Search

INTRODUCTION: The androgen receptor (AR) mediates peripheral effects of testosterone. Evidence suggests that the number of CAG repeats in exon-1 of the AR gene negatively correlates with AR transcriptional activity. The aim of this analysis was to determine the association between CAG repeat number and mortality in men. METHODS: Men aged 40-79 years were recruited from primary care for participation in the UK arm of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios(HR)/95% confidence intervals (CI). RESULTS: 312 men were followed up. The mean baseline age was 59.5 years. At follow up, 85/312(27%) men had died. CAG repeat length ranged from 14 to 39, with the highest proportion of CAG repeat number at 21 repeats(16.4%). In a multivariable model, using men with CAG repeat numbers of 22-23 as the reference, men with a lower number of CAG repeats(23) (1.37 (0.65, 2.91)). CONCLUSION: Our data suggest that CAG repeat number may partially influence the risk of mortality in men. Further larger studies are required to quantify the effect. ispartof: AGING MALE vol:25 issue:1 pages:167-172 ispartof: location:England status: published

Stadnyk, M, Sepehri, M, Cook, M, Adeeb, S, and Westover, L. Quantifying asymmetry and performance of lower limb mechanical muscle function in varsity athletes-using non-countermovement jumps. J Strength Cond Res 37(1): 98-106, 2023-The ability to automatically quantify jump performance and lower limb muscle function in athletes would be beneficial for both training and rehabilitation purposes. Countermovement jumps (CMJs) and non-CMJs (NCMJs) are simple, quick, and require relatively inexpensive equipment to effectively and reliably monitor lower limb function. In a previous study, CMJ characteristics were assessed across different varsity sports. This study is a follow-up study to incorporate NCMJs into assessing jump characteristics of the same sports and investigate the additional information provided by the complementary jump type. The main objective of this study was to look at a means of quantifying the lower limb mechanical muscle function automatically to provide information for rehabilitation and performance purposes in athletes of specific sports. Male and female varsity athletes from 4 different sports completed 5 trials of an NCMJ on dual force plates. An analysis program was developed using Wolfram Mathematica to analyze force-time jump data. Various parameters of interest were generated, including peak force, force-time curve shape classification, jump phase lengths, phase-specific kinetic impulse, asymmetry index, takeoff velocity, jump height, phase-specific center of mass displacements, and reactive strength index modified. Results obtained indicate that similar jump characteristics to the CMJ study can be quantified, which can be used for performance enhancement or injury rehabilitation. Additional data found, such as the ability of an athlete to hold a steady squat during an NCMJ, could also be meaningful in aiding trainers to design programs tailored for athletes.

The posthumanist project proposes directing the evolution of human beings by promoting their improvement through technological means to create a variety of entities that will have few or no common characteristics with current humans. Its agenda is extremely broad and this study mostly addresses enhancement of the human organism through genetic modification techniques. An overview of posthumanist values and a brief discussion of its philosophical background provide a framework to understand its ideals. Genetics and ethics are employed to assess some claims of the posthumanist program of creating evolved humans; in particular, the capabilities and limitations of techniques for somatic and germline genome editing. Consequences of the creation of posthumans are discussed in relation to accepted current human beings and values. It is concluded that the posthumanist program rests on a large number of hypotheses without sufficient evidence and with little or no consideration of the consequences of its implementation.

The transhumanist project of reshaping human beings by promoting their improvement through technological innovations has a broad agenda. This study focuses on the enhancement of the human organism through genetic modification techniques. Transhumanism values and a discussion of their philosophical background provide a framework to understand its ideals. Genetics and ethics are employed to assess the claims of the transhumanist program of human enhancement. A succinct description of central concepts in genetics and an explanation of current techniques to edit the human genome serve to assess the capabilities and limitations of editing techniques. Potential benefits and liabilities of human enhancement through genome editing are discussed to appraise its feasibility. Ethical considerations of genome editing inform a reflection on the implications of introducing heritable changes in the genome of individuals. It is concluded that the transhumanist program is underpinned by a large number of hypotheses rather than by sufficient evidence.

