The first 'molecular disease': a story of Linus Pauling, the intellectual patron

In November 1949, chemist Linus Pauling and three colleagues published an article on sickle-cell anemia, a study that opened up new and exciting possibilities for research into such 'molecular diseases'. Even before this celebrated publication appeared in Science, Pauling foresaw its potential benefits and announced it as a medical breakthrough: '... our structural chemistry and understanding of molecules is getting to the point where it should be of assistance in converting medicine into a real science' [Guiles, R. (1949) Discovery of blood disease called key to cancer research. The Detroit Times 13 Sep 1949, Newspaper Clippings 1949n.18, Pauling Papers.]. Their discovery--that this debilitating disorder was caused by an abnormal form of hemoglobin--was borne out of a rich mix of expertise, from Pauling's remarkable intuition to the careful experimental chemistry of his student Harvey A. Itano. It also relied upon technological innovation: a custom-made electrophoresis machine housed at the California Institute of Technology was the perfect tool to reveal fundamental chemical differences between normal and abnormal forms of hemoglobin. Not only did this work establish a new way of looking at inherited diseases, it also stimulated the mass production of the electrophoresis machine as an essential investigative and diagnostic tool. A close inspection of this case study illustrates just how Pauling ran his laboratory and helps to explain how one man could achieve so much over his lifetime.     

Functional impact of emotions on athletic performance: comparing the IZOF model and the directional perception approach

The aim of this study was to examine the impact of emotions on athletic performance within the frameworks of the Individual Zones of Optimal Functioning (IZOF) model and the directional perception approach. Intensity, functional impact, and hedonic tone of trait and state anxiety, self-confidence, idiosyncratic emotions, and bodily symptoms were assessed in high-level Italian swimmers and track and field athletes (N = 56). Three standards of performance (poor, average, and good), derived from retrospective self-ratings across one to three competitions (a total of 90 observations), were used as independent variables in the analysis of variance of intensity, intra-individual, and direction scores of anxiety, self-confidence, idiosyncratic emotions, and bodily symptoms. Subsequently, intra-individual scores were categorized as near to or distant from optimal/dysfunctional zones and entered as the independent variable in the analysis of direction scores. The results provided support for the predictions stemming from both the IZOF model and the directional approach, as well as help in interpreting direction of anxiety and other idiosyncratic emotions within the IZOF framework. Athletes tended to perceive emotional levels approximating an individual's optimal zone as facilitative-pleasant, and emotional levels approximating an individual's dysfunctional zone as debilitative-unpleasant.     

Child maltreatment, subsequent non-suicidal self-injury and the mediating roles of dissociation, alexithymia and self-blame

ObjectiveAlthough child maltreatment is associated with later non-suicidal self-injury (NSSI), the mechanism through which it might lead to NSSI is not well understood. The current retrospective case–control study examined associations between child maltreatment and later NSSI, and investigated the mediating roles of dissociation, alexithymia, and self-blame.MethodsParticipants were 11,423 Australian adults (response rate 38.5%), randomly selected from the Australian Electronic White Pages, aged between 18 and 100 (M = 52.11, SD = 16.89), 62.2% female. Data were collected via telephone interviewing. Main outcome measures were reported history of child maltreatment (sexual abuse, physical abuse, neglect) and reported 12-month NSSI. Dissociation, alexithymia, and self-blame were examined as potential mediating variables in the relationship between child maltreatment and later NSSI. All analyses were conducted using logistic regression and adjusted for age and psychiatric diagnosis.ResultsResults differed by gender. Compared to no child maltreatment, physical abuse (OR 2.75, 95% CI 1.68–4.51) and neglect (OR 2.56, 95% CI 1.65–3.99) independently increased the odds of NSSI among females. Physical abuse (OR 2.69, 95% CI 1.44–5.03) increased the odds of NSSI among males. Sexual abuse did not independently increase the odds of NSSI for males or females. For females, self-blame had the greatest effect on the child maltreatment–NSSI relationship (OR decreased by 14.6%, p < .000), although dissociation and alexithymia also partially mediated the relationship. For males, dissociation had the greatest effect (OR decreased by 12.9%, p = .003) with self-blame also having a relatively strong effect.ConclusionsThe results indicate that child maltreatment, and in particular, physical abuse, is strongly associated with the development of subsequent NSSI and may be partially mediated by dissociation, alexithymia, and self-blame for females and dissociation and self-blame for males. Altering attributional style (through cognitive therapy or emotion focussed therapy) and improving the capacity to regulate emotions (through dialectical behaviour therapy) may contribute to reduction or cessation of NSSI.     

