Cluster Randomised Non-inferiority Trial Comparing Malaria Incidence When Implementing R21/Matrix-M Synchronized With Seasonal Malaria Chemoprevention Distribution Versus R21/Matrix-M Given Routinely Through the EPI in Two Health Districts in Chad (CoSAV-R21)

This is a two-arm, cluster-randomised, phase IV trial conducted in Chad to assess the protective efficacy and impact in real-life conditions of a new strategy for administering the R21/MM malaria vaccine, synchronized within a seasonal malaria chemoprevention (SMC) campaign, among children living in areas of high seasonal malaria transmission.
In this study, a cluster is defined as the catchment area of a primary care health centre. In Chad, each catchment area is known as a 'zone of responsibility' (French: Zone de Responsibilité' [ZR]).
Twenty-six (26) of the total 27 ZRs in the districts of Moïssala and Dembo will be randomized in a 1:1 ratio to receive a 4-dose (3 primary doses + 1 booster) R21/MM schedule either (1) integrated into the routine EPI vaccination program (the "Routine" control arm), or (2) synchronized with an annual seasonal malaria chemoprevention (SMC) campaign (the "Synchronized" intervention arm).
Malaria incidence: R21/MM effectiveness will be assessed using the incidence of biologically confirmed clinical malaria (trial primary endpoint). The incidence of clinical malaria will be determined through enhanced surveillance of malaria cases in health centres and hospitals over a 17-month period (August 2025 - December 2026).
Coverage surveys: Cross-sectional surveys (cluster sampling) will be carried out to measure R21/MM vaccine coverage, SMC coverage, coverage of other malaria prevention measures, and coverage of other EPI vaccines.
Nested case-control study: A sub-sample of children admitted to Moïssala District Hospital with severe clinical malaria will be offered the opportunity to participate in a nested case-control study designed to estimate the individual protective efficacy of R21/MM against severe malaria.

开始日期2025-07-02

申办/合作机构

Epicentre Technologies Corp.

[+1]

NCT06860178

/ Recruiting临床4期

Integrating Malaria Vaccine With Seasonal Malaria Chemoprevention in West Africa

This is a multi-site, multi-disciplinary, Phase-4 two-arm cluster-randomised non-inferiority trial in Burkina Faso and Mali to evaluate the eﬀectiveness and real-life impact of a novel integrated delivery strategy of the R21 malaria vaccine alongside SMC among children in areas with highly seasonal malaria transmission. In this study, a cluster is defined as the catchment area of a health centre. Clusters will be randomised to receive either year-round age-based routine EPI vaccination for children aged 5-36 months ("Routine EPI Vaccination") in Burkina Faso or an annual campaign of the 3-dose primary series in children aged 5-36 months prior to the malaria season and SMC delivery (''Routine Pre-SMC vaccination'') in Mali versus an annual campaign of the 3-dose primary series aligned with SMC distribution in children aged 3-59 months ("Integrated SMC Vaccination") in each country. Eﬀectiveness will be assessed in terms of clinical malaria, vaccine coverage, acceptability, feasibility, and cost-eﬀectiveness.
Malaria incidence will be determined using routine surveillance activities for clinical malaria detection and reporting in each country. Cross-sectional surveys will be conducted to determine the prevalence of parasitaemia in the communities. In addition, the acceptability, feasibility, coverage and cost-effectiveness of the different delivery systems of R21/Matrix-M will be assessed.

开始日期2025-06-10

申办/合作机构

Epicentre Technologies Corp.

[+2]

PACTR202502765006598

/ Suspended临床4期

Integrating malaria vaccine with seasonal malaria chemoprevention in West Africa

开始日期2025-04-01

申办/合作机构

Epicentre Technologies Corp.

