Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Impact of new technologies on diabetes care

Technologies for diabetes management, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems, have improved remarkably over the last decades. These developments are impacting the capacity to achieve recommended hemoglobin A1c levels and assisting in preventing the development and progression of micro- and macro vascular complications. While improvements in metabolic control and decreases in risk of severe and moderate hypoglycemia have been described with use of these technologies, large epidemiological international studies show that many patients are still unable to meet their glycemic goals, even when these technologies are used. This editorial will review the impact of technology on glycemic control, hypoglycemia and quality of life in children and youth with type 1 diabetes. Technologies reviewed include CSII, CGM systems and sensor-augmented insulin pumps. In addition, the usefulness of advanced functions such as bolus profiles, bolus calculators and threshold-suspend features will be also discussed. Moreover, the current editorial will explore the challenges of using these technologies. Indeed, despite the evidence currently available of the potential benefits of using advanced technologies in diabetes management, many patients still report barriers to using them. Finally this article will highlight the importance of future studies tailored toward overcome these barriers to optimizing glycemic control and avoiding severe hypoglycemia.     

Crowns cemented on crown preparations lacking geometric resistance form. Part II: effect of cement.

PURPOSE: This study evaluated the effect of different cements on resistance to dislodgment of crowns cemented on preparations lacking geometric resistance form. MATERIALS AND METHODS: A preparation that offered no geometric resistance form, with 20 degrees total occlusal convergence (TOC), 0.9 mm wide shoulder finish line, and a 2.5 mm axial wall height was created on an ivorine tooth using a milling machine. Ten metal test specimen die replicas and 10 standardized metal crowns with recipient sites for the application of external forces through a universal testing machine were fabricated. The crowns were cemented on the dies under 5 and 10 kg external loads, the marginal openings measured, loaded to dislodgment, and cleaned of cement. The process was repeated using zinc oxide and eugenol (ZOE), zinc phosphate (ZPh), resin modified glass ionomer (RMGI), and composite resin (CR) cements. RESULTS: Marginal openings under 5 kg cementation loads were 74.63 (+/-15.04) for ZOE, 75.98 (+/-18.20) microm for ZPh, 98.58 (+/-22.62) microm for RMGI, and 105.82 (+/-20.07) microm for CR cements respectively; under 10 kg cementation loads they were 57.62 (+/-15.86) microm, 59.55 (+/-15.41) microm, 95.00 (+/-19.52) microm, 101.30 (+/-12.52) microm respectively. Oblique dislodgment forces, measured with a Universal testing machine, were 40.18 (+/- 6.76) N for ZOE, 215.65 (+/-45.79) N for ZPh, 165.43 (+/-19.53) N for RMGI, and 181.54 (+/-30.75) N for CR respectively when crowns were cemented under 5 kg loads. The corresponding values for 10 kg loads were 38.62 (+/-4.19), 274.86 (+/-54.22), 139.70 (+/-21.71), and 160.40 (+/-21.21) respectively. Only zinc phosphate cement produced statistically enhanced resistance when crowns were cemented under 10 kg force (p value = 0.035). CONCLUSIONS: Under the conditions of the present study only crowns cemented with zinc phosphate displayed increased resistance to dislodgment on preparations lacking resistance form.     

高原地区部队医院谋求新发展应处理好七个关系

从高原部队医院实际出发,阐述了适应新形势谋求新发展应处理好的七个关系:即继承与创新的关系;坚持“姓军为兵的服务方向与对外有偿服务的关系;基础建设与人才建设的关系;日常医疗保障与科研的关系;发挥自身特色与学习借鉴的关系;硬件建设与软件建设的关系;科技研究与成果转化的关系。     

Convergence of occipital nerve and superior sagittal sinus input in the cervical spinal cord of the cat

