A spatially and temporally localized sub-laser-cycle electron source

We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8 femtosecond low power laser pulses. This process is non-linear in the laser electric field, and the non-linearity can be tuned via the DC voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fsec 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fsec duration. Furthermore, we find that the carrier-envelope phase dependence of the emission process is smaller than 0.1% for an 8 fsec pulse but is steeply increasing with decreasing laser pulse duration.Comment: 4 pages, 5 figure

Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions

Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study

Background This study compared the fluid leakage in the new ‘tapered' shaped against the classic ‘cylindrical' shaped tracheal tube cuffs when placed in different sized tracheas. Methods The 7.5 mm internal diameter (ID) tracheal tube cuffs—Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff, Ruesch, and Portex Profile—were compared in an in vitro apparatus. Vertical artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water was applied above the unlubricated tube cuffs, and fluid leakage was measured up to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were compared for each tracheal diameter using the Mann-Whitney test. Results Median (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and 0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00-4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40-4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube cuffs was almost complete (5 ml) within 5 min (P<0.001). Conclusions The tapered PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal diameters and was more efficient than the cylindrical Microcuff PU tube cuff in larger tracheal diameter in preventing subglottic fluid leakage across the tube cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster than PU cuff

Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery

Background Thromboelastometry (ROTEM®) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. Methods Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM® analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. Results A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P<0.001). Notably, 64% of PT and 94% of aPTT measurements were outside the reference range, while impaired CT was observed in 13% and 6.3%, respectively. Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): 45-63 min], whereas 10 min values of ROTEM® results were available online after 23 min (IQR: 21-24 min). Conclusions PT and aPTT cannot be interchangeably used with ROTEM® CT. Based on the results of ROTEM®, recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM® offered faster turnaround time

Bright betatron x-ray radiation from a laser-driven-clustering gas target

Hard X-ray sources from femtosecond (fs) laser-produced plasmas, including the betatron X-rays from laser wakefield-accelerated electrons, have compact sizes, fs pulse duration and fs pump-probe capability, making it promising for wide use in material and biological sciences. Currently the main problem with such betatron X-ray sources is the limited average flux even with ultra-intense laser pulses. Here, we report ultra-bright betatron X-rays can be generated using a clustering gas jet target irradiated with a small size laser, where a ten-fold enhancement of the X-ray yield is achieved compared to the results obtained using a gas target. We suggest the increased X-ray photon is due to the existence of clusters in the gas, which results in increased total electron charge trapped for acceleration and larger wiggling amplitudes during the acceleration. This observation opens a route to produce high betatron average flux using small but high repetition rate laser facilities for applications

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs

Background It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. Methods Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg−1 min−1) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg−1 bupivacaine infused. Results Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg−1, in 80% and 0% at 2.5 mg kg−1, and in 93% and 80% at 5 mg kg−1 bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg−1 infused. Conclusions Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administere

The plasmodium lactate/H+ transporter PfFNT is essential and druggable in vivo

Malaria parasites in the blood stage express a single transmembrane transport protein for the release of the glycolytic end product l-lactate/H(+) from the cell. This transporter is a member of the strictly microbial formate-nitrite transporter (FNT) family and a novel putative drug target. Small, drug-like FNT inhibitors potently block lactate transport and kill Plasmodium falciparum parasites in culture. The protein structure of Plasmodium falciparum FNT (PfFNT) in complex with the inhibitor has been resolved and confirms its previously predicted binding site and its mode of action as a substrate analog. Here, we investigated the mutational plasticity and essentiality of the PfFNT target on a genetic level, and established its in vivo druggability using mouse malaria models. We found that, besides a previously identified PfFNT G107S resistance mutation, selection of parasites at 3 x IC(50) (50% inhibitory concentration) gave rise to two new point mutations affecting inhibitor binding: G21E and V196L. Conditional knockout and mutation of the PfFNT gene showed essentiality in the blood stage, whereas no phenotypic defects in sexual development were observed. PfFNT inhibitors mainly targeted the trophozoite stage and exhibited high potency in P. berghei- and P. falciparum-infected mice. Their in vivo activity profiles were comparable to that of artesunate, demonstrating strong potential for the further development of PfFNT inhibitors as novel antimalarials