100 项与 Illumina, Inc. 相关的临床结果

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项与 Illumina, Inc. 相关的文献（医药）

2025-11-18·mSystems

DNA reference reagents isolate biases in microbiome profiling: a global multi-lab study

Article

ABSTRACT:

When profiling the human gut microbiome, technical biases introduced by analytical approaches impede translational research, reducing data reliability and study comparability. Here, through a global study involving 23 labs, we analyzed a wide range of sequencing and bioinformatic approaches for the taxonomic profiling of two well-defined DNA reference reagents (RRs) comprised of 20 common gut bacteria. Through both shotgun and 16S rRNA gene amplicon sequencing, we aimed to isolate sources of bias and understand their impact on microbiome profiling accuracy. Importantly, minimum quality criteria (MQC) were established and are used to evaluate profiling performance. We found that the variability of shotgun sequencing data sets was greater than that of 16S rRNA gene amplicon sequencing and isolated sources of bias in wet and dry lab steps, such as sequencing depth, primer and database choices, rarefaction, and 16S copy number adjustment. This study presents well-defined RRs and MQC to combat technical bias, paving the way for reliable and comparable microbiome research.

IMPORTANCE:

This benchmark paper highlights the true level of variability in microbiome data across the world and across sectors, underscoring the critical need for the use of WHO International DNA Gut Reference Reagents (RRs) to elevate the quality of data in microbiome research. This global study is the first of its kind, revealing the reality of the bias in the field, comprehensively testing methodologies used by leading laboratories across the world, but also providing avenues for workflow optimization, to accelerate innovation and translational research and move the field forward.

2025-10-01·JCO Precision Oncology

Phase II Study of Vismodegib in Patients With SMO- or PTCH1 -Mutated Tumors: Results From the National Cancer Institute Molecular Analysis for Therapy Choice Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Trial (EAY131) Subprotocol T

Article

作者: Ajumally, Raid ; Rubinstein, Larry V. ; O'Dwyer, Peter J. ; Song, Zihe ; Tsao, Anne S. ; Ivy, Percy ; Karlovich, Chris ; Arteaga, Carlos L. ; Chen, Li ; Silhavy, Jennifer ; Chen, Alice P. ; Wang, Victoria ; Flaherty, Keith T. ; Harris, Lyndsay N. ; McShane, Lisa M. ; Hamilton, Stanley R. ; Das, Biswajit ; Patton, David R. ; Conley, Barbara A. ; Takebe, Naoko ; Tricoli, James V. ; Mehnert, Janice M. ; Williams, P. Mickey ; Lococo, Jennifer S. ; Rahmanian, Sorena ; Ho, Alan L. ; Gray, Robert J.

PURPOSE:

The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) (EAY131, ClinicalTrials.gov identifier: NCT02465060 ) trial pairs patients with targeted therapies on the basis of tumor genomic alterations. Subprotocol T assessed vismodegib, a hedgehog pathway inhibitor, in patients with Patched-1 ( PTCH1 ) and Smoothened ( SMO ) alterations (excluding basal cell carcinoma).

METHODS:

Eligible patients received oral vismodegib (150 mg daily) until progression or toxicity. The primary end point was objective response rate, with secondary end points including 6-month progression-free survival (PFS), survival, and predictive biomarkers. Optional plasma for cell-free DNA analysis was collected at enrollment, on treatment, and at progression.

RESULTS:

From June 2016 to September 2020, 34 patients enrolled; 31 eligible patients (nine SMO , 22 PTCH1 ) received treatment, with 25 confirmed by the central NCI-MATCH assay (primary analysis cohort). Median age of the 31 eligible patients was 64 years, with 48.4% being women. Sixty-one percent received ≥3 previous therapies and 74% had multiple co-occurring mutations. Objective response rate was 8% (2/25 [90% CI, 1.4 to 23.1]) in the primary analysis cohort and 6.5% (2/31 [90% CI, 1.2 to 19]) overall. Partial responses occurred in soft tissue sarcoma ( PTCH1 ) and meningioma ( SMO ), with response durations of 19 and 9.23 months, respectively. Six-month PFS rates were similar (24%, 23.2%), with an identical median PFS of 1.8 months and median overall survival of 7.3 months for the analyzable and primary analysis patient cohorts. Four patients (12.9%) discontinued therapy because of adverse events. Common toxicities included grade 1-2 fatigue, anorexia, weight loss, alopecia, and dysgeusia. Four on-study deaths occurred, none treatment-related.

CONCLUSION:

Vismodegib was well tolerated with mainly grade 1-2 toxicities, but it did not meet the primary end point. Select patients with specific SMO and PTCH1 alterations had notable responses, warranting further comprehensive molecular analyses to elucidate resistance mechanisms.

