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Finally, the benefit of maintenance therapy, especially in the low-risk category, is still a matter of debate. French investigators initially reported superior overall survival (OS) for patients receiving maintenance therapy with low-dose chemotherapy, ATRA or combined ATRA and chemotherapy [ 38 ]. This survival benefit was confirmed by a large US North Intergroup randomized trial for patients receiving ATRA maintenance after obtaining CR with ATRA plus chemotherapy regimens [ 45 ]. On the contrary, a GIMEMA study randomizing patients in molecular CR (mCR) to maintenance therapy with ATRA alone, ATRA plus low-dose chemotherapy or no maintenance, reported no significant differences in outcomes among the four groups [ 46 ]. Similarly, Japanese investigators by the JALSG reported no improvement in disease-free survival (DFS) for patients in mCR receiving intensified maintenance chemotherapy after induction and three intensive consolidation courses [ 47 ]. Despite the high cure rates, the toxicity profile of ATRA plus chemotherapy regimens includes severe hematologic toxicity with deaths in remission together with occurrence of secondary myeloid neoplasms in 2%–3% of cases [ 48 ].

In 2004, Chinese investigators from Shanghai reported a randomized trial with 61 newly diagnosed APL patients treated with ATO or ATRA or the combination of the two drugs for induction therapy [ 49 ]. CR rates were similar in the three arms ranging from 90% to 95.2%, but the median time to achieve CR was shorter in the combination arm (25.5 days) compared with the single-agent arm (40.5 days in the ATRA group and 31 days in the ATO group). After induction, all patients received chemotherapy. None of the patients treated with the ATRA–ATO combination relapsed, whereas 26% and 11% patients relapsed in the ATRA and ATO groups, respectively, with a median DFS of 13, 16 and 20 months for ATRA, ATO and combination groups, respectively. In a long-term update of the study, the estimated 5-year event-free survival (EFS) and OS rates for patients treated with ATRA–ATO were 89.2% and 91.7%, respectively [ 49 ]. The role of ATO as a consolidation therapy added to conventional ATRA plus chemotherapy was investigated in a randomized trial conducted by United States and Canadian investigators [ 50 ]. In this study, 481 newly diagnosed patients were randomly assigned to receive induction with ATRA, cytarabine and daunorubicin followed by two consolidation courses with ATRA and daunorubicin or to the same induction and consolidation and two 25-day cycles of ATO administered after induction therapy. Patients receiving ATO showed significantly better 3-year EFS compared with those receiving ATRA plus chemotherapy (80% versus 63%) as well as superior 3-year OS (86% versus 81%) and 3-year DFS (90% versus 70%) [ 50 ]. More recently, the Australasian group reported the results of the APML4 trial, combining anthracycline chemotherapy, ATO and ATRA for remission induction therapy, followed by two consolidation cycles with ATO–ATRA without further chemotherapy [ 51 ]. Compared with a previous study from the same group (APML3), this regimen resulted in improved survival outcomes, with 2-year freedom from relapse (FFR), failure-free survival and OS of 97.5%, 88% and 93%, respectively. A recent update of this study with a follow-up of 4.2 years showed 5-year FFR of 95% (95% CI 89–98), DFS of 95% as well as EFS of 90% and OS of 94% [ 51 ].

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CTO @TillerSystems - CQRS/Event Sourcing lover - AWS enthousiast

Use case — TillerPOS

Tiller is a smart POS on iPad with a powerful cloud-based back-office to analyze sales. As a cash register application, we must save everything that appends on the application. Event sourcing/CQRS fit perfectly our need as I said in this article: Laelia embroideredlace top Zimmermann Best Cheap Online HdPNSwj
(in French).

Our clients are mainly restaurants. They often use many POS (up to one per waiter) to be more efficient in taking order. Unfortunately, iPads are occasionally disconnected devices (or occasionally connected devices), and we need to work offline. In this article, I will explain to you all the issues that we encountered and how we fixed them to build an efficient and reliable synchronization mechanism.

Sending commands and getting readmodels

As any CQRS systems, we tried to send command from the iPads to the servers. Server applies the domain rules, generates event and projects read models. Then the iPads get the read models and display them locally.

This systems face a serious problem: it need a stable internet connection: the POS needs a response from the server to get and display the read models. As iPads are not always connected, we needed to find a solution.

Sending commands and gettingevents

To solve this problems, we decided to duplicate the CQRS domain part into our mobile application. The goal was to let the iPad generate their own read models before getting any answer from the server. To be able to apply the domain locally in every devices, we need these devices to get every generated events. So we created an API to get event list.

At this stage, iPads still send commands to the server. But it now gets the synchronized event list back. We arbitrary choose that the server was master in case of conflict. Once synchronized, the iPads erase their local event and project read models by replaying server events.

