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The Internet has been instrumental in patients' knowledge about health and medicine through increasing consultation of online sources that advocate self-management. For example, those patients who request referrals from their doctors for tests and procedures in radiology. Such patient-initiated referral requests can devolutionise the traditional model of health care. This study aimed to understand individuals who sought online health information (OHI) and whether requests for radiological referrals were the result of OHI seeking.The individuals targeted were those who have had a radiological procedure in the past 5 years. Using an online survey tool, individuals completed a 20-min anonymous survey. Included in the survey was a validated digital health literacy measurement scale, eHEALS.Those who scored higher on the eHEALS measure were likely to be under 55 years of age and were more inclined to request radiological referrals. Though they were not concerned with the credibility of sourced websites, most secured the desired outcome from their requests.Overall, this study indicates that patients are consulting online sites for health information, and individuals with higher digital literacy scores are asking doctors for referrals for radiological tests and procedures. These findings confirm our anecdotal experience in radiology departments. So what?: In conducting this study, we hope to better inform radiology and other health practitioners of the way OHI is impacting clinical practice.

We have read with interest the recent debate between Drs Varma and Epstein regarding the grading of intraductal carcinoma of the prostate.$^{1}$ Unfortunately, the arguments as presented do little to abate the confusion surrounding this so-called diagnostic entity.

Guanine-rich sequences of DNA are known to readily fold into tetra-stranded helical structures known as G-quadruplexes (G4). Due to their biological relevance, G4s are potential anticancer drug targets and therefore there is significant interest in molecules with high affinity for these structures. Most G4 binders are polyaromatic planar compounds which π-π stack on the G4's guanine tetrad. However, many of these compounds are not very selective since they can also intercalate into duplex DNA. Herein we report a new class of binder based on an octahedral cobalt(III) complex that binds to G4 via a different mode involving hydrogen bonding, electrostatic interactions and π-π stacking. We show that this new compound binds selectivity to G4 over duplex DNA (particularly to the G-rich sequence of the c-myc promoter). This new octahedral complex also has the ability to template the formation of G4 DNA from the unfolded sequence. Finally, we show that upon binding to G4, the complex prevents helicase Pif1-p from unfolding the c-myc G4 structure.

Introduction The aim of this work is to report diagnostic reference levels (DRLs) for hybrid positron emission tomography and x-ray computed tomography (PET/CT) exams in Australia (AU) for Queensland (QLD) and Western Australia (WA) (AU QLD/WA) and New Zealand (NZ). Methods Two-structured booklets were designed to collect dose information, patient demographics, equipment details and acquisition protocols for fluoride-18 fluorodeoxyglucose (18 F-FDG) PET/CT procedures, and any additional diagnostic CT routinely performed as part of 18 F-FDG whole-body examination. The DRL was reported based on the 75th percentile and achievable dose for 18 F-FDG, CT dose index volume (CTDIvol ) and dose length product (DLP). The effective dose and total effective dose was reported for 18 F-FDG whole-body PET/CT examination. Also, the effective dose was reported separately for identified additional diagnostic CT. Results The findings of this study show that the current DRL for 18 F-FDG in AU QLD/WA and NZ was 333.75 MBq and 332.87 MBq, respectively. The reported AU QLD/WA CTDIvol and DLP associated with 18 F-FDG whole-body PET/CT examinations from vertex to thigh (VT) was 4.41 mGy and 474 mGy.cm. In NZ, the reported VT CTDIvol and DLP was 13.07 mGy and 1319.05 mGy.cm. The effective dose for 18 F-FDG and CT component was 5.6 mSv and 4.7 mSv for AU QLD/WA. For NZ, the effective dose was 5.7 mSv and 10.9 mSv for 18 F-FDG and CT component. The total effective dose delivered from the 18 F-FDG whole-body scan from the AU QLD/WA PET/CT centres (10.44 mSv) were lower than the radiation doses delivered from the NZ (16.65 mSv). Conclusions The current DRLs were proposed for AU QLD/WA and NZ for 18 F-FDG whole-body PET/CT examinations. Variations existed in the current practice of AU QLD/WA and NZ PET/CT examinations. There is a need to optimize the radiation doses delivered from PET/CT examinations.

