Sensitivity to gains during risky decision-making differentiates chronic cocaine users from stimulant-naïve controls.

BACKGROUND: Chronic cocaine use has been consistently associated with decision-making impairments that contribute to the development and maintenance of drug-taking. However, the underlying cognitive processes of risk-seeking behaviours observed in chronic cocaine users (CU) have so far remained unclear. Here we therefore tested whether CU differ from stimulant-naïve controls in their sensitivity to gain, loss, and probability of loss information when making decisions under risk. METHOD: A sample of 96 participants (56 CU and 40 controls) performed the no-feedback version of the Columbia Card Task, designed to assess risk-taking in relation to gain, loss, and probability of loss information. Additionally, cognitive performance and impulsivity were determined. Current and recent substance use was objectively assessed by toxicological urine and hair analysis. RESULTS: Compared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the loss probability was high and the returns were low, and a tendency for increased risk aversion in more favourable decision scenarios. In comparison to controls, CU were less sensitive to gain, but similarly sensitive to loss and probability of loss information. Further analysis revealed that individual differences in sensitivity to loss and probability of loss information were related to cognitive performance and impulsivity. CONCLUSION: Reduced sensitivity to gains in people with CU may contribute to their propensity for making risky decisions. While these alterations in gain sensitivity might directly relate to cocaine use per se, the individual psychopathological profile of CU might moderate sensitivity to loss information.

Tensile fracture of a single crack in first-year sea ice.

The break-up of sea ice in the Arctic and Antarctic has been studied during three field trips in the spring of 1993 at Resolute, NWT, and the fall of 2001 and 2004 on McMurdo Sound via in situ cyclic loading and fracture experiments. In this paper, the back-calculated fracture information necessary to the specification of an accurate viscoelastic fictitious (cohesive) crack model is presented. In particular, the changing shape of the stress separation curve with varying conditions and loading scenarios is revealed.This article is part of the theme issue 'Modelling of sea-ice phenomena'.

Development of a 3D human in vitro skin co-culture model for detecting irritants in real-time.

Tissue engineered materials for clinical purposes have led to the development of in vitro models as alternatives to animal testing. The aim of this study was to understand the paracrine interactions arising between keratinocytes and fibroblasts for detecting and discriminating between an irritant-induced inflammatory reaction and cytotoxicity. We used two irritants [sodium dodecyl sulphate (SDS) and potassium diformate (Formi] at sub-toxic concentrations and studied interleukin-1 alpha (IL-1 alpha) release from human keratinocytes and activation of NF-kappaB in human fibroblasts. NF-kappaB activation in fibroblast 2D cultures required soluble factors released by prior incubation of keratinocytes with either SDS or Formi. Neither cell type responded directly to either agent, confirming a paracrine mechanism. Fibroblasts were then cultured in 3D microfiber scaffolds and transfected with an NF-kappaB reporter construct linked to GFP. Findings for 3D cultures were similar to those in 2D in that soluble factors released by prior incubation of keratinocytes with SDS or Formi was required for NF-kappaB activation in fibroblasts. Similarly, direct incubation with either agent did not directly activate NF-kappaB. A technical advantage of using transfected cells in 3D was an ability to detect NF-kappaB activation in live fibroblasts. To confirm paracrine signaling a twofold increase in IL-1 alpha was measured in keratinocyte-conditioned medium after incubation with SDS or Formi, which correlated with fibroblast NF-kappaB activity. In summary, this work has value for developing 3D tissue engineered co-culture models for the in vitro testing of irritant chemicals at sub-toxic concentrations, as an alternative to in vivo models.

Lysosomal enzymes in preeclamptic women in northern Nigeria.

BACKGROUND: The incidence of preeclampsia is high in northern Nigeria, as it is in many other developing countries, and preeclampsia is associated with significant maternal and fetal morbidity and mortality. We inquired if proteinuria or hypertension alone could account for the altered concentrations of urinary lysosomal hydrolases that have been reported in preeclamptic women and pregnant women without preeclampsia. METHODS: The activities of urinary beta-hexosaminidase and beta-galactosidase were determined fluorometrically in pregnant women assigned to one of four groups: Group I: 41 preeclamptic women; Group II: 31 hypertensive aproteinuric women; Group III: 44 normotensive proteinuric women; and Group IV: 52 healthy pregnant women (controls). RESULTS: The urinary beta-hexosaminidase concentrations were decreased in the preeclamptic women (P<0.005) and proteinuric women (P<0.001) when compared to the healthy pregnant controls. There was no significant difference in beta-hexosaminidase concentrations between the hypertensive women and the healthy pregnant controls. The urinary beta-galactosidase concentrations for preeclamptic, hypertensive, and proteinuric women did not differ significantly versus healthy pregnant controls. CONCLUSIONS: The reduced urinary excretion of beta-hexosaminidase in preeclamptic women is associated with proteinuria, but not hypertension. Measuring urinary concentrations of lysosomal hydrolases alone or in conjunction with urinary protein concentrations is not likely to be useful in predicting or monitoring the clinical course of preeclampsia; however, it might prove important in gaining a more complete understanding of the pathogenesis of renal tubular epithelial cell injury and proteinuria that occurs in preeclampsia.

