Melanoma secretion of transforming growth factor-ß2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.

Traditional Masculine Gender Role Norms and Nonsuicidal Self-Injury in Veterans.

Reducing Veteran rates of suicide has long remained a top priority for the Veterans Health Administration, and as such, identifying correlates of suicidal behaviors is important to develop targeted interventions. Nonsuicidal self-injury (NSSI) has been identified as a robust predictor of suicide attempts; however, less is known about correlates of NSSI that may aid in upstream prevention efforts. Prior research suggests adherence to various traditional masculine gender role norms may be positively associated with NSSI. Thus, as the U.S. military is widely recognized for promoting and rewarding such norms, this study sought to build off previous research by examining the association between adherence to various masculine gender role norms and engagement in NSSI behaviors among a mixed-sex sample of U.S. Veterans (N = 124). Results showed the norm of emotional control was most strongly associated with lifetime engagement in NSSI behaviors (including the behavior of wall-object punching), whereas the norm of violence was associated with NSSI disorder. Interestingly, exploratory analyses indicated that these associations were primarily driven by women Veterans and sexual orientation status. Overall, the results highlight the importance of assessing for adherence to masculine gender role norms among all Veterans and speak to additional avenues for future research.

Potentiating cutaneous wound healing in young and aged skin with nutraceutical collagen peptides.

BACKGROUND: Chronic wounds continue to be a burden to healthcare systems, with ageing linked to increased prevalence of chronic wound development. Nutraceutical collagen peptides have been shown to reduce signs of skin ageing, but their therapeutic potential for cutaneous wound healing remains undefined. AIM: To determine the potential for nutraceutical collagen peptides to promote cutaneous wound healing in vitro in the context of age. METHODS: The potential for bovine- or porcine-derived nutraceutical collagen peptides to promote wound healing of primary cutaneous fibroblasts and keratinocytes derived from young and aged individuals in vitro was assessed by two-dimensional scratch and cell-viability assays and by immunofluorescence for the cell proliferation marker, Ki67. The achievement of peptide concentrations in vivo, equivalent to those exerting a beneficial effect on wound healing in vitro, was confirmed by pharmacokinetic studies of hydroxyproline, a biomarker for collagen peptide absorption, following peptide ingestion by healthy individuals over a wide age range. RESULTS: Results demonstrated significant nutraceutical collagen peptide-induced wound closure of both young and aged fibroblasts and keratinocytes, mediated by enhanced cellular proliferation and migration. Analysis of blood levels of hydroxyproline in young and aged individuals following porcine collagen peptide ingestion revealed peak serum/plasma levels after 2 h at similar concentrations to those exerting beneficial effects on wound healing in vitro. CONCLUSION: These data demonstrate the capacity for nutraceutical collagen peptides to promote cutaneous wound closure in vitro, at pharmacologically achievable concentrations in vivo, thereby offering a potential novel therapeutic strategy for the management of cutaneous wounds in young and aged individuals.

Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

The prognostic significance and impact of the CXCR4-CXCR7-CXCL12 axis in primary cutaneous melanoma.

