The Cadia porphyry gold-copper district is the largest hydrothermal, intrusion-related gold deposit in eastern Australia. Discovered in 1992 by Newcrest Mining Limited, pre-mine resources in the ...district were in excess of 585 t Au and 2.35 Mt Cu. The Cadia district lies within shoshonitic subaqueous volcanic rocks of the Late Ordovician Molong Volcanic Belt in the eastern Lachlan Fold Belt (LFB) of New South Wales. An island arc tectonic setting is envisaged for the formation of these volcanic rocks, but the nature of the arc basement and geometry of the subduction zone(s) is debated. Mineralisation occurs in four principal porphyry deposits (Cadia Hill, Cadia Ridgeway, Cadia East/Cadia Far East and Cadia Quarry) as sheeted and stockwork quartz-sulfide veins, and locally as broadly stratabound disseminated mineralisation (Cadia East) and skarn (Big Cadia and Little Cadia). All of the porphyry deposits show a close spatial association with shoshonitic monzodiorite to quartz monzonite dykes and stocks of the Cadia Intrusive Complex (CIC). Gold-copper mineralisation is hosted by these intrusions and also by the enclosing Forest Reefs Volcanics (FRV) wall rocks. Hydrothermal alteration associated with mineralisation is potassic, which is overprinted by selectively pervasive propylitic and silica-albite assemblages. Petrological studies and major and trace element analysis of rocks of the CIC and FRV, as well as of other intrusions in the Cadia district that appear unrelated to mineralisation, have been conducted. Unaltered samples from the CIC are characterised by high K^sub 2^O contents (up to 6.5 wt%) and molecular K/Na ratios consistently >1, confirming the alkalic and shoshonitic nature of the complex. The CIC samples also fall just within the shoshonite field on Ce/Yb-Ta/Yb and Th/Yb-Ta/Yb plots, although immediately adjacent to the calc-alkaline field. The FRV are geochemically similar to the CIC, although lower in P^sub 2^O^sub 5^ and Ce (LREE). Dacitic and hornblende porphyry intrusions from within the district, but spatially unrelated to mineralisation, have a distinctive geochemical signature and are not shoshonitic in composition. The close spatial association between gold-copper mineralisation and the shoshonitic, monzonitic CIC argues strongly for a genetic link between the two. A similar association occurs at the economic Goonumbla porphyry gold-copper deposits in the eastern LFB, while sub-economic gold-copper mineralisation at Cargo and Copper Hill is associated with calc-alkaline quartz diorite and dacitic intrusions. The Cadia district is considered to be an excellent example of the association of alkaline, potassic magmas and gold-copper porphyry style mineralisation.PUBLICATION ABSTRACT
ABSTRACTThe incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. ...Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed individuals, leading, if untreated, to the development of chronic hepatitis and significant liver fibrosis. The British Transplantation Society (BTS) has developed Guidelines for “Hepatitis E and Solid Organ Transplantation” to inform clinical teams and patients about hepatitis E, to help increase the recognition of persistent hepatitis E infection, and to provide clear guidance on its management. This guideline was published on the BTS website in June 2017 and aims to review the evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients and the methods of prevention of HEV infection. In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to rate the strength of evidence and recommendations. This article includes a summary overview of hepatitis E and transplantation with key references, and the statements of recommendation contained within the guideline. It is recommended that the full guideline document is consulted for complete details of the relevant references and evidence base. This may be accessed at https://bts.org.uk/guidelines-standards/.
Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, may be the infectious cause of KS. Its prevalence in the general population, on the basis of detection of the virus ...genome, is controversial. To investigate the seroprevalence, we measured antibodies to a recombinant capsid-related (lytic cycle) KSHV antigen and a latent antigen complex.
We selected potentially immunoreactive capsidrelated proteins of KSHV by expressing them as recombinant proteins and testing them in western blot assays. We used a truncated recombinant protein encoded by KSHV open reading frame 65 (orf 65) to develop a diagnostic enzyme-linked immunosorbent assay (ELISA) and tested sera from HIV-infected individuals with KS, HIV-uninfected patients with “classic” KS, other HIV risk groups, and blood donors. We also compared the antibody response to this capsid-related protein to the response to latent antigen(s) in an immunofluorescence assay.
