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.

Structural alteration in isolated rat liver nuclei after removal of template restriction by polyanions.

Specific polyanions release DNA template restrictions for DNA synthesis in isolated rat liver nuclei. The degree to which DNA synthesis is enhanced can be correlated with a spectrum of changes in nuclear structure Each polyanion which is effective in the release of template restriction produces a characteristic alteration in nuclear ultrastructure. Polyanions which have no effect on DNA synthesis do not appear to cause any change in nuclear organization or ultrastructure. Parallel measurements of nuclear DNA release and nuclear volume changes also indicate that template-activating polyanions cause remarkable changes in the structural organization of the treated nuclei. These results indicate that DNA template activation involves direct interactions between polyanions and nuclear constituents and suggest the possibility that naturally occurring polyanions might have a role in the control of gene activity

Release of nuclear DNA template restrictions by specific polyribonucleotides.

Certain synthetic homo- and copolyribonucleotide polymers are capable of releasing the DNA template restriction of isolated nuclei of rat liver cells when assayed with an excess of or in the absence of exogenous DNA polymerase. The purine homopolyribonucleotides are far more effective than are the pyrimidine polymers.

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.

Nuclear localization of histamine in neonatal rat brain.

The concentration of histamine in the brains of neonatal rats is considerably higher than that in adults. Subcellular fractionation studies revealed that about 90 percent of the histamine content of neonatal rat brain is confined to the crude nuclear fraction obtained by differential fractionation. Purified nuclei prepared from these fractions retained 90 percent of their histamine content. The nuclear localization of histamine in the brains of neonatal rats suggests a function for histamine in modulating the growth processes of the neonatal brain.

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.

The interaction between vitamin B-12 and micelles in aqueous solution.

The apparent pK for benzimidazole displacement of a number of cobalamins is markedly affected by the presence of sodium lauryl sulfate micelles. However, micelles of cetyltrimethylammonium bromide or Triton X have little or no effect on the pK. By measuring the apparent pK as a function of sodium lauryl sulfate concentration, the association constants between the micelles and both base on and base off methylcobalamin were calculated. This calculation indicates that the base off form is strongly associated with the micelle while the base on form is not.

Effects of polyamines and methylglyoxal bis(guanylhydrazone) on Escherichia coli ribonucleic acid polymerase and the template activity of hepatic cell nuclei in vitro.

Escherichia coli RNA polymerase was assayed with 4 mM Mg2+ and 1 mM Mn2+ using native DNA, heat-denatured DNA, histone-nucleate and isolated rat liver nuclei as the template source. With purified DNA and either or both divalent metal ions, 0.1--5 mM amine stimulated enzyme activity. Spermidine resulted in the greatest stimulation (1.7-fold at 5 mM); whereas, spermine or methylglyoxal bis(guanylhydrazone) first stimulated, then above 3 mM inhibited, the reaction. The addition of unfractionated histone to purified DNA inhibited the reaction by 90%. The subsequent addition of amines resulted in a slight stimulation in incorporation (1.5-fold) in the range of 1--3 mM amine. Alternatively, when enzyme was combined with DNA before histone, only a 20% inhibition was observed and this could be completely prevented by 3 mM spermidine. The addition of amines to isolated nuclei resulted in marked alterations in ultrastructure and Mg2+ content; however, relatively small effects on RNA polymerase activity were observed. With the E. coli enzyme, 0.1--1.0 mM amine stimulated RNA synthesis (1.5-fold) whereas, none of the amines stimulated endogeneous activity in the absence or presence of 300 mM (NH4)2SO4.

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.

Crystal structure of a berenil-d(CGCAAATTTGCG) complex. An example of drug-DNA recognition based on sequence-dependent structural features.

The AT-selective drug berenil has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The crystal structure has been solved to a resolution of 2.0 A and an R factor of 18.3%, with the location of 65 water molecules. The drug is symmetrically bound in the 5'-AATT region of the minor groove, with its amidinium groups hydrogen-bonding to O-2 atoms of the thymine base at each end of the binding site. This arrangement is distinct from that previously found for berenil with the sequence d(CGCGAATTCGCG)2, which has the drug bound to the sequencing 5'-ATT via hydrogen bonds to adenine N-3 atoms with the involvement of a bridging water molecule at one end of the binding site. The reasons for these differences are discussed in terms of changes in helical parameters; in particular propeller twist and base-pair roll are considered to be important. The conformational and base-pair geometry of the dodecanucleotide in the structure reported here, is closely similar to that for the native structure, suggesting that the 5'-AAATTT sequence does not significantly alter during drug binding, either because of its inflexibility or because its geometry is nearly ideal for berenil binding.

Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution.

The crystal structure of the dodecanucleotide duplex d(CGCAAATTTGCG)2 has been solved to 2.2 A resolution and refined to an R-factor of 18.1% with the inclusion of 71 water molecules. The structure shows propeller twists of up to -20 degrees for the A.T base-pairs, although there is probably only one (weak) three-centre hydrogen bond in the six base-pair AT narrow minor-groove region. An extensive ribbon of hydration has been located in this groove that has features distinctive from the classic "spine of hydration". Solvation around phosphate groups is described, with several instances of water molecules bridging between phosphates.

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.

Nosocomial outbreak of Candida parapsilosis fungemia related to intravenous infusions.

