICE VARIANT AND RESISTANCE TO ENZALUTAMIDE AND ABIRATERONE IN MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC): OVERALL SURVIVAL RESULTS

ABSTRACT Aim: Androgen receptor splice variant-7 (AR-V7) is a truncated form of the AR that lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We previously reported (ASCO 2014; abstract 5001) that detection of AR-V7 in circulating tumor cells (CTCs) from men with mCRPC was associated with resistance to enzalutamide and abiraterone: PSA responses and progression-free survival (PFS) were inferior in AR-V7–positive men treated with both agents. Here, we present overall survival (OS) data from this study. Methods: We used qRT-PCR to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with mCRPC starting treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status and OS. Multivariable Cox regression analyses were conducted to determine the independent effect of AR-V7 status on OS. We also performed a combined analysis of OS using data from all patients. Results: 31 enzalutamide-treated men and 31 abiraterone-treated men were enrolled, of which 12/31 (38.7%) and 6/31 (19.4%) had detectable AR-V7 in pretreatment CTC samples, respectively. In men receiving enzalutamide [n = 31], AR-V7–positive patients demonstrated inferior OS compared to AR-V7–negative patients (HR 6.9, 95% CI 1.7–28.1, log-rank P = 0.002). Similarly, in men receiving abiraterone [n = 31], AR-V7–positive patients had inferior OS (HR 12.7, 95% CI 1.3–125.3, log-rank P = 0.006). In the combined analysis [n = 62], the negative prognostic impact of AR-V7 was maintained (HR 8.3, 95% CI 2.5–27.4, log-rank P Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is associated with resistance to both enzalutamide and abiraterone, as evidenced by inferior PSA responses, PFS and OS. AR-V7 status may be used as a non-invasive biomarker to predict resistance to AR-targeting agents, facilitate treatment selection, and fuel the development AR N-terminal–domain inhibitors. Disclosure: E.S. Antonarakis is a paid consultant/advisor for Janssen, Sanofi and Dendreon. He receives research funding from Janssen, Johnson & Johnson, Sanofi, Dendreon, Aragon, Exelixis, Millennium, Genentech and Novartis. All other authors have declared no conflicts of interest.
Children as Living Donors

Within three years of the first successful kidney transplant in the United States between adult identical twins (1954), physicians were in court getting permission to perform kidney transplants between minor identical twins (1957). In the 1970s and 1980s, at least two dozen additional cases involving donation from non-identical twin siblings as well as siblings with cognitive disabilities underwent judicial review. With some notable exceptions, the courts authorized the donations, usually on the grounds that it was in the best interest of both the donor and the recipient. There are data that show that children have also served as donors for other solid organs. In this chapter we examine the ethics of involving minors as living solid organ donors. Our position is that ethically children can serve as living solid organ donors only in very limited circumstances.
A Hybrid Approach to Aortic Stent Implantation

The vast majority of aortic stent placement can be performed simply and safely using percutaneous retrograde access from the femoral artery (REF-CCISC). There are, however, several settings when a hybrid approach to aortic stenting may be preferable or the only option available. Examples include:
When Women Fail to “Hold Up More Than Half the Sky”

Communist beliefs on gender equality and Chinese female athletes’ consistent ability to win national glory have lead to female athletes in Chinese sports media being primarily portrayed as legitima...
Abstract 78: Chronic Intrarenal Ghrelin Receptor Antagonism Delays the Onset and Attenuates the Magnitude of High Fat Diet-Induced Hypertension in Dahl Salt-Sensitive Rats

