The Effect of Losses Disguised as Wins and Near Misses in Electronic Gaming Machines: A Systematic Review.

Near misses and losses disguised as wins have been of interest to gambling researchers and policymakers for many years (e.g., Griffiths in J Gambl Stud 9(2):101-120, 1993). This systematic literature review describes the behavioural, psychological, and psychobiological effects of near misses and losses disguised as wins (LDWs) in an effort to evaluate their precise influence on the player and to highlight areas requiring further investigation. A systematic search for relevant studies was conducted using Scopus, PubMed, PsycINFO, ProQuest Sociology databases, and the Gambling Research Exchange Ontario Knowledge Repository. A total of 51 (from an initial pool of 802) experimental peer-reviewed studies using human participants were found between 1991 and 2015. The systematic review revealed that near misses motivate continued play, but have varying effects on the emotional state or betting behaviour of the player. Near miss events were also shown to be associated with elevated skin conductance levels and diffuse activity across the brain, most consistently in areas processing reinforcement and reward. Re-examination of the studies of near misses events after classifying the type of game feedback suggested that the effectiveness of near misses is related to the phenomenology of a near miss itself rather than as a response to auditory or visual feedback provided by a slot machine. In contrast to near misses, the presence of LDWs was found to relate to an overestimation of how much a player is actually winning and was consistently viewed as an exciting event. The effect of LDWs appears to be driven by the presence of visuals and sounds most often associated with a true win. Practical implications and directions for future research are also discussed.

At the margins: Agriculture, subsidies and the shifting fate of North America's Native Grassland.

We examined patterns of shifting cropland cultivation in the US Great Plains from the dust bowl to the beginning of the 21st century, by comparing land-cover data from 400 sample sites across the region from the 1930s, 1950s, 1970s and, 1990s and 2000s. We argue that understanding the use of marginal land for cultivation in the Great Plains since the Great Depression requires understanding the interacting dynamics of demography, technology, and policy. The small area land-cover data are nested within 50 target counties across the region. We draw on these dynamics, and their interactions with a range of policy programs aimed at reducing environmental impacts of agriculture, to tell the story of how and when marginal lands have been brought into use. In a multi-level panel design, macro- and micro-level covariates were used to predict levels of encroachment on marginal soils. We conclude that land retirement programs (like the Conservation Reserve Program) have had a generally stabilizing effect on the micro-level patterns of land use in recent decades, but that increased levels of encroachment on marginal soils and native grassland remain a problem in areas with higher or increasing population densities.

Imaging as a tumor biomarker in oncology drug trials for lung cancer: the FDA perspective.

The US Food and Drug Administration (FDA) is committed to working with the oncology community to expedite the drug evaluation process in view of the many promising new oncology drugs under laboratory development and the time and expense required for such new drugs to reach the patient population. One significant advance would be to enable quantitative imaging as a tumor biomarker. The FDA is working with the pharmaceutical industry, academia, and sister stakeholders in the government, primarily through collaborative educational and research efforts, to identify how imaging can serve this function.

Effects of nonionic surfactants on bacterial transport through porous media.

Nonionic surfactants of the form CxEy, where x is the number of carbons in the alkyl chain and y is the number of ethylene oxide units in the polyoxyethylene (POE) chain, were studied for their ability to alter the transport of Sphingomonas pacilimobilis through an aquifer sand. The surfactants C12E4 (Brij 30) and C12E23 (Brij 35) were the focus of this study. Through a systematic study, it was shown that these nonionic surfactants were able to enhance the transport of this bacterial culture through porous media. The magnitude of the enhancement increased with decreasing solution ionic strength and increasing POE chain length. The mechanism of this enhanced transport appears to be due to expansion of the electric double layer about the bacteria and aquifer sand through displacement of the counterions by the sorbed surfactant. This expanded electric double layer increases the electrostatic repulsion, with a resultant reduction in the collision efficiency and an increase in the Langmuirian blocking parameter. Application of the colloid filtration theory with the experimental parameters of this study shows that nonionic surfactants have the potential to significantly enhance the bacterial travel distance, especially for low ionic strength systems.

Physiological concentrations of K+ inhibit cytochrome c-dependent formation of the apoptosome.