Candida parapsilosis is rarely isolated from blood cultures. Our hospital surveillance detected an increased rate of isolation of C parapsilosis during a four month period. Fourteen postoperative patients receiving intravenous (IV) hyperalimentation and eight burn patients receiving IV albumin were involved. Hectic fever, the major clinical manifestation, was seen in 61% of cases. Therapy in the postoperative patients consisted merely of discontinuing IV catheters and hyperalimentation, while amphotericin B was needed in five of eight burn patients to control persistent fungemia. Epidemiologic analysis identified a source of the organism in the IV-additive preparation room where C parapsilosis was found contaminating a vacuum system. Organisms apparently refluxed into IV bottles when aliquots were removed to accommodate additives. Of 103 patients who received fluids prepared with the contaminated system, 21% became infected with C parapsilosis. Infection surveillance was instrumental in detection and control of the outbreak. Routine guideline should be established to insure the sterility of IV fluids containing additives.

67Gallium scanning in talc-induced pulmonary granulomatosis.

We describe a case of pulmonary granulomatosis in a user who habitually injected methylphenidate (Ritalin) intravenously; symptomatic and objective improvement occurred with corticosteroid therapy. A scan of the lungs using radioactive 67gallium showed an increased concentration of 67gallium throughout both lungs. There was a reduction in abnormal accumulation of 67gallium, improvement in the arterial oxygen pressure and the diffusing capacity for carbon monoxide, and a reduction in the infiltrate on the chest x-ray film two months after the institution of therapy. Before treatment the patient's symptoms and arterial deoxygenation increased despite the cessation of her drug abuse, thus raising the question of a self-perpetuating inflammatory process in a case of pulmonary deposition of talc.

Food intake and growth of burro foals after 250 roentgens of cobalt-60 whole-body gamma irradiation.

Possible late effects of sublethal levels of whole-body gamma irradiation on growth of burro foals were studied. Two trials included 31 nonirradiated foals and 32 foals that were exposed to 250 R of 60Co gamma radiation during their fourth month of life. The foals were weaned 90 days postirradiation and allotted into treatment groups based on radiation treatment, weight, sex, and size. Each group was then randomly selected to be fed a ration containing either 9 %, 14 %, or 18 % crude protein in the first trial and either 9 % or 18 % in the second trial. The length of these trials was 364 days. Criteria used to evaluate the treatments included feed consumption, body weight gains, feed efficiency, increase in height, and increase in heart girth. Least-squares analysis of these data indicated that radiation had no significant effect on any of the traits tested. There was a consistent though nonsignificant trend for irradiated foals to be less efficient in feed utilization than their nonirradiated counterparts.

Effect of light dose on the photodynamic destruction of endobronchial tumors.

The effects of various light power densities (milliwatts per centimeter of diffusing fiber [mW/cf]) and light doses (joules per centimeter of diffusing fiber [J/cf]) on the effectiveness of photodynamic therapy to endobronchial and tracheal tumors were evaluated at 46 different sites. All patients had squamous cell carcinoma or adenocarcinoma. They received 2 mg/kg body weight dihematoporphyrin ether intravenously 2 days before treatment bronchoscopy. Only one light treatment was delivered to the site. Patients were treated with diffusing cylinder light tips and underwent toilet bronchoscopy 2 days after photodynamic therapy. The percentage of obstruction was estimated before and after treatment and before and after toilet bronchoscopy. There was no difference between the effects resulting from power densities of 400 and 500 mW/cf, nor were there differences in the reactions between squamous cell carcinoma and adenocarcinoma. The amount of tumor that could be removed at the end of the treatment bronchoscopy, the amount of reobstruction by secretions and exudate seen at toilet bronchoscopy, and the final percent decrease in obstruction at the end of toilet bronchoscopy were proportional to the light dose. Because the final percentage decrease in obstruction plateaued at light doses of 400 to 500 J/cf and there was no statistically significant difference between 400 and 500 J/cf, we recommend using a power density of 500 mW/cf and a light dose of 400 J/cf during photodynamic therapy.

Inhibition of antigen-induced contraction of guinea pig trachea by ICI 198,615.

We examined the extent of peptide leukotrienes involvement in ovalbumin-induced contraction of guinea pig trachea isolated from animals passively sensitized with antiovalbumin antibodies. Antigen challenge resulted in a concentration-dependent (EC50 = 10 +/- 3 ng/ml, X +/- S.E.M., n = 6) and prolonged (greater than 60 min) contraction of guinea pig trachea. The maximal contractile response was directly proportional to the quantity of sensitizing antibodies. The maximal response (but not EC50 for ovalbumin) was significantly (P less than 0.01) enhanced by indomethacin (20%), only slightly (10%) inhibited by the histamine H1-antagonist pyrilamine and unaffected by the platelet-activating factor (PAF) antagonist CV-3988. The potent and selective leukotriene antagonist ICI 198,615 partially (45%) inhibited the antigen-induced contraction in a concentration-related fashion (1-300 nM). Even at concentrations that abolish responses to leukotrienes, ICI 198,615 did not further inhibit the response, nor could other leukotriene antagonists (i.e. LY 171883 or FPL 55712) inhibit more than 50% of this response. In contrast, the 5-lipoxygenase inhibitors AA-861 and REV 5901, also a leukotriene antagonist, abolished the contractile response. Taken together, the results suggest that in guinea pig trachea, leukotrienes, in combination with other lipoxygenase metabolites, mediate a major part of the response to antigen. In contrast, PAF, histamine and prostaglandins appear to play only a minor role.