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Reef islands are considered highly vulnerable to the impacts of anthropogenic climate change. While existing studies provide evidence of high dynamism and predominant stability over recent periods of sea-level rise, efforts to statistically link recorded morphological changes to processes are limited. We analyse shoreline changes across an expansive region of diverse oceanographic and climatic conditions and assess those observations relative to the processes potentially driving change. This record comprises 568 islands from 42 atolls spanning the western to the central Pacific Ocean from the Federated States of Micronesia, Marshall Islands, Kiribati and Tuvalu, and is one of the first robust attempts to statistically attribute the drivers of observed island changes within the past half-century. Our analyses demonstrate that island change and a range of its potential controls, including oceanographic, climatic and local-scale morphometric characteristics of reefs and islands, are not correlated, underscoring that no single variable could predict a uniform response across the study islands. The lack of association between sea-level rise and shoreline change on this large sample of islands addresses the common notion of a linear relationship between rising sea levels and magnitude of erosion in reef island systems. We emphasise the critical need to move from simplistic assessments of island change, highlight the importance of incorporating multiple predictors and the need for more computationally robust models. [ABSTRACT FROM AUTHOR]

Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol. Long-term machine perfusion of human livers outside the body is an emerging field with tremendous potential for the assessment, recovery, and modification of organs prior to transplantation. Here, the authors report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol. [ABSTRACT FROM AUTHOR]

Objective: To determine the sensitivity of dual-energy (DE) virtual non-contrast computed tomography (vNCT), generated from the excretory phase of a CT urogram, compared to true non-contrast CT (tNCT) for the detection of urinary calculi.Methods: A search of multiple medical literature databases was performed using predetermined search terms. Inclusion and exclusion criteria were applied, and bias risk was assessed by two independent reviewers using the quality assessment of diagnostic accuracy studies (QUADAS) tool. Collated estimates of sensitivity were generated, and sources of heterogeneity were identified and reviewed.Results: Thirteen studies (1760 patients; 1740 urinary calculi) were included for sensitivity assessment. Pooled sensitivity for urinary calculi on vNCT was 78.1% (95% CI: 70.2 to 85.0%); however, heterogeneity between studies was very high (I2 = 92.0%). Sources of heterogeneity between studies were explored through subgroup analysis by categorising studies according to slice thickness (≥ 2 mm and < 2 mm), use of oral hydration, and use of intravenous furosemide. Pooled sensitivity for detection of urinary calculi on vNCT for studies that used oral hydration and < 2 mm slice thickness was 92.2% (95% CI: 89.5 to 94.5%). Pooled specificity was not performed as true negatives were not reported in most studies. Potential sources of bias were identified in included studies.Conclusion: vNCT demonstrated a moderate pooled sensitivity compared to tNCT for the detection of urinary calculi in split bolus CT urogram protocols. However, subgroup analysis suggests higher sensitivity when employing oral hydration and < 2 mm slice thickness or increment.Key Points: • vNCT demonstrated moderate pooled sensitivity for the detection of urinary calculi in split bolus CT urogram protocols. • Subgroup analysis suggested higher sensitivity with oral hydration and < 2 mm slice thickness or increment. [ABSTRACT FROM AUTHOR]

3D microstructural datasets are commonly used to define the geometrical domains used in finite element modelling. This has proven a useful tool for understanding how complex material systems behave under applied stresses, temperatures and chemical conditions. However, 3D imaging of materials is challenging for a number of reasons, including limited field of view, low resolution and difficult sample preparation. Recently, a machine learning method, SliceGAN, was developed to statistically generate 3D microstructural datasets of arbitrary size using a single 2D input slice as training data. In this paper, we present the results from applying SliceGAN to 87 different microstructures, ranging from biological materials to high-strength steels. To demonstrate the accuracy of the synthetic volumes created by SliceGAN, we compare three microstructural properties between the 2D training data and 3D generations, which show good agreement. This new microstructure library both provides valuable 3D microstructures that can be used in models, and also demonstrates the broad applicability of the SliceGAN algorithm. Measurement(s) Micrographs • Phase volume fractions • Two point correlations Technology Type(s) Material characterisation techniques (SEM, EBSD, light) • Computation [ABSTRACT FROM AUTHOR]

