text:
Facebook Ordered to Stop Collecting User Data
Posted by John-Paul Tettmar-Saleh | Mar 2, 2018
On 16th February 2018, Belgian courts ordered Facebook to pay €250,000 a day or up to €100 million, until they cease using cookies to gather and store the personal data of users (including non-Facebook users). They have been ordered to delete all of the data they have gathered and used to track Belgian citizens.
In 2015, the Belgian Commission for the Protection for Privacy (CPP) conducted an investigation with the aid of researchers from Katholieke Universiteit Leuven and the Vrije Universiteit Brussel. They found that Facebook places a cookie in a user's web browser cache whenever they visit a page of the facebook.com domain or interact with a Facebook element embedded into another site, such as the ubiquitous "Like" and "Share" buttons. The cookie remains for two years and sends information to Facebook every time that person accesses the domain or interacts with any embedded element again. All of this is done without a user's knowledge or express consent.
Cookies are small, often encrypted text files, located in web browser directories (its "cache"). Used initially by web developers to help users navigate their more websites efficiently by gathering their preferences (e.g. language, accessibility and layout), they have since become progressively more complex. As developers sought to optimise their sites, the amount of data they gathered increased and the browser cookies became too small. In response, developers began storing slimmed-down cookies in users' caches while the bulk of the data is stored on the website's server, effectively allowing them to store an unlimited amount of data. Each slimmed-down cookie contains a unique identifier which unlocks this server data.
A website that has placed a cookie in a user's cache and is embedded into another host site, such as through "Like" and "Share" buttons, can place cookies, receive the unique identifier and unlock the server data as though the person is browsing on its own domain. This is referred to as a third-party cookie and it works even if the host site has not placed a cookie. The third-party cookie allows the embedded site to see, among other things, the host website the person is browsing.
This was among the chief complaints brought by the CPP to the Belgian Court of First Instance in 2015. The court held that it is "almost impossible to escape" the processing of a user's sensitive personal data due to the "uncountable number" of people who have landed on a page of the facebook.com domain, thereby unknowingly acquiring a Facebook cookie, and of the "millions of websites with Facebook's social plugins." They were concerned that receiving cookie data from host websites may involve processing a user's medical, religious, sexual life or political preferences without appropriate consents.
Although the 2015 ruling was successfully appealed by Facebook in 2016, on jurisdictional grounds, it was reaffirmed by Belgium's court of last resort, the Court Cassation, in the February ruling. The Court agreed with the CPP and the Court of First Instance that the automated processing of cookies that contain unique identifiers, including IP addresses, is a processing of personal data.
In the UK, the Data Protection Act 1998 (DPA) establishes a more stringent regime for sensitive personal data (e.g. data that relates to racial or ethnic origin, political opinions, religious beliefs, trade union activities, physical or mental health, sexual life, or details of criminal offences). This distinction is not made by the Belgian Privacy Act 1992; however, it does have a higher standard for personal data in that Article 5 requires unambiguous consent as opposed to just consent as per the DPA.
As the Belgian Court of First Instance held that "this data relates to very sensitive information," Facebook would be held to an even higher standard if a similar case were to be tried in the UK- they would require explicit consent to deploy and use third-party cookies. This distinction is soon to become irrelevant as the incoming General Data Protection Regulation (GDPR) will harmonise data protection laws across the EU from 25th May 2018. The law on consent under the GDPR is a hybrid of current Belgian and UK laws and re-enforces the differing standards between personal data and sensitive personal data.
This is just one of the many recent legal battles Facebook has been fighting in Europe. In addition to increasing pressure from European states in relation to extremist online content, Facebook's default privacy setting and use of personal data were recently ruled illegal by a Berlin court and French courts recently ordered WhatsApp (owned by Facebook) to stop sharing user data. Facebook were also fined €110 million by the European Commission for providing misleading information in their take-over of WhatsApp.
Facing tighter regulations, tougher penalties and political scrutiny, Facebook (and other technology companies) need to take their data privacy obligations seriously and ensure they obtain appropriate consents from their users (and non-users).
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Completing a beautiful craft project feels great. Things that you learn can inspire you to do different things. Continue reading the following paragraphs in order to learn something that might help you on your next craft undertaking. The future is not set in stone, so there's no telling what your next creation is.
You can use a variety of materials for crafts. You probably throw away a lot of paper, but it can be recycled into many different types of projects. You can also use paper towel or toilet paper rolls. You might also incorporate magazines and newspapers. Take a moment to think about what you can do with an item before just throwing it away.
Do not be too hard on children when they are working on arts and crafts projects. Your main objective should be to foster creativity. Telling them what they're doing wrong is not going to be helpful.
Always be mindful of the fact that any arts and crafts projects involving children is going to get messy. If that bothers you, cover the work surface with newspaper or butcher paper to contain the mess. You can use washable markers and glue too.
If you have difficulty finding supplies for arts and crafts projects that are affordable, check out secondhand stores. Places like Goodwill and other types of consignment shops have all kinds of goodies for the clever artist. Check back often, as these items often sell out quickly.
Always remember the principle of first things first in arts and crafts. Sometimes you want to try out a million different things. This will prevent projects from getting done. Finish your crafting project before starting a new one. This way, you will be more likely to finish.
When making projects with children, remember to keep things flexible. You can either forgo the examples or show them different ones so that they just use their imaginations. For instance, they may draw a foot where a hand should be. Their own ideas are more important than their execution.
Get organized. There are different ways to do this, but you should pick something that makes sense to you. If you have your supplies organized, it will be much easier to find what you need for your projects. You also will be able to do easy inventory in your head.
Many kids enjoy arts and crafts. If you are working with children, find something you think they'll enjoy. Check online for inspiration, if you need some help.
Oil paintings are easy to paint over if you're not happy with a finished product. Oil is flexible, and additional paint is not going to harm the surface. Actually, it might even give your new painting an interesting design and amazing depth.


Beneath the thick lashings of paint, there are a great many things to be discovered about Lucian Freud's work.
1. Freud's paintings are autobiographical. Almost all the people he chooses to paint tell a story about himself and his values (he rarely worked on commission).
2. Freud has only once ever, he recalled, completed a portrait of a person he did not like, a book dealer called Bernard Breslauer. He so disliked the model that he was deliberately unkind and over-egged the pudding of a man in front of him, making him "even more repulsive than he actually was". The unhappy sitter, on acquiring the portrait, sent Freud a letter saying that he had "contravened an unwritten contract between painter and sitter." The painting in question was destroyed by the model.
3. Freud did not begin to employ thick sculptural brushstrokes until later in his career, a decision which lost him some important supporters in the art world at the time.
4. Freud knew a great many artists but remained a great individualist and did not bow to other talent: he remembers Picasso as "absolutely poisonous", Man Ray as "noisy and vulgar", and German expressionist Max Ernst as a "heavy and stiff" dinner companion.
5. Freud had an almost visceral hatred of almost all art of the Renaissance. It makes sense: the Renaissance was the period, above all, during which man was celebrated as the crown of creation. Freud's belief was the opposite: man, he seems to say, must never forget the fact that he is deteriorating matter. It was Kant who first observed that an aesthetic encounter can be one that is mixed with pain, and Freud proves it eloquently.
7. Freud famously painted a rather unflattering portrait of the Queen and celebrities like Kate Moss, but he also admired – and loved to paint – friends and scallywags, including a "very clever bank robber" (his words) who is now immortalized as a scar-faced man in a Lucian Freud called 'A Man and His Daughter' (1963-4). One's overwhelming impression of that picture is that it was painted with a great deal of respect.
8. Freud used to say that time was his one great luxury in life. He took a great deal of time to get to know his subjects, and sometimes would be paintings them for years. He asks that of his audience too: every Lucian Freud portrait has a different presence, requires time to get to know.
10. Freud saw every object in the world as possessing a unique character. Even into the sixth decade of his career, he still celebrates the unique history of each material thing he drew and painted. It is his acute sensitivity to the multitudinous variety of 'being' that kept him invigorated by his work.


text:
Nadezhda Pavlovna Kozhushanaya (; 15 March 1952 in Sverdlovsk – 15 January 1997 in Moscow) was a Soviet, Russian screenwriter and writer. Nadezhda said: "I live and write with love to my crazy time". She was a philologist and a musician by education, a playwright by vocation. Although she died at the age of 44, she was referred to as "The most gifted screenwriter of the perestroika epoch".

Biography and creative work

Childhood
Nadezhda Kozhushanaya (Yamshanova), was born in Sverdlovsk (Yekaterinburg). Her father was Pavel Ivanovich Yamshanov (the Chief Engineer of a laboratory of the Uralmash plant), who had a rich library of art books and fiction. Her mother was Glafira Mihailovna Yamshanova (Smirnova) (a teacher at a local Metallurgical Technical College). Her parents divorced when Nadezhda was eight. From an early age Nadezhda wrote her own stories and fairy tales. Her story "Pustiak" was based on her first dramatic experience of reading aloud for the class.