BACKGROUND: Expression of the chemokine receptor CXCR4 is known to regulate melanoma metastasis to distant sites with high expression of the CXCL12 ligand. However, the prognostic impact of CXCR4 expression and potential for autocrine-mediated activation of prosurvival mitogen-activated protein kinase signalling remains enigmatic. Furthermore, expression of the decoy receptor CXCR7 within the local cutaneous melanoma microenvironment remains undefined. OBJECTIVES: To define the contribution and prognostic impact of CXCR4-CXCR7-CXCL12 signalling in primary cutaneous melanomas and the immediate tumour microenvironment. METHODS: Immunohistochemical/immunofluorescent expression of CXCR4, CXCR7 or CXC12 was analysed in human metastatic melanoma cell lines, primary cutaneous cell types and a retrospective cohort of primary melanomas/benign naevi. CXCL12 secretion by melanoma/cutaneous cells was evaluated by enzyme-linked immunosorbent assay, and autocrine CXCR4-CXCL12 signalling was investigated by addition of a CXCL12-neutralizing antibody. RESULTS: CXCR4 expression was significantly higher in primary melanomas that subsequently metastasized after 7 years (P = 0·037). Stratification for American Joint Committee on Cancer (AJCC) stage II disease revealed significantly decreased disease-free survival in patients with > 50% CXCR4 expression (P = 0·036), while comparative analysis of CXCL12 expression in the adjacent epidermis of all AJCC stage melanomas revealed increased CXCL12 correlated with prolonged time to metastasis (P = 0·014). CXCR7 was expressed within the primary melanoma microenvironment but was absent on primary tumours. Addition of anti-CXCL12 to BRAF-mutant melanoma cells resulted in downregulation of phospho-CXCR4 and phospho-extracellular signal-related kinase, indicating autocrine CXCR4-CXCL12 signalling. CONCLUSIONS: CXCR4 expression defines a potential prognostic biomarker for AJCC stage II melanoma. Moreover, targeting the CXCR4-CXCR7-CXCL12 axis may represent a novel therapeutic strategy to prevent early melanoma progression.

Sexual Victimization Outcomes and Adjustment Among Bisexual Women: A Review of the Quantitative Literature.

Bisexual women experience worse mental health outcomes than lesbian and heterosexual women, which may be explained by greater rates of sexual violence among bisexual women. The current comprehensive literature review aimed to synthesize research on mental health and substance use outcomes related to lifetime sexual violence among bisexual women. A comprehensive literature search was conducted within the PsycINFO and Medline databases (final search conducted in August, 2021). Inclusion criteria required articles to examine a mental health or substance use correlate/outcome of lifetime sexual victimization experiences among bisexual women. Fifteen studies met inclusion criteria and were reviewed. Results indicate that there are significant gaps in this literature, including limited research on psychological distress outcomes. Most notably, there is a limited focus on the experiences of bisexual women specifically and the role of bisexual minority stress. Findings indicate that lifetime sexual victimization experiences are linked with increased posttraumatic stress, depression, and alcohol (and other substance) use and consequences. It appears that bisexual women are vulnerable to cumulative victimization, which may further exacerbate outcomes. Clinicians working with bisexual women should provide bisexual-affirmative care, help bisexual women access positive social supports, and build more effective coping strategies for managing post-trauma distress. Future research on outcomes of violence among bisexual women would benefit from contextualizing adjustment following sexual assault within a bisexual minority stress-informed approach for a more comprehensive understanding of this process.

Waist-to-Hip Ratio Predicts Sexual Perception and Responses to Sexual Assault Disclosures.

The current work investigates the effects of target of perception's waist-to-hip ratio (WHR) on perceivers' judgments of sexual unrestrictedness and sexual victimization prototypicality. Studies 1a and 1b found that women with lower WHRs were perceived as relatively more sexually unrestricted. Studies 2a and 2b found that women with lower WHRs were perceived as relatively more prototypic of sexual victimization. Study 3 built on these findings to consider implications for responses to sexual assault disclosures. Perceivers disbelieved and minimized a disclosure of assault relatively more when made by a woman with a higher WHR. In sum, this body of work implicates WHR as a body cue that can inform consequential sexual perception. Thereby, this work identifies factors that could influence judgments of credibility of sexual violence reports, which may have implications for hesitancy to report sexual violence.

Microscopic alterations of vaginal tissue in women with pelvic organ prolapse.

The aim of this study was to identify any histological changes between the prolapsed and non-prolapsed vaginal skin to enable us to answer the broader question of whether to excise or re-suture the prolapsed tissue during vaginal reconstructive surgery. Two tissue samples were taken from 20 women who underwent prolapse surgery, one prolapsed and another non-prolapsed tissue. The samples were analysed blind histologically by a pathologist. Our study showed statistically significant differences in three tissue components namely myofibroblast differentiation (0.047), elastin (0.048) and collagen (0.095), depending on whether the tissue was prolapsed or non-prolapsed. However, the study had certain limitations and practical difficulties faced in histological approach of tissue analysis. Histology alone is an insufficient indicator to answer our question and definitive understanding of the prolapsed tissue may result from a randomised study on a larger study population.