Aortitis is found in 2–12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients' post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p < 0.01), was older (mean 70 vs. 62 years, p < 0.01) and had higher prevalence of hypertension (82.9% vs. 67.1%, p = 0.03) and pre-operative immunosuppression (9.8% vs. 1.4%, p < 0.01). There was no difference (p > 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis. Key Points • Forty-one cases of aortitis were identified from 1119 thoracic aortic repair/replacement surgeries. • Post-operative mortality, morbidity and resource utilisation were the same for aortitis and non-aortitis patients. • Withholding corticosteroid therapy post-operatively did not influence outcomes for aortitis patients. • Aortitis patients were older, had a female predominance and had higher prevalence of hypertension. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possibility of reducing the injected activity for whole-body [18F]FDG-PET/CT studies of paediatric oncology patients and to assess the usefulness of time-of-flight (TOF) acquisition on PET image quality at reduced count levels. Procedures: Twenty-nine paediatric oncology patients (12F/17M, 3–18 years old (median age 13y), weight 45±20 kg, BMI 19±4 kg/m2), who underwent routine whole-body PET/CT examinations on a Siemens Biograph mCT TrueV system with TOF capability (555ps) were included in this study. The mean injected activity was 156 ± 45 MBq (3.8 ± 0.8 kg/MBq) and scaled to patient weight. The raw data was collected in listmode (LM) format and pre-processed to simulate reduced levels of [18F]FDG activity (75, 50, 35, 20 and 10% of the original counts) by randomly removing events from the original LM data. All data were reconstructed using the vendor-specific e7-tools with standard OSEM only, with OSEM plus resolution recovery (PSF). The reconstructions were repeated with added TOF (TOF) and PSF+TOF. The benefit of TOF together with the reduced count levels was evaluated by calculating the gains in signal-to-noise ratio (SNR) in the liver and contrast-to-noise ratio (CNR) in all PET-positive lesions before and after TOF employed at every simulated reduced count level. Finally, the PSF+TOF images at 50, 75 and 100% of counts were evaluated clinically on a 5-point scale by three nuclear medicine physicians. Results: The visual inspection of the reconstructed images did not reveal significant differences in image quality between 75 and 100% count levels for PSF+TOF. The improvements in SNR and CNR were the greatest for TOF reconstruction and PSF combined. Both SNR and CNR gains did increase linearly with the patients BMI for both OSEM only and PSF reconstruction. These benefits were observed until reducing the counts to 50 and 35% for SNR and CNR, respectively. Conclusions: The benefit of using TOF was noticeable when using 50% or greater of the counts when evaluating the CNR and SNR. For [18F]FDG-PET/CT, whole-body paediatric imaging the injected activity can be reduced to 75% of the original dose without compromising PET image quality. [ABSTRACT FROM AUTHOR]

Large uncertainty surrounds the future physical stability of low-lying coral reef islands due to a limited understanding of the geomorphic response of islands to changing environmental conditions. Physical and numerical modelling efforts have improved understanding of the modes and styles of island change in response to increasing wave and water level conditions. However, the impact of sediment supply on island morphodynamics has not been addressed and remains poorly understood. Here we present evidence from the first physical modelling experiments to explore the effect of storm-derived sediment supply on the geomorphic response of islands to changes in sea level and energetic wave conditions. Results demonstrate that a sediment supply has a substantial influence on island adjustments in response to sea-level rise, promoting the increase of the elevation of the island while dampening island migration and subaerial volume reduction. The implications of sediment supply are significant as it improves the potential of islands to offset the impacts of future flood events, increasing the future physical persistence of reef islands. Results emphasize the urgent need to incorporate the physical response of islands to both physical and ecological processes in future flood risk models. [ABSTRACT FROM AUTHOR]

The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems. [ABSTRACT FROM AUTHOR]

Background: While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy. Methods: Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0–2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on days 1, 8, and 15 (28-day cycle) presurgery, and four cycles postoperatively. Early response to chemotherapy was measured with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans on day 15. Results: Preoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 (< 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months. Conclusions: The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a > 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies. [ABSTRACT FROM AUTHOR]