Excess weight gain contributes up to 65% of the risk of primary hypertension in developed countries and the increase in blood pressure (BP) in response to high-fat diet (HFD) is preceded by significant reductions in renal tubular sodium (Na+) excretion. In normal rats, direct renal infusion of ghrelin, the most potent appetite-stimulating hormone in the body, increases distal nephron-dependent Na+ reabsorption via activation of ghrelin receptors (GR) in the kidney. The present study seeks to determine the role of intrarenal GR-mediated Na+ reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats (DSS) received standard diet (STD, 10% kcal fat, N=6) or HFD (42% kcal fat, N=14) for 6 weeks (WK). Prior to the initiation of the study, all DSS underwent a uninephrectomy and osmotic minipump implantation for chronic renal interstitial (RI) delivery of 5% dextrose in water (D5W, 0.25 μL/hr x 28-day) or selective GR antagonist [D-Lys-3]-GHRP-6 (D-LYS, Tocris, IC50=0.9 μmol/L, 5 mg over 28-day) into the remaining kidney. At the end of the study, pump patency and security of RI delivery was confirmed via direct visualization. DSS with D5W pumps (N=7) demonstrated a significant increase in mean systolic BP (SBP) after 2 WK on HFD (135±4.4 mmHg vs. 118±2.7 mmHg at baseline, *P<0.05) with a mean SBP of 150±3.9 mmHg by WK 6 (\***|P<0.001 from baseline). However, DSS with D-LYS pumps (N=7) for chronic RI GR antagonism during HFD failed to become hypertensive until WK 4 (134±3.9 mmHg vs. 121±3.3 mmHg at baseline, *P<0.05) and the mean SBP achieved at WK 6 was only 139±3.6 mmHg (+P<0.05 compared to HFD D5W pump rats). DSS fed a STD failed to develop significant hypertension and served as a time control group. HFD rats with D5W pumps demonstrated significantly reduced 24-hr urine Na+ excretion prior to the onset of hypertension at WK 2 (0.94±0.15 vs. 1.35±0.09 μmol/min at baseline, *P<0.05). The reduction in Na+ excretion failed to occur in DSS with a D-LYS pump (1.24 ±0.12 vs. 1.29±0.09 μmol/min at baseline, P=NS) despite exposure to the same HFD and identical weight gain. These results indicate that increased intrarenal GR-mediated Na+ reabsorption contributes to the development of HFD-induced hypertension, offering a novel therapeutic target for obesity-induced hypertension.
Entrepreneurship Incentives for Resource-Constrained Firms

Government should not always try to encourage innovation and entrepreneurship by offering incentives. But when it does, it should consider the fact that these incentives are often less attractive to resource-constrained firms, like startups, even though startups are promising sources of innovation. Traditional tax incentives, for instance, offer larger, earlier benefits to profitable, established firms. Legal incentives can be made more accessible to startups and other resource-constrained firms. Policies can reduce or delay transaction costs. They can offer ex ante benefits through mechanisms like refundable tax credits or full loss offsets, so that startups and established firms benefit more equally. Policies can also allow firms to monetize legal benefits or finance investment in legal benefits by transferring them to investors. Policy that seeks to incentivize entrepreneurship or innovation should account for the diversity of firms that might take advantage of legal incentives. It should not assume that firms are profitable. Rather, entrepreneurial incentives should accommodate the important case of resource-constrained, loss-making firms.
The Uncoordinated Public Domain

When nations amend their copyright laws in response to calls for international harmonization, they usually expand authors’ rights without also seeking to harmonize national public domains. Divergent national copyright laws have resulted in an uncoordinated global public domain that renders authors’ works freely available for use in some countries while subjecting them to copyright or moral-rights protection in others. While the fragmented global commons thwarts many valuable uses of cultural resources, it has especially deleterious effects on the ability of researchers to access, copy, and disseminate historical and literary materials, many of which remain unpublished. These effects are mirrored and exacerbated by the inconsistent policies of cultural repositories that control access to millions of documents and images. The uncoordinated public domain shares certain features — notably, fragmented ownership and resource underuse — with an anticommons. This Article offers a theoretical framework for understanding the uncoordinated public domain, and illustrates the tragic inefficiencies of this patchwork commons by discussing its impact on a number of research and publishing projects involving modern authors — in particular, James Joyce. A balanced solution to the checkerboard effects of the commons would be to employ a treaty-based system of compulsory licenses to harmonize national public domains and to coordinate the legal conditions whereby the world’s vast informational resources could be globally disseminated by researchers and other users.
The trend toward minimally invasive complex abdominal wall reconstruction: is it worth it?