2025-09-30·Science Signaling

Defining the MYC-regulated transcriptome and kinome that support KRAS- and ERK-dependent growth of pancreatic cancer

Article

作者: Mouery, Brandon L. ; Petricoin, Emanuel F. ; Tran, Nhan L. ; Rashid, Naim U. ; Hodge, Richard G. ; Pierobon, Mariaelena ; Diehl, J. Nathaniel ; Bryant, Kirsten L. ; Mouery, Ryan D. ; Klomp, Jennifer E. ; Barker, Natalie K. ; Klomp, Jeffrey A. ; Graves, Lee M. ; Der, Channing J. ; Pita, Lily M. ; Edwards, A. Cole ; Waters, Andrew M. ; Herring, Laura A. ; Stalnecker, Clint A. ; Snare, Kayla R. ; Drizyte-Miller, Kristina ; Peng, Sen ; Hibshman, Priya S. ; Cox, Adrienne D.

Of the thousands of genes and substrates identified in KRAS-mutant signaling networks in pancreatic ductal adenocarcinoma (PDAC), more than 200 are transcription factors, implying extensive and complex transcriptional regulation. However, we observed that genetic suppression of the transcription factor MYC alone was sufficient to phenocopy the effect of KRAS suppression in signaling, growth, and metabolic processes in PDAC cells. We determined the gene transcription changes caused by acute suppression of MYC function in KRAS -mutant PDAC cell lines and performed dependency map and pathway analyses on the affected gene sets. The expression of 1685 genes was increased upon suppression of MYC, and this gene set may comprise the bulk of the MYC-regulated genes essential for PDAC growth. In contrast, the 1325 genes whose expression was inhibited may comprise a compensatory response to oncogenic stress, mediated in part by the GTPase RHO. MYC-dependent transcriptional activity was largely ERK dependent, and almost one-third of ERK-regulated genes were also regulated by MYC in PDAC cells. Furthermore, chemical proteomic profiling revealed MYC-regulated protein kinases that can be targeted therapeutically. Together, these data provide a molecular portrait of MYC-dependent signaling that encompasses potentially exploitable mechanisms for treating PDAC.

1,416

项与 Illumina, Inc. 相关的新闻（医药）

2025-12-07

·循因缉药

1352美元！Pillar真固拿到美国医保报销定价决定

环球视野，深度视角各位亲爱的股东，大家早上好中午好晚上好！今天我们聊聊肿瘤NGS，呃...其实早就写完了，一直没机会发。 2025年12月1日，Pillar Biosciences拿到美国医疗保险与医疗补助服务中心（CMS）的最终决定，其伴随诊断产品 oncoReveal CDx支付价格定为1352.09美元，2026年1月1日后开始执行。该款产品包含22个基因，其中EGFR和KRAS基因对应多个肿瘤治疗靶向药物的伴随诊断。 oncoReveal CDx使用多重PCR建库测序法，基于Illumina MiSeq Dx平台，FDA于2021年7月30日批准其PMA申请。 2023年7月25日，Illumina发布公告，宣布与Pillar Biosciences结成合作伙伴，共同推动癌症个性化治疗。 2025年4月3日，oncoReveal CDx获得CMS医保报销认定。 2025年5月七日，Pillar宣布获得3450万美元的战略投资，主要来自Illumina。一切都是最好的安排... 关于Pillar的介绍，欢迎回看。 Anyway， 1352美元不考虑汇率的话似乎中美差不多吧。 Emmm，不考虑汇率。 END 各位股东看了么？赞了么？转发了么？别忘了点赞。谢谢！所有内容均不作为投资建议，信息均来自公开资料，星球更新更快。扫码加入星球！循因缉药Elite PS:风里雨里，老编等你~ 近期原创: 杜氏肌营养不良（DMD）的新希望！暴涨371%！松绑！开放！中美NGS监管迎来史诗级利好 Regeneron：“渣男！移情别恋？！” 你们今年还有年会吗？替大家试过了，付费“涨粉”不靠谱相关资料：注1：https://www.pillarbiosci.com/products/pan-cancer-solid-tumor/ 注2：https://www.pillarbiosci.com/2025/04/03/pillar-biosciences-receives-cms-coverage-for-fda-approved-oncoreveal-cdx-pan-cancer-solid-tumor-ivd-kit/ 注3：https://www.pillarbiosci.com/2025/12/01/pillar-biosciences-announces-final-cms-pricing-determination-for-oncoreveal-cdx/

申请上市引进/卖出

2025-12-06

·雪球

【97】Top 医药 VC Atlas 2025 年报学习笔记：从不确定的政策，到中国创新...