Background: After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC.Methods: Two hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed 'cluster positive'. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated.Results: Increasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p < 0.001). Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51-2.65, p < 0.001; MR: HR 4.1, 95% CI 2.02-8.14, p < 0.001; PCSM: HR 12.2, 95% CI 1.6-93; p = 0.016). These associations were independent of other established prognostic variables.Conclusions: p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM. [ABSTRACT FROM AUTHOR]

The International Collaboration on Cancer Reporting (ICCR) was formed in 2011 to harmonise the datasets, protocols and checklists for pathological reporting of various cancers and develop internationally agreed upon, evidence-based datasets. A dataset for prostate cancer in radical prostatectomy specimens was developed in 2011-2012 as part of a pilot project; however, it required substantial revision following the ISUP Consensus Conference on Gleason Grading in 2014, the publication of the World Health Organisation (WHO) Classification of Tumours of the Urinary System and Male Genital Organs in 2016, and the 8th edition of the Tumour-Node-Metastasis (TNM) staging system in late 2016. This article presents the up-to-date, evidence-based ICCR dataset and associated commentary for reporting prostate cancer in radical prostatectomy specimens. PubMed and Google search engines were used to review the published literature on the subject, and the dataset was developed in line with the previously published ICCR framework for the development of cancer datasets. Substantial changes have been incorporated into the second edition of the ICCR prostate cancer (radical prostatectomy) dataset. These include revisions to prostate cancer grading, reporting of intraductal carcinoma of prostate and surgical margins, among others. Up-to-date cancer datasets underpin structured reporting and facilitate the production of consistent and accurate pathological data for patient care as well as comparisons between different cohorts and populations internationally. [ABSTRACT FROM AUTHOR]

Introduction: Long-term outcomes from large cohorts are not yet available upon which to base recommended follow-up protocols after prostate focal therapy. This is an updated summary of a 2015 SIU-ICUD review of the best available current evidence and expert consensus on guidelines for surveillance after prostate focal therapy.Methods: We performed a systematic search of the PubMed, Cochrane and Embase databases to identify studies where primary prostate focal therapy was performed to treat prostate cancer.Results: Multiparametric magnetic resonance imaging (mpMRI) should be performed at 3-6 months, 12-24 months and at 5 years after focal therapy. Targeted biopsy of the treated zone should be performed at 3-6 months and fusion biopsy of any suspicious lesion seen on mpMRI. Additionally, a systematic biopsy should be performed at 12-24 months and again at 5 years. In histological diagnosis, characteristic changes of each treatment modality should be noted and in indeterminate situations various immunohistochemical molecular markers can be helpful. Small volume 3 + 3 (Prognostic grade group [PGG] 1) or very small volume (< 0.2 cc or < 7 mm diameter) 3 + 4 (PGG 2) are acceptable in the treated zone at longitudinal follow-up. Significant volumes of 3 + 4 (PGG 2) or more within the treated zone should be treated. Any clinically significant cancer subsequently arising within the non-treated zone should be treated and handled in the same way as any de novo prostate cancer. Patients should be counseled regarding whole-gland and focal approaches to treating these new foci where appropriate. One or two well-delineated foci of significant cancer can be ablated to keep the patient in the 'active surveillance pool'. More extensive disease should be treated with traditional whole-gland techniques.Conclusion: Focal therapy remains a nascent field largely comprising single center cohorts with little long-term data. Our current post-focal therapy surveillance consensus recommendations represent the synthesis of the best available evidence as well as expert opinion. Further work is necessary to define the most oncologically safe and cost-effective way of following patients after focal therapy. [ABSTRACT FROM AUTHOR]

Sea-level rise (SLR) is predicted to elevate water depths above coral reefs and to increase coastal wave exposure as ecological degradation limits vertical reef growth, but projections lack data on interactions between local rates of reef growth and sea level rise. Here we calculate the vertical growth potential of more than 200 tropical western Atlantic and Indian Ocean reefs, and compare these against recent and projected rates of SLR under different Representative Concentration Pathway (RCP) scenarios. Although many reefs retain accretion rates close to recent SLR trends, few will have the capacity to track SLR projections under RCP4.5 scenarios without sustained ecological recovery, and under RCP8.5 scenarios most reefs are predicted to experience mean water depth increases of more than 0.5 m by 2100. Coral cover strongly predicts reef capacity to track SLR, but threshold cover levels that will be necessary to prevent submergence are well above those observed on most reefs. Urgent action is thus needed to mitigate climate, sea-level and future ecological changes in order to limit the magnitude of future reef submergence. Analyses of current coral reef growth rates in the tropical western Atlantic and Indian Ocean show that few reefs will have the capacity to track sea-level rise projections under Representative Concentration Pathway scenarios without sustained ecological recovery. [ABSTRACT FROM AUTHOR]