In many forms of apoptosis, cytochrome c released from mitochondria induces the oligomerization of Apaf-1 to form a caspase-activating apoptosome complex. Activation of lysates in vitro with dATP and cytochrome c results in the formation of an active caspase-processing approximately 700-kDa apoptosome complex, which predominates in apoptotic cells, and a relatively inactive approximately 1.4-MDa complex. We now demonstrate that assembly of the active complex is suppressed by normal intracellular concentrations of K(+). Using a defined apoptosome reconstitution system with recombinant Apaf-1 and cytochrome c, K(+) also inhibits caspase activation by abrogating Apaf-1 oligomerization and apoptosome assembly. Once assembled, the apoptosome is relatively insensitive to the effects of ionic strength and processes/activates effector caspases. The inhibitory effects of K(+) on apoptosome formation are antagonized in a concentration-dependent manner by cytochrome c. These studies support the hypothesis that the normal intracellular concentrations of K(+) act to safeguard the cell against inappropriate formation of the apoptosome complex, caused by the inadvertent release of small amounts of cytochrome c. Thus, the assembly and activation of the apoptosome complex in the cell requires the rapid and extensive release of cytochrome c to overcome the inhibitory effects of normal intracellular concentrations of K(+).

Effects of nonionic surfactants on the UV/visible absorption of bacterial cells.

Nonionic surfactants are used in a number of different microbiological applications, including solubilization of cell membranes, washing bacterial cultures prior to experimentation, and enhancing biodegradation of low-solubility compounds. An important consideration in these applications is the potential for the surfactant to alter the cell membrane. One potential means to monitor the impact of surfactants on the bacterial cell membrane is through monitoring the absorbance spectrum of the bacterial suspension. This is due to the colloidal nature of bacteria, where the absorbance of a bacterial suspension is related to the size and refractive index of the bacterial cells. Through a systematic study it was shown that there can be a significant change in the bacterial absorbance spectrum due to the presence of nonionic surfactants, with the effect a function of surfactant structure and concentration, solution ionic strength and cation valence. The effects were most pronounced with Na(+) as the cation, with surfactants having mid-range hydrophile-lipophile balance (HLB) values, and with surfactant concentrations above the CMC. The results indicate that measurement of the absorbance spectrum of bacterial cultures can provide a means to monitor the effects of nonionic surfactants on the bacterial cell membrane. In addition, depending on the specific application, appropriate selection of surfactant structure and media composition can be made to enhance or minimize the effects.

Spectrophotometric assay of POE nonionic surfactants and its application to surfactant sorption isotherms.

The operational range and suitability toward environmental samples of an iodine-iodide (I-I) assay for nonionic surfactants were assessed. The I-I assay provides a rapid and repeatable method for determining aqueous nonionic surfactant concentrations. Through a systematic examination of surfactant structure, the operational range of the assay was shown to be on the order of 10(-6) to 10(-3) MEO, where the concentration unit MEO is defined as the molar surfactant concentration multiplied by the number of ethylene oxide units in the surfactant molecule. For environmental samples, it was shown that the I-I assay can be applied to measurement of surfactant sorption isotherms to aquifer sands and bacteria cultures. A potential limitation of the I-I assay is interference with humic acids, with the magnitude of the interference dependent on the concentration of humic acids present. The main benefit of the I-I assay is that its high accuracy and ease of application allows measurement of low levels of surfactant sorption. Surfactant sorption to aquifer sand could be measured down to the range of 10(-9) mol/g.

Effect of cryopreservation on measurement of cytomegalovirus-specific cellular immune responses in HIV-infected patients.

To determine the feasibility of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) studies using cryopreserved cells, we compared lymphocyte proliferation assays (LPA), responder cell frequency (RCF), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production using fresh and cryopreserved peripheral blood mononuclear cells (PBMCs) from 53 HIV-infected patients and 15 uninfected controls. Qualitative CMV LPA results were concordant in >/=84% of the specimens from either HIV-infected patients or controls. Proliferation-based RCF, IL-2, and IFN-gamma comparisons showed that cryopreservation reduces the number of CMV-specific responders and decreases cytokine secretion, without changing the rank order of the results (p <.01). In contrast, the number of flow cytometry-enumerated IFN-gamma-producing CD4+ cells was not significantly changed by cryopreservation. In HIV-infected patients, the differences between fresh and frozen cell assays were not influenced by CD4 cell numbers or HIV viral load. These data indicate that cryopreserved cells are suitable for longitudinal studies of the CMV-specific immune response in HIV-infected patients and uninfected controls.

The origins of genomic duplications in Arabidopsis.