Michael Cook looks at the role of an embedded Public Health Information Specialist highlighting the ways the core evidence, information and knowledge skills are used to progress Public Health activity in local government settings. Acknowledging the current pandemic, he explores how COVID-19 has dominated all aspects of health and social care, and outlines how evidence services have work within these complex Public Health systems to lead the local response and recovery efforts.

PurposeWe sought to identify factors predictive of or associated with receipt of speech/language services during early childhood. We did so by analyzing data from the Early Childhood Longitudinal Study–Birth Cohort (ECLS-B; Andreassen & Fletcher, 2005), a nationally representative data set maintained by the U.S. Department of Education. We addressed two research questions of particular importance to speech-language pathology practice and policy. First, do early vocabulary delays increase children's likelihood of receiving speech/language services? Second, are minority children systematically less likely to receive these services than otherwise similar White children?MethodMultivariate logistic regression analyses were performed for a population-based sample of 9,600 children and families participating in the ECLS-B.ResultsExpressive vocabulary delays by 24 months of age were strongly associated with and predictive of children's receipt of speech/language services at 24, 48, and 60 months of age (adjusted odds ratio range = 4.32–16.60). Black children were less likely to receive speech/language services than otherwise similar White children at 24, 48, and 60 months of age (adjusted odds ratio range = 0.42–0.55). Lower socioeconomic status children and those whose parental primary language was other than English were also less likely to receive services. Being born with very low birth weight also significantly increased children's receipt of services at 24, 48, and 60 months of age.ConclusionExpressive vocabulary delays at 24 months of age increase children’s risk for later speech/language services. Increased use of culturally and linguistically sensitive practices may help racial/ethnic minority children access needed services.

A fundamental question in hematopoietic stem cell (HSC) biology is how self-renewal is controlled. Here we show that the molecular regulation of two critical elements of self-renewal, inhibition of differentiation and induction of proliferation, can be uncoupled, and we identify Notch signaling as a key factor in inhibiting differentiation. Using transgenic Notch reporter mice, we found that Notch signaling was active in HSCs in vivo and downregulated as HSCs differentiated. Inhibition of Notch signaling led to accelerated differentiation of HSCs in vitro and depletion of HSCs in vivo. Finally, intact Notch signaling was required for Wnt-mediated maintenance of undifferentiated HSCs but not for survival or entry into the cell cycle in vitro. These data suggest that Notch signaling has a dominant function in inhibiting differentiation and provide a model for how HSCs may integrate multiple signals to maintain the stem cell state.

Quantitative depth based on binocular resolution of visibility constraints is demonstrated in a novel stereogram representing an object, visible to 1 eye only, and seen through an aperture or camouflaged against a background. The monocular region in the display is attached to the binocular region, so that the stereogram represents an object which is only partially visible to the eye that sees it. The results show that this feature is necessary for quantitative depth, which is not found for a fully visible monocular object in the same location, and that depth in these displays, although very precise, is not based on fusional Stereopsis. The findings provide clear support for the existence of a process of da Vinci Stereopsis, but one more sophisticated than the one proposed by K. Nakayama and S. Shimojo (1990).

Therapies that suppress RIPK1 kinase activity are emerging as promising therapeutic agents for the treatment of multiple inflammatory disorders. The ability to directly measure drug binding of a RIPK1 inhibitor to its target is critical for providing insight into pharmacokinetics, pharmacodynamics, safety and clinical efficacy, especially for a first‐in‐class small‐molecule inhibitor where the mechanism has yet to be explored. Here, we report a novel method for measuring drug binding to RIPK1 protein in cells and tissues. This TEAR1 (Target Engagement Assessment for RIPK 1) assay is a pair of immunoassays developed on the principle of competition, whereby a first molecule (ie, drug) prevents the binding of a second molecule (ie, antibody) to the target protein. Using the TEAR1 assay, we have validated the direct binding of specific RIPK1 inhibitors in cells, blood and tissues following treatment with benzoxazepinone (BOAz) RIPK1 inhibitors. The TEAR1 assay is a valuable tool for facilitating the clinical development of the lead RIPK1 clinical candidate compound, GSK2982772, as a first‐in‐class RIPK1 inhibitor for the treatment of inflammatory disease.

