Man-made noise in our living environments

The ITU’s (International Telecommunication Union’s) man-made noise levels are based on measurements performed in the 1970s. Some measurements have been carried out since then, showing that noise caused by automotive ignition systems has been reduced, but manmade noise in business areas and city centers increased, especially due to the widespread use of electronic systems. The interference scenario also changed, from analog communication systems in relatively free-space conditions, to digital systems in living areas, often semi-enclosed such as offi ces, industrial production plants, and even inside cars and trains. Several measurements have therefore been carried out to estimate the level of man-made noise in these semi-enclosed environments

Nonoperatively treated type A spinal fractures:mid-term versus long-term functional outcome

This study focuses on the mid-term (four years) and long-term (ten years) functional outcome of patients treated nonoperatively for a type A spinal fracture without primary neurological deficit. Functional outcome was measured using the visual analogue scale spine score (VAS) and the Roland–Morris disability questionnaire (RMDQ). The 50 patients included were on average 41.2 years old at the time of injury. Four years post injury, a mean VAS score of 74.5 and a mean RMDQ score of 4.9 were found. Ten years after the accident, the mean VAS and RMDQ scores were 72.6 and 4.7, respectively (NS). No significant relationships were found between the difference scores of the VAS and RMDQ compared with age, gender, fracture sub-classification, and time between measurements. Three (6%) patients had a poor long-term outcome. None of the patients required surgery for late onset pain or progressive neurological deficit. Functional outcome after a nonoperatively treated type A spinal fracture is good, both four and ten years post injury. For the group as a whole, four years after the fracture a steady state exists in functional outcome, which does not change for ten years at least after the fracture

Predictable and robust performance of a Bi-2223 superconducting coil for compact isochronous cyclotrons

The development of ever smaller medical particle accelerators is motivated by a desire to make proton therapy accessible to more patients. Reducing the footprint of particle accelerators and subsequently proton therapy facilities allows for cheaper and broader usage of proton therapy. By employing superconducting technologies for field shaping, the size of particle accelerators can be reduced further below what is possible with saturated iron. This article discusses experiments on a first-of-its-kind double pancake (DP), and an assembly of six DP coils, designed to be used as a so-called ‘flutter coil’ for a compact isochronous cyclotron for proton therapy, fabricated from high-temperature superconducting (HTS) Bi 2 − x Pbx Sr2Ca2Cu3Oy (Bi-2223) tape. The coils were mounted under pre-stress within a stainless-steel structure to maintain mechanical stability during the experiments. The critical current as a function of the temperature of both coils was measured in a conduction-cooled setup. A model describing the coils, based on tape data, was created and revealed that the measurements were in excellent agreement with the predictions. Additional experiments were performed to study the quench and thermal runaway behaviour of the HTS coils, determining whether such coils can be protected against fault scenarios, using realistic quench-detection levels and discharge extraction-rates. These experiments demonstrate that the coils are very robust and can be well protected against quenches and thermal-runaway events using common quench-protection measures with realistic parameters.</p

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Performance of Tablet Splitters, Crushers, and Grinders in Relation to Personalised Medication with Tablets

Swallowing problems and the required dose adaptations needed to obtain optimal pharmacotherapy may be a hurdle in the use of tablets in daily clinical practice. Tablet splitting, crushing, or grinding is often applied to personalise medication, especially for the elderly and children. In this study, the performance of different types of (commercially available) devices was studied. Included were splitters, screwcap crushers, manual grinders, and electric grinders. Unscored tablets without active ingredient were prepared, with a diameter of 9 and 13 mm and a hardness of 100–220 N. Tablets were split into two parts and the difference in weight was measured. The time needed to pulverise the tablets (crush time) was recorded. The residue remaining in the device (loss) was measured. The powder was sieved to obtain a particle fraction >600 µm and <600 µm. The median particle size and particle size distribution of the later fraction were determined using laser diffraction analysis. Splitting tablets into two equal parts appeared to be difficult with the devices tested. Most screwcap grinders yielded a coarse powder containing larger chunks. Manual and especially electric grinders produced a finer powder, making it suitable for administration via an enteral feeding tube as well as for use in individualised preparations such as capsules. In conclusion, for domestic and incidental use, a screwcap crusher may provide sufficient size reduction, while for the more demanding regular use in hospitals and nursing residences, a manual or electric grinder is preferred

A high urea-to-creatinine ratio predicts long-term mortality independent of acute kidney injury among patients hospitalized with an infection

