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Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.

ObjectivesChildhood trauma is a common risk factor for adult psychiatric disorders, such as schizophrenia (SZ) and bipolar‐I disorder (BD). However, its association with schizotypal personality traits, as well as cognitive and social cognitive abilities, is less well studied in these populations.MethodsIn a cohort of 79 SZ cases, 84 BD cases, and 75 healthy controls (HCs), clinically significant levels of childhood trauma exposure (according to scores on the Childhood Trauma Questionnaire; CTQ) were evident in 54 SZ, 55 BD, and 26 HC individuals. Trauma‐exposed and non‐exposed groups were compared on schizotypal personality features (schizotypy) measured with the Schizotypal Personality Questionnaire (SPQ). Cognitive assessments included executive function, working memory, attention, and immediate and delayed memory. Social cognitive measures assessed facial emotion processing and theory‐of‐mind abilities.ResultsTrauma‐exposed participants showed higher levels of schizotypy, especially suspiciousness, relative to non‐exposed individuals, regardless of clinical or HC status. Furthermore, trauma‐exposed individuals showed deficits specifically in social cognitive, but not general cognitive abilities, regardless of clinical or HC status. These trauma‐related results were found in the context of higher schizotypy levels in both SZ and BD relative to HC, and lower cognitive and social cognitive performance in SZ, relative to BD and HC groups.ConclusionsThese findings suggest that childhood trauma exposure impacts long‐term schizotypy outcomes, especially paranoid ideation (suspiciousness), as well as complex social cognitive abilities in both healthy and psychotic populations. However, cognitive deficits associated with psychotic illness may not be distinguishable from those related to trauma exposure in previous studies.

Background Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task. Methods We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not. Results In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity. Conclusions Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

Childhood trauma is a significant risk factor for the development of psychotic disorders, and may influence executive brain functions. We thus set out to investigate the long-term effects of childhood trauma exposure on brain function of adult chronic patients diagnosed with schizophrenia, schizoaffective disorder and (psychotic) bipolar-I disorder while performing a standard 2/0-back working memory task. Participants were 50 cases diagnosed with schizophrenia/schizoaffective disorder (SCZ), 42 cases with bipolar-I disorder (BD), and 47 healthy controls (HC). Among this sample, 56 clinical cases (SCZ = 32; BD = 24) and 17 HC reported significant levels of childhood trauma, while 36 clinical cases (SCZ = 18; BD = 18) and 30 HC did not. Effects of childhood trauma on working memory-related brain activation were examined in combined samples of clinical cases (independently of diagnosis) relative to HCs, as well as within each diagnostic category. Case–control analyses revealed increased activation of the left inferior parietal lobule as a main effect of trauma exposure. In addition, trauma exposure interacted with a diagnosis of SCZ or BD to reveal trauma-related increased activation in the cuneus in clinical cases and decreased activation in this region in controls. Disorder-specific functional alterations were also evident in the SCZ sample, but not BD. Childhood trauma exposure elicits aberrant function of parietal regions involved in working memory performance regardless of clinical status, as well as task-relevant visual regions that participates to attentional processes. Childhood trauma may therefore contribute to alterations in attention in SCZ and BD while performing an n-back working memory task.

Markers of HPA axis function, including diurnal cortisol rhythm and cortisol responses to stress or pharmacological manipulation, are increasingly reported as disrupted in schizophrenia (SZ) and bipolar disorder (BD). However, there has been no direct comparison of cortisol responses to stress in SZ and BD in the same study, and associations between cortisol dysfunction and illness characteristics remain unclear. In this study we used spline embedded linear mixed models to examine cortisol levels of SZ and BD participants at waking, during the first 45 min after waking (representing the cortisol awakening response; CAR), during the period of rapid cortisol decline post the awakening response, and in reaction to a stressor (MRI scan), relative to healthy controls (HC). Contrary to expectations, neither SZ nor BD showed differences in waking cortisol levels, CAR, or immediate post-CAR decline compared to HC; however, waking cortisol levels were greater in BD relative to SZ. In response to the MRI stressor, the SZ group showed a significant absence of the expected increase in cortisol responsivity to stress, which was seen in both the BD and HC groups. Clinical factors affecting the CAR differed between SZ and BD. In SZ, higher antipsychotic medication dosage was associated with a steeper incline of the CAR, while greater positive symptom severity was associated with a more blunted CAR, and greater levels of anxiety were associated with the blunted cortisol response to stress. In BD, longer illness duration was associated with a steeper incline in CAR and lower levels of waking cortisol. These results suggest that cortisol responses may normalize with medication (in SZ) and longer illness duration (in BD), in line with findings of aberrant cortisol levels in the early stages of psychotic disorders.

Why is it that Tim Winton - one of Australia's most popular and literary novelists - has received little sustained critical attention? This collection of essays examines the impact of Winton's work on understanding what it is to be Australian, to be human, to make and question meaning. His novels and short stories are vernacular and lyrical, optimistic and dark, holding up a peculiarly 'Wintonesque' mirror through which Australians - and international readers, differently - can see themselves, refracted. Exploring various themes - such as childhood, masculinity, love, death, landscape, and beauty - the book explores, questions, and debates Winton's fictional works and their contexts in order to understand more fully what is appealing, or unconsciously submerged, or worthy of celebration or interrogation.