Open abdominal wall reconstruction (AWR) was previously one of the only methods available to treat complex ventral hernias. We set out to identify the impact of laparoscopy and robotics on our AWR program by performing an economic analysis before and after the institution of minimally invasive AWR. We retrospectively reviewed inpatient hospital costs and economic factors for a consecutive series of 104 AWR cases that utilized separation of components technique (57 open, 38 laparoscopic, 9 robotic). Patients were placed into two groups by date of procedure. Group 1 (Pre MIS) was July 2012–June 2015 which included 52 open cases. Group 2 (Post MIS) was July 2015–August 2016 which included 52 cases (5 open, 38 laparoscopic, 9 robotic). A total of 104 patients (52 G1 vs. 52 G2) with mean age (54.2 vs. 54.1 years, p = 0.960), BMI (34.7 vs. 32.1 kg/m2, p = 0.059), and ASA score (2.5 vs. 2.3, p = 0.232) were included in this review. Total length of stay (LOS) was significantly shorter for patients in the Post MIS group (5.3 vs. 1.4 days, p < 0.001). Although operating room (OR) supply costs were $1705 higher for the Post MIS group (p = 0.149), total hospital costs were $8628 less when compared to the Pre MIS group (p < 0.001). Multiple linear regressions identified increased BMI (p = 0.021), longer OR times (p = 0.003), and LOS (p < 0.001) as predictors of higher total costs. Factors that were predictive of longer LOS included older patients (p = 0.003) and patients with larger defect areas (p = 0.004). MIS was predictive of shorter hospital stays (p < 0.001). Despite an increase in operating room supply costs, transition to performing MIS AWR in cases that were previously done through an open approach decreased LOS and translated into significant overall total cost savings.
Application of Artificial Neural Network-Based Survival Analysis on Two Breast Cancer Datasets

This paper applies artificial neural networks (ANNs) to the survival analysis problem. Because ANNs can easily consider variable interactions and create a non-linear prediction model, they offer more flexible prediction of survival time than traditional methods. This study compares ANN results on two different breast cancer datasets, both of which use nuclear morphometric features. The results show that ANNs can successfully predict recurrence probability and separate patients with good (more than five years) and bad (less than five years) prognoses. Results are not as clear when the separation is done within subgroups such as lymph node positive or negative.
The Role of the Adeno-Associated Virus Capsid in Gene Transfer

Adeno-associated virus (AAV) is one of the most promising viral gene transfer vectors that has been shown to effect long-term gene expression and disease correction with low toxicity in animal models, and is well tolerated in human clinical trials. The surface of the AAV capsid is an essential component that is involved in cell binding, internalization, and trafficking within the targeted cell. Prior to developing a gene therapy strategy that utilizes AAV, the serotype should be carefully considered since each capsid exhibits a unique tissue tropism and transduction efficiency. Several approaches have been undertaken in an effort to target AAV vectors to specific cell types, including utilizing natural serotypes that target a desired cellular receptor, producing pseudotyped vectors, and engineering chimeric and mosaic AAV capsids. These capsid modifications are being incorporated into vector production and purification methods that provide for the ability to scale-up the manufacturing process to support human clinical trials. Protocols for small-scale and large-scale production of AAV, as well as assays to characterize the final vector product, are presented here. The structures of AAV2, AAV4, and AAV5 have been solved by X-ray crystallography or cryo-electron microscopy (cryo-EM), and provide a basis for rational vector design in developing customized capsids for specific targeting of AAV vectors. The capsid of AAV has been shown to be remarkably stable, which is a desirable characteristic for a gene therapy vector; however, recently it has been shown that the AAV serotypes exhibit differential susceptibility to proteases. The capsid fragmentation pattern when exposed to various proteases, as well as the susceptibility of the serotypes to a series of proteases, provides a unique fingerprint for each serotype that can be used for capsid identity validation. In addition to serotype identification, protease susceptibility can also be utilized to study dynamic structural changes that must occur for the AAV capsid to perform its various functions during the virus life cycle. The use of proteases for structural studies in solution complements the crystal structural studies of the virus. A generic protocol based on proteolysis for AAV serotype identification is provided here.
Quantitative Analysis of Ultralow-Density Materials Using Laboratory-Based Quasi-Monochromatic Radiography

The measurement of the density of materials, especially ultralow-density foams, is difficult in that the measurement must be precise and localizable. The density of the material is often governed b...
TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice.

