Finding Hope in the Stories: Alexis Wright’s Carpentaria and the Carnivalesque Search for a New Order

Alexis Wright’s Carpentaria is the story of the Phantom family, members of the Pricklebush people, who live in the fictional town of Desperance in the Gulf country of north-western Queensland. It is a long and sprawling carnivalesque novel that offers a cautiously positive outlook for Aboriginal people that also recognises the difficulties of contemporary Aboriginal experience. Carpentaria is not an historical novel in the sense of retelling an historical event; however, the past pervades the narrative as it grapples with the many ways that the past is recorded. It challenges mainstream or dominant representations of Aboriginal people in historiography, language, literature, and politics, to propose new ways of thinking. It suggest that it is the people who are responsible for passing on the essential stories of history and culture to their families as lived history, not the official history held in archives and managed by institutions. The novel’s fluid time and ambivalence presents history and historic change outside the usual historical and literary framework. By bringing together myth, history, memory and imagination, by combining humour and seriousness, Dreamtime and Christianity, ambivalence and certainty, and politics and art the novel seeks to switch to a different sense of unity and harmony. But there is a deep sense of ambivalence towards the possibility of a future where good and evil, and black and white are no longer clearly defined and the old rules no longer apply

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient\u27s ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; \u3e80% cycling protocol delivery; \u3e80% outcomes measured and \u3e80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830

Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child:an 11-year follow-up from a randomised controlled trial

Background: Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child. Methods: Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 μg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging. Results: Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13–30 Hz, p = 0.01) and High Gamma (49–70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language. Conclusions: Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions. Trial registration: ISRCTN ISRCTN19917787. Registered on 15 May 2013

Spiritual Well-Being and Depression in Patients with Heart Failure

BACKGROUND: In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. OBJECTIVE: To identify the relationship between spiritual well-being and depression in patients with heart failure. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty patients aged 60 years or older with New York Heart Association class II–IV heart failure. MEASUREMENTS: Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy—Spiritual Well-being scale, depression using the Geriatric Depression Scale—Short Form (GDS-SF). RESULTS: The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman’s correlation −0.55, 95% confidence interval −0.70 to −0.35). In particular, greater meaning/peace was strongly associated with less depression (r = −.60, P < .0001), while faith was only modestly associated (r = −.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients’ sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population

Efficient Targeting of Head and Neck Squamous Cell Carcinoma by Systemic Administration of a Dual uPA and MMP-Activated Engineered Anthrax Toxin

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with HNSCC remains poor, underscoring the need for development of additional treatment modalities. HNSCC is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (uPA) and an assortment of matrix metalloproteinases (MMPs) that may be expressed by tumor cells, by tumor-supporting stromal cells or by both. Here we explored the use of an intercomplementing anthrax toxin that requires combined cell surface uPA and MMP activities for cellular intoxication and specifically targets the ERK/MAPK pathway for the treatment of HNSCC. We found that this toxin displayed strong systemic anti-tumor activity towards a variety of xenografted human HNSCC cell lines by inducing apoptotic and necrotic tumor cell death, and by impairing tumor cell proliferation and angiogenesis. Interestingly, the human HNSCC cell lines were insensitive to the intercomplementing toxin when cultured ex vivo, suggesting that either the toxin targets the tumor-supporting stromal cell compartment or that the tumor cell requirement for ERK/MAPK signaling differs in vivo and ex vivo. This intercomplementing toxin warrants further investigation as an anti-HNSCC agent

The Apache Point Observatory Galactic Evolution Experiment (APOGEE)

The Apache Point Observatory Galactic Evolution Experiment (APOGEE), one of the programs in the Sloan Digital Sky Survey III (SDSS-III), has now completed its systematic, homogeneous spectroscopic survey sampling all major populations of the Milky Way. After a three-year observing campaign on the Sloan 2.5 m Telescope, APOGEE has collected a half million high-resolution (R ~ 22,500), high signal-to-noise ratio (>100), infrared (1.51–1.70 μm) spectra for 146,000 stars, with time series information via repeat visits to most of these stars. This paper describes the motivations for the survey and its overall design—hardware, field placement, target selection, operations—and gives an overview of these aspects as well as the data reduction, analysis, and products. An index is also given to the complement of technical papers that describe various critical survey components in detail. Finally, we discuss the achieved survey performance and illustrate the variety of potential uses of the data products by way of a number of science demonstrations, which span from time series analysis of stellar spectral variations and radial velocity variations from stellar companions, to spatial maps of kinematics, metallicity, and abundance patterns across the Galaxy and as a function of age, to new views of the interstellar medium, the chemistry of star clusters, and the discovery of rare stellar species. As part of SDSS-III Data Release 12 and later releases, all of the APOGEE data products are publicly available

Chris Healy. Forgetting Aborigines. Sydney: University of New South Wales Press 2008 [Book review]

The topic of Chris Healy's book Forgetting Aborigines is not new. Probably the best known critique of white Australia's treatment of indigenous Australians is W E H Stanner's 1968 Boyer Lecture After the Dreaming in which he coined the term the "Great Australian Silence." Stanner refers not only to the physical treatment of indigenous Australians but also to the way they had been excluded from modern Australian history. He argues that the changes that had occurred in the 1930s had been confined to a small group and that the referendum of 1967 had similarly had little impact