Traumatic injury to a joint is known to increase the risk for the development of secondary osteoarthritis, but it is unclear how this process occurs. The existence of such a discrete event that can lead to an increased risk of osteoarthritis has spurred interest in developing in vitro models of traumatic joint injury. The current authors review some of the recent insights gained from these model systems into the pathogenesis of osteoarthritis, including the evidence for an initial, irreversible insult to chondrocytes during mechanical injury, the occurrence of apoptotic chondrocyte death, and attempts to identify the effects of trauma on chondrocyte metabolic response. Results also are presented from the authors' ongoing studies of the degradative pathways initiated by traumatic mechanical loads, the mechanism by which chondrocytes are affected during compression, and possible contributions of the joint capsule to posttraumatic cartilage degradation.

Perspective is usually considered a monocular pictorial cue, distinct from other cues such as occlusion and stereopsis. We cut across these distinctions by asking whether purely binocular (cyclopean) contours, created by stereoscopically shifting a region of homogeneous texture nearer or further than its surround, can act as a linear-perspective cue and whether the contours' ability to do this is influenced by their surface belongingness. We found that the left/right orientation of cyclopean trapezoids nearer than a surround strongly influenced perceived slant, showing that perspective constraints are applied to stereoscopically derived contours. Further regions, however, appeared as surfaces seen through a trapezoidal aperture. Because the aperture “owned” the trapezoidal contours, their orientation had little effect on perceived slant. We conclude that the application of perspective constraints depends critically on how contours are classified by stereo-specified occlusion relationships among surfaces and that perspective, stereopsis, and occlusion are not distinct processing systems.

In current functional models of person recognition it is proposed that there exists a single common body of semantic information concerning people accessible from all modalities (e.g. names, faces). In this paper, we present evidence that challenges this view. Two experiments are discussed investigating residual autobiographical and public knowledge in a patient suffering from retrograde amnesia. Knowledge about people was investigated in each case by asking a series of questions, ranging from the very general to the very specific. Experiment 1 examined knowledge about famous people. The results showed that the patient accessed more information about famous people when cued with names than when cued with faces. Experiment 2 examined knowledge about people known personally to the patient. Again, the same pattern of results emerged. While the patient responded accurately to all questions posed with name cues, her ability to recall the same information when prompted with face cues was clearly inferior. This modality-based difference in accessing biographical knowledge is discussed in relation to models of person recognition.

Nucleotide-binding domain leucine-rich repeat proteins (NLRs) play a key role in immunity and disease through their ability to modulate inflammation in response to pathogen-derived and endogenous danger signals. Here, we identify the requirements for activation of NLRP1, an NLR protein associated with a number of human pathologies, including vitiligo, rheumatoid arthritis, and Crohn disease. We demonstrate that NLRP1 activity is dependent upon ASC, which associates with the C-terminal CARD domain of NLRP1. In addition, we show that NLRP1 activity is dependent upon autolytic cleavage at Ser(1213) within the FIIND. Importantly, this post translational event is dependent upon the highly conserved distal residue His(1186). A disease-associated single nucleotide polymorphism near His(1186) and a naturally occurring mRNA splice variant lacking exon 14 differentially affect this autolytic processing and subsequent NLRP1 activity. These results describe key molecular pathways that regulate NLRP1 activity and offer insight on how small sequence variations in NLR genes may influence human disease pathogenesis.

A comparison was made between trajectories of reaches to visual targets by 6-months-old infants, with and without lateral prismatic displacement. In the No Prism condition, the major element of the movement veered towards the target, confirming the results of Mathew and Cook (1990). In the Prism condition, the prism did not affect hand position or movement direction at the beginning of the major element, but a lateral displacement was evident by the end of the element. This is taken as evidence that shifts in trajectory during the element were not due to visual guidance. It is suggested instead that these shifts may reflect correction based upon somatic feedback about position in relation to the visually specified goal of the movement. Evidence that the hand approached the virtual target supports the suggestion that any visual guidance was confined to the approach phase of the reach. Nevertheless, it appears that visual guidance was operating at this stage, since movement direction was displaced away from the virtual target and towards the real target.