This architecture has a very good side effect: it allow the POS and the analytics platform to have different read models. But it suffers of some offline concurrency problems when two devices are editing in the same time the same resource. The server can reject some commands that were accepted by the local domain. How to be sure to have the right data when the local event store and the main event store can be different?

Sending events

That's why we made a very small change to this architecture. Commands are intended so they can be rejected. We assume that if this event has been accepted by the local domain it is now considered as happened. So we update our synchronisation mechanism by sending events instead of commands. That insures that the main database stores every single generated event. With a good conflict resolution layer (see http://danielwhittaker.me/2014/09/29/handling-concurrency-issues-cqrs-event-sourced-system/) this solution is now quite reliable.

The last problem we face was about scalability. How to be sure to handle up to 5.000 events per seconds during rush hour without loosing any data. Conflict resolution are very heavy and not so efficient. We needed to find a solution that allowed us to scale up.

Sending Accounting ReadModels

I think this was one of the hardest decision I made as a CTO. But we decided to accept our system can’t always be consistent . How is it possible to have an inconsistent POS system?

First, I need to explain you a little bit more about our business. An order has a a lifecycle:

As I said, we assume that we can have inconsistent orders during their hot period. I mean, we can have different state of the same order during the hot period. But when a waiter closes an order, we need to freeze its state and save it. We added a service to synchronize the final order state read model and save it in the cold order database.

With this final steps, we split the operational part where the event sourcing is the best solution so far and the accountant/analytics part where the data is immutable.

Conclusion

You now understand the path we took to build a reliable architecture to synchronize our POS and save every transaction from a naive CQRS approach to a very powerful implementation.

There are a lot of small adjustment I voluntary hide from this article.

If you have any questions, I will be happy to answer them.

More where this camefrom

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100 Julia Cage, “Even in France, Money Rules Politics,” Institute for New Economic Thinking, February 15, 2018, https://www.ineteconomics.org/perspectives/blog/even-in-france-money-rules-politics .

101 Ben Knight, “Anger at German AfD’s Hidden Campaign Donors,” Deutsche Welle, May 7, 2017, http://www.dw.com/en/anger-at-german-afds-hidden-campaign-donors/a-38742956 .

102 Kate Holton and Guy Faulconbridge, “UK Investigates Brexit Campaign Funding Amid Speculation of Russian Meddling,” Reuters, November 1, 2017, Le Reconstructed cropped patchwork jeans Frame Denim Buy Cheap Footlocker Finishline Outlet For Sale Fashion Style Sale Online WWPUD
; and Carole Cadwalladr, “Leave.EU, Arron Banks and New Questions About Referendum Funding,” Guardian , April 14, 2018, https://www.theguardian.com/politics/2018/apr/14/leave-eu-arron-banks-new-question-referendum-funded-brexit-cambridge-analytica .

103 Raphael Kergueno, “Fraud and Boats: Funding European Political Parties,” Transparency International EU, November 9, 2017, https://transparency.eu/boatfraud/ .

104 Pippa Norris, Holly Ann Garnett, and Max Grömping, “Electoral Integrity in All 50 US States, Ranked by Experts,” Vox, December 27, 2016, https://www.vox.com/the-big-idea/2016/12/24/14074762/electoral-integrity-states-gerrymandering-voter-id .

105 Jennifer S. Rosenberg with Margaret Chen, “Expanding Democracy: Voter Registration Around the World,” Brennan Center for Justice, New York University School of Law, 2009, https://www.brennancenter.org/sites/default/files/legacy/publications/Expanding.Democracy.pdf , 9.

106 “U.S. Voter Turnout Trails Most Developed Countries,” Pew Research Center, May 15, 2017, http://www.pewresearch.org/fact-tank/2017/05/15/u-s-voter-turnout-trails-most-developed-countries/ .

107 “New Voting Restrictions in America,” Brennan Center for Justice, accessed on April 25, 2017, http://www.brennancenter.org/new-voting-restrictions-america .

108 See, for example: Lorraine C. Minnite, The Myth of Voter Fraud (Ithaca, NY: Cornell University Press, 2011).

109 Matt A. Barreto, Stephen A. Nuno, and Gabriel R. Sanchez, “The Disproportionate Impact of Voter-ID Requirements on the Electorate—New Evidence From Indiana,” PS: Political Science Politics 42, no. 1 (2009): 111–16, and Zoltan Hajnal, Nazita Lajevardi, and Lindsay Nielson, “Voter Identification Laws and the Suppression of Minority Votes,” Journal of Politics 79, no. 2 (April 2017).

110 Keith G. Bentele and Erin E. O’Brien, “Jim Crow 2.0? Why States Consider and Adopt Restrictive Voter Access Policies,” Perspectives on Politics 11, no. 4 (December 2013): 1088–116.

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