University
After school 1968 Nadezhda went to Ural State University to study philology. She actively took part as an actress and an accompanist in student theatres of the University and Ural State Academy of Architecture and Arts. She composed music and easily played in the piano, guitar and accordion that gave a nudge to the decision to study in the Urals Mussorgsky State Conservatoire, but her mother made a requirement that Nadezhda should graduate the University first. In preparation to her thesis, Nadezhda worked in the museum of Muranovo, where she also gave guided tours about Fyodor Tyutchev. After graduation, according to the common Soviet practice, she was posted as a teacher of Russian to a remote village of Kunara, Sverdlovsk Oblast.   In 1975 Nadezhda married Boris Kozhushany and moved to Moscow, where her husband studied at the Moscow Architectural Institute.

Moscow
In Moscow, first she had a clerical job (later she wrote comic stories about it). Plays and other works of this period almost did not survive, but it was the time when she created her own style. Nadezhda said: "Everything that I wrote is needed to be read aloud." On 1 December 1980 her daughter Ekaterina was born. In 1982–1984 Nadezda studied at the High Courses for Scriptwriters and Film Directors in Moscow as a Screenwriter. After her admission interview, Valentin Chernykh, one of the leaders of the courses, formulated his reluctance to take Nadezhda as: "She is a person with the character like  Gennady Shpalikov, Vladimir Vysotsky, Oleg Dahl. Also she is a woman, so it will be even harder for her ". In the end she was accepted into the workshop of Semyon Lungin. In addition to Semyon Lungin, she studied under Valeri Frid, Merab Mamardashvili, Alexander Mitta, Paola Volkova. During this time she wrote three full-length scripts:   "The Fence", "The Very First Happy Day" (graduation work) and  "The Last Doll Game". The last script was set in 2010.

Nadezhda Kozhushanaya died in 1996 from pneumonia. After her death she got an honorary title. Overall, she wrote scripts for eight short films, five animation films, four full-length films and a number of scripts which did not turn into films.

Scenography
Full-length films:
 1987 – Mirror for a Hero directed by Vladimir Khotinenko, (Nomination for the Nika Award)
 1989 – Husband and daughter of Tamara Alexandrovna directed by Olga Narutskaya, (Nomination at the Venice Film Festival)
 1991 –  Leg  directed by Nikita Tyagunov, (FIPRESSI award at Rotterdam International Film Festival)
 1992 – Prorva directed by Ivan Dykhovichny, (Nomination at the Venice Film Festival)
 2010 – The Last Doll Game directed by Georgiy Negashev

Short films and animation:
 1983 –  Walking Around the City, short feature directed by Aleksandr Zeldovich
 1984 –  Most, short feature.
 1985 –  We Can't Predict..., short feature directed by Olga Narutskaya.
 1985 –  Buzkashi, short feature, directed by Pulat Achmatov
 1986 –  Toro!, short feature directed by Talgat Temenov
 1990 –  A Thing of the Past, animation film directed by Oksana Cherkasova
 1991 –  Terrorist, short feature directed Mihail Rozenshteyn
 1993 –  Cuckoo's Nephew, animation film directed by Oksana Cherkasova Awards at KROK, Drezden, Parn, Oberhauzen and Hiroshima Animation film festivals.
 1994 – Oh, My God!, directed Tatyana Skabard
 1994 –   Tenderness and Affection for  You, Sick; documentary about the centre of Alcoholics Anonymous, VGTRK, directed by Tatyana Lebedeva
 1995 –   Nyurka's Bath, animation film directed by Oksana Cherkasova Awards at Zagreb, Leipzig and Espinho Animation film festivals, Nomination for the Nika Award.
 1996 – Babushka (Grandma), animation film directed by Andrey Zolotukhin Awards at KROK and Fantoche.
 1996 – The Pink Doll, directed by Valentin Olshvang, Awards at KROK, Leipzig, Zagreb and Hiroshima Animation film festivals.
 1996 –  Unliving Beast, short feature directed by Marina Lubakova

Actor works
 1988 – Husband and daughter of Tamara Alexandrovna as  a cleaner
 1992 – Leg as a nurse

Gallery

References

External links

Soviet screenwriters
Soviet women writers
20th-century Russian women writers
20th-century Russian writers
1952 births
1997 deaths
Writers from Yekaterinburg
Russian film actresses
Burials in Troyekurovskoye Cemetery
Ural State University alumni
20th-century Russian screenwriters
Animation screenwriters
Deaths from pneumonia in Russia
High Courses for Scriptwriters and Film Directors alumni
Academic staff of High Courses for Scriptwriters and Film Directors
Actors from Yekaterinburg

redpajama_set_name: RedPajamaWikipedia


Many great knots winter in Australia, along with smaller numbers of their close relative the red knot. These winter-plumage birds were photographed on a tidal mudflat off Buffalo Creek, near Darwin in the Northern Territory, where they were flocking with black-tailed godwits. They were very shy and difficult to photograph; a long lens helped but these images are strongly cropped. During processing I noticed that several were color-banded; it turns out they were captured in the area a few weeks earlier. Another page shows birds retaining the heavily-spotted summer plumage.