Effects of slow and deep breathing on reducing obstetric intervention in women with pregnancy-induced hypertension: a feasibility study protocol.

Objective: To evaluate whether a slow and deep breathing (SDB) intervention is acceptable to pregnant women. Methods: The trial aims to recruit 67 pregnant women who have developed pregnancy-induced hypertension (clinicaltrials.gov: NCT04059822). SDB will be undertaken daily for 10 min using a video aid and women will self-monitor blood pressure (BP) daily. At 36-weeks gestation women will complete an online questionnaire. Adherence, recruitment rates, and acceptance of the intervention will be evaluated. Conclusion: The findings from this trial will evaluate if women accept SDB as a treatment method. Initial analysis will evaluate if BP and/or obstetric interventions reduce following SDB intervention.

Inspiratory muscle training for the treatment of dynamic upper airway collapse in racehorses: A preliminary investigation.

Exercise-induced upper airway collapse (UAC) probably occurs when the stabilising muscles of the upper airway are unable to withstand the dramatic changes in airflow and pressure that occurs during exercise. In racehorses, the mainstay of treatment is surgical intervention. In human athletes, exercise-induced laryngeal obstruction has been treated successfully with inspiratory muscle training (IMT). The aims of this study were: (1) to assess the feasibility of IMT in racehorses; and (2) describe the exercising endoscopy findings pre- and post-IMT in racehorses diagnosed with dynamic UAC. Horses undergoing IMT wore a mask with an attached threshold-valve to apply an additional load during inspiration, creating a training stimulus with the purpose of increasing upper airway muscle strength. Each horse underwent IMT once daily, while standing in the stable, 5-6 days/week for 10 weeks. Endoscopy recordings were analysed in a blinded manner using an objective grading scheme and subjective pairwise analysis. Seventeen horses successfully completed the IMT protocol, with full information available for 10 horses. Objective grading analysis showed a lower grade of vocal fold collapse (6/9 horses), palatal instability (7/10 horses) and intermittent dorsal displacement of the soft palate (5/7 horses) post-IMT. Pairwise subjective analysis suggested better overall airway function post-IMT in 3/10 horses. The main limitations of this preliminary investigation were the low number of horses examined and lack of a control population. Further research is required to investigate the effects of IMT on upper airway muscle strength and to evaluate its efficacy for prevention and treatment of UAC.

Clinical and Histologic Manifestations of a Novel Rectus Femoris Myotendinous Junction Injury in Rats.

Background: Animal models of muscle injury have primarily relied on methods which do not mimic the chronic scarring that typically occurs adjacent to the myotendinous junction (MTJ). The goal of this study was three-fold: (i) to create a strain-induced in vivo model of rectus femoris MTJ injury in rats; (ii) to document clinical manifestations of injury using longitudinal tracking of individual animals via voluntary and compulsory (treadmill) mobility analyses and (iii) to validate and assess the model for persistent scarring through serial histologic assessment and development of a semi-quantitative grading scheme to characterize injury response over time. Methods: Strain-induced MTJ injury was generated in male Sprague Dawley rats via needle tension directed along the transverse axis between the rectus femoris muscle and distal tendon that attaches to the patella. Animals received mobility assessments (gait analysis using a DigiGait Treadmill System and weight bearing using a Tekscan Rodent Walkway System) at days 0, 1, 3, 6, 13, 20, and 27 of the experimental protocol. Rats were euthanized at 1, 3, 7, 14, and 28 days post-injury (n = 6 rats per time-point) and hindlimbs were processed for histology. Results: Significant changes in locomotor parameters included injured and contralateral limb paw area, max dA/dt (limb deceleration/breaking time), stride time, stance time, force time impulse, and fore/hind symmetry, and injured limb maximum force. The most significant and consistent histologic finding was a pathologic fibrotic adhesive lesion at the muscle and tendon interface along the proximal aspect of the patella just distal to the injury site. This lesion was composed of reactive fibroblasts, disorganized collagen fibers, vascular profiles, and a myxomatous ground substance stroma. Conclusions: This work is the first to characterize the clinical and pathologic development of a chronic model of rectus femoris MTJ injury, which resulted in altered mobility likely caused by a strain-induced fibrotic scar along the anterior patella. Notably, both the functional and pathologic changes recapitulated the course of injury progression similar to what is described in humans. This work provides a unique model to study MTJ injury mechanisms for the identification of enhanced treatment options for patients who suffer from activity-related muscle conditions.