Sea-level rise and climatic change threaten the existence of atoll nations. Inundation and erosion are expected to render islands uninhabitable over the next century, forcing human migration. Here we present analysis of shoreline change in all 101 islands in the Pacific atoll nation of Tuvalu. Using remotely sensed data, change is analysed over the past four decades, a period when local sea level has risen at twice the global average (~3.90 ± 0.4 mm.yr-1). Results highlight a net increase in land area in Tuvalu of 73.5 ha (2.9%), despite sea-level rise, and land area increase in eight of nine atolls. Island change has lacked uniformity with 74% increasing and 27% decreasing in size. Results challenge perceptions of island loss, showing islands are dynamic features that will persist as sites for habitation over the next century, presenting alternate opportunities for adaptation that embrace the heterogeneity of island types and their dynamics. [ABSTRACT FROM AUTHOR]

Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer. [ABSTRACT FROM AUTHOR]

Low-lying coral reef islands are considered highly vulnerable to climate change, necessitating an improved understanding of when and why they form, and how the timing of formation varies within and among regions. Several testable models have been proposed that explain inter-regional variability as a function of sea-level history and, more recently, a reef platform size model has been proposed from the Maldives (central Indian Ocean) to explain intra-regional (intra-atoll) variability. Here we present chronostratigraphic data from Pipon Island, northern Great Barrier Reef (GBR), enabling us to test the applicability of existing regional island evolution models, and the platform size control hypothesis in a Pacific context. We show that reef platform infilling occurred rapidly (~4-5 mm yr) under a 'bucket-fill' type scenario. Unusually, this infilling was dominated by terrigenous sedimentation, with platform filling and subsequent reef flat formation complete by ~5000 calibrated years BP (cal BP). Reef flat exposure as sea levels slowly fell post highstand facilitated a shift towards intertidal and subaerial-dominated sedimentation. Our data suggest, however, a lag of ~1500 yr before island initiation (at ~3200 cal BP), i.e. later than that reported from smaller and more evolutionarily mature reef platforms in the region. Our data thus support: (1) the hypothesis that platform size acts to influence the timing of platform filling and subsequent island development at intra-regional scales; and (2) the hypothesis that the low wooded islands of the northern GBR conform to a model of island formation above an elevated reef flat under falling sea levels. [ABSTRACT FROM AUTHOR]

Background:Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.Methods:We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.Results:The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged 70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002).Conclusion:Patients aged 70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

This study measured reading workstation monitors and the viewing environment currently available within BreastScreen New South Wales (BSNSW) centres to determine levels of adherence to national and international guidelines. Thirteen workstations from four BSNSW service centres were assessed using the American Association of Physicists in Medicine Task Group 18 Quality Control test pattern. Reading workstation monitor performance and ambient light levels when interpreting screening mammographic images were assessed using spectroradiometer CS-2000 and chroma meter CL-200. Overall, radiologic monitors within BSNSW were operating at good acceptable levels. Some non-adherence to published guidelines included the percentage difference in maximum luminance between pairs of primary monitors at individual workstations (61.5 % or 30.8 % of workstations depending on specific guidelines), maximum luminance (23.1 % of workstations), luminance non-uniformity (11.5 % of workstations) and minimum luminance (3.8 % of workstations). A number of ambient light measurements did not comply with the only available evidence-based guideline relevant to the methodology used in this study. Larger ambient light variations across sites are shown when monitors were switched off, suggesting that differences in ambient lighting between sites can be masked when a standard mammogram is displayed for photometric measurements. Overall, BSNSW demonstrated good adherence to available guidelines, although some non-compliance has been shown. Recently updated United Kingdom and Australian guidelines should help reduce confusion generated by the plethora and sometimes dated nature of currently available recommendations. [ABSTRACT FROM AUTHOR]

Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management. [ABSTRACT FROM AUTHOR]