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

有助改善人体健康的纳米生物科技

纳米技术是20世纪80年代末期兴起的新技术。此种新技术是指在1-100nm这一尺度范围内对原子和分子运动规律和特性进行研究和应用。通过直接操纵和安排原子、分子将物质转变成具有特殊性能的新材料的科学技术。纳米技术研究的最终目标是直接以原子和分子为起点，从纳米材料出发或采用纳米加工技术，制造出具有特殊功能的产品，从而改变人类的生产和生活模式。纳米科技保健产品对促进人类健康有积极作用。     

The dual effect of L-proline on spreading depression in the chicken retina

Evidence was presented for a glutamate agonistic effect of L-proline which promotes K+-based spreading depressions (SD) in chick retinas at relatively high concentrations (5 mM), in addition to an antagonistic effect which inhibits glutamate-based SDs at lower (2 mM) concentrations. Together these effects explain the observed biphasic effect of L-proline on the incidence of SD in the retina.     

Fusion of vestibular and podokinesthetic information during self-turning towards instructed targets

When observers step about their vertical axis ("active turning") without vision they dispose of essentially two sources of information that can tell them by how much they have turned: the vestibular cue which reflects head rotation in space and the "podokinesthetic" cue, a compound of leg proprioceptive afferents and efference copy signals which reflects the observer's motion relative to his support. We ask how these two cues are fused in the process leading to the perception of self-displacement during active turning. To this end we compared the performance of observers in three angular navigation tasks which differed with regard to the number and type of available motion cues: (1) Passive rotation, vestibular cue ( ves) only; observers are standing on a platform which is being rotated. (2) Treadmill stepping, podokinesthetic cue ( pod) only; observers step counter to the rotating platform so as to remain stable in space. (3) Active turning, ves and pod available; observers step around on the stationary platform. In all three tasks, angular velocity varied from trial to trial (15, 30, 60 degrees /s) but was constant during trials. Perception was probed by having the observers signal when they thought to have reached a previously instructed angular displacement, either in space or relative to the platform ("target"; range 60-1080 degrees ). Performance was quantified in terms of the targeting gain (displacement reached by the observer divided by target angle) and of the random error ( E(r)), which records an observer's deviation during single trials from his average performance. Confirming previous observations, E(r) was found to be significantly smaller during active turning than during passive turning, and we now complement these observations by showing that it is also significantly smaller than during treadmill stepping. This behaviour of E(r) is compatible with the idea that ves and pod be averaged during active turning. On the other hand, the observed characteristics of the targeting gain ( G(T)) support this idea only for the case of fast rotations (60 degrees /s); at lower velocities, the gain found during active turning was clearly not the average of the G(T) values recorded in the passive and the treadmill modes. We therefore also discuss alternative scenarios as to how ves and pod could interact, among these one based on the concept of a vestibular eigenmodel. A common denominator of these scenarios is that ves assumes the role of a prerequisite for an optimal use of pod during turning on a stationary support, without itself entering the calculation of displacement perception; this perception would be based exclusively on pod. Finally, it was a consistent observation that during passive rotations cognitive mechanisms fill in for the decaying vestibular signal in the context of the present navigation task, enabling observers to achieve large displacements surprisingly well although the duration of these movements exceeds by far the conventionally cited value of the central vestibular time constant (=20 s).     

Computational simulations of mitral regurgitation quantification using the flow convergence method: Comparison of hemispheric and hemielliptic formulae

Mitral regurgitation results from the incomplete closure of the mitral valve, and the noninvasive diagnosis of this disease remains an important clinical goal. In this study, steady flow computer simulations were used to evaluate flow convergence method for flow rate estimation. The hemispheric and hemielliptic formulae were compared for accuracy in the presence of complicating factors such, as ventricular confinement, orifice shape, and aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the hemispheric formula approximated the true flow rate, independent of orifice shape. However, in the presence of complicating factors such as aortic outflow and ventricular confinement, there was no clear zone where the hemispheric formula could be applied. The hemielliptic formula, however, worked in, all cases, regardless of chamber size or magnitude of aortic outflow. Therefore, application of the hemielliptic formula shold be considered in future clinical studies.