Harnessing the power of genomics and immunoinformatics to produce improved vaccines

The role of cellular immunity as a mediator of protection against disease is gaining recognition, particularly with regard to the many pathogens for which we presently lack effective vaccines. As a result, there is an ever-increasing need to understand the T-cell populations induced by vaccination and, therefore, T-cell epitopes responsible for triggering their activation. Although the characterization and harnessing of cellular immunity for vaccine development is an active area of research interest, the field still needs to rigorously define T-cell epitope specificities, above all, on a genomic level. New immunoinformatic epitope mapping tools now make it possible to identify pathogen epitopes and perform comparisons against human and microbial genomic data sets. Such information will help to determine whether adaptive immune responses elicited by a vaccine are both pathogen-specific and protective, but not crossreactive against host or host-associated sequences that could jeopardize self-tolerance and/or human microbiome-host homeostasis. Here, we discuss advances in genomics and vaccine design and their relevance to the development of safer, more effective vaccines.     

Saving newborn lives in Asia and Africa: cost and impact of phased scale-up of interventions within the continuum of care

BACKGROUND: Policy makers and programme managers require more detailed information on the cost and impact of packages of evidenced-based interventions to save newborn lives, particularly in South Asia and sub-Saharan Africa, where most of the world's 4 million newborn deaths occur. METHODS: We estimated the newborn deaths that could be averted by scaling up 16 interventions in 60 countries. We bundled the interventions in a variety of existing maternal and child health packages according to time period of delivery and service delivery mode, and calculated the additional running costs of implementing these interventions at scale (90% coverage) in sub-Saharan Africa and South Asia. The phased introduction and expansion of interventions was modelled to represent incremental strategies for scaling up neonatal care in developing country health systems. RESULTS: Increasing coverage of 16 interventions to 90% could save 0.59-1.08 million lives in South Asia annually at an additional cost of US dollars 0.90-1.76 billion. In sub-Saharan Africa, 0.45-0.80 million lives saved would cost US dollars 0.68-1.32 billion. Additional costs for increased antenatal interventions are low, but given relatively high baseline coverage and lower impact, fewer additional newborn lives can be saved through this package (5-10%). Intrapartum care has higher impact (19-34% of deaths averted) but is costly (US dollars 1.66-3.25 billion). Postnatal family-community care, with potential for high impact at low cost (10-27%, US dollars 0.38-0.75 billion), has been neglected. A first phase of scaling up care in 36 high (NMR 30-45) and 15 very high (NMR >45) mortality countries would cost approximately US dollars 0.56-1.10 and US dolars 0.09-0.17 billion annually, respectively, and would avert 15-32% and 13-29% of neonatal deaths, respectively, in these countries. Full coverage with all interventions in the 51 high and very high mortality countries would cost US dollars 2.23-4.37 billion, and avert 38-68% of neonatal deaths (1.13-2.05 million), at an extra cost per death averted of US dollars 1100-3900. CONCLUSIONS: Low-cost, effective newborn health interventions can save millions of lives, primarily in South Asia and sub-Saharan Africa. Modelling costs and impact of intervention packages scaled up incrementally as health systems capacity increases can assist programme planning and help policy makers and donors identify stepwise targets for investments in newborn health.     

Community attitudes towards a Jewish community <Emphasis Type="Italic">BRCA1/2</Emphasis> testing program

About 2.5 % of the Ashkenazi-Jewish population carry one of three “founder” mutations in BRCA1 and BRCA2 (BRCA1/2). Currently, testing is offered to Jewish people with a personal and/or family history of breast and/or ovarian cancer; however less than half of BRCA1/2 carriers within the Jewish population are aware of their family history. Population-based testing in other countries has shown to greatly increase the number of mutation carriers identified, compared to targeted testing of people with a family history. We aimed to assess the Australian Jewish community’s attitudes towards such a program, including acceptability and interest in having education and testing offered online. Members of Sydney-based Jewish organisations who self-identified as being Jewish were invited by e-mail to participate in an online survey. Of 370 individuals who completed the survey, 96.8 % supported a Jewish community-based BRCA1/2 testing program, and 65.6 % reported being personally interested in undergoing the test. Younger adults aged below 50 years were more interested in undergoing the test than those aged 50 years and above. Almost half (42.9 %) were aware of a family member with breast and/or ovarian cancer; however, of these, 77.1 % had not yet undergone testing. Sixty-five (65.1 %) percent were satisfied with providing consent online, while only 39.6 % of participants’ first preference for method of information provision was online. Given the high level of support, and interest in a community testing program, the development and evaluation of a cost-effective and interactive, online BRCA1/2 community testing program appears warranted.     

Giant aneurysm treated by bilateral cervical carotid artery to proximal middle cerebral artery bypass and balloon embolisation: a case report

The authors describe a case of a 59 year-old Chinese lady with a history of spontaneous left caroticocavernous fistula in 1988 treated by left internal carotid artery clipping and muscle embolisation. She subsequently presented with a subarachnoid haemorrhage in November 1997 secondary to rupture of an unclippable giant right internal carotid artery aneurysm. This was treated satisfactorily with bilateral cervical carotid artery to proximal middle cerebral artery bypass followed by balloon occlusion. Postoperatively, the patient has no neurological deficit and CT angiogram shows good patency of both grafts 6 months after surgery.     

正常人口服磷酸川芎嗪的药代动力学研究

本文建立了用高效液相色谱法测定人体内川芎嗪血药浓度的方法,以C18化学键合硅胶(10μgm)为固定相,以甲醇—水(58:42)为流动相,280 nm俭测,安眠酮为内标,进行定量测定,得出俭测限为3.5 ng(S/N=4),最低检测血清浓度为17.4 ng/ml,川芎嗪血药浓度在0.029～5.82μg/ml范围内,线性关系良好,方法回收率为99.84%。方法重现性好,专一性强,内源性物质、代谢产物及同时服用的药物均不干扰。用本法测定了健康人口服川芎嗪的药代动力学参数。     

β-阻滞剂塞利洛尔的合成

报道了β－阻滞剂塞利洛尔的简便制备方法，即以对乙氧基苯胺为原料，经酰胺化，傅克反应，以环氧氯丙烷取代，最后用叔丁胺直接与环氧基反应开环等４步反应制得。比文献五步反应缩短了一步，产物经元素分析、红外光谱、核磁共振谱、质谱等分析确定结构。