Manipulating avatar age and gender in level-2 visual perspective taking.

Visual perspective taking (VPT) represents how the world appears from another person's position. The age, group status and emotional displays of the other person have been shown to affect task performance, but tasks often confound social and spatial outcome measures by embedding perspective taking in explicitly social contexts or theory-of-mind reasoning. Furthermore, while previous research has suggested that visual perspective taking may be impacted by avatar characteristics, it is unknown whether this is driven by general group processing or a specific deficit in mentalizing about outgroups, for example, children. Therefore, using a minimally social task (i.e., the task was not communicative, and acknowledging the "mind" of the avatar was not necessitated), we examined whether avatar age and avatar gender affect performance on simpler (low angular disparity) and more effortful, embodied (high angular disparity) perspective judgments. Ninety-two participants represented the visuospatial perspectives of a boy, girl, man, or woman who were presented at various angular disparities. A target object was placed in front of the avatar and participants responded to the orientation of the object from the avatar's position. The findings suggest that social features of visuospatial perspective taking (VSPT) are processed separately from the fundamental spatial computations. Further, Level-2 VSPT appears to be affected by general group categorization (e.g., age and gender) rather than a deficit in mentalizing about a specific outgroup (e.g., children).

Does the smell of alcohol make it harder to resist? The impact of olfactory cues on inhibitory control and attentional bias.

BACKGROUND: It is well known that, owing to associative processing, olfactory cues can impact memory, emotion and behaviour. Research also points to a link between the smells of particular substances and craving. Yet, to date, little research has investigated how smell may impact other cognitive processes that are known to drive alcohol consumption. AIM: To assess how exposure to alcohol-related (vodka) relative to neutral (citrus) olfactory cues impacts inhibitory control and attentional bias. METHOD: Participants took part in a go/no-go (Study 1) and Stroop task (Study 2) while wearing masks that were pre-treated with vodka or citrus oil of equivalent intensity. STUDY 1 RESULTS: Response error rates were higher in participants in the alcohol-related (versus neutral) olfactory condition, with no interaction between olfactory and visual cue. STUDY 2 RESULTS: Responses to alcohol-related versus neutral words were similar, while performance appeared significantly impaired among participants wearing alcohol (relative to citrus) infused masks. Conclusion The smell of alcohol may impair signal detection performance on the go/no-go and Stroop task. As inhibitory control and attentional processes are known to be associated with decisions to drink or exercise restraint, these results may have implications for our understanding of alcohol consumption and for tailoring interventions.

Smells like inhibition: The effects of olfactory and visual alcohol cues on inhibitory control.

RATIONALE: How the smell of alcohol impacts alcohol-related thoughts and behaviours is unclear, though it is well-documented that alcohol-related stimuli and environments may trigger these. OBJECTIVES: The current study, therefore, aimed to investigate the priming effects of both visual and olfactory alcohol cues on inhibitory control. METHOD: Forty individuals (M age = 23.65, SD = 6.52) completed a go/no-go association task (GNAT) which measured reaction times, response accuracy and false alarm rates whilst being exposed to alcohol-related (or neutral) olfactory and visual cues. RESULTS: Alcohol-related visual cues elicited lower false alarm rates, slower reaction times and higher accuracy rates relative to neutral pictorial cues. False alarm rates were significantly higher for those exposed to alcohol as opposed to neutral olfactory cues. CONCLUSIONS: By highlighting that exposure to alcohol-related olfactory cues may impede response inhibition, the results indicate that exposure to such stimuli may contribute to the activation of cognitive responses which may drive consumption.

Student perceptions of a healthy university.

UNLABELLED: As complex environments within which individuals and populations operate, universities present important contexts for understanding and addressing health issues. The healthy university is an example of the settings approach, which adopts a whole system perspective, aiming to make places within which people, learn, live, work and play supportive to health and well-being. The UK Healthy Universities Network has formulated an online toolkit, which includes a Self-Review Tool, intended to enable universities to assess what actions they need to take to develop as a healthy university. This paper presents findings from consultative research undertaken with students from universities in England, Scotland and Wales, which explored what they believe, represents a healthy university. METHODS: Student surveys and focus groups were used to collect data across eleven universities in England, Scotland and Wales. A priori themes were used to develop our own model for a healthy university, and for the thematic coding phase of analysis. FINDINGS: A healthy university would promote student health and well-being in every aspect of its business from its facilities and environment through to its curriculum. Access to reasonably priced healthy food and exercise facilities were key features of a healthy university for students in this study. The Self-Review Tool has provided a crucial start for universities undertaking the journey towards becoming a healthy university. In looking to the future both universities and the UK Healthy Universities Network will now need to look at what students want from their whole university experience, and consider how the Self-Review Tool can help universities embrace a more explicit conceptual framework. CONCLUSION: The concept of a healthy university that can tailor its facilities and supportive environments to the needs of its students will go some way to developing students who are active global citizens and who are more likely to value and prioritise health and well-being, in the short and long term through to their adult lives.