Fluorescence-based flow cytometry measures multiple cellular characteristics, including levels of receptor expression, by assessing the fluorescence intensity from a population of cells whose cell surface receptors are bound by a fluorescently labeled antibody or ligand for that receptor. Functionalized noble metal nanoparticles provide a complementary method of receptor labeling based on plasmonics for population analysis by flow cytometry. The potential benefits of using plasmonic nanoparticles to label cell surface receptors in flow cytometry include scattering intensity from a single particle that is equivalent to fluorescence intensity of 105 fluorescein molecules, biocompatibility and low cytotoxicity, and nonquenching optical properties. The large spectral tunability of nanorods also provides convenient access to plasmonic markers with peak surface plasmon resonances ranging from 600 to 2,200 nm, unlike gold nanosphere markers that are limited to visible wavelengths. Gold nanorod-based plasmonic flow cytometry is demonstrated herein by comparing the scattering of cells bound to anti-epidermal growth factor receptor (EGFR)-conjugated nanorods to the emission of cells bound to anti-EGFR-conjugated fluorescent labels. EGFR-expressing cells exhibited a statistically significant six-fold increase in scattering when labeled with anti-EGFR-conjugated nanorods compared with labeling with IgG1-conjugated nanorods. Large scattering intensities were observed despite using a 1,000-fold lower concentration of nanorod-conjugated antibody relative to the fluorescently labeled antibody. © 2010 International Society for Advancement of Cytometry

In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient.In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later attached to an external drug infusion pump.We report the successful use of the Medtronic Indura 1P, one piece intrathecal catheter, connected to the external drug pump for a 3 week period in a patient with metastatic cervical cancer for palliative pain control.Case report only.This technique is simple to perform by pain specialists. The catheter modification allows the use of the Medtronic intrathecal catheter with standard external drug infusion pumps. This facilitates the patient's care in the hospice setting.

Samples of reaches were obtained from groups of infants aged 4.5, 6, and 7.5 months. Split-screen video recordings were transcribed as sequences of (x, y, z) hand coordinates, and the hand path was examined for evidence of initial aiming and subsequent correction of the movement path. At all ages, the initial direction of the movement was correlated with target direction, providing evidence that the hand was aimed toward the target. Additionally, changes in movement direction made after the commencement of the movement tended to curve the hand path toward the target, providing evidence of error correction. Local minima of hand speed evident within segments of continuous motion were associated with turn toward the target. However, the movement path was also curved toward the target within the movement elements bounded by these minima. This finding was seen as consistent with “continuous” correction of movement errors and as contrary to the suggestion that infant movements are concatenations of ballistic movement units whose boundaries are marked by troughs in the speed profile.

Purpose: The role of motion contrast and motion capture in the ‘Ouchi’ effect was investigated in a simplified stimulus. Methods: Sinewave gratings were rapidly oscillated vertically within two concentric stationary ‘apertures’, an innerdisc surrounded by an annulus. Results: A strong illusion of relative motion between the disc and annulus is observed in the horizontal direction for 8 and 12 cycles/deg given small orientation differences between the two gratings. Conclusion: These parameters coincide with those of the ‘Ouchi’ effect, suggesting a sharing of the same causal mechanism.

Aims This study explored the Magnet accreditation process in the first health care organization outside the USA to attempt to gain the award, Rochdale NHS Trust United Kingdom. The development was supported by the American Nurses Credentialing Center as a pilot project and the research conducted as a case study in organizational response to the requirements of a new accreditation system. Method Information was collected via 23 face-to-face and three telephone interviews carried out with 11 senior figures at Rochdale during the 2-year period of the Magnet project, from field notes of meetings attended by the researchers and from analysis of documents associated with the project. Results The work of applying for Magnet accreditation built upon a previous 2–3 year programme of shared governance and clinical leadership throughout the Trust which senior staff felt had been an essential foundation for the Magnet project. The process enabled staff to assemble evidence which held up a mirror to their practice and contributed to other quality-related initiatives. The experience at Rochdale suggests that Magnet enables care areas to identify and celebrate examples of good practice and for lessons to be learned and shared within the organization. Although the Magnet concept is primarily nursing oriented, medical and allied health professionals were able to contribute and benefit. The application was successful and Rochdale was awarded Magnet status in April 2002. Conclusions The Magnet project at Rochdale was essentially a process of collecting evidence to formally recognize previous leadership initiatives and their effects within the organization. The emergent approach to implementing the Magnet project was one which attempted to integrate and utilize existing systems and resources. The project provides evidence that Magnet can be transferred to non-US health care systems. The principal issues associated with this transfer were the costs incurred, the interpretation of terminology and the engagement of medical and allied health professionals.