77/92 (84%) sera from KS patients reacted with the KSHV orf 65 protein and 84/103 (81·5%) reacted with KSHV latent antigen(s). The dominant immunogenic region of orf 65 is within the carboxyterminal 80 aminoacids, a region with little sequence similarity to the related Epstein-Barr virus, suggesting that orf 65 is a KSHV specific antigen. Only three sera from patients with haemophilia (1/84) or from intravenous drug users (2/63) had KSHV specific antibodies in the orf 65 assay whereas none of these sera reacted with latent antigen. Antibodies to KSHV were also infrequently found in UK and US blood donors by either assay (UK, 3/174 with orf 65 and 4/150 with latent antigen; US, 6/117 with orf 65 and 0/117 with latent antigen). They were more common among HIV-infected gay men without KS (5/16 by orf 65 ELISA, 10/33 by IFA), HIV-uninfected STD clinic attenders (14/166 by IFA), and Ugandan HIV-uninfected controls (6/17 by orf 65 ELISA, 9/17 by IFA). Antibody reactivity to the orf 65 protein (ELISA) and to latent antigen(s) (IFA) was concordant in 89% of 462 sera tested but reactive blood donor sera were discordant in both assays. Four AIDS-KS sera were unreactive in both assays.
The distribution of antibodies to both a capsid-related recombinant protein and latent antigen(s) of KSHV strongly supports the view that infection with this virus is largely confined to individuals with, or at increased risk for, KS. However, infection with KSHV does occur, rarely, in the general UK and US population and is more common in Uganda. Antibodies to latent antigen(s) or to orf 65 encoded capsid protein will not detect all cases of KSHV infection, and a combination of several antigens will probably be required for accurate screening and confirmatory assays.
Type 2 diabetes mellitus (T2DM) patients suffer premature development of cardiovascular disease and commonly require cardiac revascularization using the autologous saphenous vein (SV). Smooth muscle ...cells (SMCs) are the principal cell type within the vascular wall and are dysfunctional in T2DM SV-SMCs, yet the mechanisms underpinning this are incompletely understood. The purpose of this study was to interrogate differential microRNA (miRNA) expression in SV-SMCs to enhance our understanding of T2DM SV-SMC phenotypic change. miRNA expression in primary human SV-SMCs from T2DM and non-diabetic (ND) donors was determined using an array (n = 6 each of ND and T2DM SV-SMCs). Differentially expressed miRNAs were ranked, and functional annotation of the 30 most differentially expressed miRNAs using DAVID and KEGG analysis revealed pathways related to SMC phenotype, including proliferation, migration, cytokine production and cell signaling. After selecting miRNAs known to be involved in SMC phenotypic regulation, miR-17, miR-29b-2, miR-31, miR-130b and miR-491 were further validated using qRT-PCR (n = 5 each of ND and T2DM SV-SMC), with miR-29b-2 subsequently being removed from further investigation. Potential mRNA targets were identified using mirDIP. Predicted target analysis highlighted likely dysregulation in transcription, epigenetic regulation, cell survival, intracellular signaling and cytoskeletal regulation, all of which are known to be dysfunctional in T2DM SV-SMCs. In conclusion, this paper identified four miRNAs that are dysregulated in T2DM SV-SMCs and are implicated in functional changes in the behavior of these cells. This provides a step forward in our understanding of the molecular and epigenetic regulation of vascular dysfunction in T2DM.
The immune system works through leukocytes interacting with each other, with other cells, with tissue matrices, with infectious agents, and with other antigens. These interactions are mediated by ...cell-surface glycoproteins and glycolipids. Antibodies against these leukocyte molecules have provided powerful tools for analysis of their structure, function, and distribution. Antibodies have been used widely in hematology, immunology, and pathology, and in research, diagnosis, and therapy. The associated CD nomenclature is commonly used when referring to leukocyte surface molecules and antibodies against them. It provides an essential classification for diagnostic and therapeutic purposes. The most recent (8th) Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Adelaide, Australia, in December 2004, allocated 95 new CD designations and made radical changes to its aims and future operational strategy in order to maintain its relevance to modern human biology and clinical practice.