PURPOSE: Selective Estrogen Receptor Modulators (SERMs) reduce the risk of breast cancer for women at increased risk by 38%. However, uptake is extremely low and the reasons for this are not completely understood. The aims of this study were to utilize time trade-off methods to determine the degree of risk reduction required to make taking SERMs worthwhile to women, and the factors associated with requiring greater risk reduction to take SERMs. METHODS: Women at increased risk of breast cancer (N = 107) were recruited from two familial cancer clinics in Australia. Participants completed a questionnaire either online or in pen and paper format. Hierarchical multiple linear regression analysis was used to analyze the data. RESULTS: Overall, there was considerable heterogeneity in the degree of risk reduction required to make taking SERMs worthwhile. Women with higher perceived breast cancer risk and those with stronger intentions to undergo (or who had undergone) an oophorectomy required a smaller degree of risk reduction to consider taking SERMs worthwhile. CONCLUSION: Women at increased familial risk appear motivated to consider SERMs for prevention. A tailored approach to communicating about medical prevention is essential. Health professionals could usefully highlight the absolute (rather than relative) probability of side effects and take into account an individual's perceived (rather than objective) risk of breast cancer.

Background Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. Objectives To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. Methods Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography-mass spectrometry (LC-MS) analysis. Results Eighty per cent (21 ⁄26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62- and 83-kDa proteins of B. oleronius, compared with 40% (9 ⁄22) of controls (P = 0Æ004). The 62-kDa protein was characterized by LC-MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83-kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. Conclusions The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium.

When the colonisers first came to Australia there was an urgent desire to map, name and settle. This desire, in part, stemmed from a fear of the unknown. Once these tasks were completed it was thought that a sense of identity and belonging would automatically come. In Anglo-Australian geography the map of Australia was always perceived in relationship to the larger map of Europe and Britain. The quicker Australia could be mapped the quicker its connection with the ‘civilised’ world could be established. Official maps could be taken up in official history books and a detailed monumental history could begin. Australians would feel secure in where they were placed in the world. However, this was not the case and anxieties about identity and belonging remained. One of the biggest hurdles was the fear of the open spaces and not knowing how to move across the land. Attempts to transpose colonisers’ use of space onto the Australian landscape did not work and led to confusion. Using authors who are often perceived as writers of national fictions (Henry Lawson, Barbara Baynton, Patrick White, David Malouf and Peter Carey) I will reveal how writing about space becomes a way to create a sense of belonging. It is through spatial knowledge and its application that we begin to gain a sense of closeness and identity. I will also look at how one of the greatest fears for the colonisers was the Aboriginal spatial command of the country. Aborigines already had a strongly developed awareness of spatial belonging and their stories reveal this authority (seen in the work of Lorna Little, Mick McLean) Colonisers attempted to discredit this knowledge but the stories and the land continue to recognise its legitimacy. From its beginning Australian spaces have been spaces of hybridity and the more the colonisers attempted to force predetermined structures onto these spaces the more hybrid they became.

Within Australia, the concentration of the “field of cultural production” in Sydney and Melbourne results in the perception that the local and specific of these places constitutes the “universal.” Any attention paid to the local and specific in the cultural products of other Australian locations, such as Western Australia, therefore constitutes the “regional.” In an international or global context, however, Australia constitutes the “regional” rather than the “universal,” since the relatively greater concentrations of instruments of cultural production in places such as London and New York City indirectly confers upon them the latter title. Clearly, there is a parallel between the dynamic that governs Australia’s negotiations with the international literary community, and the dynamic that governs the negotiations of a more conventionally conceived region (such as Western Australia) with its national literary culture. Furthermore, there are parallels between this dynamic and the dynamic responsible for producing postcolonial literature, a literary movement that “asserted [itself] by foregrounding the tension with the colonial power, and emphasising ... differences from the assumptions of the imperial centre.” This chapter hopes that by emphasizing the postcolonial nature of Australian literature and analyzing Australian texts from a postcolonial theoretical perspective, it might diversify our understanding of Australian literature by supporting the introduction of a regional perspective. (Supplied by author).

We describe a generalization of the Bernoulli inverse method, which produces an estimate of Sea Surface Height (SSH) across the region of interest rather than simply at station positions. Real-time ‘float’ observations and satellite altimetry measurements are used to map a ‘sea surface elevation’ to study the large-scale ocean circulation in the North Atlantic. The inverse has been applied to simulated Argo floats and satellite altimetry tracks in the Ocean Circulation and climate model (OCCAM). The Bernoulli inverse method predicts the SSH by finding geostrophic streamlines along which the Bernoulli function is conserved. These streamlines are defined where modified potential temperature and salinity are conserved. This predicted SSH is combined with that measured by the satellite altimetry. The revised method uses linear regression to give a surface solution for the region rather than solving the function at fixed positions, hence increasing the resolution of the problem by combining the altimetry measurements for the region. We will present results of a comparison study where real-time Argo and satellite altimetry have been used in combination with OCCAM using the same method to see how robust the solutions are for the NorthAtlantic.

We describe a generalization of the Bernoulli inverse method, which produces an estimate of Sea Surface Height (SSH) across the region of interest rather than simply at station positions. Real-time ‘float’ observations and satellite altimetry measurements are used to map a ‘sea surface elevation’ to study the large-scale ocean circulation in the North Atlantic. The inverse has been applied to simulated Argo floats and satellite altimetry tracks in the Ocean Circulation and climate model (OCCAM). The Bernoulli inverse method predicts the SSH by finding geostrophic streamlines along which the Bernoulli function is conserved. These streamlines are defined where modified potential temperature and salinity are conserved. This predicted SSH is combined with that measured by the satellite altimetry. The revised method uses linear regression to give a surface solution for the region rather than solving the function at fixed positions, hence increasing the resolution of the problem by combining the altimetry measurements for the region. We will present results of a comparison study where real-time Argo and satellite altimetry have been used in combination with OCCAM using the same method to see how robust the solutions are for the NorthAtlantic.