Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients

BACKGROUND: During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. METHODS: Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. RESULTS: Completed questionnaires (n = 71) revealed a mean +/- SD patient age of 34 +/- 4.1 yrs. Most (83.1%) had no prior IVF experience; 2.8% reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7% patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/- 11.75 and$654.55 +/- 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. CONCLUSIONS: This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level

The geometry of spontaneous spiking in neuronal networks

The mathematical theory of pattern formation in electrically coupled networks of excitable neurons forced by small noise is presented in this work. Using the Freidlin-Wentzell large deviation theory for randomly perturbed dynamical systems and the elements of the algebraic graph theory, we identify and analyze the main regimes in the network dynamics in terms of the key control parameters: excitability, coupling strength, and network topology. The analysis reveals the geometry of spontaneous dynamics in electrically coupled network. Specifically, we show that the location of the minima of a certain continuous function on the surface of the unit n-cube encodes the most likely activity patterns generated by the network. By studying how the minima of this function evolve under the variation of the coupling strength, we describe the principal transformations in the network dynamics. The minimization problem is also used for the quantitative description of the main dynamical regimes and transitions between them. In particular, for the weak and strong coupling regimes, we present asymptotic formulas for the network activity rate as a function of the coupling strength and the degree of the network. The variational analysis is complemented by the stability analysis of the synchronous state in the strong coupling regime. The stability estimates reveal the contribution of the network connectivity and the properties of the cycle subspace associated with the graph of the network to its synchronization properties. This work is motivated by the experimental and modeling studies of the ensemble of neurons in the Locus Coeruleus, a nucleus in the brainstem involved in the regulation of cognitive performance and behavior

Multisensory cue combination after sensory loss: audio-visual localization in patients with progressive retinal disease

Human adults can combine perceptual estimates from different senses to minimize uncertainty, by taking a reliability-weighted average (the maximum likelihood estimate, MLE). Although research has shown that healthy human adults reweight estimates as their reliability changes from one trial to the next, less is known about how humans adapt to gradual long-term changes in sensory reliability. This study assessed whether individuals diagnosed with progressive visual deterioration, due to retinal disease, combined auditory and visual cues to location according to optimal (MLE) predictions. Twelve patients with central visual loss, 10 patients with peripheral visual loss, and 12 normally sighted adults were asked to localize visual and/or auditory targets in central (1°–18°) and peripheral (36°–53°) locations. Normally sighted adults and patients with peripheral visual loss showed multisensory uncertainty reduction and cue weighting in line with MLE predictions. In contrast, patients with central visual loss did not weight estimates appropriately in either the center or the periphery, and failed to meet MLE predictions in the periphery. Our results show that one visual loss patient group succeeded at optimal cue combination, whereas the other patient group (patients with central vision loss) did not. We propose that sensory remapping due to changes in fixation behavior may contribute to apparent failures in the latter group

Using a cognitive architecture to examine what develops

Different theories of development propose alternative mechanisms by which development occurs. Cognitive architectures can be used to examine the influence of each proposed mechanism of development while keeping all other mechanisms constant. An ACT-R computational model that matched adult behavior in solving a 21-block pyramid puzzle was created. The model was modified in three ways that corresponded to mechanisms of development proposed by developmental theories. The results showed that all the modifications (two of capacity and one of strategy choice) could approximate the behavior of 7-year-old children on the task. The strategy-choice modification provided the closest match on the two central measures of task behavior (time taken per layer, r = .99, and construction attempts per layer, r = .73). Modifying cognitive architectures is a fruitful way to compare and test potential developmental mechanisms, and can therefore help in specifying “what develops.

The (LATTICE) QCD Potential and Running Coupling: How to Accurately Interpolate between Multi-Loop QCD and the String Picture

We present a simple parameterization of a running coupling constant, defined via the static potential, that interpolates between 2-loop QCD in the UV and the string prediction in the IR. Besides the usual \Lam-parameter and the string tension, the coupling depends on one dimensionless parameter, determining how fast the crossover from UV to IR behavior occurs (in principle we know how to take into account any number of loops by adding more parameters). Using a new Ansatz for the LATTICE potential in terms of the continuum coupling, we can fit quenched and unquenched Monte Carlo results for the potential down to ONE lattice spacing, and at the same time extract the running coupling to high precision. We compare our Ansatz with 1-loop results for the lattice potential, and use the coupling from our fits to quantitatively check the accuracy of 2-loop evolution, compare with the Lepage-Mackenzie estimate of the coupling extracted from the plaquette, and determine Sommer's scale $r_0$ much more accurately than previously possible. For pure SU(3) we find that the coupling scales on the percent level for $\beta\geq 6$.Comment: 47 pages, incl. 4 figures in LaTeX [Added remarks on correlated vs. uncorrelated fits in sect. 4; corrected misprints; updated references.