Abstract
Dominance often indicates one or a few species being best suited for resource capture and retention in a given environment. Press perturbations that change availability of limiting resources ...can restructure competitive hierarchies, allowing new species to capture or retain resources and leaving once dominant species fated to decline. However, dominant species may maintain high abundances even when their new environments no longer favour them due to stochastic processes associated with their high abundance, impeding deterministic processes that would otherwise diminish them.
Here, we quantify the persistence of dominance by tracking the rate of decline in dominant species at 90 globally distributed grassland sites under experimentally elevated soil nutrient supply and reduced vertebrate consumer pressure.
We found that chronic experimental nutrient addition and vertebrate exclusion caused certain subsets of species to lose dominance more quickly than in control plots. In control plots, perennial species and species with high initial cover maintained dominance for longer than annual species and those with low initial cover respectively. In fertilized plots, species with high initial cover maintained dominance at similar rates to control plots, while those with lower initial cover lost dominance even faster than similar species in controls. High initial cover increased the estimated time to dominance loss more strongly in plots with vertebrate exclosures than in controls. Vertebrate exclosures caused a slight decrease in the persistence of dominance for perennials, while fertilization brought perennials' rate of dominance loss in line with those of annuals. Annual species lost dominance at similar rates regardless of treatments.
Synthesis.
Collectively, these results point to a strong role of a species' historical abundance in maintaining dominance following environmental perturbations. Because dominant species play an outsized role in driving ecosystem processes, their ability to remain dominant—regardless of environmental conditions—is critical to anticipating expected rates of change in the structure and function of grasslands. Species that maintain dominance while no longer competitively favoured following press perturbations due to their historical abundances may result in community compositions that do not maximize resource capture, a key process of system responses to global change.
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Introduction:
Hepatitis E Virus (HEV) is one of the leading causes of acute infectious hepatitis worldwide; while usually a self-limiting, sub-clinical illness, genotype 3 HEV infection may become ...chronic in immunosuppressed patients such as solid organ transplant (SOT) or haematopoietic stem cell transplant (HSCT) recipients and rapid progression to cirrhosis may occur. Recent seroprevalence from screening of English blood donors shows antibody prevalence of ~13%. RNA prevalence in donors has increased in the UK from 1:2850 to 1:1460 over the past 3 years. This study examines the point-prevalence of HEV in SOT and HSCT recipients transplanted between January 2013 - December 2015 at a major UK transplant centre. Data on HEV clearance rates and risk factors for infection were collected in the patient cohort.
Methods:
Stored extracts of blood from patients undergoing liver transplant (OLT), renal transplant (RT) or HSCT were tested by real-time reverse-transcriptase polymerase chain reaction for HEV RNA. Samples were tested at baseline, 30, 60 and 90 days post-transplant +/- 7 days. Time points were chosen to give good coverage of the early post-transplant period whilst avoiding a patient becoming viraemic and clearing the infection between sample time points. All positive samples were sent to the Public Health England reference laboratory for verification, viral RNA genotyping and quantification. Patients with confirmed positive samples underwent further testing and evaluation of clinical parameters to determine chronology of infection, blood product exposure, organ function and histopathology results.
Results:
259 HSCT, 262 OLT and 349 RT patients met the inclusion criteria. Of the HSCTs there were 111 allogeneic stem cell transplants, 145 autologous transplants and 3 CD34 "top ups". The OLTs comprised 259 deceased donor, 2 live donor and 2 domino liver transplant patients. The RTs comprised 241 deceased donor, 38 live unrelated, 63 live related transplants and 1 live transplant where the relationship of the donor was unrecorded. In total 4 patients (1 HSCT and 3 OLT) were found to have HEV viraemiain our study period. This represents 0.39% of the HSCT and 1.15% of the OLT patients. All were positive with HEV genotype 3.
