text:
More than 100 scientists and policymakers met in Canberra to discuss burning issues in Australian science and technology.
At a time where society is facing numerous challenges that can and should be informed by science and technology, experts will discuss why evidence, research, and reason lead to the best policy outcomes.
2017's Science meets Policymakers focuses on two issues in particular – a plan for the future of Australian science and innovation; and how to best synthesise technology and economics to improve planning for the natural environment.
Experts in policy, science, and technology are actively workshopping solutions in these two critical areas, with findings to inform the creation of the 2030 Strategic Plan for the Australian Innovation, Science and Research System, and Australian environmental policies.
CEO of Science & Technology Australia, Kylie Walker, said it was heartening to see representatives from a range of Departments, professionals from across numerous science, technology, engineering and mathematics (STEM) disciplines.
"We've given Canberra's collective brain-power a significant boost: we're proud to bring Australia's best policymakers together with some of the brightest scientific minds," Ms Walker said.
"By bringing together leaders from government, and science and technology, we hope to move forward important areas of policy-making for Australia's future, as well as spark new networks and relationships which will make it easier for those creating policy to access the evidence they need."
Ms Walker said science and technology play an important part in defining problems, measuring their impact, and proposing solutions to address them, while great policy finds ways to integrate these solutions into society.
"The more science and technology can play a part in the way we address some of the biggest problems in our community, the stronger and more effective federal policy will be.
"We're also pleased to have an environmental management focus ahead of National Science Week, which has 'Future Earth' as its theme."
Source: Science & Technology Australia


text:
Facebook recently changed the way groups work and although there are many advantages when it comes to marketing your business there are also some disadvantages.
The way groups used to work was that someone would set up a group, invite people to join and start discussing things, creating events etc. But importantly as an admin of a group you could send a message to every single group member at once, whether friends of yours or not, it was like an email campaign within Facebook.
With the new version of groups this is not possible, if you are admin of an old group you still have access but groups started since the change at the end of last year, do not.
One of the disadvantages of the old groups was that people could join them and then never think about them again! (unless the group's admin used the message function to communicate with you!). This is because there were no notifications of things that happened in the group and even if a friend of yours posted on the wall of a group you were both members of it would not show up in your news feed. In fact the only time anything to do with the group would show up in news feeds was when someone first joined them, seriously limiting the possibility of them going viral!
If you want to use an old style group to promote your page on Facebook, the best way is to comment on other people's posts, politely, and add a link to your page. This way the person that wrote the post will at least get a notification, although no one else will, so doing this frequently is important. This is very time-consuming however.
You can also write blog posts that show you know your field and post them onto discussion forums but the quickest way is to look to see who the administrator of the group is and approach them. They may agree to sending out a message on your behalf, they may even allow you to become an administrator yourself which would allow you to message as often as you like, I know I don't need to remind you to use this privilege regularly but not over frequently! If you are the admin of an old style group maybe you could offer to do the same in return?
New groups have one very important feature that allows membership to grow very quickly. They give you the ability to add anybody you think would like to join, and you don't need their permission to do this. Although this can also means that it can diminish very quickly and you risk irritating the very people you want to prove valuable too.
One way to avoid this is to send a message to each person before you add them to let them know what you are doing and why, and letting them know how they can leave if they wish too. Good manors, but very time-consuming!
You could also add a paragraph saying this to the introduction that all the group members will see. This solution isn't as personal but it's better than nothing, once the group is established you can remove this.
New groups do have the distinct advantage of notifying members whenever anything new is posted which keeps interaction going. You can post any promotion, link announcement or discussion safe in the knowledge that people will know something's been posted and may well go into the group to se what's happening and view your post. This being so make sure you offer them links to your page, blog, website etc as often as is appropriate.
So what types of groups should you look for? Well that depends on your business, if I manufactured dolls house furniture for example, I would join a group for doll's house enthusiasts.
It's also often a good idea to join groups that are geographically based, the county I live on has plenty of these and being a member of them certainly has it's advantages as people often want to do business with other local businesses.
Building your audience is often the most time-consuming thing about social media, which is why so many people neglect this area, but spending even 30 minutes a week will reap results. But if you want to reach a lot more of your ideal clients now instead of in 6 months or a year then please feel free to call me!