Tacrolimus-associated hypomagnesemia in renal transplant recipients.

BACKGROUND: Since hypomagnesemia occurs frequently in tacrolimus treated patients, we studied the correlation between renal magnesium wasting and tacrolimus blood levels in renal transplant patients. METHODS: Serum magnesium, fractional excretion of magnesium (FEMg), and 24-hour urinary excretion of magnesium were measured in 41 transplant patients and 10 healthy volunteers for correlation with tacrolimus level. RESULTS: Of tacrolimus-treated patients, 43% displayed hypomagnesemia. FEMg (7.42+/-3.59% versus 1.88+/-0.43%) and 24-hour urinary excretion (112.36+/-51.43 mg/dL versus 6.7+/-2.79 mg/dL) were significantly higher among tacrolimus-treated patients than controls. Magnesium replacement did not influence FEMg or 24-hour urinary magnesium excretion. Tacrolimus level was the best predictor of 24-hour urinary magnesium excretion and FEMg. Serum magnesium levels correlated inversely with tacrolimus concentrations and creatinine clearance. CONCLUSION: Hypomagnesemia in renal transplant recipients results from renal magnesium wasting. Tacrolimus levels and renal function impact on the excess renal magnesium excretion. Studies of longer duration are warranted to assess the long-term effects of this early posttransplant hypomagnesemia.

The experimental neuroprotectant leukaemia inhibitory factor (LIF) does not compromise antitumour activity of paclitaxel, cisplatin and carboplatin.

PURPOSE: Peripheral neuropathy caused by the anticancer agents cisplatin and paclitaxel is a significant dose-limiting toxicity of these drugs. The growth factor leukaemia inhibitory factor (LIF) has neuroprotectant activity in preclinical models of nerve injury and degeneration and is now in a phase II trial in chemotherapy-induced peripheral neuropathy (CIPN). It is therefore important to ensure that LIF neither inhibits the antitumour activity of these drugs, nor stimulates tumour growth. METHODS: Mature female Dark Agouti rats were implanted subcutaneously with a mammary carcinoma, DAMA. It was confirmed that the tumour expressed LIF receptors by reverse transcriptase polymerase chain reaction. Paclitaxel was administered at a dose of 5 mg/kg daily for 6 days, cisplatin at a dose of 3 mg/kg twice weekly and carboplatin at a dose of 10 mg/kg twice weekly. The effect of LIF on tumour growth and response to chemotherapy was assessed at two doses (2 and 10 microg/kg per day). Peripheral neuropathy was assessed in terms of gait disturbance and tail-flick threshold. RESULTS: Neither dose of LIF stimulated growth of control tumours. Mean tumour volumes were lower on day 14 in all paclitaxel-, cisplatin- and carboplatin-treated groups, compared to controls (ANOVA P<0.001). LIF did not interfere with this antitumour effect. Cisplatin- and paclitaxel-treated groups had developed increasing tail-flick thresholds by day 14. These manifestations of sensory neuropathy were prevented by LIF administration. CONCLUSIONS: These results suggest that LIF may be safely used in human trials as a neuroprotectant for patients receiving cisplatin, paclitaxel and carboplatin without concern for impairment of antitumour effect.

Effectiveness and acceptability of a newly designed hip protector: a pilot study.