Virologicaland clinical data regarding these patients are presented in tables below.
Conclusion:
Chronic HEV, genotype 3 in transplant patients is associated with significant morbidity. With the increasing incidence of HEV, immunosuppressed patients with high transfusion burden have an infection risk equivalent to 7-9 years' dietary exposure.
Our results show that prevalence of HEV viraemia in OLT, RT and HSCT patients is higher than expectedbased on comparison from UK blood donors. Secondly, infection is not cleared as would be expected in the general population with 3 of the 4 patients requiring treatment to clear the virus.
The source of infection for these patients is unclear; on a population wide basis HEV is usually a dietary acquired infection, with pork products carrying the greatest risk. In the transplant patient population, the risk of iatrogenic infection via infected blood products or an infected transplanted organ is an important consideration and UK guidance has recently changed so that transplant recipients receive dietary advice and HEV-negative blood to avoid infection (SaBTO2016).
In this study 2 patients were found to be positive for HEV RNA in the baseline sample. One, the recipient of HSCT, did not acquire it through transfusion as testing of the transfused products that the patient had received were negative for the virus. It is not clear how the two OLT patients who tested positive acquired the virus. The absence of any positive results in the renal transplant recipients may reflect the lower transfusion burden in this patient group. Given the multiple routes of possible infection with HEV, a strategy if screening recipients for the virus in addition to screening blood and organ donors would be an effective way of detecting viral transmission via all routes.
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Sekhar:Novartis: Research Funding.
Purpose: To evaluate the safety and efficacy of a novel optical coherence tomography (OCT)–guided atherectomy catheter in treating patients with symptomatic femoropopliteal disease. Methods: The ...VISION trial ( ClinicalTrials.gov identifier NCT01937351) was a single-arm, multicenter, global investigational device exemption study enrolling 158 subjects (mean age 67.2±10.5 years; 87 men) across 20 participating sites. In this cohort, 198 lesions were treated with an average length of 53±40 mm using the Pantheris catheter alone or Pantheris + adjunctive therapy. The primary safety endpoint was the composite of major adverse events (MAEs) through 6 months (objective performance goal 43.2%). Technical success (primary efficacy outcome) was defined as the percent of target lesions with a residual diameter stenosis ≤50% after treatment with the Pantheris device alone (objective performance goal 87.0%). Procedural success was defined as reduction in stenosis to ≤30% after Pantheris ± adjunctive therapy. Tissue specimens retrieved from each treated lesion were histologically analyzed to evaluate the accuracy and precision of OCT image guidance. Results: The primary efficacy outcome was achieved in 192 (97.0%) of the 198 lesions treated with the Pantheris catheter. Across all lesions, mean diameter stenosis was reduced from 78.7%±15.1% at baseline to 30.3%±11.8% after Pantheris alone (p<0.001) and to 22.4%±9.9% after Pantheris ± adjunctive therapy (p<0.001). Of the 198 target lesions, 104 (52.5%) were treated with the Pantheris alone, 84 (42.4%) were treated with Pantheris + adjunctive angioplasty, and 10 (5.1%) with Pantheris + angioplasty + stenting. The composite MAE outcome through 6 months occurred in 25 (16.6%) of 151 subjects. There were no clinically significant perforations, 1 (0.5%) catheter-related dissection, 4 (2%) embolic events, and a 6.4% clinically driven target lesion revascularization rate at 6 months. The 40-lesion chronic total occlusion (CTO) subset (mean lesion length 82±38 mm) achieved a similar significant reduction in stenosis to 35.5%±13.6% after Pantheris alone (p<0.001). Histological analysis of atherectomy specimens confirmed <1% adventitia in 82.1% of the samples, highlighting the precision of OCT guidance. Characterization of the OCT-guided lesions revealed evidence of an underestimation of disease burden when using fluoroscopy. Conclusion: OCT-guided atherectomy for femoropopliteal disease is safe and effective. Additionally, the precision afforded by OCT guidance leads to greater removal of plaque during atherectomy while sparing the adventitia.
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