A variety of biomedical technologies are being developed that can be used for purposes other than treating disease. Such "enhancement technologies" can be used to improve our appearance and regulate our emotions, with the goal of feeling "better than well." While these technologies can help people adapt to their rapidly changing lifestyles, their use raises important ethical issues.

We have previously demonstrated that, in the presence of the lysine analogue epsilon-aminocaproic acid, apolipoprotein(a) [apo(a)] undergoes a conformational change from a closed to an open structure that is characterized by a change in tryptophan fluorescence, an increase in the radius of gyration, an alteration of domain stability, and an enhancement in the efficiency of covalent lipoprotein(a) [Lp(a)] formation. In the present study, to identify sequences within apo(a) that maintain its closed conformation, we used epsilon-aminocaproic acid to probe the conformational status of a variety of recombinant apo(a) isoforms using analytical ultracentrifugation, differential scanning calorimetry, intrinsic fluorescence, and in vitro covalent Lp(a) formation assays. We observed that the closed conformation of apo(a) is maintained by intramolecular interaction(s) between sequences within the amino- and carboxyl-terminal halves of the molecule. Using site-directed mutagenesis, we have identified the strong lysine-binding site present within apo(a) kringle IV type 10 as an important site within the C-terminal half of the molecule, which is involved in maintaining the closed conformation of apo(a). Apo(a) exhibits marked isoform size heterogeneity because of the presence of varying numbers of copies of the kringle IV type-2 domain located within the amino-terminal half of the molecule. Using recombinant apo(a) species containing either 1, 3, or 8 copies of kringle IV type 2, we observed that, while apo(a) isoform size does not alter the affinity of apo(a) for low-density lipoprotein, it affects the conformational status of the protein and therefore influences the efficiency of covalent Lp(a) assembly. The inverse relationship between apo(a) isoform size and the efficiency of covalent Lp(a) formation that we report in vitro may contribute to the inverse relationship between apo(a) isoform size and plasma Lp(a) concentrations that has been observed in vivo.

While searching for an object in a cluttered scene, in some situations, the visual system adopts a pre-attentive parallel search, where the time taken is independent of the number of items in the scene. In others, the search is serial, time taken being a function of the set size. We show that detecting the number of targets (2, 3 or 4) that differ in depth from background items is a parallel process, but only when they are all in the same surface in depth. The search is serial if the targets are in different depth planes, but parallel even if the targets were on a surface tilted in depth, showing that surface segregation influences a parallel, apparently pre-attentive, stage.

Da Vinci stereopsis is defined as apparent depth seen in a monocular object laterally adjacent to a binocular surface in a position consistent with its occlusion by the other eye. It is widely regarded as a new form of quantitative stereopsis because the depth seen is quantitatively related to the lateral separation of the monocular element and the binocular surface (Nakayama and Shimojo 1990 Vision Research30 1811–1825). This can be predicted on the basis that the more separated the monocular element is from the surface the greater its minimum depth behind the surface would have to be to account for its monocular occlusion. Supporting evidence, however, has used narrow bars as the monocular elements, raising the possibility that quantitative depth as a function of separation could be attributable to Panum's limiting case (double fusion) rather than to a new form of stereopsis. We compared the depth performance of monocular objects fusible with the edge of the surface in the contralateral eye (lines) and non-fusible objects (disks) and found that, although the fusible objects showed highly quantitative depth, the disks did not, appearing behind the surface to the same degree at all separations from it. These findings indicate that, although there is a crude sense of depth for discrete monocular objects placed in a valid position for uniocular occlusion, depth is not quantitative. They also indicate that Panum's limiting case is not, as has sometimes been claimed, itself a case of da Vinci stereopsis since fusibility is a critical factor for seeing quantitative depth in discrete monocular objects relative to a binocular surface.