Abstract Numerous studies have demonstrated that short-term air pollution exposure causes cardiac autonomic imbalance as measured by heart rate variability (HRV). We previously showed that a single exposure to acrolein, a ubiquitous gaseous component of air pollution, not only causes autonomic imbalance, but also increases arrhythmia through transient receptor potential A1 (TRPA1) cation channels. Thus, the goal of this study was to characterize acrolein-induced autonomic changes in both normal and TRPA1-knockout mice (KO). Conscious, unrestrained C57BL/6 (WT) and KO mice were exposed to 3 ppm acrolein for 3 h. Separate groups were treated with either atenolol (sympathetic blocker), atropine (parasympathetic blocker) or hexamethonium (autonomic neurotransmission blocker), immediately before exposure. Electrocardiogram (ECG) and heart rate (HR) were recorded continuously before, during and after exposure. Exposure to acrolein produced significant increases in standard deviation of normal-to-normal R-R intervals (SDNN), Root Mean Square of the Successive Differences (RMSSD) and Low-Frequency (LF), as well as an increase in arrhythmia in WT mice. Treatment with atenolol reduced this response while atropine enhanced it, and both drugs blocked the acrolein-induced increase in arrhythmia; hexamethonium had no effect. On the other hand, neither acrolein nor any drug had an effect in the KO mice. Thus, acrolein-induced HRV responses appear to be mediated by a combined parasympathetic and sympathetic modulation. KO mice did not demonstrate any increases in HRV with exposure to acrolein. These data demonstrate that the cardiac effects of irritant air pollutants likely involve disruption of homeostatic balance and altered regulation even in healthy animals.
Radiographic Vasospasm and Clinical (Symptomatic) Vasospasm

Abstract Cerebral vasospasm is a focal or diffuse, temporary narrowing of cerebral arteries as evidenced by digital subtraction angiography, transcranial Doppler, magnetic resonance, or computed tomography angiography. Cerebral vasospasm often results when cerebral vessels are exposed to blood in the subarachnoid space (subarachnoid hemorrhage), but may also occur after traumatic brain injury or secondary to inflammatory conditions such as meningitis and vasculitis. Radiographic spasm may progress to clinical (symptomatic) vasospasm as evidenced by neurologic deterioration and eventual permanent neurologic defect secondary to infarction. Autoregulatory dysfunction, inflammation, microcirculatory failure, and spreading cortical depolarization are multiple facets of the disease process that must be addressed with multimodal treatment to achieve improved neurologic outcomes. Rapid identification of symptomatic vasospasm with urgent treatment is essential to prevent permanent neurologic deficit. Ultimately, symptomatic vasospasm is best managed with hypertension followed by endovascular treatment with intra-arterial spasmolytics and/or balloon angioplasty.
Matoy jirofo, masaka lavany: Rural–urban migrants' livelihood strategies through the lens of the clove commodity cycle in Madagascar

Residents of many African cities face economic uncertainty due to high rates of under‐ and unemployment and lack of government support. In response, many urban Africans have fortified their links to rural areas as a strategy to weather uncertainty and reduce vulnerability. Scholars have documented high rates of ownership of rural resources (e.g., land, housing, and livestock) by people living in cities as proof of the strength of rural–urban linkages in Africa. In this article, I argue that the use of rural resources to reduce urban expenditures or increase income cannot be assumed and depends on the social relationships between city and village residents. I draw on twenty‐four months of ethnographic fieldwork with rural–urban migrants in northeastern Madagascar. I focus on the clove season of 2011–12, a spectacular moment in which high yields and prices created a market boom for this agricultural commodity. While many urban migrants had claimed access to clove trees, not all of these individuals were successful in actually accessing the clove crop or the income generated from its sale during the 2011–12 season. Exploring the winners and losers in this commodity boom reveals that investing in social relationships with rural family and friends has important economic consequences for urban migrants.
Perrone, Charles A. Brazil, Lyric, and the Americas. UP of Florida, 2010.

The appearance of Charles Perrone’s new book on lyric poetry in the Americas is cause for celebration. As the field of inter-American literature grows, and as the crucial role of Brazilian literature in it becomes more and more apparent, the importance of discerning and comparative book-length studies like Brazil, Lyric, and the Americas cannot be overestimated. A renowned scholar of Brazilian literature and culture, and a leading inter-Americanist, Perrone has here done both these disciplines a great service.
Typology of cannabis use among adults: A latent class approach to risk and protective factors.