Acute kidney injury (AKI) occurs frequently in patients with sepsis. Persistent AKI is, in contrast to transient AKI, associated with reduced long-term survival after sepsis, while the effect of AKI on survival after non-septic infections remains unknown. As prerenal azotaemia is a common cause of transient AKI that might be identified by an increased urea-to-creatinine ratio, we hypothesized that the urea-to-creatinine ratio may predict the course of AKI with relevance to long-term mortality risk. We studied the association between the urea-to-creatinine ratio, AKI and long-term mortality among 665 patients presented with an infection to the ED with known pre-existent renal function. Long-term survival was reduced in patients with persistent AKI. The urea-to-creatinine ratio was not associated with the incidence of either transient or non-recovered AKI. In contrast, stratification according to the urea-to-creatinine-ratio identifies a group of patients with a similar long-term mortality risk as patients with persistent AKI. Non-recovered AKI is strongly associated with all-cause long-term mortality after hospitalization for an infection. The urea-to-creatinine ratio should not be employed to predict prerenal azotaemia, but identifies a group of patients that is at increased risk for long-term mortality after infections, independent of AKI and sepsis

EMC testing of electricity meters using real-world and artificial current waveforms

In 2015, the energy measurement of some static electricity meters was found to be sensitive to specific conducted electromagnetic disturbances with very fast current changes caused by highly nonlinear loads, leading to meter errors up to several hundred percent. This article describes new results on the electromagnetic compatibility (EMC) of 16 different meters from all over Europe when exposed to real-world disturbance signals. Those test signals were obtained from household appliances and onsite measurements at metered supply points all over Europe. The results show that also the interference signals recorded onsite can cause measurement errors as large as several hundred percent, even for meters that pass the present EMC standards. This unambiguously demonstrates that the present immunity testing standards do not cover the most disturbing conducted interference occurring in present daily-life situations due to the increased use of nonlinear electronics. Furthermore, to enable the adoption of potential new test waveforms in future standards for electricity meter testing, artificial test waveforms were constructed based on real-world waveforms using a piece-wise linear model. These artificial test waveforms were demonstrated to cause meter errors similar to those caused by the original real-life waveforms they are representing, showing that they are suitable candidates for use in improved standardization of electricity meter testing.Postprint (published version

Laboratory evolution of Pyrococcus furiosus alcohol dehydrogenase to improve the production of (2S,5S)-hexanediol at moderate temperatures

There is considerable interest in the use of enantioselective alcohol dehydrogenases for the production of enantio- and diastereomerically pure diols, which are important building blocks for pharmaceuticals, agrochemicals and fine chemicals. Due to the need for a stable alcohol dehydrogenase with activity at low-temperature process conditions (30°C) for the production of (2S,5S)-hexanediol, we have improved an alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus (AdhA). A stable S-selective alcohol dehydrogenase with increased activity at 30°C on the substrate 2,5-hexanedione was generated by laboratory evolution on the thermostable alcohol dehydrogenase AdhA. One round of error-prone PCR and screening of ∼1,500 mutants was performed. The maximum specific activity of the best performing mutant with 2,5-hexanedione at 30°C was tenfold higher compared to the activity of the wild-type enzyme. A 3D-model of AdhA revealed that this mutant has one mutation in the well-conserved NADP(H)-binding site (R11L), and a second mutation (A180V) near the catalytic and highly conserved threonine at position 183

Structural basis of catalysis in the bacterial monoterpene synthases linalool synthase and 1,8-cineole synthase

Terpenoids form the largest and stereochemically most diverse class of natural products, and there is considerable interest in producing these by biocatalysis with whole cells or purified enzymes, and by metabolic engineering. The monoterpenes are an important class of terpenes and are industrially important as flavors and fragrances. We report here structures for the recently discovered Streptomyces clavuligerus monoterpene synthases linalool synthase (bLinS) and 1,8-cineole synthase (bCinS), and we show that these are active biocatalysts for monoterpene production using biocatalysis and metabolic engineering platforms. In metabolically engineered monoterpene-producing E. coli strains, use of bLinS leads to 300-fold higher linalool production compared with the corresponding plant monoterpene synthase. With bCinS, 1,8-cineole is produced with 96% purity compared to 67% from plant species. Structures of bLinS and bCinS, and their complexes with fluorinated substrate analogues, show that these bacterial monoterpene synthases are similar to previously characterized sesquiterpene synthases. Molecular dynamics simulations suggest that these monoterpene synthases do not undergo large-scale conformational changes during the reaction cycle, making them attractive targets for structured-based protein engineering to expand the catalytic scope of these enzymes toward alternative monoterpene scaffolds. Comparison of the bLinS and bCinS structures indicates how their active sites steer reactive carbocation intermediates to the desired acyclic linalool (bLinS) or bicyclic 1,8-cineole (bCinS) products. The work reported here provides the analysis of structures for this important class of monoterpene synthase. This should now guide exploitation of the bacterial enzymes as gateway biocatalysts for the production of other monoterpenes and monoterpenoids