During lipoprotein(a) (Lp(a)) assembly, non-covalent interactions between apolipoprotein(a) (apo(a)) and low density lipoprotein precede specific disulfide bond formation. Studies have shown that the non-covalent step involves an interaction between the weak lysine-binding sites (WLBS) present within each of apo(a) kringle IV types 6, 7, and 8 (KIV(6-8)), and two lysine residues (Lys(680) and Lys(690)) within the NH(2) terminus of the apolipoprotein B-100 (apoB) component of low density lipoprotein. In the present study, we introduced single point mutations (E56G) into each of the WLBS present in apo(a) KIV(6-8) and expressed these mutations in the context of a 17-kringle (17K) recombinant apo(a) variant. Single mutations that disrupt the WLBS in KIV(6), KIV(7), and KIV(8), as well as mutants that disrupt the WLBS in both KIV(6) and KIV(7), or both KIV(7) and KIV(8), were assessed for their ability to form non-covalent and covalent Lp(a) complexes. Our results demonstrate that both apo(a) KIV(7) and KIV(8), but not KIV(6), are required for maximally efficient non-covalent and covalent Lp(a) assembly. Single mutations in the WLBS of KIV(7) or KIV(8) resulted in a 3-fold decrease in the affinity of 17K recombinant apo(a) for apoB, and a 20% reduction in the rate of covalent Lp(a) formation. Tandem mutations in the WLBS in both KIV(7) and KIV(8) resulted in a 13-fold reduction in the binding affinity between apo(a) and apoB, and a 75% reduction in the rate of the covalent step of Lp(a) formation. We also showed that KIV(7) and KIV(8) specifically bind with high affinity to apoB-derived peptides containing Lys(690) or Lys(680), respectively. Taken together, our data demonstrate that specific interactions between apo(a) KIV(7) and KIV(8) and Lys(680) and Lys(690) in apoB mediate a high affinity non-covalent interaction between apo(a) and low density lipoprotein, which dictates the efficiency of covalent Lp(a) formation.

Objective Traumatic joint injury leads to an increased risk of osteoarthritis (OA), but the progression to OA is not well understood. We undertook this study to measure aspects of proteoglycan (PG) degradation after in vitro injurious mechanical compression, including up-regulation of enzymatic degradative expression and cytokine-stimulated degradation. Methods Articular cartilage tissue explants were obtained from newborn bovine femoropatellar groove and from adult normal human donor knee and ankle tissue. Following injurious compression of the cartilage, matrix metalloproteinase 3 (MMP-3) and MMP-13 messenger RNA (mRNA) expression levels were measured by Northern analysis, and PG loss to the medium after cartilage injury was measured in the presence and absence of added exogenous cytokine (interleukin-1α [IL-1α] or tumor necrosis factor α [TNFα]). Results During the first 24 hours after injury in bovine cartilage, MMP-3 mRNA levels increased 10-fold over the levels in control cartilage (n = 3 experiments), whereas MMP-13 mRNA levels were unchanged. PG loss was significantly increased after injury, but only by 2% of the total PG content and only for the first 3 days following injury. However, compared with injury alone or cytokine treatment alone, treatment of injured tissue with either 1 ng/ml IL-1α or 100 ng/ml TNFα caused marked increases in PG loss (35% and 54%, respectively, of the total cartilage PG content). These interactions between cytokine treatment and injury were statistically significant. In human knee cartilage, the interaction was also significant for both IL-1α and TNFα, although the magnitude of increase in PG loss was lower than that in bovine cartilage. In contrast, in human ankle cartilage, there was no significant interaction between injury and IL-1α. Conclusion The cytokines IL-1α and TNFα can cause a synergistic loss of PG from mechanically injured bovine and human cartilage. By attempting to incorporate interactions with other joint tissues that may be sources of cytokines, in vitro models of mechanical cartilage injury may explain aspects of the interactions between mechanical forces and degradative pathways which lead to OA progression.