Abstract Background Cannabis is among the most widely used substances worldwide. The United States has seen an increase in the number of adult daily cannabis users and in the number of adults diagnosed with cannabis use disorder. However, little work has examined patterns of use or unique subgroups of adult cannabis users, which may be useful in developing targeted treatment interventions for problematic cannabis users. Therefore, the current study used latent profile analysis to identify whether cannabis users can be categorized across distinct subgroups of adult users. Method The sample included 374 current cannabis using adults (64.2% Male; Mage = 32.6). Cannabis use frequency, quantity, and related problems were used to differentiate subgroups. Further, age, race, emotion dysregulation, affect, anxiety sensitivity, other substance use, and motives for cannabis use were examined as class correlates. Results Results supported five unique classes of cannabis users, generally ranging from light, infrequent users with few problems to heavy, frequent users with more problems. Additionally, race, negative affectivity, anxiety sensitivity, emotion regulation, cannabis use motives, and alcohol use emerged as unique predictors of class membership. The current findings substantiate past work for heterogeneous latent classes that underlie the larger cannabis using population, however, this study provides novel evidence for subgroups of adult users. Conclusion The identification of different classes of cannabis users may inform future treatment interventions, and ultimately, lead to the development of personalized treatments for each class based on correlates of group membership.
SP0097 Check-point inhibitors: what are they used for, about side-effects and prediction of efficacy

The development of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) have significantly improved the treatment of a variety of metastasized cancers, such as melanoma, lung cancer, renal and bladder cancer. Immune checkpoint inhibitors enhance antitumor immunity by blocking negative regulators of T-cell function that exist both on immune cells and on tumour cells. Although these agents can lead to remarkable responses, their use can also be associated with unique immune-related adverse effects (irAEs). Consensus guidelines regarding the treatment of the most common irAEs including rash, colitis, hepatitis, endocrinopathies, and pneumonitis have been established. The mainstay of irAE treatment consists of immunosuppression with corticosteroids or other immunosuppressant agents such as infliximab; most irAEs will resolve with appropriate management. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors do not respond. Several markers have shown promising predictive value, including baseline and post-treatment changes in leucocyte counts, lactate dehydrogenase and C-reactive protein. To date, research on routinely available blood, biopsies and clinical markers has focused primarily on checkpoint inhibitors use in melanoma and lung cancer, but preliminary evidence is emerging for other cancer types. Disclosure of Interest None declared
Academic Writing: A Handbook for International Students (3rd Ed.)

For many international students, academic writing is a significant challenge because of the rules used in Standard English. Writing in academia consists of producing college essays, reflections, reports, and research papers which all require a working knowledge of the English language. Nevertheless, English Composition instructors, English as a Second Language (ESL) program staff, and freshmen international students will find Bailey’s book Academic Writing text a helpful resource manual both in and out of class.
Abstract 153: Predictors of Aspirin Nonadherence in Adults with Prior Myocardial Infarction

Background: Medication nonadherence is an alarming public health concern due to its effect on both individual treatment success and overall health care costs. In this study, we sought to identify t...
Toward the Development of Weather-Dependent Microsimulation Models:

Adverse weather conditions severely affect transportation networks. Decades of research have been dedicated to analyzing these impacts and developing countermeasures to reduce their negative effect...
Dark disk substructure and superfluid dark matter

Abstract Dark matter substructure has the potential to discriminate between broad classes of dark matter models. With this in mind, we construct novel solutions to the equations of motion governing condensate dark matter candidates, namely axion Bose-Einstein condensates and superfluids. These solutions are highly compressed along one axis and thus have a disk-like geometry. We discuss linear stability of these solutions, consider the astrophysical implications as a large-scale dark disk or as small scale substructure, and find a characteristic signal in strong gravitational lensing. This adds to the growing body of work that indicates that the morphology of dark matter substructure is a powerful probe of the nature of dark matter.
Semiconductor Quantum Dot FRET: Untangling Energy Transfer Mechanisms in Bioanalytical Assays

Abstract Since their development at the turn of the millennium, bright and water-soluble semiconductor quantum dots (QDs) have been applied in analytical chemistry. QDs serve as excellent platforms for ratiometric sensing of biologicals via analyte-dependent manipulation of dipolar energy transfer. Several examples are provided, such as sandwich assays comprised of lanthanide donors and QD acceptors and highly multiplexed sensing schemes that have been realized due to QDs’ supermolecular sizes. However, QDs do not conform to the standard Forster energy transfer mechanism. For example, QDs are excellent donors but poor acceptors when coupled to organic dyes; yet, the same is not true for inorganic phosphors. Furthermore, QDs may reduce or oxidize substrates while engaging in dipolar energy transfer with them. Many of these observations have yet to be explained. Fortunately, optical methods are being developed to untangle these competing mechanisms, which will lead to a complete understanding of QD energy transfer processes.