Clinical and economic comparison of an individualised immunoglobulin protocol vs. standard dosing for chronic inflammatory demyelinating polyneuropathy

Background The clinical and economic implications of an individualised intravenous immunoglobulin (IVIg) protocol for chronic inflammatory demyelinating polyneuropathy (CIDP) are unknown. Comparison with standard dosing regimens has not been performed. Methods We retrospectively studied 47 IVIg-treated subjects with CIDP over 4 years with an individualised, outcome-measured, dose-modifying protocol. We evaluated responder and remission rates, clinical improvement levels and dose requirements. We compared clinical benefits and costs with those reported with standard dosing at 1 g/kg every 3 weeks. Results The IVIg-responder rate was 83% and the 4-year remission rate was 25.6%. Mean IVIg dose requirements were 22.06 g/week (SD:15.29) in patients on ongoing therapy. Dose range was wide (5.83–80 g/week). Mean infusion frequency was every 4.34 weeks (SD:1.70) and infusion duration of 2.79 days (SD:1.15). Mean Overall Neuropathy Limitation Scale improvement was 2.54 (SD:1.89) and mean MRC sum score improvement of 12.23 (SD:7.17) in IVIg-responders. Mean modified-INCAT (Inflammatory Neuropathy Cause and Treatment) score improvement was similar (p = 0.47) and mean MRC sum score improvement greater (p < 0.001) in our cohort, compared to the IVIg-treated arm of the ICE Study. Mean drug costs were GBP 37,660/patient/year (€ 43,309) and mean infusion-related costs of GBP 17,115/patient/year (€ 19,682), totalling GBP 54,775/patient/year (€ 62,991). Compared to standard dosing using recorded weight, mean savings were of GBP 13,506/patient/year (€ 15,532). Compared to standard dosing using dosing weight, savings were of GBP 6,506/patient/year (€ 7,482). Conclusion Our results indicate that an individualised IVIg treatment protocol is clinically non-inferior and 10–25% more cost-effective than standard dosing regimens in CIDP

Offshore wind farm layout optimization using particle swarm optimization

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordThis article explores the application of a wind farm layout optimization framework using a particle swarm optimizer to three benchmark test cases. The developed framework introduces an increased level of detail characterizing the impact that the wind farm layout can have on the levelized cost of energy by modelling the wind farm’s electrical infrastructure, annual energy production, and cost as functions of the wind farm layout. Using this framework, this paper explores the application of a particle swarm optimizer to the wind farm layout optimization problem considering three different levels of wind farm constraint faced by modern wind farm developers. The particle swarm optimizer is found to yield improvements in the layout with respect to the levelized cost of energy for the three benchmark cases when compared to two past studies. This highlights both applicability of the particle swarm optimizer to the problem and the ways in which a wind farm developer could make use of the present framework in the development and design of future wind farms.This work is funded in part by the Energy Technologies Institute (ETI) and RCUK energy program for IDCORE (EP/J500847/1) and supported by EDF Energy R&D UK Centre

The Age of the 20 Meter Solo River Terrace, Java, Indonesia and the Survival of Homo erectus in Asia

Homo erectus was the first human lineage to disperse widely throughout the Old World, the only hominin in Asia through much of the Pleistocene, and was likely ancestral to H. sapiens. The demise of this taxon remains obscure because of uncertainties regarding the geological age of its youngest populations. In 1996, some of us co-published electron spin resonance (ESR) and uranium series (U-series) results indicating an age as young as 35–50 ka for the late H. erectus sites of Ngandong and Sambungmacan and the faunal site of Jigar (Indonesia). If correct, these ages favor an African origin for recent humans who would overlap with H. erectus in time and space. Here, we report 40Ar/39Ar incremental heating analyses and new ESR/U-series age estimates from the “20 m terrace" at Ngandong and Jigar. Both data sets are internally consistent and provide no evidence for reworking, yet they are inconsistent with one another. The 40Ar/39Ar analyses give an average age of 546±12 ka (sd±5 se) for both sites, the first reliable radiometric indications of a middle Pleistocene component for the terrace. Given the technical accuracy and consistency of the analyses, the argon ages represent either the actual age or the maximum age for the terrace and are significantly older than previous estimates. Most of the ESR/U-series results are older as well, but the oldest that meets all modeling criteria is 143 ka+20/−17. Most samples indicated leaching of uranium and likely represent either the actual or the minimum age of the terrace. Given known sources of error, the U-series results could be consistent with a middle Pleistocene age. However, the ESR and 40Ar/39Ar ages preclude one another. Regardless, the age of the sites and hominins is at least bracketed between these estimates and is older than currently accepted