There have been several reports in the literature, mainly anecdotal, of amnesic patients demonstrating an ability to learn and remember song. Yet there has been little systematic investigation of this phenomenon. In this paper we report findings from three experiments investigating memory for song in two amnesic patients, Joan and Nellie. In the first study we explored recognition memory for various elements of song (i.e. lyrics, melody, lyrics and melody combined) and found that amnesic patients were better than chance at distinguishing studied from novel materials when given explicit instructions. In experiment 2, the ability to generate lyrics and melody was explored in one patient. Although this patient could only generate melodies, her performance in this modality was equivalent to that of matched controls. Memory for the semantic content of song was investigated in a final study using explicit testing conditions. The results showed that both patients were significantly better than chance at identifying correct responses, indicating that they acquired and retained knowledge of the general content of studied songs. These findings not only highlight the special nature of song in facilitating memory in amnesic patients, but given the level of accuracy in memory performance observed, suggest an alternative direction in rehabilitation.

DEVELOPING CLINICAL nurse leaders is a major priority in the health service today. Following a study tour of three states in Australia, I believe we have a great deal to learn by studying their approach. I visited New South Wales, Victoria and Queensland, within each state I spent time in both rural and metropolitan health care settings.

The spatial parameters underlying a novel illusion of relative motion are characterized. A simple stimulus composed of two sine-wave gratings was sufficient to generate the illusion. We measured the response of subjects to rapid, small-amplitude oscillations of this stimulus behind a fixation point. The effect was clearly strongest for acute angles between the gratings, but only when spatial frequency was between 6 and 11 cpd. We surmise that activity in the grating cells of the primate visual cortex (von der Heydt, Peterhans, & Dursteler, 1992) might be the cause of the illusion. The illusion is potentially an important tool in understanding how higher cortical areas combine disparate motion signals.

Background Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells. Purpose The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects. Methods The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis. Results LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase. Conclusions Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.

Panum's limiting case—a perceived depth difference between two lines in one eye combined with only one in the other eye—has long been considered weak or reversible. In the last few years this has led to strong promotion of the view that Panum's case is not based on a stereoscopic process involving double fusion, that only one line is fused, with the depth of the other one attributable either to fixation disparity or to occlusion cues. This view is refuted in two ways. First it is shown that when the separation of the two lines, considered as a disparity, is within the range of ‘patent stereopsis’, depth is perceived with a precision and accuracy indistinguishable from regular stereopsis. The predictions of nonstereoscopic theories concerning the effects of fixation are not borne out at small disparities. Second, very compelling Panum versions of orientation and curvature disparity are introduced, which are difficult to account for except by a process of double fusion. Finally it is shown that at large disparities the depth in Panum's case deviates from prediction more frequently than does regular stereoscopic depth.

Simultaneous spatial-discrimination thresholds of 6 human subjects were measured at luminances between 0.2 and 2000 cd/m2. Subjects were tested on a forced-choice discrimination task which required them to distinguish between test and control stimuli of high contrast square-wave gratings with similar space-average luminances. The form of the function depicting the relationship between acuity and luminance is similar to that obtained by other researchers. The estimated maximum acuity of 72 cycles/degree (c/deg) is higher than the commonly cited value of 60 c/deg and this is probably due to the combination of the high stimulus luminance and the psychophysical technique employed in this study.

Observers scanned a stationary pattern comprising a tilted sine-wave grating completely surrounding another grating of similar spatial frequency but tilted in the opposite direction (Fig. 2). They reported an illusory “sliding” motion of the inset grating with respect to the surround grating and the effect was clearly strongest for angles between the gratings of less than 60° and for spatial frequencies between 6–11 cpd. In a second experiment, a similar pattern was moved (2.0 deg/sec) either up or down for a presentation time of 167 msec. Simultaneously, the inset grating was drifted at different speeds in each of its two directions. Using the method of constant stimuli, it was shown that the relative motion illusion could be cancelled by physically drifting the grating in the opposite direction to the illusory movement. The illusion arises because there is a failure to integrate two motion signals into the single motion vector which characterises rigid motion.