Large segmental duplications cover much of the Arabidopsis thaliana genome. Little is known about their origins. We show that they are primarily due to at least four different large-scale duplication events that occurred 100 to 200 million years ago, a formative period in the diversification of the angiosperms. A better understanding of the complex structural history of angiosperm genomes is necessary to make full use of Arabidopsis as a genetic model for other plant species.

Transforming growth factor-beta(1) induces apoptosis in rat FaO hepatoma cells via cytochrome c release and oligomerization of Apaf-1 to form a approximately 700-kd apoptosome caspase-processing complex.

In mammalian cells, non receptor-mediated apoptosis occurs via the cytochrome c-dependent assembly of a approximately 700-kd apoptotic protease-activating factor 1 (Apaf-1)/caspase-9 containing apoptosome complex. This initiates the postmitochondrial-mediated effector caspase cascade. We now show that receptor mediated transforming growth factor beta(1) (TGF-beta(1))-induced apoptosis in rat hepatoma cells is accompanied by processing and activation of caspases-2, -3, -7, and -8. Furthermore, we show that caspase activation is mediated via the release of cytochrome c and the oligomerization of Apaf-1 into an approximately 700-kd apoptosome complex. Similarly, in vitro activation of hepatoma cell lysates with 2'-deoxyadenosine 5'-triphosphate (dATP) results in the formation of the approximately 700-kd apoptosome complex, which recruits and processes caspases-3 and -7. Z-VAD.FMK [benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone], the pan-caspase inhibitor totally inhibits dATP-stimulated caspase activation but does not block the assembly of the large Apaf-1 containing apoptosome complex. However, the recruitment and subsequent processing of caspases-3 and -7 to the apoptosome is blocked. Similarly, in intact cells, although Z-VAD.FMK blocked TGF-beta(1)-induced apoptosis, it did not prevent the oligomerization of Apaf-1 into the apoptosome. However, recruitment and processing of caspases-3 and -7 were prevented by Z-VAD.FMK. These data show that TGF-beta(1) induces apoptosis via release of cytochrome c and activation of the Apaf-1 apoptosome complex, which initiates the caspase cascade.

Selective mapping: a strategy for optimizing the construction of high-density linkage maps.

Historically, linkage mapping populations have consisted of large, randomly selected samples of progeny from a given pedigree or cell lines from a panel of radiation hybrids. We demonstrate that, to construct a map with high genome-wide marker density, it is neither necessary nor desirable to genotype all markers in every individual of a large mapping population. Instead, a reduced sample of individuals bearing complementary recombinational or radiation-induced breakpoints may be selected for genotyping subsequent markers from a large, but sparsely genotyped, mapping population. Choosing such a sample can be reduced to a discrete stochastic optimization problem for which the goal is a sample with breakpoints spaced evenly throughout the genome. We have developed several different methods for selecting such samples and have evaluated their performance on simulated and actual mapping populations, including the Lister and Dean Arabidopsis thaliana recombinant inbred population and the GeneBridge 4 human radiation hybrid panel. Our methods quickly and consistently find much-reduced samples with map resolution approaching that of the larger populations from which they are derived. This approach, which we have termed selective mapping, can facilitate the production of high-quality, high-density genome-wide linkage maps.

Apaf-1 oligomerizes into biologically active approximately 700-kDa and inactive approximately 1.4-MDa apoptosome complexes.

Apaf-1, by binding to and activating caspase-9, plays a critical role in apoptosis. Oligomerization of Apaf-1, in the presence of dATP and cytochrome c, is required for the activation of caspase-9 and produces a caspase activating apoptosome complex. Reconstitution studies with recombinant proteins have indicated that the size of this complex is very large in the order of approximately 1.4 MDa. We now demonstrate that dATP activation of cell lysates results in the formation of two large Apaf-1-containing apoptosome complexes with M(r) values of approximately 1.4 MDa and approximately 700 kDa. Kinetic analysis demonstrates that in vitro the approximately 700-kDa complex is produced more rapidly than the approximately 1.4 MDa complex and exhibits a much greater ability to activate effector caspases. Significantly, in human tumor monocytic cells undergoing apoptosis after treatment with either etoposide or N-tosyl-l-phenylalanyl chloromethyl ketone (TPCK), the approximately 700-kDa Apaf-1 containing apoptosome complex was predominately formed. This complex processed effector caspases. Thus, the approximately 700-kDa complex appears to be the correctly formed and biologically active apoptosome complex, which is assembled during apoptosis.

Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex.

In mammals, apoptotic protease-activating factor 1 (Apaf-1), cytochrome c, and dATP activate caspase-9, which initiates the postmitochondrial-mediated caspase cascade by proteolytic cleavage/activation of effector caspases to form active approximately 60-kDa heterotetramers. We now demonstrate that activation of caspases either in apoptotic cells or following dATP activation of cell lysates results in the formation of two large but different sized protein complexes, the "aposome" and the "microaposome". Surprisingly, most of the DEVDase activity in the lysate was present in the aposome and microaposome complexes with only small amounts of active caspase-3 present as its free approximately 60-kDa heterotetramer. The larger aposome complex (M(r) = approximately 700,000) contained Apaf-1 and processed caspase-9, -3, and -7. The smaller microaposome complex (M(r) = approximately 200,000-300,000) contained active caspase-3 and -7 but little if any Apaf-1 or active caspase-9. Lysates isolated from control THP.1 cells, prior to caspase activation, showed striking differences in the distribution of key apoptotic proteins. Apaf-1 and procaspase-7 may be functionally complexed as they eluted as an approximately 200-300-kDa complex, which did not have caspase cleavage (DEVDase) activity. Procaspase-3 and -9 were present as separate and smaller 60-90-kDa (dimer) complexes. During caspase activation, Apaf-1, caspase-9, and the effector caspases redistributed and formed the aposome. This resulted in the processing of the effector caspases, which were then released, possibly bound to other proteins, to form the microaposome complex.

Statistical properties of estimates of signal-to-noise ratio and number of scatterers per resolution cell.

Elementary theory underlying the relationship between the number of scatterers per resolution cell (N) and echo intensity signal-to-noise ratio (SNR) is reviewed. A relationship between the probability density functions for estimates of N and SNR2 is derived. This relationship is validated using a computer simulation. Phantom and in vitro experiments are described. In one set of experiments on phantoms, empirical distributions of estimates of N and SNR2 are measured and compared to theoretical predictions. The utility of SNR2 for discrimination of phantoms with different values for N is assessed using receiver operating characteristic (ROC) analysis. In another set of experiments, the frequency dependence of the SNR2 estimate is investigated for a two-component phantom and for excised dog kidney. It is shown that the frequency dependence of the SNR can help to identify the presence of two or more scattering components that are spatially mixed. With regard to kidney data, measurements performed both parallel and perpendicular to the predominant nephron orientation are reported. The observed anisotropy is compared to the anisotropy of backscatter coefficient encountered in previous investigations.

Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: characterization of the apoptotic death.

We examined the susceptibility of a variety of human leukemic cell lines to the induction of apoptosis. K562, a chronic myelogenous leukemic cell line which expresses the bcr-abl fusion gene, was found to be extremely resistant to apoptosis, irrespective of the inducing agent. This resistance can be attributed to the deregulated Abl kinase activity of bcr-abl, as downregulation of its expression using antisense oligodeoxynucleotides targeted to the beginning of the abl sequence in this chimeric gene rendered these cells susceptible to cytotoxic drug-induced apoptosis. Examination of the morphological and biochemical features of apoptosis in K562 cells revealed the typical membrane blebbing and chromatin condensation associated with this form of cell death. In situ TdT-mediated end labeling of the DNA revealed the presence of strand breaks in the treated cells and field inversion gel electrophoresis revealed the presence of large 10-50 kb fragments. However there was an absence of oligonucleosomal DNA fragmentation, whether or not Bcr-Abl was expressed. Thus, while inhibition of expression of Bcr-Abl renders K562 cells susceptible to apoptosis, the absence of oligonucleosomal DNA fragmentation in these cells is independent of the function of this molecule.

Dorsal midbrain syndrome due to mesencephalic hemorrhage. Case report with serial imaging.

Spontaneous, nontraumatic, nonhypertensive, midbrain hemorrhage is an uncommon cause of the dorsal midbrain syndrome. We describe a patient with this syndrome in whom the initial neuroimaging studies failed to clearly identify the lesion. Subsequent magnetic resonance imaging studies disclosed a dorsal midbrain hemorrhage. The patient experienced gradual spontaneous resolution of her dorsal midbrain signs and symptoms over several months. The evolution on serial neuroimaging studies of the dorsal midbrain hemorrhage in this patient is described.