text:
THEOPHANO
FOUNDATION & BOARD
The Empress Theophano Prize Honours the Contribution of Science to Humankind
Dr Uğur Şahin and Dr Özlem Türeci, the scientist couple who developed the first vaccine against the coronavirus, are the recipient of this year's Theophano Prize for saving millions of lives and giving hope to the entire world.
© Studio 8 Photos, Efi Panagoula
You may watch the Ceremony Award (Wednesday 13th October 2021 | 17:30 CET, 18:30 EET) HERE
FOR TRANSLATION IN GREEK HERE
FIND THE PROGRAMME OF THE EVENT HERE
The Empress Theophano Prize in 2021 focuses on the critical role science serves in society and on its contribution to the Common Good. The Governing and Advisory Councils of the Theophano Foundation chose to turn our attention to the manifold manners in which science improves people's lives, by acknowledging the couple who developed the very first vaccine against the novel coronavirus, Dr Uğur Şahin and Dr Özlem Türeci. Setting an example and constituting motivation for young people everywhere, the two scientists have demonstrated solid and persistent efforts to solve an unprecedented health crisis, dedication to the Common Good, and high quality of research and expertise, leading to a discovery that has given hope not only to Europe, but to Humankind.
Just a few months before visiting Thessaloniki for the Empress Theophano Award Ceremony, Dr Uğur Şahin and Dr Özlem Türeci stated that "The Empress Theophano Prize is a great recognition and an honour for us. Thank you for deeming us worthy ambassadors of the cause that this Prize represents: Improving lives is indeed the most noble purpose of science, and a mission which is close to our hearts. We are thrilled to accept this prestigious award and do this on behalf of an extraordinary team that made Project Lightspeed – Made in Europe possible." Echoing the story of Empress Theophano, a Byzantine princess who became Empress of the German Empire in the 10th century, Dr Uğur Şahin and Dr Özlem Türeci also represent Europe's diversity, as it becomes a space for tremendous achievement and a field for transnational cooperation.
The Award Ceremony for the Empress Theophano Award 2021 will take place on Wednesday, the 13th of October 2021 in Thessaloniki, in the unique setting of the Rotunda, a landmark monument that epitomises the Roman, Byzantine, Orthodox, Ottoman, and Greek influence on the shaping of Europe.
HE the President of the Hellenic Republic Katerina Sakellaropoulou will honour the Ceremony with her presence and address the distinguished guests.
Alexis Papahelas, journalist and Executive Editor of Kathimerini newspaper, will present the Award Ceremony of the Empress Theophano Prize.
Additionally, the Governing and the Advisory Councils of the Theophano Foundation, chaired by Mr Stavros Andreadis and President Herman Count Van Rompuy respectively, intend to launch – for the first time this year – the Theophano Round Table, a panel discussion on a topic of international importance that will be related to and inspired by each year's award. This initiative seeks to create a dynamic forum of discussion around critical issues regarding the future of Europe. This year's event will take place on Thursday the 14th of October, under the title Securing Future Wellbeing Through Science and focusing on themes related to science for the Common Good, science and innovation in Europe, science and competitiveness, science and education, and science and healthy living.
Since its establishment, the Empress Theophano Foundation has set the goal of rewarding individuals and organisations for their impact to the understanding and strengthening of the contemporary European Idea, and their contribution to the social good, to welfare and to the improvement of lives. The start was made in 2020, with the inaugural prize and its focus on Education. The President of the European Commission, Ursula von der Leyen, accepted the first Theophano Prize on behalf of an institution that strengthens mobility, cooperation, and mutual understanding of the younger generations of Europeans: the ERASMUS Student Exchange Programme. Continuing its course into a second year, the Empress Theophano Prize aims to be established, year by year, as a notable means of highlighting the contribution of organisations and individuals in our mutual understanding and cooperation, as well as in facing the challenges of contemporary era within the European framework and beyond.
INFORMATION: Vicky Papadimitriou, Project Coordination | E: info@theophano.eu | T: +30 6937 229858
The award ceremony will take place with the kind support of:
Official air carrier sponsor:
With the kind support of:
The Governing Council
Stavros Andreadis
Chairman, SANI/IKOS Group
Chairman, Cultural Society of Entrepreneurs of Northern Greece (GR)
Nikolaos Efthymiadis
Chairman, EFTHYMIADIS Agrotechnology Group
Honorary Chairman, Federation of Greek Industries (GR)
Evangelos Gerovassiliou
Chairman, Gerovassiliou Wines (GR)
Constantinos Gleoudis
Chairman, KAVEX
Member of the Board, Hellenic Society for the Environment and Cultural Heritage (GR)
Theodoros Ikonomou
Chairman, Greek Forest Property Association
Head of a forest management and wood production firm (GR)
Nada Korac Kakabadse
Professor of Policy, Governance and Ethics, Henley Business School, University of Reading (UK)
George Mylonas
Chairman, ALUMIL Group (GR)
Sonja Puntscher-Riekmann
Professor Emeritus of Political Theory and European Politics, University of Salzburg (AT)
Stefan Schepers
Secretary General, High Level Groups on Policy Innovation (BE)
Vassos Konstantinidis
Chairman, INART (GR)
The Advisory Council
Herman Van Rompuy
President Emeritus of the European Council
Former Minister of State of Belgium (BE)
Former President of Ireland | Professor of Children, Religion and Law, University Glasgow (IRL)
Leonie Bell
Trustee Edinburgh International Festival | Director Victoria & Albert Museum Dundee (UK)
Nikiforos Diamandouros
Former European Ombudsman (GR)
Élisabeth Guigou
President, Anna Lindh Foundation | Former Secretary of State (F)
Tarja Halonen
Former President of Finland (FI)
Author and film director (PL)
Maria Luisa Poncela
Former Secretary of State (ES)
Michel Praet
Vice-President Museum of European History (BE)
Georges Prevelakis
Professor Emeritus, Paris-Sorbonne University (FR)
Sir Ivan Rogers
Former UK Ambassador to the EU (UK)
Chiara Saraceno
Honorary fellow Collegio Alberto, University of Turin (IT)
Vassilios Skouris
Former President, European Court of Justice of the EU (GR)
Karl Prince zu Schwarzenberg
Former Minister of Foreign Affairs (CZ)
Rita Süssmuth
Former President of the German Parliament (DE)
Panos Tzonos
Professor Emeritus, Aristotle University of Thessaloniki (GR)
Luuk Van Middelaar
Professor of EU Foundations and Institutions, University of Leiden (NL)
EMPRESS THEOPHANO
Empress Theophano, who inspired this prize, is a historic figure of Europe who played a significant role in its development during the 10th century.
The niece of Emperor John I Tzimiskes, she married Otto II and was crowned Holy Roman Empress as his wife. Following his death, she maintained the title of Empress. Her historic presence in Western Europe, dedicated to improving relations between East and West, offered a positive contribution to the cultural renaissance of western European territories, introducing to the west the central role women had in Byzantine society and transferring significant influence from the flourishing Byzantine empire in the fields of education, the arts, commerce, and health, while working to advance civil governance, promoting it over the military.
Empress Theophano is buried at the Cathedral of St Pantaleon in Cologne, Germany.
THE ROTUNDA MONUMENT
The emblematic monument of Thessaloniki, was constructed in the early 4th century AD, on the turning point between the pagan with the Christian world, probably as a temple for ancient cult worship or as a mausoleum for Constantine the Great (306-337). This circular, domed building measures 29.80 meters in height, 24.50 meters in diameter, its walls are 6.30 meters thick and can only be compared architecturally to the Pantheon in Rome. Not long after it was built and during the early years of the long-lived Byzantine Empire (330-1453), the Rotunda was turned into a Christian church with the addition of a sanctuary on its eastern side. The interior was decorated with Early Byzantine (4th- 6th c. AD) wall mosaics of unique artistry and beauty. It was Thessaloniki's cathedral church (metropolis) between 1524 and 1591, the year in which it was converted to a mosque by the Ottoman conquerors. It remained in use as a mosque until the city's liberation in 1912. Its dedication since that time to Saint George (Agios Georgios) is owing to the small neighboring church of this name. The mosaic decoration of the Rotunda is a masterpiece of Late Antique art.
Text source: http://galeriuspalace.culture.gr/en/monuments/rotonta/
Photo credits: Ephorate of Antiquities of Thessaloniki City.
Photo credits: Studio 8 Photos, Efi Panagoula.
@Thessaloniki
6-8 Frangon str. GR-54626 Thessaloniki
E: info@theophano.eu / info@theophano-thessaloniki.gr
@Brussels
E: carine.renaer@eppa.com
Empress Theophano Prize
Tax ID 0996880221

redpajama_set_name: RedPajamaCommonCrawl


text:
Таубман () — фамилия немецкого или еврейского происхождения. Известные носители:

 Таубман, Белинда Джейн (род. 1950) — австралийско-американская актриса, фотомодель, танцовщица и психолог.
 Таубман, Ефим Исаакович (1933—1990) — советский учёный в области теплотехники и электротехники, эколог.
 Таубман, Отто (1859—1929) — немецкий композитор и дирижёр.
 Таубман, Самуил Маркович (1911—1986) — советский разведчик.
 Таубман, Уильям (род. 1940) — американский политолог и историк.
 Таубман, Фридрих (1565—1613) — немецкий учёный-филолог, гуманист и поэт, педагог.


text:
Q: Calling an ES6 class middleware using KOA I have a function in an ES6 class that i'm trying to call as a middleware but to no success. In my index file, i have:
*I have only included relevant code
"use strict";
    const http        = require('http')
    const Koa         = require('koa')
    const app         = new Koa()
    const bodyParser  = require('koa-better-body')
    const Install     = require('./.system/install/install')
    const install     = new Install()

class index {
  /**
  * Class constructor function
  * @Class Index
  * @method constructor
  * @return {undefined}
  */
  constructor () {
  }

  /**
  * Main entry method
  * @Class Index
  * @method init async
  * @return {undefined}
  */
  async init(){
    // install helper
    app.use(install.setup)

    // response
    app.use(async ctx => {
      ctx.body = 'Hello World';
    });

    http.createServer(app.callback()).listen(8080);
  }
}

let init = new index(); init.init()

And in my install.js, I have:
       "use strict";
        const process = require('./library/process')
        const fs      = require('async-file')

    module.exports = class install {
        async setup (ctx, next) {
            ctx.body = 'install';
        }
    }

But the koa app keeps giving me a 404 not found error. I know a static method might solve this but i'd rather not use static methods. The install class has both a middleware function and standard functions.

A: You have 404, because you don't use koa-router

A: you should call next() in your middleware function

redpajama_set_name: RedPajamaStackExchange


text:
>International Journal of Asian Studies
>THE QIAOBAN, THE PRC INFLUENCE AND NATIONALIST CHINESE...
International Journal of Asian Studies
THE QIAOBAN, THE PRC INFLUENCE AND NATIONALIST CHINESE IN THE NORTHERN THAI BORDERLAND
Aranya Siriphon
Aranya Siriphon*
Chiang Mai University, Thailand E-mail aranya.s@cmu.ac.th
From 1989 onwards, the People's Republic of China's use of the Qiaoban, the Overseas Chinese Affairs Bureau, has burgeoned notably in regard to attracting investment and loyalty from overseas Chinese outside mainland China. This article analyses the impact of the Qiaoban and the PRC influence upon "diasporic Chinese" living along the northern Thai border, particularly ethnic Chinese (e.g. Teochiu, Hakka, Hainanese) and Nationalist Chinese (Kuomintang-KMT). It finds that, while the Qiaoban has largely succeeded in the engagement with the ethnic Chinese of northern Thailand, the active efforts of the PRC to engage the Nationalist Chinese have been notably unfruitful. However, the Qiaoban's efforts have caused increasing tension between different generations in Nationalist Chinese communities.
QiaobanOverseas Chinese Affairs BureauNationalist Chinesenorthern Thai borderland
International Journal of Asian Studies , Volume 13 , Issue 1 , January 2016 , pp. 1 - 17
DOI: https://doi.org/10.1017/S1479591415000200[Opens in a new window]
Copyright © Cambridge University Press 2016
Aranya 2015 Aranya, Siriphon. "'Xinyimin', Border Guanxi and the Influence of the People's Republic of China (PRC) and Taiwan on the Northern Thai Border." In Impact of China's Rise on the Mekong Region, ed. Santasombat, Yos. Palgrave Macmillan, 2015.Google Scholar
Chand 2013 Chand, Masud. "Diasporas and Their Rising Importance to the International Political Economy." In Handbook on the Geopolitics of Business, ed. Munoz, Joseph Mark, pp. 36–49. Cheltenham, UK: Edward Elgar Publishing, 2013.CrossRefGoogle Scholar
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Chinh 2013 Chinh, Nguyen Van. 2013. "China's Confucius Institute and Its Civilizing Mission in the Mekong Region." The Work of the 2010/2011 API Fellows, pp. 234–43, www.api-fellowships.org/.../P5-Nguyen-Van-Chinh.pdf (Accessed 8 January 2014).Google Scholar
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Aranya Siriphon (a1)
DOI: https://doi.org/10.1017/S1479591415000200


