Reducing the risk of iatrogenic Creutzfeldt–Jakob disease by improving the cleaning of neurosurgical instruments

Background: In all, there have been 178 variant Creutzfeldt–Jakob disease (vCJD) patients diagnosed in the UK, with an estimated maximum 1:2000 carriage rate based on archived appendix and tonsil tissue, implying that infection may be rare but carriage relatively frequent. Previous workers have identified that maintenance of surgical instruments in a humid atmosphere after use and prior to cleaning assists cleaning efficacy. Recently the Department of Health/Advisory Committee on Dangerous Pathogens UK have recommended a surgical instrument cleanliness threshold post cleaning of <5 μg protein per instrument side. Aim: To quantify cleanliness of neurosurgical instruments and to investigate cost-effective measures for improved cleaning. Methods: Two instrument protein quantification methods were used: one based on the International Standard (15883 series) using sodium dodecyl sulphate elution and ortho-phthalaldehyde reaction, and a second in-situ protein fluorescence detection system (ProReveal) providing results per instrument side. In-vitro investigation of the efficacy of some commercial and in-house pre-clean wetting agents was undertaken using artificial test soil and stainless steel discs under standard conditions. In-vivo evaluation of best-performing in-vitro agents was undertaken on craniotomy sets. Findings: ProReveal technology demonstrated that 163 out of 187 (87%) neurosurgical instruments had <5 μg residual protein per instrument side. The use of proprietary National Health Service plastic bags and sterile water-soaked wound pads were equivalent in efficacy to commercial pre-cleaning wetting products and significantly less expensive. Conclusion: Although we demonstrate low in-situ protein levels on neurosurgical instruments and the beneficial effects of keeping instruments moist, other cleaning critical-control points such as instrument loading patterns should also be monitored

The VLT-FLAMES Tarantula Survey III: A very massive star in apparent isolation from the massive cluster R136

VFTS 682 is located in an active star-forming region, at a projected distance of 29 pc from the young massive cluster R136 in the Tarantula Nebula of the Large Magellanic Cloud. It was previously reported as a candidate young stellar object, and more recently spectroscopically revealed as a hydrogen-rich Wolf-Rayet (WN5h) star. Our aim is to obtain the stellar properties, such as its intrinsic luminosity, and to investigate the origin of VFTS 682. To this purpose, we model optical spectra from the VLT-FLAMES Tarantula Survey with the non-LTE stellar atmosphere code CMFGEN, as well as the spectral energy distribution from complementary optical and infrared photometry. We find the extinction properties to be highly peculiar (RV ~4.7), and obtain a surprisingly high luminosity log(L/Lsun) = 6.5 \pm 0.2, corresponding to a present-day mass of ~150Msun. The high effective temperature of 52.2 \pm 2.5kK might be explained by chemically homogeneous evolution - suggested to be the key process in the path towards long gamma-ray bursts. Lightcurves of the object show variability at the 10% level on a timescale of years. Such changes are unprecedented for classical Wolf-Rayet stars, and are more reminiscent of Luminous Blue Variables. Finally, we discuss two possibilities for the origin of VFTS 682: (i) the star either formed in situ, which would have profound implications for the formation mechanism of massive stars, or (ii) VFTS 682 is a slow runaway star that originated from the dense cluster R136, which would make it the most massive runaway known to date.Comment: 5 pages, 5 figures, accepted by A&A Letter

Safety Implications of Mandated Truck Speed Limiters on Freeways

ABSTRACT This paper presents the results of a study funded by Transport Canada to investigate the safety implications of mandated truck speed limiters. The study adopted a microscopic simulation approach that was applied to a number of maximum speed control strategies including 105km/h. The sensitivity of safety performance with respect to changes in geometric and traffic scenarios was investigated. The study found that truck speed limiters produced positive safety gains for different assumed volumes and percentage trucks and different compliance levels. Under certain conditions such as high volumes and high percentage of trucks, speed limiters produced a reduction in safety

Normal calcium-activated anion secretion in a mouse selectively lacking TMEM16A in intestinal epithelium

Calcium-activated anion secretion is expected to ameliorate cystic fibrosis, a genetic disease that carries an anion secretory defect in exocrine tissues. Human patients and animal models of the disease that present a mild intestinal phenotype have been postulated to bear a compensatory calcium-activated anion secretion in the intestine. TMEM16A is calcium-activated anion channel whose presence in the intestinal epithelium is contradictory. We aim to test the functional expression of TMEM16A using animal models with Cftr and/or Tmem16a intestinal silencing. Expression of TMEM16A was studied in a wild type and intestinal Tmem16a knockout mice by mRNA-seq, mass-spectrometry, q-PCR, Western blotting and immunolocalization. Calcium-activated anion secretion was recorded in the ileum and proximal colon of these animals including intestinal Cftr knockout and double mutants with dual Tmem16a and Cftr intestinal ablation. Mucus homeostasis was studied by immune-analysis of Mucin-2 (Muc2) and survival curves were recorded. Tmem16a transcript was found in intestine. Nevertheless, protein was barely detected in colon samples. Electrophysiological measurements demonstrated that the intestinal deletion of Tmem16a did not change calcium-activated anion secretion induced by carbachol or ATP in ileum and proximal colon. Muc2 architecture was not altered by Tmem16a silencing as was observed when Cftr was deleted from mouse intestine. Tmem16a silencing neither affected animal survival nor modified the lethality observed in the intestinal Cftr-null mouse. Our results demonstrate that TMEM16A function in the murine intestine is not related to electrogenic calcium-activated anion transport and does not affect mucus homeostasis and survival of animals