Aims: Prostate cancer is very common and is the second most common cause of cancer death in males in Australia; however, brain metastases are exceedingly rare. Materials and methods: We review four cases of biopsy-proven brain metastases from prostate cancer and review the relevant literature. Results: Three of four patients had acinar adenocarcinoma of prostate with one patient having ductal adenocarcinoma variant on histopathology. Three patients had the brain as the only site of metastatic disease. All patients underwent surgery, and three of four patients underwent adjuvant palliative radiotherapy to the brain. Conclusion: Brain metastases from prostate cancer are rare, but brain metastases without other sites of metastatic disease are exceedingly rare and may be more common with ductal adenocarcinoma variant. [ABSTRACT FROM AUTHOR]

Census-based approaches can provide important measures of the ecological processes controlling reef carbonate production states. Here, we describe a rapid, non-destructive approach to carbonate budget assessments, termed ReefBudget that is census-based and which focuses on quantifying the relative contributions made by different biological carbonate producer/eroder groups to net reef framework carbonate production. The methodology is presently designed only for Caribbean sites, but has potential to be adapted for use in other regions. Rates are calculated using data on organism cover and abundance, combined with annual extension or production rate measures. Set against this are estimates of the rates at which bioeroding species of fish, urchins and internal substrate borers erode reef framework. Resultant data provide a measure of net rates of biologically driven carbonate production (kg CaCO m year). These data have potential to be integrated into ecological assessments of reef state, to aid monitoring of temporal (same-site) changes in rates of biological carbonate production and to provide insights into the key ecological drivers of reef growth or erosion as a function of environmental change. Individual aspects of the budget methodology can also be used alongside other census approaches if deemed appropriate for specific study aims. Furthermore, the methodology spreadsheets are user-changeable, allowing local or new process/rate data to be integrated into calculations. Application of the methodology is considered at sites around Bonaire. Highest net rates of carbonate production, +9.52 to +2.30 kg CaCO m year, were calculated at leeward sites, whilst lower rates, +0.98 to −0.98 kg CaCO m year, were calculated at windward sites. Data are within the ranges calculated in previous budget studies and provide confidence in the production estimates the methodology generates. [ABSTRACT FROM AUTHOR]

GATA-2, a member of the GATA family of transcription factors, is involved in androgen receptor (AR) signaling, however, little is known regarding its role in prostate cancer. Here, we report that GATA-2 is expressed in a substantial proportion of prostate cancers and that high expression of GATA-2 is associated with biochemical recurrence and distant metastatic progression in a validation set of 203 cancers. In vitro data show that GATA-2 is directly recruited to the promoter region of the AR upon androgen stimulation of LNCaP prostate cancer cells with 5α-dihydroxytestosterone (DHT) for 24 h. Ectopic GATA-2 expression causes the induction of AR transcript levels under androgen-depleted conditions (P<0.05). The expression of the AR target gene, AZGP1, is induced upon androgen stimulation and this effect is repressed by GATA-2. In contrast, GATA-2 significantly increases transcript levels of KLK2, which increases further in a time-dependent manner on DHT treatment and in the presence of GATA-2. These results indicate that upregulation of GATA-2 may contribute to the progression to aggressive prostate cancer through modulation of expression of AR and key androgen-regulated genes, one of which, AZGP1, is associated with the progression to metastatic disease. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the effect of ecological phase-shift and changes in the production of coral reef sites. It reveals that the changes in coral reefs are caused by the disturbances as well as alterations in its health condition and resilience that cause abnormal phase shift. The study was administered by evaluating the impact of ecological and environmental changes on coral communities and variations in different coral and macroalgae activities as well as the role of herbivorous taxa. The study shows that modification of rates in reef carbonate production affects the development of reef structures as well as its communities and geomorphology.

Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resection, whereas the survival of those patients whose tumours had low or no LMO4 expression was not significantly different when resection was compared with operative biopsy alone. [ABSTRACT FROM AUTHOR]

Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/ db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 ( Atf4), DNA-damage inducible transcript 3 ( Ddit3, previously known as C/EBP homologous protein [ Chop]) and DnaJ homologue (HSP40) C3 ( Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/ db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 ( Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure. [ABSTRACT FROM AUTHOR]

Complex relationships exist between tropical reef ecology, carbonate (CaCO3) production and carbonate sinks. This paper investigated census-based techniques for determining the distribution and carbonate production of reef organisms on an emergent platform in central Torres Strait, Australia, and compared the contemporary budget with geological findings to infer shifts in reef productivity over the late Holocene. Results indicate that contemporary carbonate production varies by several orders of magnitude between and within the different reef-flat sub-environments depending on cover type and extent. Average estimated reef-flat production was 1.66 ± 1.78 kg m-2 year-1 (mean ± SD) although only 23% of the area was covered by carbonate producers. Collectively, these organisms produce 17,399 ± 18,618 t CaCO3 year-1, with production dominated by coral (73%) and subordinate contributions by encrusting coralline algae (18%) articulated coralline algae, molluscs, foraminifera and Halimeda (<4%). Comparisons between the production of these organisms across the different reef-flat zones, surface sediment composition and accumulation rates calculated from cores indicate that it is necessary to understand the spatial distribution, density and production of each major organism when considering the types and amounts of carbonate available for storage in the various reef carbonate sinks. These findings raise questions as to the reliability of using modal production rates in global models independent of ecosystem investigation, in particular, indicating that current models may overestimate reef productivity in emergent settings. [ABSTRACT FROM AUTHOR]

Top quartile serum prolactin levels confer a twofold increase in the relative risk of developing breast cancer. Prolactin exerts this effect at an ill defined point in the carcinogenic process, via mechanisms involving direct action via prolactin receptors within mammary epithelium and/or indirect action through regulation of other hormones such as estrogen and progesterone. We have addressed these questions by examining mammary carcinogenesis in transplants of mouse mammary epithelium expressing the SV40T oncogene, with or without the prolactin receptor, using host animals with a normal endocrine system. In prolactin receptor knockout transplants the area of neoplasia was significantly smaller (7 versus 17%; P<0.001 at 22 weeks and 7 versus 14%; P=0.009 at 32 weeks). Low-grade neoplastic lesions displayed reduced BrdU incorporation rate (11.3 versus 17% P=0.003) but no change in apoptosis rate. Tumor latency increased (289 days versus 236 days, P<0.001). Tumor frequency, growth rate, morphology, cell proliferation and apoptosis were not altered. Thus, prolactin acts directly on the mammary epithelial cells to increase cell proliferation in preinvasive lesions, resulting in more neoplasia and acceleration of the transition to invasive carcinoma. Targeting of mammary prolactin signaling thus provides a strategy to prevent the early progression of neoplasia to invasive carcinoma.Oncogene (2007) 26, 543–553. doi:10.1038/sj.onc.1209838; published online 24 July 2006 [ABSTRACT FROM AUTHOR]

OBJECTIVES: Fibrotic severity, biochemical indices of poor liver function, and sporadic transmission are independent predictors of liver complications among people with chronic hepatitis C. After accounting for these factors, we tested whether interferon treatment or the treatment response reduces the rate of liver cancer, liver-related death or transplantation, and other liver complications during extended follow-up.METHODS: Liver clinic cohort of 455 patients with histologically proven chronic hepatitis C was followed prospectively for median 9 yr (IQ 6, 11 yr); 384 received interferon, 343 completed a treatment course. Liver complications were assessed in relation to treatment and treatment response in univariate and multivariate models, and survival to onset of liver-related complications was determined.RESULTS: The annual incidence of total liver complications was 1.5% in treated and 2.9% in untreated patients and appeared quasilinear throughout 9-yr follow-up. Interferon treatment did not influence the rate of liver complications. However, the rate of complications increased exponentially with transition of the treatment response from sustained viral response (SVR), through response-relapse to nonresponse (or no treatment). By univariate analysis, response to interferon treatment was a significant predictor of complications. After adjustment for fibrosis score, serum albumin concentration and mode of transmission in a multivariate model, treatment response just failed to reach significance (p= 0.058) as a predictor of outcome.CONCLUSIONS: Response to antiviral therapy, and particularly SVR, appears to reduce liver complications in chronic hepatitis C. However, in the absence of an antiviral treatment response, a course of interferon does not reduce risks of liver cancer or liver failure. [ABSTRACT FROM AUTHOR]