大家好！这里是汉靓的医药科技前沿第97期！本周，我把全球顶级医药VC——AtlasVenture发布的2025年年度回顾（YearinReview）认真看了一遍，PPT内容篇幅很大（约80页），视频网上也能找到。这份报告每年都是业内风向标，今年依然信息量巨大。这期我就按照自己感兴趣的角度，挑选出最值得分享的几个点，和大家一起解读这份“医药创新年度观察”。整体来看，这份年报覆盖面很广：从宏观政策的不确定性，到药价机制，到行业收入驱动方式，再到中国创新、AI、拥挤竞争、新模态、以及Atlas自身的投资框架，几乎涵盖整个生物医药创新生态。本期我重点挑选我认为最值得关注的内容，与大家分享。第一部分：宏观政策的不确定性令人不安，但行业在年底出现回暖1.1过去一年，政策的不确定性令人不安这份大约80页PPT的开篇，都在阐述过去整体宏观环境的不够友好，关于生物医药行业的政策，一句话总结就是，不可预测和令人不安。过去一年的各种政策呼声，从要求大药企降药价，到讨论消减NIHfunding，再到提高药品进口关税。与此同时，FDA的人员流失，加上领导层频繁更换，行业对监管方向缺乏稳定预期。过去一年，行业几乎一直在政策“混乱”中前行。虽然还有很多宏观层面的潜在担忧，但Atlas给出的建议是：“保持冷静，继续前行（KeepCalmandCarryOn）”。而也确实如此，随着部分担忧的缓和，生物医药板块出现明显回暖。1.2生物医药板块估值仍处于历史低位从图1可以看出，过去的一年，虽然上半年生物医药板块因为政策影响，板块明显下跌，但是随着下半年的情绪稳定，板块反弹，过去一年生物医药板块的整体回报已经跑赢大盘。图1：过去一年XBI（生物科技指数）、DRG（大型制药指数）和S&P500指数比较资料来源：Atlas此外，从更长期、积极的角度看，Atlas指出，当前医药和生物技术板块的估值水平，处于过去30年区间的底部位置。具体来看，PharmaIndustry的PE水平在2025Q2一度跌至13x的水平（图2左）。再看图2右侧，无论是Pharma还是Biotech板块，在30年的视角下对比标普500，都处于明显的估值低位。因此，展望未来，Atlas认为：在全球药企收入强劲、盈利稳定、未来估值有望继续修复的背景下，当前的低估值反而可能为生物医药板块奠定一个良好的起点。图2：生物医药板块的PE接近历史最低水平资料来源：Atlas第二部分：药价难再上涨，收入增长主要依靠新药+已有药的适应症拓展2.1未来五年，预计药价整体将进入负增长过去十年，美国品牌药一直在涨价，也成为了药企收入增长的重要因素。我自己查的资料（下图3）可以看出，2012-2015年的美国品牌药平均年涨价超过10%，近几年已经放缓很多，但仍然保持上涨趋势。图3：2012-2025年美国品牌药标价（WAC）加权平均涨幅趋势资料来源：46brooklynResearch展望未来，美国的品牌药价其实已经到了非常高的地步。Atlas认为未来情况将彻底改变，预计药价将出现负增长（如图4所示），因为受到竞争和医保/PBM的双重压力。所以药企除了需要推出新药，另外一个常见手法就是拓展已有产品的适应症。图4：预计未来5年药物价格呈现负增长趋势资料来源：Atlas2.2药企需要拓展现有产品的适应症关于现有产品的拓展适应症，Atlas举了3个非常有代表性的例子（如图5所示）：Vivgart（FCRN抑制剂）在重症肌无力获批后，又开始向大量其他自身抗体相关疾病扩展Vutrisiran（Alnylam）先是在淀粉样变获批，三年后扩展至心肌病，销售一路“起飞Tezspire也是从哮喘起步，正在向多种适应症拓展。图5：三款成功拓展适应症的药物资料来源：Atlas第三部分：中国创新力量的崛起我相信过去一年，所有国内的小伙伴都能感受到中国创新药板块的强势复苏。在年初的JPM大会上，“全球大药企都在找中国创新资产”已经成为热门话题，而这股热潮持续了一整年。在Atlas的这份年报中，也重点强调了这一点，他们首先放了一张图展示了中国创新药的繁荣（图6），香港biotech指数年初至8月，涨幅超过90%。并提出了这样的观点：中国在全球创新生态中的角色发生了重大变化。图6：2025年中国创新药市场火热资料来源：Atlas为什么呢？Atlas对中国Biotechboom的分析包括如下几个方面：大量在中国启动的临床研究，催生了大量的资产和迅速扩张的管线；创新资产催生了大量license合作，带来了资金的活跃；中国创新药人才的聚集（很多之前在海外大药企工作过）；中国的成本优势。当然这一切离不开国内监管层面的政策，让中国在“更便宜、更快”两个维度上构成了对海外药企的强有力的挑战。所以，面对挑战，Atlas也对海外的生物科技公司提出了“行动号召”：必须学会在更便宜、更快甚至更好的维度上竞争。第四部分：AI对药物研发的影响，Atlas给出冷静态度还有一点，我觉得非常值得讨论，就是AI对于整个生物医药行业的影响，尤其是药物研发。展望未来，似乎AI会颠覆每一个现有行业，那么AI对于制药界的影响会是如何呢？