Co-infections with multiple dengue virus serotypes in patients from 3 different Provinces of Sri Lanka, a dengue hyper endemic country [Poster Abstract]

This is an open access article under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0

Twenty-first-century projections of shoreline change along inlet-interrupted coastlines

Sandy coastlines adjacent to tidal inlets are highly dynamic and widespread landforms, where large changes are expected due to climatic and anthropogenic influences. To adequately assess these important changes, both oceanic (e.g., sea-level rise) and terrestrial (e.g., fluvial sediment supply) processes that govern the local sediment budget must be considered. Here, we present novel projections of shoreline change adjacent to 41 tidal inlets around the world, using a probabilistic, reduced complexity, system-based model that considers catchment-estuary-coastal systems in a holistic way. Under the RCP 8.5 scenario, retreat dominates (90% of cases) over the twenty-first century, with projections exceeding 100 m of retreat in two-thirds of cases. However, the remaining systems are projected to accrete under the same scenario, reflecting fluvial influence. This diverse range of response compared to earlier methods implies that erosion hazards at inlet-interrupted coasts have been inadequately characterised to date. The methods used here need to be applied widely to support evidence-based coastal adaptation

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy. Exome sequencing of the probands revealed an ultra-rare homozygous pathogenic missense DPM3 variant NM_018973.4:c.221A>G, p.(Tyr74Cys) which segregated with the phenotype in all families. Haplotype analysis indicated that the variant arose independently in three families. Functional analysis did not reveal any alteration in the N-glycosylation pathway caused by the variant; however, this does not exclude its pathogenicity in the function of the DPM complex and related cellular pathways. This report provides supporting evidence that, besides DPM1 and DPM2, defects in DPM3 can also lead to a muscle and brain phenotype

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Thysanotus unicupensis (Laxmanniaceae), a new species discovered in Unicup Nature Reserve, south-west Western Australia

Sirisena, U.M., Macfarlane, T.D. and Conran, J.G. Thysanotus unicupensis (Laxmanniaceae), a new species discovered in Unicup Nature Reserve, south-west Western Australia. Nuytsia 19(2): 259–263 (2009). Thysanotus unicupensis is described as a new species from south-west Western Australia. This species shows some affinities to T. chinensis, T. formosus and T. parviflorus and is apparently localised on lateritic soils in moderately sunny areas within Jarrah/Marri (Eucalyptus marginata/Corymbia calophylla) woodlands. The key published in Flora of Australia (1987) is amended to include the new species.Udani M. Sirisena, Terry D. Macfarlane and John G. Conra

Hydrological model calibration with streamflow and remote sensing based evapotranspiration data in a data poor basin

Conventional calibration methods adopted in hydrological modelling are based on streamflow data measured at certain river sections. However, streamflow measurements are usually sparse and, in such instances, remote-sensing-based products may be used as an additional dataset(s) in hydrological model calibration. This study compares two main calibration approaches: (a) single variable calibration with streamflow and evapotranspiration separately, and (b) multi-variable calibration with both variables together. Here, we used remote sensing-based evapotranspiration data from Global Land Evaporation: the Amsterdam Model (GLEAM ET), and measured streamflow at four stations to calibrate a Soil and Water Assessment Tool (SWAT) and evaluate the performances for Chindwin Basin, Myanmar. Our results showed that when one variable (either streamflow or evapotranspiration) is used for calibration, it led to good performance with respect to the calibration variable but resulted in reduced performance in the other variable. In the multi-variable calibration using both streamflow and evapotranspiration, reasonable results were obtained for both variables. For example, at the basin outlet, the best NSEs (Nash-Sutcliffe Efficiencies) of streamflow and evapotranspiration on monthly time series are, respectively, 0.98 and 0.59 in the calibration with streamflow alone, and 0.69 and 0.73 in the calibration with evapotranspiration alone. Whereas, in the multi-variable calibration, the NSEs at the basin outlet are 0.97 and 0.64 for streamflow and evapotranspiration, respectively. The results suggest that the GLEAM ET data, together with streamflow data, can be used for model calibration in the study region as the simulation results show reasonable performance for streamflow with an NSE > 0.85. Results also show that many different sets of parameter values (‘good parameter sets’) can produce results comparable to the best parameter set

Comparison of process-based and lumped parameter models for projecting future changes in fluvial sediment supply to the coast

Fluvial sediment supply (FSS) is one of the primary sources of sediment received by coasts. Any significant change in sediment supply to the coast will disturb its equilibrium state. Therefore, a robust assessment of future changes in FSS is required to understand the coastal system’s status under plausible climatic variations and human activities. Here, we investigate two modelling approaches to estimate the FSS at two spatially heterogeneous river basins: the Irrawaddy River Basin (IRB), Myanmar and the Kalu River Basin (KRB), Sri Lanka. We compare the FSS obtained from a process-based model (i.e., Soil Water Assessment Tool: SWAT) and an empirical model (i.e., the BQART model) for mid- (2046–2065) and end-century (2081–2100) periods under climate change and human activities (viz, planned reservoirs considered here). Our results show that SWAT simulations project a higher sediment load than BQART in the IRB and vice versa in KRB (for both future periods considered). SWAT projects higher percentage changes for both future periods (relative to baseline) compared to BQART projections in both basins with climate change alone (i.e., no reservoirs) and vice versa when planned reservoirs are considered. The difference between the two model projections (from SWAT and BQART) is higher in KRB, and it may imply that empirical BQART model projections are more in line with semi-distributed SWAT projections at the larger Irrawaddy River Basin than in the smaller Kalu River Basin