Day and McKenzie determined the rate of habituation of fixation of young infants to repeated visual presentations of a cube. They found the habituation rate to be the same when the stimulus orientation changed between presentations as when it was fixed, and they interpreted this as evidence of shape constancy. However, a failure to discriminate between cubes in different orientations is only evidence of shape constancy if the infant can at the same time discriminate the cube from other cubelike forms. The experiment described here contrasted the rate of habituation of fixation of 12-week-old infants to a homogenous stimulus series (a cube presented in different orientations) with the rates of habituation to various heterogeneous series, in each of which a cube was alternated with some other solid. It was found that, while the infant could distinguish a cube from a photograph of a cube and a concave solid (an L-form), there was no evidence of discrimination between the cube and either a wedge or a truncated pyramid. The results imply limits to the young infants capacity to resolve solid form.

Two groups of children aged 6 and 8 years were given three tasks requiring graphical representations of solid geometric forms. These tasks were drawing from life models, copying from photographs, and copying from line drawings of these objects. Performance was assessed on the basis of level of approximation to correct perspective. Older children used more perspective features than younger children in their drawings. At all ages, the drawings from life were most difficult. Results on the two copying tasks were not consistent. Drawings made by copying photographs were either as advanced as or poorer than copies of line drawings. The results are explained in terms of the difficulties exhibited by young children in translating the three-dimensional scene to a two-dimensional picture plane and strategies adopted by them to cope with these problems.

The perception of three-dimensional attributes of solid objects by twelve-week-old infants was studied. In the first experiment the rates of habituation of fixation to a cube in a fixed orientation, to one which changed in orientation between presentations, and to a sequence of photographs of cubes in different orientations were determined. Habituation rate was also determined for a photograph of a cube in a fixed orientation. No difference was found between the initial fixation times for solids and photographs, or between the habituation curves for the solids in fixed and varying orientation. For the photographs habituation was much greater for the fixed orientation than the varying orientation condition. These data were interpreted as providing strong evidence that the infants were responding to the stimuli on the basis of their three-dimensional attributes. In the second experiment the same discriminations were examined by a recovery-from-habituation technique. One group was habituated to a cube in a fixed orientation and tested for recovery of fixation to a new orientation. A second group was habituated to a photograph of a cube in a single orientation and tested for recovery to a photograph of a new orientation. Both groups showed recovery and the recovery was the same for both conditions. These data demonstrated that the subjects were, after all, capable of discriminating between different orientations of a solid cube, and they provided no further evidence that the infants were perceiving three-dimensional attributes of the stimuli.

This study investigated whether defective copying of multiple-line figures in lesion patients is associated with a deficit in perceptually processing and copying elementary attributes. Lesion and Control patients were assessed on a copying test comprising multi-line figures, and on parallel perceptual and motor forms of single-attribute tasks for Size, Orientation, Angle, Position and Direction. Copying test performance was correlated with perceptual attribute performance for the Lesion but not the Control group. Mean attribute performance of the Lesion patients who showed a copying disability (defined as a copying performance below the minimum performance of the Control group) was inferior to that of the non-disabled and Control subjects. The non-disabled patients did not differ from the Controls on any of these tasks. Performance in the copying test for left-and-right- hemisphere patients did not differ, but left-hemisphere patients showed less impairment in the simple attribute tasks. The results are discussed in terms of the role of elementary perceptual deficits in copying disability and hemispheric differences in the nature of this condition.

Informants' rating, self-report questionnaires and observers' ratings were compared in the assessment of assertive skills of five mildly retarded young adults. Of the three standard assertion scales administered, only the Wolpe-Lazarus correlated positively with behavioral ratings obtained from role-playing. Scores on the Wolpe-Lazarus scale, however, were negatively correlated with those obtained on the Rathus and Adult Self-expression scales. Neither the informants' ratings nor self-reports correlated with behavioral ratings. These data suggest a multi-modal assessment of assertive behavior is needed. The implications for treatment and further research are considered.

A test was made of the scalability of interval-ordering judgments of distance along the median path of a plane horizontal surface. Scales were derived from different subsets of judgments. It was found that scale values were related to distance by a power function with marked individual differences in exponent, but that different subsets of judgment yielded the same mean exponent. This finding was taken as positive evidence of scalability. The individual differences in judgment were shown to be reliable over a period of 3 weeks.