Influence of prior activity (warm-up) and inspiratory muscle training upon between- and within-day reliability of maximal inspiratory pressure measurement.

BACKGROUND: A specific inspiratory muscle 'warm-up' (IWU) prior to assessment of maximal inspiratory mouth pressure (PI(max)) may reduce the number of measurements required to obtain reproducible, representative estimates of PI(max). The influence of inspiratory muscle training (IMT) upon this phenomenon is unknown. OBJECTIVE: Compare the impact of an IWU on the between- and within-day reliability of PI(max) before and after IMT. METHOD: Eight participants were assessed on 4 separate occasions: 2 trials preceded IMT and 2 followed it. At each assessment, the highest of 3 initial efforts was recorded as the pre-IWU value (PI). The highest of 9 subsequent efforts that followed 2 sets of 30 breaths at 40% PI was recorded as PI(max). Following 4 weeks of IMT, the trials were repeated. RESULTS: IWU increased PI by 11-17% (p < or = 0.01), irrespective of IMT status. After IWU, 5-6 efforts were required to determine PI(max), irrespective of IMT status. PI(max) was similar between the 2 trials before IMT and the 2 trials after IMT (p > or = 0.05), and was 21% higher after IMT (p < or = 0.01). The coefficient of variation was excellent before and after IWU, both before (1.9 and 0.6%, respectively) and after IMT (1.1 and 0.3%, respectively). Limits of agreement and sample sizes for effect sizes < or =10% were substantially smaller after IWU in all trials. CONCLUSIONS: (1) IWU enhances the between-day reliability of PI(max) measurement, and this is unaffected by IMT, and (2) judgements regarding acceptability in relation to PI(max) reliability should be made in relation to analytical goals and we present data to facilitate this.

Report on the donation of supernumerary embryos from fresh IVF and ICSI treatment cycles for human stem cell research.

BACKGROUND: Research involving human embryos promises exciting therapeutic advances but raises ethical and moral dilemmas for scientists and potential donors. The aim of this study is to report the proportion of couples donating supernumerary fresh embryos for development of stem cell lines from a single centre and the characteristics of those who donate. METHODS: Couples undergoing assisted conception treatment in a teaching hospital received research information between January 2005 and July 2006. Counselling and consenting was performed by a dedicated research nurse. Demographic data was collected for couples who enrolled in the study. MAIN OUTCOME MEASURES: To determine the proportion of couples willing to donate surplus embryos for stem cell derivation and to examine the characteristics of those who consent to donate. RESULTS: Of 508 couples, 353 (69%) expressed an interest in research on their treatment consent forms. Sixty-six percent of those interested in research and 87% of counselled couples consented to donation. The demographic characteristics of those who agreed to donate were similar to those of all couples attending the unit. CONCLUSIONS: Approximately half of couples consented to donate under the described system in our centre. Detailed information provision helps the majority of those counselled to proceed to donation.

Toxicologic/transport properties of NCS-382, a γ-hydroxybutyrate (GHB) receptor ligand, in neuronal and epithelial cells: Therapeutic implications for SSADH deficiency, a GABA metabolic disorder.