Hip fracture has a significant economic and personal cost, involving hospital admission and functional impairment for elderly people. To assess the benefit of using a newly designed hip protector (new material and new design) to prevent fracture in a realistic setting, a randomised intervention-control design was used to trial the effectiveness of pads worn by high falls risk residents (n=71) in nursing home for 9 months. 40 residents were in the intervention group and 31 were in the control group. A profile of falls, including time of day, and orientation was obtained to demonstrate the potential effectiveness of the protectors for injury prevention. Acceptance of the hip protector was also surveyed amongst nursing home staff and residents. One hundred and one falls and six fractures occurred in the control group. In contrast, one hundred and ninety one falls and three fractures occurred in the hip protector (pads) group. The three fractures in the protector wearing group occurred when pads were not in place. This was extrapolated as 1 in every 16.8 falls and 1 in every 63.7 falls resulting in fracture in the two groups, respectively. The relative risk of fracture was 0.264 (95% CI=0.073-0.959) when the fracture incidence rate in the intervention group (three fractures per 191 falls) was compared to the control group (six fractures per 101 falls). This is a statistically significant result and implies that this newly designed hip protector is effective in preventing hip fracture. The majority of falls occurred during the day, which was when protectors were worn in this study, but the data on orientation was incomplete, with direction unknown in 74% of falls. Compliance was an issue, which was interpreted as only 50.3% of falls recorded with protectors in place. Dementia was identified as the explanation for this as the pads were often removed by these residents who comprised the majority of participants. Perception of low risk was the primary barrier to residents accepting the intervention. Comfort of protectors was not a significant concern for staff or residents, and only staff described appearance as an issue. In conclusion, the newly designed hip protector is protective against fractures in a realistic setting. Compliance and acceptance of the protectors will ultimately determine the viability of this prophylaxis.

Electrolyte quintet: Calcium.

Abnormalities in serum calcium concentration may have profound effects on neurological, gastrointestinal, and renal function. Maintenance of the normal serum calcium is a result of tightly regulated ion transport by the kidney, intestinal tract, and bone, mediated by calcaemic hormones especially parathyroid hormone and 1,25-dihydroxyvitamin D3. Abnormalities in calcium transport that result in uncompensated influx into, or efflux from, the extracellular fluid, will result in hypercalcaemia or hypocalcaemia, respectively. When possible the biologically important ionised calcium concentration should be measured. A variety of common disorders are responsible for abnormalities in the serum calcium. Treatment of both hypercalcaemia and hypocalcaemia is dependent on the underlying disorder, the magnitude of the deviation of the serum calcium, and the severity of symptoms. Fortunately, in the case of hypercalcaemia, there is a broad selection of effective medications, especially the bisphosphonates. Treatment of hypocalcaemia relies on the provision of calcium and often vitamin D. In this article we review the mechanisms responsible for abnormalities in calcium homoeostasis, the differential diagnosis of hypercalcaemia and hypocalcaemia, and appropriate therapy.

Renal sonography: can it be used more selectively in the setting of an elevated serum creatinine level?

The objectives of our study were to (1) assess the outcomes resulting from the use of sonography in patients referred to our institution's ultrasound laboratory for an elevated serum creatinine level and (2) determine relevant clinical parameters in these patients to better triage them for sonography. We retrospectively identified and determined outcomes of 60 patients (20 women, 40 men; mean age, 61 years; range, 33 to 100 years) referred for sonographic evaluation because of an increased serum creatinine level (> or = 1.3 mg/dL). Ultrasound findings (hydronephrosis, renal size, and echogenicity) were correlated with clinical outcomes. Twenty-one patients (35%) had hydronephrosis, with 14 of these patients confirmed to be obstructed and five not obstructed. Two were indeterminate for obstruction. Eight of 14 obstructed patients were successfully treated. All obstructed patients had a suggestive history for obstruction with at least one of the following: pelvic mass (n = 9), stone disease (n = 4), or flank pain (n = 1). Only 2 of 44 patients, who were not obstructed, had any of these parameters (statistically significant difference, P < 0.0001). Thirty of the patients, who were not obstructed, had more likely alternative causes for renal failure, with sonography having no effect on patient management. Renal size and echogenicity had little effect on patient management. Sonography was efficacious in guiding management in patients with a suggestive history for obstruction (eg, pelvic mass, stone disease, or flank pain) but not in most patients who had no suggestive history and other more likely causes for renal failure.

Clinical approach to adults.

Acute episodes of renal colic are associated with severe pain and often necessitate invasive procedures and costly absences from work. A medical approach to evaluate all patients with kidney stones is generally recommended to detect underlying systemic disorders associated with nephrolithiasis and prevent further stone formation. patients with a single stone require a limited evaluation, whereas those with metabolically active stones, stones not composed of calcium oxalate, all children, and patients in demographic groups not commonly associated with nephrolithiasis should undergo a more extensive workup. The major classes of stones formed are calcium oxalate, calcium phosphate, uric acid, struvite, and cystine. This article focuses on etiologic factors that predispose to nephrolithiasis in general, as well as to specific stone types. A thorough review of the evaluation and therapy required for all stones is presented.

Hormonal regulation of Na(+)-Ca2+ exchange in osteoblast-like cells.