A plethora of individual candidate biomarkers for predicting biochemical relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with biochemical relapse. In the current study, these biomarkers were re-analyzed for biochemical relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n = 324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with biochemical relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95% CI, 1.6-32; p = 0.01) and multivariable analysis (HR 5.4, 95% CI, 1.2-25; p = 0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p < 0.001). Our findings indicate that biochemical relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.

Introduction An ideal organ‐specific insert phantom should be able to simulate the anatomical features with appropriate appearances in the resultant computed tomography (CT) images. This study investigated a 3D printing technology to develop a novel and cost‐effective cardiac insert phantom derived from volumetric CT image datasets of anthropomorphic chest phantom. Methods Cardiac insert volumes were segmented from CT image datasets, derived from an anthropomorphic chest phantom of Lungman N‐01 (Kyoto Kagaku, Japan). These segmented datasets were converted to a virtual 3D‐isosurface of heart‐shaped shell, while two other removable inserts were included using computer‐aided design (CAD) software program. This newly designed cardiac insert phantom was later printed by using a fused deposition modelling (FDM) process via a Creatbot DM Plus 3D printer. Then, several selected filling materials, such as contrast media, oil, water and jelly, were loaded into designated spaces in the 3D‐printed phantom. The 3D‐printed cardiac insert phantom was positioned within the anthropomorphic chest phantom and 30 repeated CT acquisitions performed using a multi‐detector scanner at 120‐kVp tube potential. Attenuation (Hounsfield Unit, HU) values were measured and compared to the image datasets of real‐patient and Catphan® 500 phantom. Results The output of the 3D‐printed cardiac insert phantom was a solid acrylic plastic material, which was strong, light in weight and cost‐effective. HU values of the filling materials were comparable to the image datasets of real‐patient and Catphan® 500 phantom. Conclusions A novel and cost‐effective cardiac insert phantom for anthropomorphic chest phantom was developed using volumetric CT image datasets with a 3D printer. Hence, this suggested the printing methodology could be applied to generate other phantoms for CT imaging studies.

Background Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models. Methods Docetaxel-resistant CRPC cells, mice with PC3 xenografts, and ex vivo cultures of patient-derived primary prostate tumors were treated with VS-6063 and/or docetaxel, or vehicle control. Cell counting, immunoblotting, and immunohistochemistry techniques were used to evaluate the treatment effects. Results Docetaxel and VS-6063 co-treatment caused a greater decrease in the viability of docetaxel-resistant CRPC cells, and a greater inhibition in PC3 xenograft growth compared to either monotherapy. FAK expression in human primary prostate cancer was positively associated with advanced tumor stage. Patient-derived prostate tumor explants cultured with both docetaxel and VS-6063 displayed a higher percentage of apoptosis in cancer cells, than monotherapy treatment. Conclusions Our findings suggest that co-administration of the FAK inhibitor, VS-6063, with docetaxel represents a potential therapeutic strategy to overcome docetaxel resistance in prostate cancer.

Reef islands are low-lying accumulations of unconsolidated sediment formed from the skeletal remains of carbonate-producing reef organisms and are therefore perceived as highly vulnerable to environmental change. However, basic elements of island composition are not well described and given their high inter- and intra-basinal variability a better understanding of reef and island sedimentary environments (and the connections between them) are needed to predict future morphological response. Here, we use detailed ecological and sedimentological datasets to delineate key sediment production zones and biosedimentary depositional facies across the surface of Vabbinfaru platform, Maldives. Field measurements of platform hydrodynamics are applied to sedimentary deposits to determine the potential mobility of grains and identify transport pathways. Carbonate production was dominated by coral framework (mean: 52%) within a narrow zone on the outer reef rim (22% of platform area) resulting in coral-rich detrital sediments (reef: 51%, island: 64%) that closely resemble living assemblages. The net transfer of sediment occurred lagoonward by wave-driven processes leading to a decrease in grain size towards the island (R2 = 0.502) which acts as a major control on depositional facies development within the lagoon. Island sediments were distinct from reefal deposits, comprising a restricted suite of durable sands (mean: 1.34ϕ) throughout long-term development. Our findings suggest that the production, breakdown and redistribution of coral-derived sediment by platform currents is fundamental to future island stability at Vabbinfaru, and although alterations away from current ecological states may reduce sediment supply, the timescales over which island morphological response will occur depends upon phase lags between initial coral mortality and the conversion of this material into island-grade sand. Copyright © 2016 John Wiley & Sons, Ltd.