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Under PLA, L.A. Project Will Create 6K Jobs, Become 6th LEED Platinum-Certified High-Rise in U.S.
The Los Angeles City Council recently approved the Century City Center, a 37-story development project that will become only the sixth LEED Platinum-certified high-rise in the nation. It will be built under a Project Labor Agreement (PLA).
The project was delayed by intense scrutiny from critics despite estimates that it will create 6,000 high-quality jobs. The project was supported by labor unions (who will do much of the work), community groups, environmental groups, and the Clergy and Laity United for Economic Justice.
Via Westside Today:
The project's 700,000 square foot office building will include approximately 10,338 square feet of low-rise, one- and two-story office space, a 2,389-square foot Mobility Hub (to encourage Century City employees to utilize public and alternative transit options), a 39,037-square foot Transit Plaza, approximately 17,102 square feet of retail, and a partially subterranean parking structure with 1,530 stalls on the project site.
Century City Center will include a 2.14-acre landscaped green roof deck on the parking structure which would be open to members of the public between 6 am and 8 pm, seven days per week, as an additional public amenity.
Los Angeles Councilman Paul Koretz spoke before the final vote. He represents the Century City neighborhood and is thrilled about the project's possibilities:
"This project will represent a landmark achievement for the city and for my district. It will include the first new built LEED platinum high-rise in Los Angeles. A beautifully designed building that will represent the city's commitment to green and sustainable development.
This project will include more than two acres of green public space, it will provide numerous benefits to the community including a portal for the Metro Purple Line Century City station, extensive and creative traffic mitigation efforts, a peak hour shuttle service from Century City to the future Expo line, and substantial funding for regional transportation planning and improvements in the South Robertson and the Beverlywood areas,"
The PLA governing Century City Center's construction will ensure a living wage and proper health care benefits. Other highlights of the development plans include:
The Century City Center will be the first LEED Platinum-certified high-rise building in Los Angeles and only the sixth in the nation. Here are just some of the features that the City Council approval has guaranteed:
It will also generate $4.3 million to the City of Los Angeles every year and generate $400 million in annual economic activity throughout the county.
* The environmentally friendly aspects of the project include: 7,000 square feet of solar photovoltaic panels; one of the largest habitable green roof spaces in California; a high-performance central plant that produces ice at night to melt during the day and provide efficient cooling; a passively cooled lobby using windows, fresh air, and a chilled lobby floor with a high-tech water feature that rejects heat; and reclaimed water from the building for landscape irrigation.
* Century City Center will feature a large public plaza. with shops, kiosks, and plentiful plantings, trees and shade, that will take advantage of existing transit options, as well as provide a ready connection to future advances as a potential portal location for the planned Purple Line mass transit Metro station. One of the key ways that the project will encourage transit use is the inclusion of a 1,300 square-foot mobility hub to assist the 50,000 employees who work in Century City and who want to get out of their cars and use alternative commuting strategies.
The Los Angeles City Council voted unanimously (12-0) to approve the project which features Bill Clinton's Clinton Global Initiative as a partner.
Category: CALIFORNIA, PLA!
Tags: century city center, Construction, PLA!, Project Labor Agreement
No Comments on "Under PLA, L.A. Project Will Create 6K Jobs, Become 6th LEED Platinum-Certified High-Rise in U.S."
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Poll by GOP Firm: 88% of Likely WI Voters Don't Think "Right-to-Work" Would Benefit Them
Maryland Bill Introduced to Ensure Employers Fully Fund Apprenticeship Programs
Judge Orders Pacer Cartage to Pay 7 Misclassified Truckers $2M; Teamsters Were Key Supporters
New Mexico GOP Advances "Right-to-Work" Through Committee In Order to Hurt 46,000 People
Scores of Amputations, 1000s of Injuries Lead to $1.76M Fine at Ashley Furniture Facility
On a Roll: Canadian Supreme Court Follows Right-to-Unionize Vote with Affirmation of Right to Strike


The Clifton Hotel Scarborough features its very own on-site restaurant and bar facilities, where we serve a variety of dishes and beverages throughout the day and evening.
The Castle Restaurant is a traditionally decorated dining area, and is home to our breakfast buffet, where guests can choose from a variety of hot or cold foods. We also serve a variety of dinner dishes, from traditional to international meals.
Our bar is open to all of our guests throughout the day, and serves a variety of hot and cold beverages, snacks and light meals.


The dispersion of sodium bicarbonate in oil forms an osmotic film on the skin that blocks the enzymatic process that is responsible for unpleasant odours. Sodium bicarbonate is alkaline and thus prevents odour-causing bacteria from increasing. The deodorant cream contains various waxes, butters and oils that care for sensitive underarm skin.


text:
Q: Make a button inside an element clickable while the element itself is also clickable I have a simple sidebar, that has a bunch of list items in it, and a button right next to the list item, like so:

I attached a click handler to the
 element like in the code below:

 props.selectNote(props.note)} role="button">
    <button className="delete-note" onClick={() => console.log('Fired')}>Delete dis</button>
    2hr

            {title}

            {notePreview.substr(0, 80)}...

But as expected, when I click the button next to it, the actual li gets clicked and not the button inside it. I think this is some sort of issue with how the event bubbles, and how it's a bad practice to attach onClick handlers to non-interactive elements (My ESLint says that).
What I want instead:

*

*When the list item gets clicked, the attached onClick event fire.

*When the button gets clicked, fire the onClick event on the button, and not the
.

A: Hack incoming!
I solved this by adding a name attribute to the elements that I didn't want to trigger the main click event:
handleClick = (e) => {
    if(e.target.name === 'deleteButton') {
        e.preventDefault();
        e.stopPropagation();
    }else {
        this.props.selectNote(this.props.note)
    }
}

    <button className="delete-note" name="deleteButton" onClick={() => console.log('Fired')}>Delete dis</button>
    2hr

            {title}

            {notePreview.substr(0, 80)}...

You need to check which element triggered the event, and prevent it if it was the button.

A: For Button onClick the default click parameter event args is passed as 'event'. Use the event.stopPropagation() to stop propogate the click event back to li.

 props.selectNote(props.note)} role="button">
<button className="delete-note" onClick={(event) => event.stopPropagation(); console.log('Fired')}>Delete dis</button>
2hr

        {title}

        {notePreview.substr(0, 80)}...

A: What you need is to prevent further propagation of the current event (click) in the capturing and bubbling phases.
See the example on event propagation: https://developer.mozilla.org/en-US/docs/Web/API/Document_Object_Model/Examples#Example_5:_Event_Propagation

A:
 e.target.getAttribute('data-is-parent') && props.selectNote(props.note)} role="button">
    <button className="delete-note" onClick={() => console.log('Foreground Fired')}>Delete dis</button>
    2hr

            {title}

            {notePreview.substr(0, 80)}...

A: you should wrap your li in a div
like below

 props.selectNote(props.note)} role="button">
        2hr

                {title}

                {notePreview.substr(0, 80)}...

    <button className="delete-note" onClick={() => console.log('Fired')}>Delete dis </button>


Total 8 Hours and 30 minutes. Ride in comfort of a Private Luxury SUV. This tour will make a stop at a Local Restaurant for lunch. Explore the most Haunted Plantation Home in North America.
Pick up is at 9:00 am from your point of pickup in New Orleans Area. You and up to 5 of your guest will travel 2 hours and 15 minutes to St. Francisville, LA. At 11:15am you will stop at Magnolia Cafe a local Spot for lunch. Lunch is NOT INCLUDED IN THE PRICE. After lunch, you will spend 2.5 hours at the most haunted plantation in North America. The guided tour is 45 minutes and will have plenty of time to walk the grounds and explore yourself. This tour will leave the plantation at 3:15 pm and will return you to your point of pickup at approximately 5:30pm.


Like most chronic illnesses, diabetes is treated most successfully when diagnosed early. But too many people are being given a diagnosis of "pre-diabetes," which not only subjects them to unnecessary treatment, but places unsustainable burdens on the health-care infrastructure.
The title of a commentary published last month in the journal BMJ pretty much summed up the problem: "Too Much Medicine," by Dr. Victor Montori, an endocrinologist who specializes in diabetes at the Mayo Clinic, and Dr. John Yudkin, an emeritus professor of medicine at University College London, calls a diagnosis of pre-diabetes dubious. It's an important assessment, because a dubious diagnosis is an unreliable predictor of who will actually develop the disease.
As we regularly write, overtreatment, which is what the writers are dealing with here, is not just inefficient and wasteful, but leads to unnecessary worry and the possibility of complications from procedures that stem from this unacceptably aggressive use of medical care.
Rather than turning people who are at risk of developing diabetes into patients who are given inappropriate care, the writers argue that those resources should be directed toward educating this population on how to prevent the disorder. That means helping them understand the role of diet and exercise in developing diabetes. It also means expending energy on public policies that address the obesity epidemic that promotes diabetes.
The artificial problem is the result of one segment of the medical industrial complex – the American Diabetes Association – lowering the threshold for what is defined as disease, and it's disgraceful.
Diabetes is diagnosed when levels of blood glucose, or blood sugar, are too high. It's a hormonal disorder – the hormone insulin helps deliver necessary amounts of energy (glucose) to cells, but sometimes the body does not make enough. That's type 1 diabetes, a condition that usually develops when you're young.