The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein

In mammalian cells, MCTs (monocarboxylate transporters) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4, and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT (reverse transcription)–PCR, we have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-Lactate Km values for these constructs were determined and revealed that the TM (transmembrane) domains of an MCT, most probably TM7–TM12, but not the C-terminus, are the major determinants of L-lactate affinity, whereas the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin

Mead-halls of the Oiscingas: a new Kentish perspective on the Anglo-Saxon great hall complex phenomenon

Widely cited as a metaphor for the emergence of kingship in early medieval England, the great hall complex represents one of the most distinctive and evocative expressions of the Anglo-Saxon settlement record, yet interpretation of these sites remains underdeveloped and heavily weighted towards Yeavering. Inspired by the results of recent excavations at Lyminge, this paper undertakes a detailed comparative interrogation of three great hall complexes in Kent and exploits this new regional perspective to advance understanding of the agency and embodied meanings of these settlements as ‘theatres of power’. Explored through the thematic prisms of place, social memory and monumental hybridity, this examination leads to a new appreciation of the involvement of great hall sites in the genealogical strategies of 7th-century royal dynasties and a fresh perspective on how this remarkable yet short-lived monumental idiom was adapted to harness the symbolic capital of Romanitas

On the origin of the O and B-type stars with high velocities II Runaway stars and pulsars ejected from the nearby young stellar groups

We use milli-arcsecond accuracy astrometry (proper motions and parallaxes) from Hipparcos and from radio observations to retrace the orbits of 56 runaway stars and nine compact objects with distances less than 700 pc, to identify the parent stellar group. It is possible to deduce the specific formation scenario with near certainty for two cases. (i) We find that the runaway star zeta Ophiuchi and the pulsar PSR J1932+1059 originated about 1 Myr ago in a supernova explosion in a binary in the Upper Scorpius subgroup of the Sco OB2 association. The pulsar received a kick velocity of about 350 km/s in this event, which dissociated the binary, and gave zeta Oph its large space velocity. (ii) Blaauw & Morgan and Gies & Bolton already postulated a common origin for the runaway-pair AE Aur and mu Col, possibly involving the massive highly-eccentric binary iota Ori, based on their equal and opposite velocities. We demonstrate that these three objects indeed occupied a very small volume \sim 2.5Myr ago, and show that they were ejected from the nascent Trapezium cluster. We identify the parent group for two more pulsars: both likely originate in the 50 Myr old association Per OB3, which contains the open cluster alpha Persei. At least 21 of the 56 runaway stars in our sample can be linked to the nearby associations and young open clusters. These include the classical runaways 53 Arietis (Ori OB1), xi Persei (Per OB2), and lambda Cephei (Cep OB3), and fifteen new identifications, amongst which a pair of stars running away in opposite directions from the region containing the lambda Ori cluster. Other currently nearby runaways and pulsars originated beyond 700 pc, where our knowledge of the parent groups is very incomplete.Comment: Accepted for publication in the A&A. 29 pages, 19 figure

A comparison of vas occlusion techniques: cautery more effective than ligation and excision with fascial interposition

BACKGROUND: Vasectomy techniques have been the subject of relatively few rigorous studies. The objective of this analysis was to compare the effectiveness of two techniques for vas occlusion: intraluminal cautery versus ligation and excision with fascial interposition. More specifically, we aimed to compare early failure rates, sperm concentrations, and time to success between the two techniques. METHODS: We compared semen analysis data from men following vasectomy using two occlusion techniques. Data on intraluminal cautery came from a prospective observational study conducted at four sites. Data on ligation and excision with fascial interposition came from a multicenter randomized controlled trial that evaluated the efficacy of ligation and excision with versus without fascial interposition. The surgical techniques used in the fascial interposition study were standardized. The surgeons in the cautery study used their customary techniques, which varied among sites in terms of type of cautery, use of fascial interposition, excision of a short segment of the vas, and use of an open-ended technique. Men in both studies had semen analyses two weeks after vasectomy and then approximately every four weeks. The two outcome measures for the analyses presented here are (a) time to success, defined as severe oligozoospermia, or <100,000 sperm/mL in two consecutive semen analyses; and (b) early vasectomy failure, defined as >10 million sperm/mL at week 12 or later. RESULTS: Vasectomy with cautery was associated with a significantly more rapid progression to severe oligozoospermia and with significantly fewer early failures (1% versus 5%). CONCLUSION: The use of cautery improves vasectomy outcomes. Limitations of this comparison include (a) the variety of surgical techniques in the cautery study and differences in methods of fascial interposition between the two studies, (b) the uncertain correlation between sperm concentrations after vasectomy and the risk of pregnancy, and (c) the use of historical controls and different study sites