Atlas对AI的态度非常“冷静务实”。4.1一方面承认AI对药物研发的巨大潜力Atlas承认AI将重塑很多行业，包括生物医药，并且指出，2025年，美国GDP增长中，约有50%来自AI/机器学习相关投资的贡献，“药物发现”同样会被深刻改变，同时，Atlas列出了目前和正在出现的一系列应用场景（如图7）。我们先看图7左侧，展示了AI如何通过整合多模态生物医学数据，利用机器学习算法进行建模，从而嵌入并支持整个药物发现流程。图7右侧列出了当下已经落地的典型应用，包括蛋白折叠/配体–蛋白共折叠预测、ADME（吸收、分布、代谢、排泄）性质预测、新靶点识别、毒性评估、化学路线优化等。图7:AI有望重塑药物研发资料来源：Atlas4.2Atlas同时指出，AI药物研发真正的落地贡献是什么？挑战依然巨大Atlas认为，现在的AI药物研发领域，极易被炒作和过度宣传，我们仍然需要冷静评估：AI/机器学习在今天真正的“落地贡献”是什么？我们在这条“变革之路”上究竟走到了哪一步？同时Atlas举了一个非常有意思的例子：蛋白质协同折叠/配体结合预测。最近有论文研究指出，如果是基于“已知口袋”的AI预测，在熟悉靶点上成功率很高；但一旦进入真正新颖的结合口袋，预测能力立刻变得非常有限。因此，就今天而言AI/ML在这方面的作用有点像“只在路灯下找钥匙”：在已知靶点、已知化学空间里很有帮助，但在真正的“生成式新化学空间”上，挑战仍然巨大。当然这份年报，还包括了很多方面，提到了在这一两年，美国大药企的效率精简，股份回购，让股价更加吸引力，但未来面临重磅药专利到期的挑战，以及对新模态的热情与谨慎并存（从基因治疗到细胞治疗，风险和复杂度都远超小分子与抗体），以及未来5-7年，美国的医药制造业回流的趋势。视频和PPT在网上都能找到，我这里也只是选择了我部分认为最值得分享的部分，和大家一起交流。最后感谢大家的收看，这里是汉靓的医药科技前沿第97期！我们下期再见！往期节目（最近30期）：【67】再谈PARP抑制剂：GSK的尼拉帕尼如何向AZ的奥拉帕尼发起挑战？【68】阻击埃博拉：从默沙东和康希诺的疫苗到再生元的抗体药物【69】再谈JAK抑制剂：当辉瑞的托法替尼和Incyte/诺华的鲁索替尼已成重磅药物【70】读书笔记之《猎药师》：从植物时代到基因工程时代，新药探寻走过了怎样的旅程【71】Illumina的2019年报解读，兼谈测序龙头如何抗击COVID-19【72】从Guardant的2019年报&Q1财报，谈液体活检在肿瘤早筛、复发监测等领域的最新进展【73】读书笔记之《基因泰克》：40年前创立的伟大生物科技公司的传奇经历【74】一张图展示Illumina的2020Q1业绩&NGS如何抗击COVID-19【75】CD47系列报告之一：从49亿美金被Gilead收购的FortySeven说起【76】读书笔记之《坏血》：硅谷明星血检公司Theranos的崛起和陨落【77】燃石医学的招股书解读&个人思考（内含和Guardant的比较）【78】CD47系列报告之二：Trillium、ALX和宜明昂科的Fc融合蛋白【79】再谈CDK4/6:从嘉和生物的招股书说起【80】再谈BCL-2：从亚盛的BCL-2抑制剂和阿斯利康BTK的合作谈起【81】从Illumina、Guardant、燃石和泛生子的二季报谈NGS行业的最新动态【82】荣昌生物招股书解读之一：从泰它西普（Telitacicept）谈系统性红斑狼疮新药进展【83】荣昌生物招股书解读之二：从RC48谈Her2靶向抗体偶联药物（ADC）【84】从Thrive、Freenome、Exact等几家早肿瘤早筛公司，谈Illumina收购Grail的战略布局【85】Illumina和Guardant的2020Q3业绩跟踪：疫情下的NGS产业动态【86】燃石和泛生子的2020Q3业绩跟踪：肿瘤早筛项目均有所突破【87】从今年的ASH会议，谈BioMarin、UniQure等公司的血友病基因疗法最新进展【88】《解药》读书笔记：《十亿美元分子》续篇，药企Vertex的发展之路【89】读书笔记之《解码者：珍妮弗·杜德纳，基因编辑的历史与未来》【90】读书笔记之《ForBloodandMoney》：想了解美国Biotech，不能错过的一本2023年新书【91】读书笔记之《TheMessenger》：mRNA基础研究的40年沉淀，Moderna十年如一日的执着坚守【92】《BreakingThrough》读书笔记：新晋诺奖得主KatalinKariko亲笔自传，讲述她和mRNA的故事【93】Moderna的肿瘤个性化疫苗离甲骨文董事长LarryEllison的畅想还有多远？【94】BCMA/CD3双抗Lynozyfic获批上市，再生元能否实现“后发先至”?—再生元研究笔记（一）【95】200亿美金抗凝市场迎来新变量：再生元FactorXI项目解析—再生元研究笔记（二）【96】“合成生物学第一股”Ginkgo：站在最艰难的转型十字路口