BACKGROUND Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome. METHODS A cohort of 275 consecutive patients with margin-positive localized PC following surgery were assessed for Gleason grade and AZGP1 expression at the PSM. BR-free survival was the primary end-point, while CR-free survival and PC-specific death were secondary endpoints. Kaplan-Meier Analysis and Cox Proportional Hazards Modeling were performed. RESULTS Absent AZGP1 expression was significantly associated with increased risk of BR (P = 0.001) and PC-specific death (P = 0.02). Gleason grade ≥4 at PSM was associated with BR (P = 0.02), CR (P = 0.003), and PC-specific death (P = 0.004). On multivariable analysis, absent AZGP1 expression remained an independent predictor of BR (HR 2.4, 95%CI 1.5-3.9, P

Most field studies of wave processes on shore platforms in front of eroding cliffs focus on a single site, revealing aspects of wave dynamics at that location. Here, we analyse data from six platforms around northeastern New Zealand and describe the fundamental control of shore platform width, gradient and elevation on wave processes, including greater attenuation of short-period waves at lower tidal stages and increases in longer period wave energy towards the cliff toe. These data suggest that empirical formulae developed from coral-reef environments provide better predictions of wave height on platforms than formulae currently used in shore platform models.

The future of low-lying reef islands has been the subject of international concern, scientific debate, and media interest in the last decade. As a result of sea-level rise, atoll islands are expected to become increasingly unstable and to be susceptible to potential depopulation by the end of the 21st century. Some have suggested that sea-level rise has already resulted in widespread erosion and inundation of atoll islands. Here, we analyze the physical changes in over 200 islands on 12 atolls in the central and western Pacific in the past few decades when sea level in the region increased at rates three to four times the global average. Results show little evidence of heightened erosion or reduction in island size. Instead island shores have adjusted their position and morphology in response to human impacts such as seawall construction and to variations in climate–ocean processes. These changes are reviewed and the role of sea-level rise is evaluated. The implications of this analysis are addressed in two parts. First, we consider the proposition that future sea-level rise will destabilize atoll islands to such an extent that their inhabitants will be forced to migrate offshore. And second, we identify a series of new challenges relating to risk reduction and adaptation policy for atoll island governments, international agencies, and island communities. These require a substantial shift away from the present adaptation paradigm of external migration and focus on the persistence of atoll islands and in-country solutions. WIREs Clim Change 2015, 6:445–463. doi: 10.1002/wcc.350 For further resources related to this article, please visit the WIREs website.

Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1 mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.

Objective To examine the association between histopathological factors of extraprostatic prostate cancer and outcome. Patients and Methods Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002–2006) for: (i) distance of EPE from the margin; (ii) Gleason score of the EPE; and (iii) extent of EPE. Log-rank, Kaplan–Meier, and Cox regression analyses were performed. Results The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of ≥8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of ≤7 (P = 0.03). The proximity of the EPE to the margin (0.01–7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR. Conclusion Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score ≥8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer.

METHODS: Clinicopathologic features were assessed in a cohort of 766 patients who had been diagnosed with pancreatic ductal adenocarcinoma (PC). Patients were classified with FPC if they had ≥1 affected first-degree relatives; otherwise, they were classified with sporadic PC (SPC).