We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurological phenotype. We demonstrate for the first time using MDCK cells that NCS-382 is actively transported and capable of inhibiting GHB transport. Following these in vitro assays with in vivo studies in aldh5a1-/- mice, we found the ratio of brain/liver GHB to be unaffected by chronic NCS-382 administration (300mg/kg; 7 consecutive days). Employing a variety of cellular parameters (reactive oxygen and superoxide species, ATP production and decay, mitochondrial and lysosomal number, cellular viability and necrosis), we demonstrate that up to 1mM NCS-382 shows minimal evidence of pharmacotoxicity. As well, studies at the molecular level indicate that the effects of NCS-382 at 0.5mM are minimally toxic as evaluated using gene expression assay. The cumulative data provides increasing confidence that NCS-382 could eventually be considered in the therapeutic armament for heritable SSADH deficiency.

In vitro toxicological evaluation of NCS-382, a high-affinity antagonist of γ-hydroxybutyrate (GHB) binding.

γ-Hydroxybutyric acid (GHB), a minor metabolite of the inhibitory neurotransmitter GABA, can accumulate to significant concentrations in the heritable disorder of GABA degradation, succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD). Moreover, GHB may be employed in therapeutic settings (treatment of narcolepsy), as well as instances of illicit activity, including acquaintance sexual assault and the induction of euphoria. High-affinity binding sites for GHB in the brain have been identified, although the absolute identity of these receptors remains unclear. Pharmacological antagonism of GHB binding may have multiple instances of therapeutic relevance. The high affinity GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid) has not been piloted in humans. To address the potential clinical utility of NCS-382, we have piloted initial studies of its toxicology in HepG2 and primary hepatocyte cells. At high dose (0.5mM), NCS-382 showed no capacity for inhibition of microsomal CYPs (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and minimal potential for activation of xenobiotic nuclear receptors. Additional cellular integrity and functional assays (viability, oxidative stress, apoptosis, ATP production) revealed little evidence for cytotoxicity, and a low degree of dysregulation of >370 genes actively engaged in the mediation of cellular toxicity. In vitro testing indicates a low probability of cellular toxicity associated with NCS-382.

Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods.

BACKGROUND: The reported prevalence of exercise induced asthma (EIA) in elite winter athletes ranges from 9% to 50%. Many elite winter athletes do not report symptoms of EIA. At present there is no gold standard test for EIA. OBJECTIVE: To establish the efficacy of screening for EIA and examine the role of the eucapnic voluntary hyperventilation (EVH) challenge and laboratory based and sport specific exercise challenges in the evaluation of elite winter athletes. METHODS: 14 athletes (mean (SD) age 22.6 (5.7) years, height 177.2 (7.0) cm, body mass 68.9 (16.9) kg) from the Great Britain short-track speed skating (n = 10) and biathlon teams (n = 4) were studied. Each athlete completed a laboratory based and sport specific exercise challenge as well as an EVH challenge, in randomised order. RESULTS: All 14 athletes completed each challenge. Two had a previous history of asthma. Ten (including the two with a previous history) had a positive test to at least one of the challenges. Ten athletes had a positive response to EVH; of these, only three also had a positive response to the sport specific challenge. No athletes had a positive response to the laboratory based challenge. CONCLUSIONS: Elite athletes should be screened for EIA. EVH is a more sensitive challenge in asymptomatic athletes than sport specific and laboratory based challenges. If sporting governing bodies were to implement screening programmes to test athletes for EIA, EVH is the challenge of choice.

Serum alanine transaminase (ALT) reference ranges estimated from blood donors.

It has been suggested that an increase in serum alanine transaminase (ALT) activity in blood donors may identify infection with non-A, non-B hepatitis. To facilitate identification of such donors, the reference range for ALT was measured on a Technicon SMAC 1 Analyser, using serum from 364 blood donors and 567 plasmapheresis donors. The distribution of ALT activities displayed a positive skewness, and so both logarithmic transformation and subsequent calculation of mean and standard deviation as well as non-parametric analysis were used to obtain best estimates of reference ranges for men and women, 5-65 IU/1 and 5-35 IU/1, respectively. ALT activities were found to be higher in plasmapheresis donors than in normal blood donors of both sexes, and it is postulated that this difference may be related to the increased frequency of donation in the former group.