I test experimentally the predictions of neoclassical theory for a radial electricity market without rights to the transmission line, with rights that give the owner a financial right to a share of the transmission congestion charges collected by a network operator, and with physical rights which give the owner the exclusive right to utilize a portion of the transmission line. I find that physical rights lead to more “right” market signals, diminish some market-power, and remove an uncertainty about electricity transmission congestion better than financial rights or the absence of rights. [ABSTRACT FROM AUTHOR]

We have utilized oligonucleotide microarrays to identify novel genes of potential clinical and biological importance in prostate cancer. RNA from 74 prostate cancers and 164 normal body samples representing 40 different tissues were analysed using a customized Affymetrix GeneChip® oligonucleotide microarray representative of over 90% of the expressed human genome. The gene for the zinc transporter ZnT4 was one of several genes that displayed significantly higher expression in prostate cancer compared to normal tissues from other organs. A polyclonal antipeptide antibody was used to demonstrate ZnT4 expression in the epithelium of all 165 elements of benign and 326 elements of localized prostate cancers examined and in nine of 10 advanced prostate cancer specimens by immunohistochemistry. Interestingly, decreased intensity of ZnT4 immunoreactivity occurred in the progression from benign to invasive localized prostate cancer and to metastatic disease. Immunofluorescence analysis and surface biotinylation studies of cells expressing ZnT4 localised the protein to intracellular vesicles and to the plasma membrane. These findings are consistent with a role for ZnT4 in vesicular transport of zinc to the cell membrane and potentially in efflux of zinc in the prostate.Oncogene (2003) 22, 6005-6012. doi:10.1038/sj.onc.1206797 [ABSTRACT FROM AUTHOR]

: ObjectiveWe tested whether fibrotic progression in chronic hepatitis C could be predicted by liver tests, antipyrine clearance, or platelet count.: MethodsIn 58 patients (6 untreated, 52 interferon-treated), a second liver biopsy was taken median 4.5 yr after first histologic diagnosis. We used receiver operating characteristic curves to determine whether changes in conventional liver tests, antipyrine clearance, or platelet count were predictive of altered hepatic fibrosis score.: ResultsApart from a weak association with change in ALT, conventional liver tests (albumin, bilirubin, prothrombin time) failed to correlate with changes (Δ) in hepatic fibrosis, but there were significant correlations between Δantipyrine clearance or Δplatelet count and Δfibrosis score (p < 0.01). As indicated by areas under the receiver operating characteristic curves, the diagnostic accuracy of Δantipyrine clearance for fibrotic progression was 68%; for Δplatelet count it was 80%. With defined cut-off values (−0.05 ml/min/kg for Δantipyrine clearance; −41 × 109/L for Δplatelet count), the negative predictive values for fibrotic progression were 85% with antipyrine clearance and 89% with platelet count. Corresponding positive predictive values were 48% and 91%, respectively.: ConclusionsChanges in antipyrine clearance and platelet count are more sensitive than conventional tests for indicating fibrotic change in chronic hepatitis C. Both could be used to reliably identify those who do not have fibrotic progression, and platelet count also has a high positive predictive value for disease progression. [Copyright &y& Elsevier]

The techniques of enzyme-linked immunosorbent assay (ELISA) and immunoblotting were used to examine a total of 1667 sera, from apparently healthy members of rural communities in England, for antibodies to the lipopolysaccharide (LPS) of Escherichia coli O157 and Verocytotoxins (VT). Twenty-nine sera from 22 individuals were shown to have antibodies specific for E. coli O157 LPS. Some of these lived on livestock farms and had occupational contact with cattle, suggesting that personnel working with farm animals may produce serum antibodies to the O157 LPS antigens. Fifteen people had IgG class antibodies to O157 LPS, suggesting long-term exposure to E. coli O157 and five people had serum antibodies on more than one occasion showing evidence of persistent antibodies to O157 LPS. Thirteen sera from 12 of 22 individuals also contained antibodies to VT1, VT2 or both toxins. Ten sera contained antibodies to VT1 and VT2, three sera contained antibodies to VT2 only. [ABSTRACT FROM AUTHOR]

Presents a case of a patient with achalasia of the esophagus with suppurative pericarditis. Medical analysis of the patient; Medical treatment done on the patient; Study findings.