Davis Mountain State Park sunset Pano at the rock overlook at dusk just after sunset. This old rock building was built by the CCC as a place to rest up after a day of working the area and has a nice sweeping view over the desert and mountain landscape below. The sky picked up these wonderful colors right after sunset over the rock shelter and the distant landscape with some nice post sunset colors of pinks and oranges which made for a nice end of the day. The park was built by the Civilian Conservation Corps (CCC) which was created to help put young males to work during the depression. The CCC helped build structures like this rock shelter along with other building, picnic tables, fire pits in the park which was officially open in 1938, The park is 2709 acreas with an elevation between 5,000 and 6,000 feet above sea level. The nearist town is Fort Davis Texas in Jeff Davis County. Also located in the area is the National Historic site establish as protection in the area from the Comanche War Trail and Mescalero Apache war trails. It bacame a historic site in 1961 to preserve one of the best remaining military post of that era.
Davis Mountain State Park Pano at the CCC overlook at dusk just after sunset. This old rock building was built as a place to rest up after a day of working the area and has a nice view over the desert and mountain landscape. This west Texas landscape in the Davis Mountain just as it captures the colors and residual of the sunset after dusk as the sky lights up with oranges and pink colors post sunset was a nice end to the day.
Posted in Photo of the Day and tagged CCC, Civilian Conservation Corps, color, colorful sky, Davis Mountain State Park, Davis Moutains State Park Pano, desert, landscape, National Historic site, overlook, pano, panorama, rays, rest area, rock building, sunset, texas landscape, texas sunsets, views on March 23, 2018 March 23, 2018 by Bee Creek Photo.


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10 notable blue plaques of London – 10. A man…and his work…
by exploringlondon July 20, 2016
We finish our series looking at notable English Heritage blue plaques with a look at a plaque which not only commemorates a prominent Londoner but, unusually, also displays there for all to see the reason (well, an important part of it, anyway) for his prominence.
Yes, we're talking about Edward Johnston (1872-1944), a master calligrapher who was not only credited with starting the modern revival of the art but is also noted for having created the famous Johnston typeface which he developed for London Transport in the early 20th century.
In a lovely touch, the sans serif typeface he created is that used on the plaque – located at premises at 3 Hammersmith Terrace in Chiswick where he lived from 1905-1912 – itself.
The plaque, which was erected on the building in 1977 by the Greater London Council, was the first to feature the typeface but isn't the only one: in fact there are four, all of which commemorate people related to London Transport.
The other three commemorated include Frank Pick (1878-1941), a London transport administrator who steered the development of London's corporate identity – he's commemorated with a plaque on his former property at 15 Wildwood Road, Hampstead Garden Suburb, with a Greater London Council plaque erected in 1981).
They also include Albert Henry Stanley, Lord Ashfield (1874-1948), the first chairman of London Transport (placed on his former home at 43 South Street, Mayfair, in 1984 by London County Council); and, the most recent plaque commemorating Harry Beck (1902-1974), designer of the London Underground map (placed by English Heritage in 2013 on his former property at 14 Wesley Road in Leyton).
PICTURE: Edwardx/CC BY-SA 4.0
10 notable blue plaques of London Blue Plaques Chiswick Hampstead Mayfair Transport Twentieth century UndergroundChiswick Edward Johnston English Heritage Blue Plaques Frank Pick Harry Beck Leyton London Transport London Underground Lord Ashfield Mayfair
Around London – Bedchamber secrets at Hampton Court; Roman remains at the British Museum; Easter chocolate at Kew Gardens; Harry Beck's blue plaque; and, Underground art…
by exploringlondon March 28, 2013
Happy Easter! We're taking a break over the Easter weekend…Our next update will be on Tuesday, 2nd April.
• A new exhibition exploring the secrets of the bedchambers of the Stuart and Hanoverian courts of the 17th and 18th centuries opened at Hampton Court Palace this week. At the heart of Secrets of the Royal Bedchamber are six royal beds which tell the story of why the bedchamber became the most important part of the palace and detail some of the events that took place there before an audience of courtiers, politicians and family members – from births and deaths to the consummation of marriages and the discussion of important affairs of state. It tells of why courtiers would fight for positions such as the 'groom of the stool' or 'necessary woman' and how beds which could cost the same as a London townhouse were sometimes never slept in. Among the beds on display is the 'Warming Pan Bed' (pictured), the State Bed of King James II's queen, Mary of Modena, and scene of the royal birth that ultimately led to the end of the Stuart line, and the 'Travelling Bed' of King George II which travelled as far afield as Hanover and the battlefields of Europe. The exhibition also gives rare access into the Prince of Wales' Apartments, designed by 17th and 18th architect Sir John Vanbrugh, and now open for the first time in 20 years. Admission charge applies. Runs until 3rd November. For more, see www.hrp.org.uk. PICTURE: HRP
• The Roman cities of Pompeii and Herculaneum are the subject of a major exhibition opening at the British Museum today. Life and death in Pompeii and Herculaneum brings together more than 250 objects from the two cities which were buried in just 24 hours during the eruption of Mount Vesuvius in 79 AD. The objects include celebrated finds and recent discoveries, many of which have never before been seen outside Italy, and help explore what daily life was like for the inhabitants. Artefacts include a beautiful wall painting from Pompeii showing baker Terentius Neo and his wife, wooden furnishings including a linen chest, inlaid stool, and even a baby's crib from Herculaneum, and casts of victims including a family of four and a dog who died at Pompeii. Runs until 29th September. Admission charge applies. For more, see www.britishmuseum.org.
• Find out more about the history of chocolate at Kew Gardens this Easter, from the ritualistic use of cacao in ancient Mayan and Aztec cultures to the arrival of chocolate in 17th century London, where it was a luxury item for high society to indulge in at newly fashionable chocolate houses. Running from tomorrow until 14th April, there will be a range of workshops taking place at the gardens around the chocolate theme along with a traditional Easter Egg Hunt on Easter Sunday (31st March). The garden's cocoa tree can be found in the Princess of Wales Conservatory. Admission charge applies. See www.kew.org.
• Harry Beck, designer of the innovative first diagrammatic Tube map, has been honoured by an English Heritage blue plaque – inscribed in the Underground's new Johnston typeface – at his birthplace in Leyton in London's east. Beck, who was born in a small terraced house at 14 Wesley Road in 1902, was working with London Transport as a draughtsman in the London Underground Serial Engineer's Office, when, in 1931, he produced his first design for a diagrammatic map. He continued to update the map with new stations and lines even after leaving London Transport with the last version of his map published in 1960. Beck died in 1974. Meanwhile, a blue plaque commemorating railway engineer Sir Nigel Gresley (1876-1941) has been returned to King's Cross station following the completion of building work. It can be found on platform 8. For more, see www.english-heritage.org.uk/discover/blue-plaques/.
• On Now: The Underground. A commission from Art on the Underground, this exhibition of artist Mark Wallinger's work at the Anthony Reynolds Gallery (60 Great Marlborough Street) features some examples of 270 labyrinth designs – one representing each of the Underground stations – which are being installed at the Tube stations themselves. Among those stations represented at this showing are Westminster, St James's Park, Oxford Circus, Victoria, Embankment, Green Park, King's Cross St Pancras, Baker Street and Tottenham Court Road. While labyrinths are already in place at these locations, the remainder of Wallinger's labyrinth designs will be appearing at Tube stations over the coming months. Runs until 27th April. For more, see www.anthonyreynolds.com.
Bloomsbury Blue Plaques Gardens George II Georgian Hampton Court Palace James II Kew Museums News Railways Underground14 Wesley Road Anthony Reynolds Gallery Art on the Underground Blue plaques British Museum chocolate Easter Hampton Court Palace Hanoverian Harry Beck Herculaneum John Vanbrugh Kew Gardens King George II King James II King's Cross Station Leyton Life and death in Pompeii and Herculaneum London Underground map Mark Wallinger Mary of Modena Mount Vesuvius Pompeii Prince of Wales' Apartments Princess of Wales Conservatory Secrets of the Royal Bedchamber Sir Nigel Gresley Spanish Conquistadors State Bed Stuart travelling bed warming pan bed
10 Historic London Markets – 6. Old (and New) Spitalfields Market…
by exploringlondon November 7, 2012 November 7, 2012
There has been a market on the site now known as Old Spitalfields Market, located on the eastern outskirts of the City of London next to what was the Priory and Hospital of St Mary Spital, since the thirteenth century.
But it was centuries later when, following the tumult of the Civil War, in 1682, John Balch was formally granted a Royal Charter by King Charles II to hold a "flesh, fowl and roots" market on Thursdays and Saturdays in or on the rectangle of land known as Spital Square. A 'market-house' was built on the site around this time for administrators with traders selling their wares from stalls.
The success of the market drew people to the area – in particular, Huguenots fleeing France who brought with them new skills in silk-weaving, and later Irish fleeing the Potato Famine and Jews escaping the harsh political climate in Eastern Europe – and the market gained a name for itself as a place to buy fresh produce.
By late in the 19th century, the market had fallen into decline. So, in 1876, a former market porter by the name of Robert Horner decided it needed an upgrade and, buying the lease, had the central market square roofed with glass and new market buildings, known as the Horner Buildings (pictured above), constructed around the northern, eastern and southern sides of the site. Having cost £80,000, it was completed in 1893.
In 1920, the City of London took over control of the market and later than decade expanded the original buildings. Having continued to grow over the ensuing years and with traffic congestion continuing to increase in the surrounding streets, it was decided to move the fresh produce aspect of the market to a new location at Leyton to the north-east.
The new market, known as New Spitalfields Market, covers more than 31 acres and boasts more than 100 traders.
Meanwhile, Old Spitalfields Market, the western end of which was redeveloped in the late 20th century, continues to operate on the original market site – now known as Horner Square, with stalls selling everything from contemporary and vintage fashion to music, gems and jewellery, bric-a-brac and antiques as well as various themed market days – check the website for more details.
Old Spitalfields Market
WHERE: Horner Square, Spitalfields (nearest Tube stations are Shoreditch High Street and Liverpool Street); WHEN: Markets are held every day – times vary so check website for details; COST: Free; WEBSITE: www.oldspitalfieldsmarket.com.
New Spitalfields Market
WHERE: 23 Sherrin Road, Leyton (nearest Tube station is Leyton); WHEN: Trading hours midnight to around 9am, Monday to Saturday; COST: Free; WEBSITE: www.cityoflondon.gov.uk/business/wholesale-food-markets/new-spitalfields/Pages/default.aspx.
10 Historic London Markets Charles II City Civil War East London Markets MedievalCivil War Edict of Nantes Horner Buildings Horner Square Hospital of St Mary Spittel Huguenots John Balch King Charles II Leyton New Spitalfields Market Old Spitalfields Market Robert Horner Spital Square Spitalfields