Excitation of High-Spin States by Inelastic Proton Scattering

This work was supported by National Science Foundation Grant PHY 76-84033 and Indiana Universit

Excitation of High-Spin States by Inelastic Proton Scattering

This work was supported by National Science Foundation Grant PHY 75-00289 and Indiana Universit

A measurement of parity-violating gamma-ray asymmetries in polarized cold neutron capture on 35Cl, 113Cd, and 139La

An apparatus for measuring parity-violating asymmetries in gamma-ray emission following polarized cold neutron capture was constructed as a 1/10th scale test of the design for the forthcoming n+p->d+gamma experiment at LANSCE. The elements of the polarized neutron beam, including a polarized 3He neutron spin filter and a radio frequency neutron spin rotator, are described. Using CsI(Tl) detectors and photodiode current mode readout, measurements were made of asymmetries in gamma-ray emission following neutron capture on 35Cl, 113Cd, and 139La targets. Upper limits on the parity-allowed asymmetry $s_n \cdot (k_{\gamma} \times k_n)$ were set at the level of 7 x 10^-6 for all three targets. Parity-violating asymmetries $s_n \cdot k_{\gamma}$ were observed in 35Cl, A_gamma = (-29.1 +- 6.7) x 10^-6, and 139La, A_gamma = (-15.5 +- 7.1) x 10^-6, values consistent with previous measurements.Comment: 19 pages, 4 figures, submitted to Nucl. Instr. and Meth.

A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

Background: In the USA, the breast cancer mortality rate is 41% higher for African-American women than non-Hispanic White women. While numerous gene expression studies have classified biological features that vary by race and may contribute to poorer outcomes, few studies have experimentally tested these associations. CRYβB2 gene expression has drawn particular interest because of its association with overall survival and African-American ethnicity in multiple cancers. Several reports indicate that overexpression of the CRYβB2 pseudogene, CRYβB2P1, and not CRYβB2 is linked with race and poor outcome. It remains unclear whether either or both genes are linked to breast cancer outcomes. This study investigates CRYβB2 and CRYβB2P1 expression in human breast cancers and breast cancer cell line models, with the goal of elucidating the mechanistic contribution of CRYβB2 and CRYβB2P1 to racial disparities. Methods: Custom scripts for CRYβB2 or CRYβB2P1 were generated and used to identify reads that uniquely aligned to either gene. Gene expression according to race and tumor subtype were assessed using all available TCGA breast cancer RNA sequencing alignment samples (n = 1221). In addition, triple-negative breast cancer models engineered to have each gene overexpressed or knocked out were developed and evaluated by in vitro, biochemical, and in vivo assays to identify biological functions. Results: We provide evidence that CRYβB2P1 is expressed at higher levels in breast tumors compared to CRYβB2, but only CRYβB2P1 is significantly increased in African-American tumors relative to White American tumors. We show that independent of CRYβB2, CRYβB2P1 enhances tumorigenesis in vivo via promoting cell proliferation. Our data also reveal that CRYβB2P1 may function as a non-coding RNA to regulate CRYβB2 expression. A key observation is that the combined overexpression of both genes was found to suppress cell growth. CRYβB2 overexpression in triple-negative breast cancers increases invasive cellular behaviors, tumor growth, IL6 production, immune cell chemoattraction, and the expression of metastasis-associated genes. These data underscore that both CRYβB2 and CRYβB2P1 promote tumor growth, but their mechanisms for tumor promotion are likely distinct. Conclusions: Our findings provide novel data emphasizing the need to distinguish and study the biological effects of both CRYβB2 and CRYβB2P1 as both genes independently promote tumor progression. Our data demonstrate novel molecular mechanisms of two understudied, disparity-linked molecules

Results of the First Coincident Observations by Two Laser-Interferometric Gravitational Wave Detectors

We report an upper bound on the strain amplitude of gravitational wave bursts in a waveband from around 800Hz to 1.25kHz. In an effective coincident observing period of 62 hours, the prototype laser interferometric gravitational wave detectors of the University of Glasgow and Max Planck Institute for Quantum Optics, have set a limit of 4.9E-16, averaging over wave polarizations and incident directions. This is roughly a factor of 2 worse than the theoretical best limit that the detectors could have set, the excess being due to unmodelled non-Gaussian noise. The experiment has demonstrated the viability of the kind of observations planned for the large-scale interferometers that should be on-line in a few years time.Comment: 11 pages, 2 postscript figure