An analysis was made of the relation between the strain sensitivity of plated wire memory elements and the chemical composition in the film. According to this analysis, torsion sensitivity, which measures the easy-axis skew when the wire is twisted, depends on the average permalloy composition in the film. On the other hand, tension sensitivity, which measures the change in anisotropy field, H , when the wire is stretched, should depend on both the average composition and the degree of variation, or composition inhomogeneity. In general, the inhomogeneity contribution is negative. Experimental results supporting this analysis showed that 1) films with nearly zero torsion strain sensitivity invariably exhibit negative tension strain sensitivity and 2) the measured tension strain sensitivity is in approximate agreement with that predicted from electron microprobe measurements of composition inhomogeneity. The strain sensitivity analysis provides a means of estimating the discrepancy between torsion and tension zeromagnetostrictive compositions. [ABSTRACT FROM AUTHOR]

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease. [ABSTRACT FROM AUTHOR]

Coral reefs experienced the third global bleaching event in 2015–2016 due to high sea-surface temperature (SST) anomalies. Declines in net carbonate production associated with coral bleaching are implicated in reef structural collapse and cascading impacts for adjacent coral reef islands. We present the first carbonate budget study of a reef platform surface (reef crest and reef flat) in the southern Maldives and the first record of upper reef flat condition in the central Indian Ocean post the 2015–2016 coral bleaching event. Scleractinian corals were the primary carbonate producers, with live coral cover averaging between 11.1 ± 6.5 and 31.2 ± 21.8% and dominated by massive corals. Gross carbonate production rates averaged 5.9 ± 2.5 G (kg CaCO3 m2 yr−1). Bioerosion was estimated at 3.4 ± 0.4 G, resulting in an average net carbonate production rate of 2.5 ± 2.4 G. Comparison of results with a study of the fore-reef slope highlights major differences in post-bleaching carbonate budget state between the fore-reef slope and the reef platform surface. The positive reef flat carbonate budget is attributed to the persistence of massive corals (Porites spp. and Heliopora spp.) through the bleaching event. [ABSTRACT FROM AUTHOR]

Wave-driven flooding is a serious hazard on coral reef-fringed coastlines that will be exacerbated by global sea-level rise. Despite the global awareness of atoll island vulnerability, little is known about the physical processes that control wave induced flooding on reef environments. To resolve the primary controls on wave-driven flooding at present and future sea levels, we present a globally applicable method for calculating wave overtopping thresholds on reef coastlines. A unique dataset of 60,000 fully nonlinear wave transformation simulations representing a wide range of wave energy, morphology and sea levels conditions was analysed to develop a tool for exploring the future trajectory of atoll island vulnerability to sea-level rise. The proposed reef-island overtopping threshold (RIOT) provides a widely applicable first-order assessment of reef-coast vulnerability to wave hazards with sea-level. Future overtopping thresholds identified for different atoll islands reveal marked spatial variability and highlight distinct morphological characteristics that enhance coastal resilience. Sea-level rise will exacerbate wave overtopping on low-lying coral reef islands. Here the authors present a novel method that quantifies wave overtopping thresholds and associated reef-island vulnerability trajectories based on differences in local wave climate, reef morphology and island height. [ABSTRACT FROM AUTHOR]

Deterioration of coral health and associated change in the coral holobiont's bacterial community are often a result of different environmental stressors acting synergistically. There is evidence that water flow is important for a coral's resistance to elevated seawater temperature, but there is no information on how water flow affects the coral-associated bacterial community under these conditions. In a laboratory cross-design experiment, Acropora muricata nubbins were subjected to interactive effects of seawater temperature (27 °C to 31 °C) and water flow (0.20 m s−1 and 0.03 m s−1). In an in situ experiment, water flow manipulation was conducted with three colonies of A. muricata during the winter and summer, by partially enclosing each colony in a clear plastic mesh box. 16S rRNA amplicon pyrosequencing showed an increase in the relative abundance of Flavobacteriales and Rhodobacterales in the laboratory experiment, and Vibrio spp. in the in situ experiment when corals were exposed to elevated temperature and slow water flow. In contrast, corals that were exposed to faster water flow under laboratory and in situ conditions had a stable bacterial community. These findings indicate that water flow plays an important role in the maintenance of specific coral-bacteria associations during times of elevated thermal stress. [ABSTRACT FROM AUTHOR]