This package contains Diablo II and Diablo II: Lord of Destruction Expansion Pack.
Features: Five New Character Classes with Unique Abilities Battle Hell's minions as the Amazon, Sorceress, Necromancer, Paladin or Barbarian each with unique skills and spells. Four Expansive Realms Storm a vast underworld of twisted dungeons and uncharted wilderness as you journey across an immense, ever-changing world. Fiendishly Enhanced Multiplayer Advanced Battle.net technology unleashes support for up to 8 players over the Internet, including multiplayer quests, trading posts, and much more. Dynamic Character Imaging Composite character animation system enables dynamic display of differences in weapons, armor and items. Powerful New Weapons & Magic Summon and command nightmarish creatures, harness the elemental powers of nature, and master the energies of light and darkness through arcane spells and enchantments.
Features: Two New Character Classes Unleash the fury of 60 new unique skills and spells as the stealthy assassin or the shape-shifting druid. Each character can be played through the original four acts as well as the new act. Wickedly Enhanced Graphics For the first time, wage your never-ending quest for vengeance in stunning 800×600 resolution. A New Army of Evil Battle over a dozen fiendish new monsters, including Overseers, Putrid Defilers, and the Reanimated Horde as you fight through fortified battlements and face relentless siege engines. Expanded Arsenal & Stash Wield thousands of new magical, unique, set and exceptional items and secure them in your expanded private stash.