2025-12-05

·循因缉药

另外两件事：奕检融资、翱路融资

环球视野，深度视角各位亲爱的股东，大家早上好中午好晚上好！行业是真的好起来了... 第一件事是精准肿瘤检测领域的。奕检健康： 2025年12月5日，奕检健康宣布完成数千万元A+轮融资。本轮融资由财通资本领投，将主要用于AI技术研发和试剂开发及商业化推广。事实上，这已经是奕检今年第二次融资了。 2025年6月，奕检宣布完成了4000万元A轮融资，由零度资本和均为资本领投，久华恒创跟投。看来，咱们上次说的，把老板吊起来打一顿融资就能进来是靠谱的（误）。第二件事，也是关于融资的，但不全是。翱路医药： 2025年12月5日，翱路生物宣布已于今年5月完成1亿美元A轮融资，由淡马锡旗下淡明资本、礼来亚洲基金、辉瑞风险投资及Sirona Capital共同出资完成。之所以关注翱路，一个重要原因是我们的老朋友、原燃石联合创始人揣少坤博士也是翱路的联创。她与另一位联创、CEO陈椎博士还是原来诺华的同事，据悉揣博士目前担任翱路的首席运营官（COO）。我们也将继续关注... END 各位股东看了么？赞了么？转发了么？别忘了点赞。谢谢！所有内容均不作为投资建议，信息均来自公开资料，星球更新更快。扫码加入星球！循因缉药Elite PS:风里雨里，老编等你~ 近期原创: 松绑！开放！中美NGS监管迎来史诗级利好 Regeneron：“渣男！移情别恋？！” 替大家试过了，付费“涨粉”不靠谱不是，哥们，你原来不是跟Illumina合作的吗？

100 项与 Illumina, Inc. 相关的药物交易

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100 项与 Illumina, Inc. 相关的转化医学

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