We proposed a role for Na-Ca exchange in hormonally mediated bone resorption and recently characterized Na-dependent Ca transport in an osteoblast-like rat osteosarcoma cell line (UMR-106). To test whether calcemic agents alter Na(+)-Ca2+ exchange in osteoblasts, UMR cells were treated acutely or cultured in the absence or presence of calcemic agent for 24 h. Cells were then loaded with the Ca-sensitive dye fura-2 in the presence of 140 mM NaCl, no Ca, and the absence or presence of 0.3 mM ouabain. Cells were resuspended at 22 degrees C, and the fluorescence ratio at excitation wavelength of 340 and 380 nm was measured. An outward Na gradient was generated by removing extracellular Na and maintaining isotonicity with choline chloride. Na(+)-Ca2+ exchange was demonstrated by enhanced Ca uptake in ouabain-treated (Na-loaded) cells after the addition of 1.5 mM Ca. Acute addition of 10(-7) M PTH or 10(-6) M PGE2 had no effect on Na-dependent Ca uptake. However, 24 h treatment of cells with PTH, PGE2, or 1,25(OH)2D3 caused a dose-dependent inhibition of Na(+)-Ca2+ exchange. Using the Na-sensitive dye, SBFI, we also demonstrated that the effect was bidirectional; PTH inhibited Ca-dependent Na uptake comparably to its inhibition of Na-dependent Ca uptake. The effects of the calcemic agents were mimicked by 24 h treatment of the cells with 1 microM forskolin or 2 microM PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct determination of the point mutation rate of a murine retrovirus.

The point mutation rate of a murine leukemia virus (MuLV) genome (AKV) was determined under conditions in which the number of replicative cycles was carefully controlled and the point mutation rate was determined by direct examination of the RNA genomes of progeny viruses. A clonal cell line infected at a low multiplicity of infection (2 x 10(-3)) was derived to provide a source of virus with high genetic homogeneity. Virus stocks from this cell line were used to infect cells at a low multiplicity of infection, and the cells were seeded soon after infection to obtain secondary clonal cell lines. RNase T1-oligonucleotide fingerprinting analyses of virion RNAs from 93 secondary lines revealed only 3 base changes in nearly 130,000 bases analyzed. To obtain an independent assessment of the mutation rate, we directly sequenced virion RNAs by using a series of DNA oligonucleotide primers distributed across the genome. RNA sequencing detected no mutations in over 21,000 bases analyzed. The combined fingerprinting and sequencing analyses yielded a mutation rate for infectious progeny viruses of one base change per 50,000 (2 x 10(-5)) bases per replication cycle. Our results suggest that over 80% of infectious progeny MuLVs may be replicated with complete fidelity and that only a low percentage undergo more than one point mutation during a replication cycle. Previous estimates of retroviral mutation rates suggest that the majority of infectious progeny viruses have undergone one or more point mutations. Recent studies of the mutation rates of marker genes in spleen necrosis virus-based vectors estimate a base substitution rate lower than estimates for infectious avian retroviruses and nearly identical to our determinations with AKV. The differences between mutation rates observed in studies of retroviruses may reflect the imposition of different selective conditions.

Regulation of blood glucose to human levels by human fetal pancreatic xenografts.

Previous experiments xenografting human fetal pancreas into athymic mice made diabetic with streptozotocin have demonstrated that normoglycemia can be achieved 1-3 months after implantation, but that the blood glucose levels obtained were significantly lower than those of control mice. These lower levels could be due either to genetic regulation by the grafted human beta cell--human neonatal blood glucose levels are lower than those of athymic mice--or to excess release of insulin from the increasing number of beta cells in the implant. In order to address the latter possibility, human fetal pancreas was grafted beneath the renal capsule of athymic mice, the pancreas of which was intact, and they and their ungrafted litter mates monitored during their life span--71 +/- 17 weeks after surgery for the 4 successfully grafted mice. The random blood glucose level in all mice was the same initially and remained so until a significant lowering 20 weeks later--2.0 +/- 0.2 vs. 3.4 +/- 0.4; this difference was maintained thereafter. Data obtained from the oral glucose tolerance tests conducted at 8 weekly intervals paralleled these results. Human C-peptide was detectable in blood by 26 weeks, with a rise demonstrable during the oral glucose tolerance test. Peak levels did not change during the ensuing year. At no stage did any of the mice develop clinical hypoglycemia, despite an annual 23 +/- 6-fold increase in size of the graft and the presence of 0.3-9.2 U insulin therein. The insulin content of the mouse pancreas (0.08 +/- 0.03 U) was unaffected by the presence of the human fetal beta cells. These data show that the xenografted human fetal pancreas grows and releases insulin in a controlled but not excessive manner, with the blood glucose levels probably being determined by genetic information stored in the grafted beta cell.

