智慧医疗——从物联网到云计算

新型信息化技术是解决中国医疗服务需求的关键手段.智慧医疗是医疗信息化的重要研究方向,它融合了物联网、云计算与大数据处理技术,以"感、知、行"为核心,旨在建立一个智能的远程疾病预防与护理平台."感"即以物联网技术为基础,利用多种传感器实时跟踪各种生命体征数据并通过无线网络技术传送到医疗数据中心,然而如何能够长期、精确、便捷、及时、无创地采集各种人体关键生命体征数据是一个巨大挑战;"知"即利用大数据存储与处理平台,应用数据挖掘和知识发现理论对医疗历史数据进行建模与分析,如何从大数据信息中挖掘关键生理特征,可靠、快速、高效地发现早期疾病和预测健康风险,也是一个巨大挑战;"行"即将实时跟踪与历史数据的分析结果,通过云服务的方式提供给医务人员作为诊疗参考,或为终端用户直接提供医疗护理方案,如何建立有效的数据模型以实现大规模复杂健康查询的快速和准确响应,同样也是一个巨大挑战.本文将讨论"感"、"知"、"行"所面临的技术挑战,并探讨解决这些挑战的可行方案.     

XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome

The homeostasis of the immune response requires tight regulation of the proliferation and apoptosis of activated lymphocytes. In humans, defects in immune homeostasis result in lymphoproliferation disorders including autoimmunity, haemophagocytic lymphohystiocytosis and lymphomas. The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency that is characterized by lymphohystiocytosis, hypogammaglobulinaemia and lymphomas, and that usually develops in response to infection with Epstein-Barr virus (EBV). Mutations in the signalling lymphocyte activation molecule (SLAM)-associated protein SAP, a signalling adaptor molecule, underlie 60% of cases of familial XLP. Here, we identify mutations in the gene that encodes the X-linked inhibitor-of-apoptosis XIAP (also termed BIRC4) in patients with XLP from three families without mutations in SAP. These mutations lead to defective expression of XIAP. We show that apoptosis of lymphocytes from XIAP-deficient patients is enhanced in response to various stimuli including the T-cell antigen receptor (TCR)-CD3 complex, the death receptor CD95 (also termed Fas or Apo-1) and the TNF-associated apoptosis-inducing ligand receptor (TRAIL-R). We also found that XIAP-deficient patients, like SAP-deficient patients, have low numbers of natural killer T-lymphocytes (NKT cells), indicating that XIAP is required for the survival and/or differentiation of NKT cells. The observation that XIAP-deficiency and SAP-deficiency are both associated with a defect in NKT cells strengthens the hypothesis that NKT cells have a key role in the immune response to EBV. Furthermore, by identifying an XLP immunodeficiency that is caused by mutations in XIAP, we show that XIAP is a potent regulator of lymphocyte homeostasis in vivo.     

Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability

Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.     

Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2

We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.     

Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.     

Synchronized path following control of multiple homogenous underactuated AUVs

This paper addresses the problem of synchronized path following of multiple homogenous underactuated autonomous underwater vehicles(AUVs).The dedicated control laws are categorized into two envelopes:One is steering individual underwater vehicle to track along predefined path,and the other is ensuring tracked paths of multiple vehicles to be synchronized,by means of decentralized speed adaption under the constraints of multi-vehicle communication topology.With these two tasks formulation,geometric path following is built on Lyapunov theory and backstepping techniques,while injecting helmsman behavior into classic individual path following control.Synchronization of path parameters are reached by using a mixture of tools from linear algebra,graph theory and nonlinear control theory.A simple but effective control design on direct inter-vehicle speed adaption with min- imized communication variables,enables the multi-AUV systems to be synchronized and stabilized into an invariant manifold,and all speeds converge to desired assignments as a byproduct.Simulation results illustrate the performance of the synchronized path following control laws proposed.     

Effect of natural iron fertilization on carbon sequestration in the Southern Ocean

The availability of iron limits primary productivity and the associated uptake of carbon over large areas of the ocean. Iron thus plays an important role in the carbon cycle, and changes in its supply to the surface ocean may have had a significant effect on atmospheric carbon dioxide concentrations over glacial-interglacial cycles. To date, the role of iron in carbon cycling has largely been assessed using short-term iron-addition experiments. It is difficult, however, to reliably assess the magnitude of carbon export to the ocean interior using such methods, and the short observational periods preclude extrapolation of the results to longer timescales. Here we report observations of a phytoplankton bloom induced by natural iron fertilization--an approach that offers the opportunity to overcome some of the limitations of short-term experiments. We found that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean was sustained by the supply of iron and major nutrients to surface waters from iron-rich deep water below. The efficiency of fertilization, defined as the ratio of the carbon export to the amount of iron supplied, was at least ten times higher than previous estimates from short-term blooms induced by iron-addition experiments. This result sheds new light on the effect of long-term fertilization by iron and macronutrients on carbon sequestration, suggesting that changes in iron supply from below--as invoked in some palaeoclimatic and future climate change scenarios--may have a more significant effect on atmospheric carbon dioxide concentrations than previously thought.