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Home > Vol 103, No 10 (2013) >	Ukpe
SAMJ MALARIA 1.6
Case management of malaria: Treatment and chemoprophylaxis
I S Ukpe,1,2 MB BCh, MMed (Fam Med); D Moonasar,3 DrPh; J Raman,4 PhD; K I Barnes,5 MB ChB, MMed (Clin Pharm); L Baker,6 Dip Pharm; L Blumberg,7 MMed (Path Microbiol)
1 Department of Family Medicine, University of Pretoria, South Africa
2 Mpumalanga Department of Health, Nelspruit, South Africa
3 Malaria Directorate, National Department of Health, Pretoria, South Africa
4 Malaria Research Unit, South African Medical Research Council, Durban, South Africa
5 Division of Clinical Pharmacology, University of Cape Town, South Africa
6 Amayeza Drug Information Centre, Johannesburg, South Africa
7 Division of Public Health Surveillance and Outbreak Response, National Institute for Communicable Diseases, Johannesburg, South Africa
Corresponding author: D Moonasar (moonad@health.gov.za)
Malaria case management is a vital component of programmatic strategies for malaria control and elimination. Malaria case management encompasses prompt and effective treatment to minimise morbidity and mortality, reduce transmission and prevent the emergence and spread of antimalarial drug resistance. Malaria is an acute illness that may progress rapidly to severe disease and death, especially in non-immune populations, if not diagnosed early and promptly treated with effective drugs. In this article, the focus is on malaria case management, addressing treatment, monitoring for parasite drug resistance, and the impact of drug resistance on treatment policies; it concludes with chemoprophylaxis and treatment strategies for malaria elimination in South Africa.
S Afr Med J 2013;103(10 Suppl 2):793-798 DOI:10.7196/SAMJ.7443
Malaria case management is a vital component of programmatic strategies for malaria control and elimination.1-3 Malaria case management encompasses prompt and effective treatment to minimise morbidity and mortality, reduce transmission and prevent the emergence and spread of antimalarial drug resistance. 1-3 The number of malaria-related deaths is a key epidemiological indicator in malaria programmes used to evaluate performance in delivering effective malaria case management.1
Malaria is an acute illness that may progress rapidly to severe disease and death, especially in non-immune populations, if not diagnosed early and promptly treated with effective drugs. South Africans, including those living in the malaria transmission areas within the country, are generally non-immune. All age groups are therefore at risk of developing severe disease when infected.4 , 5
Some important considerations to ensure effective malaria case management include availability and accessibility of antimalarial medicines, training of healthcare workers at all levels of healthcare delivery and dealing with the problem of antimalarial drug resistance.1 In this article, the focus is on malaria case management, addressing treatment, monitoring for parasite drug resistance, and the impact of drug resistance on treatment policies; it concludes with chemoprophylaxis and treatment strategies for malaria elimination in the country.
1. Malaria treatment in endemic and non-endemic provinces
Stratification of malaria risk areas in South Africa (SA) into endemic and non-endemic areas followed the first malaria survey in the country in 1921 by Park Ross, who was then the Assistant Secretary of Health of the Union of SA. Malaria-endemic parts at that time included the Pretoria and Durban districts.6 , 7 Malaria endemic areas in today's SA are the north-eastern part of KwaZulu-Natal (KZN) Province and the low altitude regions of Mpumalanga and Limpopo provinces.4 , 8 Although the Northern Cape and North West provinces are classified as non-endemic, malaria transmission occurs occasionally in areas adjacent to the Molopo and Orange rivers.5 Malaria treatment strategies in the country differ slightly in endemic and non-endemic provinces.
Historically, before the advent of chloroquine (CQ) in the late 1940s, quinine was used for both treatment and prophylaxis, but the measures could not be practically extended to the population in the endemic areas as a whole.6 , 7 During the 1970s, the malaria control programme in the country became more structured. Treatment was based on definitive diagnosis by blood smear microscopy. Malaria case detection and treatment was mainly through active case finding during house-to-house surveys and mass blood examination and between 1987 and 1990, >50% of all malaria cases in the country were detected by active case finding. 6 , 7 Passive case detection and treatment, whereby symptomatic patients at healthcare facilities were tested for malaria and treated if found positive only played a minor role in parasite control. In KZN Province, 30% of all cases in the same period were detected at hospitals and clinics, of which clinics contributed only 12%.6 , 7
In the 1990s, Sharp et al.6 , 7 hypothesised that the relatively minor role of clinics in malaria case detection in the country could be addressed in a cost-effective manner by community involvement and enhanced service at the clinic level, effectively reducing the need for active case detection, and reducing costs. This was realised in the mid-1990s. The adoption of the District Health System (DHS) based on primary healthcare (PHC) as the healthcare strategy for SA since 1994,9 the subsequent integration of passive diagnosis and treatment of malaria into PHC within the DHS10 and the introduction of malaria rapid diagnostic tests (RDTs) at the PHC level starting in Mpumalanga Province in 1996,11 revolutionised malaria case detection and treatment across the country. Passive detection and treatment of malaria at healthcare facilities based on a parasitological diagnosis with RDTs at PHC facilities and prompt, effective treatment is currently the major malaria case management strategy to reduce transmission in endemic areas. In Mpumalanga Province, passive case detection contributes >90% of reported total malaria cases each year in this era of PHC-based DHS in SA (Fig. 1) (Mpumalanga Malaria Programme, unpublished data).
Fig. 1. Malaria in Mpumalanga Province, 1996/97 - 2012/13 season (CFR = case fatality rate).
Malaria diagnosis and treatment are provided free-of-charge at public healthcare facilities in both endemic and non-endemic provinces in the country. Evidence-based national or provincial guidelines informed by expert recommendations dictate the selection of preferred antimalarials, and drug choice policies have differed between provinces at various times (Table 1). Drug resistance surveillance data driving these policies are discussed later.
Currently in all endemic and non-endemic provinces, artemether-lumefantrine (AL) is the recommended first-line antimalarial medicine for the treatment of uncomplicated falciparum malaria. Primaquine is used for radical cure of Plasmodium vivax and P. ovale infections.5 Primaquine is currently unregistered but is available through a Section 21 process.5 The second-line antimalarial medicines for the treatment of uncomplicated malaria remain oral quinine plus doxycycline (for adults) or clindamycin (for pregnant women and children under the age of 8 years).5
Parenteral quinine has been the mainstay of treatment of severe malaria, and is still widely used in most African countries today. 12 , 13 Intravenous artesunate is a new parenteral antimalarial currently recommended by the World Health Organization (WHO) for the treatment of severe malaria in adults and children.2 , 14 Intravenous artesunate is not yet registered for use in SA, but there is limited availability through a special access programme for compassionate use on a named-patient basis.5
In the endemic provinces, treatment with the recommended first-line antimalarial medicines for uncomplicated malaria is accessible at any level of public healthcare facility, including fixed and mobile PHC facilities. Parenteral antimalarial medicines for the treatment of severe malaria are only available at hospital level. In the non-endemic provinces, antimalarial treatments are mostly accessible at the hospital level. In both endemic and non-endemic provinces, uncomplicated malaria is treated at outpatient level, except for high-risk population groups (pregnant and postpartum women, infants and young children, the elderly (>65 years) and immunocompromised patients, including those with HIV/AIDS), who constitute a definite indication for hospital admission.5 Severe malaria is a medical emergency that requires high-level hospital care; thus, for severe malaria patients diagnosed at PHC and private general practitioner facilities, emergency transfer to hospital is the norm in both endemic and non-endemic provinces.5 The WHO recommends pre-referral treatment of severe malaria with intramuscular artesunate, artemether, quinine or rectal artesunate if the transfer time to hospital is longer than 6 hours.2 This recommendation is not implemented in SA.
The major challenge facing malaria case management in the country is reduction of malaria-related deaths. Late presentation, lack of awareness of malaria in communities, and a low index of suspicion in healthcare workers, particularly in non-endemic provinces in the country,15-18 are major contributing factors to malaria-related deaths. Even in the endemic provinces, case fatality rates (CFRs), defined as the number of deaths per 100 cases of malaria is above the national target of <0.5% (Fig. 2). The importance of continuing education of healthcare workers on malaria diagnosis and treatment19
Fig. 2. Malaria case fatality rates (CFR) in malaria-endemic provinces and the national target, 1999/2000 season to 2011/2012 season.
2. Antimalarial drug resistance across SA and neighbouring countries
Antimalarial drug resistance has greatly influenced malaria case management strategies in SA since the 1980s. Stringent control interventions comprising indoor residual spraying, periodic larviciding, and treatment with CQ from the late 1940s ensured malaria posed no severe public health burden until the mid-1980s.20 Unfortunately by this time CQ resistance had reached Africa and was becoming firmly entrenched in southern Africa.21
2.1 KZN
KZN Province first reported in vitro CQ resistance in 1985.22 Under sustained CQ pressure, resistance spread, resulting in an increase in malaria cases and treatment failures. By 1987, 3% of all malaria-treated patients remained malaria-positive despite being treated four times with CQ.23 The rise in cases and treatment failures prompted the KZN Department of Health to replace CQ with sulphadoxine-pyrimethamine (SP) in 1988. This policy change caused case numbers to gradually decline from a high of 6 757 in 1987 to <500 by 1992.
However, between 1993 and 2000 malaria case numbers began rising sharply, peaking in 2000 with over 40 000 cases reported in KZN.24 An in vivo efficacy trial revealed the 42-day cure rate following SP treatment had fallen from above 75% in 1997 to 11% by 2000.25 Retrospective genetic analyses on samples collected during a community-based prevalence survey in 2000 confirmed the presence of highly SP-resistant parasites, with 47% of all parasites analysed in carrying the SP quintuple mutation associated with SP treatment failure.26 This high prevalence of SP-resistant parasites most likely enhanced transmission, as individuals infected with SP-resistant parasites have increased gametocyte loads,27 which are more infectious to mosquitoes than SP-sensitive gametocytes.
KZN responded to this SP resistance epidemic by becoming the first province to deploy the artemisinin-containing combination treatment (ACT), AL, in 2001. 24 Although malaria morbidity declined by 99% following this policy change,24 the SP quintuple mutation remained extremely prevalent in the province. By 2012, 75% of the parasites analysed carried the mutation (J Raman, unpublished data). Sustained antimicrobial pressure by co-trimoxazole, an antifolate-sulphonamide combination used as prophylaxis against opportunistic infections in HIV/AIDS patients28 may be the reason, given the high HIV/AIDS prevalence in KZN.
Encouragingly, however, parasites carrying molecular markers associated with CQ sensitivity, namely, crtK76T and mdr186N29 are beginning to resaturate the KZN P. falciparum population.30 A similar phenomenon has been seen in both Mozambique31 and Malawi32 following the prolonged removal of CQ drug pressure. This re-emergence of CQ sensitivity may allow for the use of CQ as an antimalarial partner drug in the future.
2.2 Mpumalanga and Limpopo
Like KZN Province, reports of CQ resistance from Mpumalanga23 and Limpopo provinces33 first emerged in the 1980s. However, CQ treatment failures in both of these provinces remained relatively rare until the 1990s. A possible reason for the delay in treatment failures is the lower incidence of immigrant asymptomatic malaria carriers entering Mpumalanga and Limpopo provinces compared with KZN. The border between KZN and Mozambique is extremely porous, with people crossing the border on a daily basis.6 A border-screening malaria survey in 1996 revealed 58% of the individuals entering KZN were asymptomatic malaria carriers who remained untreated in the province for long periods, thereby contributing to local transmission. 20
Both in vitro and in vivo studies revealed a growing population of CQ-resistant parasites in both Mpumalanga and Limpopo provinces21 , 34 in the 1990s, which led to SP becoming the antimalarial of choice in Mpumalanga Province in 1997 and a year later in Limpopo Province. Although therapeutic efficacy studies demonstrated sustained SP efficacy in Mpumalanga five years after SP introduction,35 with SP quintuple mutation prevalence only at 10% (J Raman, unpublished data), patients successfully treated with SP displayed enhanced gametocyte carriage.35
