Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.     

Respiratory care protocols in postanesthesia care

IS1311 is an insertion sequence from Mycobacterium avium and M. avium subsp. paratuberculosis. Using a 180 bp fragment of IS 1311 as a probe, 7-10 copies of IS1311 were revealed in strains of M. avium subsp. paratuberculosis. With a given restriction enzyme, the restriction fragment length polymorphism patterns obtained from isolates of M. avium subsp. paratuberculosis from cattle were all identical, but they differed from those of isolates from sheep, which could be separated into two types. A 1259 bp fragment of IS1311 produced by polymerase chain reaction (PCR) from two isolates of M. avium subsp.paratuberculosis from cattle and two isolates from sheep was sequenced and compared to the sequence known from M. avium. Apart from five point differences the sequences were identical. Restriction endonuclease analysis (REA) of the PCR product was used to distinguish isolates of M. avium subsp. paratuberculosis from M. avium, in addition to the conventional test for IS900. In isolates of M. avium subsp. paratuberculosis from cattle the IS1311 gene was polymorphic at position 223, which enabled isolates from sheep and cattle to be distinguished by PCR-REA. These simple tests will be used to enhance disease control programmes for Johne's disease in ruminants. The findings of this study raise interesting questions about the evolution of M. avium subsp. paratuberculosis.     

The aetiology of Raynaud''s phenomenon

Among the most abundant components of myelin are the galactolipids galactocerebroside (GalC) and sulfatide. In spite of this abundance, the roles that these molecules play in the myelin sheath are not well understood. Until recently, our concept of GalC and sulfatide functions had been principally defined by immunological and chemical perturbation studies that implicate these lipids in oligodendrocyte differentiation, myelin formation, and myelin stability. Recently, however, genetic studies have allowed us to re-analyze the functions of these lipids. Two laboratories have independently generated mice that are incapable of synthesizing either GalC or sulfatide by inactivating the gene encoding the enzyme UDP-galactose:ceramide galactosyltransferase (CGT), which is required for myelin galactolipid synthesis. These galactolipid-deficient animals exhibit a severe tremor, hindlimb paralysis, and display electrophysiological deficits in both the central and peripheral nervous systems. In addition, ultrastructural studies have revealed hypomyelinated white matter tracts with unstable myelin sheaths and a variety of myelin abnormalities including altered node length, reversed lateral loops, and compromised axo-oligodendrocytic junctions. Collectively, these observations indicate that cell-cell interactions, which are essential in the formation and maintenance of a properly functioning myelin sheath, are compromised in these galactolipid-deficient mice.     

Entwicklung eines Ionisationsmanometers mit Feldemitterkathode

Development of an ion gauge with field emissionin cryogenic vacuum environments cathode for pressure measurements The measurement of UHV or even XHV pressures in low‐temperature vacuum systems has always been considered as a metrological problem. In principle, conventional hot‐cathode ion gauges can be used for pressure measurement in cryogenic vacuum environments. However, as a consequence of their high heat generation several disadvantages must be taken into account. With the development of an ion gauge of extractor‐type whose heat‐generating thermionic cathode is replaced by a non‐thermal field emission cathode, a promising approach to realize a reliable pressure gauge for cryogenic vacuum applications can be presented in this paper. The gauge equipped with a CNT cathode was investigated both experimentally and by numerical simulations in terms of their operating characteristics. It has been successfully demonstrated that the modified extractor gauge works reliably under low temperature conditions and provides meaningful pressure readings.     

An On-Heating Dilation Conversional Model for Austenite Formation in Hypoeutectoid Steels

Dilatometry is often used to study solid-state phase transformations. While most steel transformation studies focus on the decomposition of austenite, this article presents an on-heating dilation conversional model to determine phase fraction based on measured volume changes during the formation of austenite in ferrite-pearlite hypoeutectoid steels. The effect of alloying elements on the transformation strain is incorporated into the model. Comparison of the conversional model predictions to measured transformation temperature (A _c3) shows excellent agreement. The pearlite decomposition finish temperature (A _pf ) predicted by the conversional model more closely matches experimental results when compared to standard lever rule calculations. Results show that including the effects of substitutional alloying elements (in addition to carbon) improves phase fraction predictions. The conversional model can be used to quantitatively predict intercritical austenite fraction with application to modeling, induction heating, intercritical annealing, and more complex heat treatments for hypoeutectoid steels.     

Lack of effectiveness of bed rest for sciatica

BACKGROUND AND METHODS: Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments. RESULTS: After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups. CONCLUSIONS: Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting.     

Milk Fat-Globule Membrane as Possible Origin of Proteose-Peptone Glycoproteins,

Affinity chromatography on a Concanavalin A-Sepharose support was used to isolate glycoprotein fractions from proteose-peptone and the soluble protein of the milk fat-globule membrane. The proteose-peptone glycoprotein was shown by compositional and electrophoretic analyses to consist principally of component 3. Immuno-double diffusion experiments indicated at least one antigenetically similar component in the proteosepeptone glycoprotein and the soluble protein of milk fat globule membrane glycoprotein fraction-1. Electrophoretic comparison (sodium dodecyl sulfate – polyacrylamide gel electrophoresis) of these two glycoprotein fractions revealed four protein zones common to both fractions with apparent molecular weights of 18,000 to 21,000, 24,800, 28,200, and 32,200. Immunological techniques identified the 18,000 to 21,000 molecular weight component as the antigenically common species. The fat globule membrane as a possible source of proteose-peptone component 3 is considered.     

Foot strike and the properties of the human heel pad

Many force-plate records of human locomotion show an impulse (the foot strike) shortly after ground contact. The authors' hypothesis is that this results from the rapid deceleration of a mass (the 'effective foot') under forces which compress the heel pad. The quantitative implications are investigated through an illustrative calculation. The observations used are (a) the peak force reached in foot strike (b) the vertical velocity of the foot immediately before ground contact and (c) the properties of the heel pad in compression. Data for (a) and (b) are available in the literature; measurements for (c) are presented here. The deductions are: (a) the time taken to reach peak force is about 5.4 ms, which agrees with published measurements; (b) the mass of the effective foot is about 3.6 kg. The effective foot thus includes a substantial portion of the leg: this seems reasonable. The models used for the calculations clarify the relationship between the foot strike and the shock wave, which it generates.     

Acute vibration--its effect on digital blood flow by central and local mechanisms.

In order to establish underlying mechanisms responsible for the vasospastic disorder vibration white finger (VWF), the acute effect of vibration on digital blood flow was assessed. Thirteen patients with primary Raynaud's phenomenon (RP), 15 patients with WVF and 13 controls were exposed to acute vibration in the middle digit of one hand for 1 and 3 minutes. Blood flow was measured in that digit and in the middle finger of the contralateral hand using strain gauge plethysmography before and after vibration. The measurements were then repeated following digital nerve blockade using 2% Lignocaine in the vibrated digit. The results demonstrate that vibration affects digital blood flow through two independent mechanisms. Vibration appears to cause both an axonal vasoconstrictor reflex and an active local vasodilation phenomenon. In patients with established vasospastic disorders this vasoconstrictor reflex is exaggerated.