Mammals have multiple genes for individual ribosomal proteins.

The reiteration frequency of the genes that encode the structural proteins of the mammalian ribosome was studied with a set of cloned cDNA probes containing several different mouse r-protein mRNA sequences. Results from a reassociation kinetics analysis, Southern blotting experiments and gene cloning studies collectively indicate that each individual r-protein species is represented by multiple genes in mammals. Among the examples studied, the multiplicity of mouse r-protein genes varied from about 7 to 20, a striking contrast to the low copy numbers observed in less evolutionarily advanced eucaryotes. The multiplicity of individual r-protein genes in humans and rodents is similar.

Heavy-chain mutants derived from gamma 2b mouse myeloma: characterization of heavy-chain messenger ribonucleic acid, proteins, and secretion in delection mutants and messenger ribonucleic acid in gamma2a mutant progeny.

Mouse myeloma mutants isolated from cell line 45.6 (gamma 2b) producing structurally altered immunoglobulin heavy (H) chains have been characterized. The mutant 10-1 synthesizes an H chain of 47 000 daltons containing a CH1 deletion; two mutants, G251 and I17, derived from 10-1 synthesize H chains of 40 000 and 35 000 daltons, respectively. The messenger ribonucleic acids (mRNAs) in these mutants have been shown to be smaller in molecular weight than mRNAs produced in 45.6 cells and lack a portion, but not all, of the CH1 domain. The H chains of G251 and I17 no longer express IgG subclass-specific determinants, are not secreted, and are structurally altered in the carboxyl-terminal portion of the molecule. In vitro the mRNAs of the mutants code for the synthesis of a polypeptide precursor characteristic of secreted proteins; the shortened proteins are apparently glycosylated intracellularly. Somatic cell hybrids between a structurally altered nonsecretor and a drug-marked wild-type myeloma cell secret only the wild-type protein. Reversion to secretion for G251 or I17 is accompanied by a change in the amino acid composition of the H chain such that gamma 2a subclass-specific determinants are expressed. Therefore, the primary structure of the H chain is an important factor in determining secretion. The gamma 2a-secreted chains from G251 and I17 fall into two classes: (1) those synthesizing proteins of approximately 47 000 daltons producing H-chain mRNAs of approximately 1.66 kilobases that are deleted for a portion, but not all, of CH1; (2) those synthesizing gamma2a proteins of approximately 55 000 daltons that are encoded in mRNAs of apparently wild-type size and that have regained CH1 sequences. The molecular explanations for the production of these alterations is discussed.

Allosteric activation of the hydrolysis of specific substrates by chymotrypsin.

A variety of azobenzene compounds having bis-quaternary nitrogens have been shown to accelerate the hydrolysis by chymotrypsin of certain specific substrates by an allosteric mechanism. One of the most potent, 2,2'-bis[alpha-(benzyldimethylammonium)methyl]azobenzene dibromide (2,2'-QBzl) accelerated the hydrolysis of glutaryl-L-phenylalanine p-nitroanilide 40-fold at saturating concentration. Acceleration was by increasing kcat without altering Km. The hydrolysis of acetyl-L-tyrosine p-nitroanilide and acetyl-L-tyrosine anilide was also accelerated by Q-Bzl (25-fold and 1.8-fold respectively) while the hydrolysis of hemoglobin, azocoll and a number of esters was not affected. The inactivation of chymotrypsin by diphenylcarbamyl chloride and diphenylcarbamyl fluoride was accelerated by 2,2'-Q-Bzl. Reac;ivation in the presence of NH2OH was also accelerated, but in the absence of added nucleophile (i.e. of NH20H) no increase in rate was detectable. An allosteric effector was covalently attached to chymotrypsinogen A by reaction with 2,2'-bis[alpha-(o-bromomethylbenzyldimethylammonium)methyl]azobenezene dibromide. The product, when converted to active enzyme, was about 4 times more active than chymotrypsin as a result of an increase in kcat of hydrolysis; Km was unaffected. The mechanism of the allosteric acceleration process is not known but, because for all of the substrates affected acylation of the enzyme is rate-limitimg, it is tentatively suggested that the effectors facilitate proton transfer to the leaving group by an inductive effect on the 'charge relay system'. Spectral studies indicate that the allosteric site is a portion of the enzyme with a polarity near that of water, possibly on the outside surface of the enzyme molecule.