In an attempt to reduce gametocyte carriage and malaria case numbers the ACT, artesunate-SP, replaced SP as the antimalarial of choice in Mpumalanga Province in 2001. While this change resulted in the quintuple mutation prevalence declining to <10%, malaria case numbers remained largely unchanged in the next few years. The low SP quintuple mutation prevalence suggested that something other than SP resistance was sustaining malaria transmission.
In accordance with the South African National Malaria Treatment guidelines, AL became the first-line treatment in Mpumalanga in 2006. This policy change was very timely as the SP quintuple mutation prevalence had risen to 48% by 2007 (J Raman, unpublished data). As seen in KZN, AL introduction resulted in a decline in malaria cases, but had no effect on quintuple mutation prevalence. By 2011 confirmed malaria case numbers had declined by 35% while quintuple mutation prevalence has risen to above 80% (J Raman, unpublished data). The crt76T and mdr186N molecular markers associated with CQ sensitive had become re-established in the population and were approaching fixation by 2011 (J Raman, unpublished data).
Although AL became the first-line treatment in Limpopo Province in 2004, there was no major decline in malaria case numbers by 2011. Unfortunately, drug resistance surveillance data are limited, with only one study in 2010 showing quintuple mutation at 41% and <1% of parasites analysed carrying markers associated with CQ resistance.
2.3. Regional drug pressure
Despite stringent efforts, drug-resistant malaria epidemics still occurred in SA, in part due to the importation of drug-resistant parasites. Resistance to both CQ and SP arose in Southeast Asia and spread into Africa via gene flow rather than evolving de novo,26 , 36 highlighting the need for regional malaria control, and more importantly, a clear understanding of the malaria epidemiology in neighbouring countries. As the movement of both the malaria vector and parasite is not restricted by national boundaries regional drug pressure can influence drug efficacy within countries, as seen in KZN Province, SA20 and Maputo Province, Mozambique.37 Given the first-line antimalarial in all southern African countries is AL and that artemisinin resistance has been confirmed in Southeast Asia,38 routine monitoring of AL efficacy is recommended, particularly in Limpopo Province, which currently experiences the highest incidence of African immigrant visitors.
3. Antimalarial drug efficacy monitoring and the impact of drug resistance on treatment policies
The inevitable emergence and spread of drug resistant parasites has had profound effects on South African malaria case management strategies. Thus, sustained and rigorous monitoring for antimalarial resistance provides the essential backbone for informing evidence-based malaria treatment policies. During the malaria control phase, such monitoring can effectively be conducted through regular in vivo therapeutic efficacy studies. Such studies were conducted regularly in all three malaria endemic provinces (KZN, Mpumalanga and Limpopo) until 2004. These data were complemented by data on antimalarial drug exposure and molecular markers of resistance for the treatments recommended. In vitro assays have occasionally been used to monitor for antimalarial resistance in SA.21 , 34
The dramatic reductions in local malaria transmission following strengthening of vector control and large-scale deployment of ACT subsequently precluded an adequate sample size being recruited in any sentinel site in SA. Drug resistance monitoring is currently based primarily on monitoring for known molecular markers of resistance, complemented by surveillance to define geographic and temporal trends in malaria case numbers, and routine follow-up of malaria cases post-treatment to detect potential treatment failures.
Malaria treatment policies are decentralised to the provincial level, which has resulted in the three malaria endemic provinces at times having different policies, as summarised in Table 1. The major driver for changes in malaria treatment policies in SA has been evidence of parasite resistance to the recommended treatment reaching unacceptable levels, as outlined above. Factors usually considered for the selection of each new treatment policy include recommendations by the WHO, regulatory requirements of the South African Medicines Control Council, international peer-reviewed evidence on efficacy, safety and tolerability, cost, and likelihood of compliance and adherence (including duration and complexity of treatment course).
In KZN, AL was selected as the preferred ACT as there was no established resistance to the partner drug, lumefantrine, unlike SP or amodiaquine. By contrast, in Mpumalanga and Limpopo, where SP remained highly effective, the ACT artesunate-SP was selected. This combination had the advantage of not requiring co-administration with fat and the majority of patients likely to be cured even if they were not fully adherent, given that SP treatment only requires a single dose. However, a number of disadvantages were detected with careful monitoring following the deployment of this combination, including: suboptimal SP exposure in young children given the recommended dose of SP (K Barnes, unpublished data); that it could not be manufactured as a fixed dose combination, and so risked use of artesunate monotherapy; and that molecular markers of SP resistance continued to increase despite SP being used in combination with artesunate (J Raman, unpublished data).
However, additional factors have influenced policy and practice. The malaria control programme in KZN added a single dose of primaquine to SP in the mid-1990s, to reduce transmission. This strategy was curtailed when the manufacturer, Winthrop, withdrew the product from the South African market. Primaquine is currently only available for compassionate use on a named-patient basis.5 Clinicians in KZN started using CQ in addition to SP in the late 1990s when they suspected clinically that SP efficacy was waning, although no formal resistance studies were conducted.
4. Malaria chemoprophylaxis
Malaria chemoprophylaxis entails the use of antimalarial medicines to prevent malaria especially in non-immune people travelling to malaria endemic areas.3 In SA, chemoprophylaxis is recommended for residents in non-endemic areas travelling to endemic areas within and outside the country.39 Up until the early 1990s, CQ was the recommended antimalarial medicine for chemoprophylaxis. It could be given to pregnant women and young children. CQ plus pyrimethamine was also used, but in 1991 it was determined that due to pyrimethamine resistance, little benefit was conferred by the combination. There was an increase in side-effects, and a folic acid supplement was necessary when given to pregnant women.40 CQ alone was therefore preferable. Dapsone-pyrimethamine was another potential option but had a number of side-effects such as agranulocytosis, methaemoglobinaemia and megaloblastic anaemia. These, however, were more common when the recommended dose was exceeded.40 There was also concern over efficacy and it was therefore not usually officially recommended.40
CQ plus proguanil was another option recommended internationally; however, proguanil was only registered in SA in 1997, at which time the combination became the chemoprophylaxis of choice. It was, however, a complicated regime as CQ was taken once weekly and proguanil daily. Up until this point, all chemoprophylactic options were classified Schedule 1 and could thus be given out without a prescription. They were also available from those who were employed by any department responsible for environmental affairs or tourism at a provincial government level, such as the tourist shops in the Kruger National Park.
The emergence of widespread CQ resistance eventually led to its abandonment as antimalarial medicine for chemoprophylaxis. Thereafter, the selection of antimalarial medicines for chemoprophylaxis recommendations in the country has been following the WHO recommendations for CQ-resistant malaria transmission areas. Currently, doxycycline, mefloquine, and atovaquone-proguanil are the recommended choices.39 , 41 Unlike CQ and the other earlier medicines, these drugs are only available on prescription and are not free of charge, even in the public healthcare sector.
5. Considerations for malaria elimination
5.1 Drug efficacy monitoring
As countries undergo transition towards malaria elimination, routine monitoring of drug efficacy is essential, particularly as any artemisinin-resistant malaria outbreak could result in severe morbidity and mortality given the low or absent immunity to malaria within the population and current dependence on ACT. Conducting in vivo efficacy trials in regions approaching malaria elimination is virtually impossible due to the low case numbers. Hence, alternative methods such as the routine surveillance of molecular resistance markers should be considered. Molecular analysis should be conducted on samples collected from various sentinel sites to ensure robust data is obtained. Technological advances now mean that a liquid blood sample is no longer needed for molecular analysis. Filter paper blood spots and even malaria-positive RDTs42 can be used as sources of parasite DNA. This routine surveillance must become part of the elimination agenda in all South African malaria endemic regions, particularly in malaria hot spots.
Inability to monitor for molecular markers of resistance rapidly and effectively during the pre-elimination phase is a major threat to our ability to eliminate malaria. Drug resistance has almost invariably emerged in areas of very low-intensity malaria transmission. As the population in these areas is non-immune, infections are usually symptomatic so most patients will seek treatment, thereby increasing drug pressure. Furthermore, they lack the immunity that is needed to suppress replication of resistant parasites. With artemisinin resistance already confirmed in four countries in the Greater Mekong Region of Southeast Asia, and no molecular marker yet validated for detecting artemisinin-resistant parasites, there is a real possibility of this resistance spreading to (or emerging in) SA.
Because malaria cases have become too few at any single health facility in the endemic provinces in the country, a complete in vivo therapeutic efficacy study is not feasible. Until validated molecular markers are available for artemisinin resistance, our best options are to continue to monitor routinely for molecular markers of resistance to lumefantrine (or future ACT partner drugs), and whenever possible to test for the presence of P. falciparum parasites 3 days post-treatment, and to follow up patients 4 - 6 weeks post-treatment, to establish whether they remain malaria-free. The result of the malaria blood smear on day 3 (72 hours post-treatment) is a good predictor of subsequent treatment failure, and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100 000 parasites/ml, who have a positive smear result on day 3 after ACT treatment, is <3%.43
5.2 Radical cure
The malaria situation in SA has now moved from control phase to the pre-elimination and elimination phases. ACT policy is fully implemented in the country. As malaria becomes less common, finding and treating the last few cases becomes increasingly onerous and expensive, so it is important to maximise all opportunities for interrupting transmission. One such intervention, which is endorsed by the WHO,44 is to treat all positive malaria cases with a single dose of primaquine. This drug efficiently inactivates gametocytes but in persons with genetically determined glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency of red blood cells, it may cause haemolysis and subsequent anaemia of variable severity. Historically, the South African black population has a low rate of G6PD deficiency, and the enzyme defect locally is generally quantitatively fairly mild, so severe reactions are uncommon.45 However, with increasing immigration from other parts of Africa, the demographics of G6PD deficiency may have changed. Before the elimination programme decides to go ahead with primaquine use, it needs to update local knowledge about G6PD deficiency in SA, for ethical and scientific reasons.
5.3 Community-level treatment
As part of the malaria elimination programme, SA is seriously considering community-level treatment of uncomplicated and asymptomatic malaria detected during active case investigation by malaria surveillance officers. The feasibility of community-level treatment will require extensive training of community health workers and malaria field investigators, as well as drug regulatory changes, for this to happen.
5.4 Free prophylaxis
The currently recommended chemoprophylactic options, which are all very effective if taken correctly, are mefloquine, doxycycline and atovaquone-proguanil.39 , 41 They are all only available on prescription. This significantly hinders accessibility by the public. As SA moves towards elimination, it will be imperative to make these products readily accessible to all those travelling to malaria-risk areas, including those who can ill afford chemoprophylaxis. This is important not only for reducing the risk of the travellers becoming sick with malaria but also for elimination purposes – the prevention of importation of parasites into the country which could result in infection of local mosquitoes and local malaria transmission.
While there is a strong case and support for the provision of free chemoprophylaxis for travellers to malaria-endemic areas for malaria elimination purposes, questions around feasibility, cost effectiveness, regulation, accessibility and drug scheduling will need to be answered before the strategy can be considered in SA.
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