Prior psychiatric problems in rehabilitation clients with work-related injuries.

Psychiatric histories were obtained in 56 patients beginning rehabilitation following a work-related injury in order to establish the temporal relationship between the onset of psychiatric problems and the date of the work injury. The presence of major depression and alcohol abuse was determined using structured, directed interviews and the criteria set forth in the Diagnostic and Statistical Manual of Mental Disorders. A history of either alcohol abuse or depression was found in 36 (64.3%) of the 56 subjects. Of these 36 subjects, 32 (88.9%) reported a history of psychiatric problems that antedated the work injury. These data suggest that, in injured workers, the conceptualization of psychiatric problems solely as reactive illnesses in otherwise psychiatrically healthy persons is often inaccurate. Furthermore, these data suggest the hypothesis that the presence of clinical depression or alcohol abuse may increase the risks of a work-related injury.

Prediction of return to work by rehabilitation professionals.

Rehabilitation therapists made predictions of return to work for 57 patients evaluated prior to beginning a work-hardening program. These predictions, along with 14 specific demographic, injury, and physical function measures were entered into a stepwise discriminant analysis to develop a predictive model for return to work. Therapists correctly predicted the eventual return to work for 47 (73.7%) of the 57 subjects. Therapist prediction was the most powerful variable in the model, explaining 29% of the variance (p≤.0001). Only two other variables, self-report of pain severity and injury type, contributed significantly to the prediction model, accounting respectively for 12% and 9% of the variance (p's<.05). These data highlight the predictive acuity of rehabilitation therapists and suggest that the process involved in formulating clinical predictions merits further study. The findings also suggest that weighing information such as self-report of pain severity and injury type might further enhance the practitioner's ability to predict return to work.

Newborn screening for hemoglobinopathies in Colorado. The first 10 years.

In Colorado, newborn screening for hemoglobinopathies by cellulose acetate and citrate agar electrophoresis of dried capillary blood spots was established in 1979. We reviewed the results of screening 528,711 infants through 1988. Forty-seven infants with sickle cell diseases and 27 infants with other hemoglobin diseases were identified. The initial screening failed to detect sickle cell anemia in 4 infants, but the hemoglobinopathy in 3 of these infants was diagnosed correctly by routine retesting of those with suspected sickle cell trait. A total of 47 infants with sickle cell diseases were followed through September 1989. There was no mortality among these infants. The screening test identified 3779 infants (1:140 births) with a suspected hemoglobin trait; confirmatory retesting was obtained in 53%. The results of our experience confirm the value of newborn screening for hemoglobinopathies but suggest that a more sensitive test would improve the program.

The role of frequency modulation in the perception of complex stimuli by primates.

Frequency modulation is a common feature of acoustic communication signals, including both human speech and many animal calls. In this study, linear frequency upsweeps were used as simple abstractions of the modulations found in communication signals. Macaque monkeys were trained using positive reinforcement operant conditioning procedures to respond when an ongoing repetitive acoustic signal changed from unmodulated (pure tone) to modulated (sweep). Thresholds for detecting modulation were determined using the psychophysical method of constant stimuli. In the first experiment, it was shown that the monkeys were most sensitive to modulation around a center frequency of 500 Hz. Subsequent experiments were carried out at that frequency, and varied stimulus duration and the frequency relationship between standard and comparison stimuli. The results of these studies indicated that subjects were responding primarily to discrete frequency cues rather than to the presence of modulation. When a premium was placed on attending to modulation by presenting discrete shifts between successive unmodulated stimuli thereby making such shifts an unreliable indicator of the presence of modulation, subjects continued to respond to the presence of the discrete shifts. These results are taken as evidence that the auditory system may deal with frequency modulation near threshold by recoding it as a discrete frequency percept.