An Application of Generalizability Theory to Evaluate the Technical Quality of an Alternate Assessment

Although federal regulations require testing students with severe cognitive disabilities, there is little guidance regarding how technical quality should be established. It is known that challenges exist with documentation of the reliability of scores for alternate assessments. Typical measures of reliability do little in modeling multiple sources of error, which are characteristic of alternate assessments. Instead, Generalizability theory (G-theory) allows researchers to identify sources of error and analyze the relative contribution of each source. This study demonstrates an application of G-theory to examine reliability for an alternate assessment. A G-study with the facets rater type, assessment attempts, and tasks was examined to determine the relative contribution of each to observed score variance. Results were used to determine the reliability of scores. The assessment design was modified to examine how changes might impact reliability. As a final step, designs that were deemed satisfactory were evaluated regarding the feasibility of adapting them into a statewide standardized assessment and accountability program.     

Back to the Future: Warlpiri Encounters with Drawings,Country and Others in the Digital Age

Since the early 1900s, Warlpiri people living in the central desert region of Australia have experienced an intense process of adaption to the changing circumstances of postcolonial life. From the earliest days, their encounters with kardiya, non-Aboriginal people, have been mediated by diverse visual technologies that have, over time, become integral to the ways Warlpiri orient themselves to each other and their wider world. In this paper I trace the key elements of the complex visual environment that has emerged from this history of mediation. The central part of the paper considers events around the repatriation to Warlpiri communities in 2011 of a collection of drawings made in the 1950s by their forebears. In responses to a medium that once was new but now is old, several points of interest emerge, among them a clear sense of a hierarchy of value Warlpiri apply to modes of visual communication. In the context of the return of the drawings, the significance Warlpiri ascribe to other visual media comes to the fore. I consider some of the ways visual forms are deployed in support of public projections of cultural identity on the one hand and everyday modes of expression and address on the other. The paper's central argument is that contemporary Warlpiri attitudes to images – whether they be drawn, painted or broadcast – reveal the complex postcolonial workings of mimetic desire.     

Increasing label-free stem cell sorting capacity to reach transplantation-scale throughput

Dielectrophoresis (DEP) has proven an invaluable tool for the enrichment of populations of stem and progenitor cells owing to its ability to sort cells in a label-free manner and its biological safety. However, DEP separation devices have suffered from a low throughput preventing researchers from undertaking studies requiring large numbers of cells, such as needed for cell transplantation. We developed a microfluidic device designed for the enrichment of stem and progenitor cell populations that sorts cells at a rate of 150,000 cells/h, corresponding to an improvement in the throughput achieved with our previous device designs by over an order of magnitude. This advancement, coupled with data showing the DEP-sorted cells retain their enrichment and differentiation capacity when expanded in culture for periods of up to 2 weeks, provides sufficient throughput and cell numbers to enable a wider variety of experiments with enriched stem and progenitor cell populations. Furthermore, the sorting devices presented here provide ease of setup and operation, a simple fabrication process, and a low associated cost to use that makes them more amenable for use in common biological research laboratories. To our knowledge, this work represents the first to enrich stem cells and expand them in culture to generate transplantation-scale numbers of differentiation-competent cells using DEP.