Estimation of arterial PCO2 in the elderly.

Arterial PCO2 (PaCO2), determined directly in the radial artery, was compared with indirect estimates of PCO2 in six elderly men (mean age 73.8 yr). Estimates of PaCO2 included arterialized venous PCO2 (PavCO2); end-tidal PCO2; mean alveolar PCO2, calculated by using a reconstruction of the alveolar oscillation in PCO2 and accounting for the presence of dead space (time-weighted mean for PCO2 throughout the respiratory cycle); and values calculated by using the empirical formula developed by Jones et al. (N. L. Jones, D. G. Robertson, and J. W. Kane. J. Appl. Physiol. 47: 954-960, 1979), which incorporates end-tidal PCO2 and tidal volume (PaCO2 derived from end-tidal PCO2 and VT). Measurements were made at rest and during cycle ergometry at 25 and 50 W while the subjects breathed various gas mixtures (euoxic-eucapnic, hypoxic-eucapnic, hyperoxic-eucapnic, and hyperoxic-hypercapnic). The mean differences between the estimates and the actual PaCO2 at rest and in 25- and 50-W exercise were as follows: PavCO2, 0.3 +/- 0.7 (SD), -0.1 +/- 0.7, and 1.8 +/- 1.2 Torr; end-tidal PCO2, 2.9 +/- 1.7, 4.0 +/- 3.1, and 3.7 +/- 3.2 Torr; time-weighted mean of alveolar PCO2, 2.6 +/- 1.9, 3.3 +/- 3.1, and 3.6 +/- 3.8 Torr; and PaCO2 derived from end-tidal PCO2 and VT, 2.4 +/- 1.3, 1.3 +/- 3.0, and 0.6 +/- 2.9 Torr. It is concluded that mean PavCO2 agreed most closely with mean PaCO2 both at rest and in exercise. All methods of deriving PaCO2 using measurements from the respired gases overestimated arterial values at rest. Of the noninvasive techniques, mean estimates calculated using the regression equation developed by Jones et al. corresponded most closely with PaCO2 in exercise.

On-line and memory-based aspects of individual and group target judgments.

Ss were given instruction sets to induce either on-line or memory-based processing while reading behavioral statements about individual and group targets. Impression-set instructions induced online judgments, and comprehensibility-set (comp) instructions induced memory-based judgments regardless of target type. More important, with nondirective instructions (memory set), natural differences in processing information about individuals and groups were observed, with more online judgments for individuals. As expected, illusory correlations between minority targets and infrequent behaviors (a memory-based product) emerged with comp instructions (which induced memory-based judgments for both target types) and in the memory-set condition for group targets only. These data provide insights into the differences in impression formation for groups and individuals and furnish direct evidence of the processes responsible for illusory correlations.

Illusory correlation in the perception of groups: an extension of the distinctiveness-based account.

The prevailing explanation for illusory correlation in the stereotyping of groups is that distinctive information (minority groups' infrequent behaviors) is salient, receives enhanced encoding, and becomes highly accessible, thus biasing subsequent judgments. This distinctiveness-based explanation (DBE) depends on information distinctiveness at the time of its encoding. Information distinctiveness at encoding was manipulated, while ultimate distinctiveness was kept constant. Experiment 1, contrary to the DBE, found illusory correlations emerge regardless of distinctiveness at encoding. Experiment 2 collected process data that showed that ultimately distinctive behaviors were highly accessible at the time of judgment even when they were not distinctive at encoding. Experiments 3-5 ruled out an alternative account. A basis for illusory correlation that depends on postpresentation, but prejudgment, encoding of distinctive information is suggested.