subset: commoncrawl


text:
algae control system Applications
Algae control in sea chests
Prevent biofouling with ultrasound in sea chests and reduce maintenance costs. Improve the efficiency of the system. Reduce fuel consumption. Easy installation.
By LG Sonic based in Zoetermeer, NETHERLANDS.
Algae control solutions in ponds and lakes for Aquaculture sector
By QM Environmental International B.V. based in The Hague, NETHERLANDS.
Cover and Liner Systems for Agriculture Apllications
We specialize in cover and liner systems designed specifically for agricultural applications. We work directly with farmers and Technical Service Providers from initial planning through final installation and inspection on solutions that fit both current and future needs. Our covers and liners can be found in a variety of agricultural applications, from family farms to large feed lots.
Our innovative solutions solve a variety of problems including gas collection, biogas management, odor control, rainwater collection, algae control, wildlife control, and wastewater management, to name a few.
We are interested in learning more about your needs and unique requirements. To learn more about our products and services or to request additional information, call us today!
By Industrial & Environmental Concepts, Inc. (IEC) based in Lakeville, MINNESOTA (USA).
Chlorine Dioxide Water Treatment for Power Plants
Chlorine dioxide is a significant product in the control of algae, planktonic and sessile bacteria, bio-film and scale in power plants, cooling towers, loops and cooling systems. CleanOxide helps maintain the efficiency of heat exchanger surfaces, reservoir intakes and ancillary equipment. Traditional oxidising agents such as chlorine and bromine, on the other hand, are associated with pH constraints and corrosion problems.
By NW Solutions based in Perth, AUSTRALIA.
By Scalewatcher North America Inc. based in Oxford, PENNSYLVANIA (USA).
Need help finding the right suppliers? Try XPRT Sourcing. Let the XPRTs do the work for you


text:
Welcome to SpeechRecovery.com!
SpeechRecovery.com offers a neuroplastic speech recovery method to those who suffer from mild to severe aphasia and apraxia. Our award-winning programs are used by brain injury and stroke survivors of all ages!
Our "brain friendly" speech practice programs use the Sensory Trigger Method to tap into brain pathways from early childhood and the undamaged speech centers on the other side of the brain. These special techniques are based on the brain research that shows that new pathways can reconnect speech.
After the new connections are made and a substantial level of speech returns, the sensory trigger will not be needed. New abilities will continue to expand on their own. We call this "neuroplastic speech recovery".
It works by something called "sensory substitution". The sensory trigger uses touch signals to substitute for the damaged or lost connections in the brain. These signals travel the neuro-pathways that are responsible for initiating and producing speech.
The touch signals learn how to communicate with the brain in a new way. They adapt and function just like speech signals and which are recognized by the undamaged speech centers.
It's much like Braille or American Sign Language; the fingertips and hand become the organ of speech. For the blind, the fingertips can be trained to read the tiny bumps on a page of a book or sign. For the deaf, the hands become their speech using gestures along with facial expressions and body language.
The Sensory Trigger Method uses the fingertips and hand movements. The touch signals teach the brain how to develop new speech areas capable of initiating speech independently and spontaneously.
Our programs have simple, motivating exercises. With daily practice and functional communication with family and others, one can now take charge of their speech recovery.


text:
Title: Hold Me Like A Breath
Author: Tiffany Schmidt
Publisher: Bloomsbury
Publication Date: May 19, 2015
Penelope Landlow has grown up with the knowledge that almost anything can be bought or sold—including body parts. She's the daughter of one of the three crime families that control the black market for organ transplants. Penelope's surrounded by all the suffocating privilege and protection her family can provide, but they can't protect her from the autoimmune disorder that causes her to bruise so easily. And in her family's line of work no one can be safe forever. All Penelope has ever wanted is freedom and independence. But when she's caught in the crossfire as rival families scramble for prominence, she learns that her wishes come with casualties, that betrayal hurts worse than bruises, that love is a risk worth taking . . . and maybe she's not as fragile as everyone thinks.
Time for the trailer reveal
Meet The Author
You can find her on her website, Goodreads, Twitter, Facebook, Tumblr, and Instagram.
Boldly Bookish Order Campaign
This spring, Bloomsbury's sending four amazing authors—Trish Doller, A.C. Gaughen, Emery Lord, and Tiffany Schmidt—to bookstores together for our Boldly Bookish tour. To celebrate it, they are giving away some goodies! All you have to do is buy one of the following books: The Devil You Know, Lion Heart, The Start of Me and You and/or Hold Me Like A Breath and email your receipt to email@example.com, in order to receive one of the following prizes:
Preorder 1 of the books pictured above, and get a Boldly Bookish logo sticker.
Preorder 2 of the books pictured above, and get a sticker + a Boldly Bookish bookmark!
Preorder 3 of the books pictured above, and get a sticker + bookmark + a Boldly Bookish button!
Preorder all 4 of the books pictured above, and get a sticker + bookmark + button + a Boldly Bookishmagnet!
And remember, the more books you preorder, the more Boldly Bookish swag you get!
Time for the giveaway!


text:
Working in partnership with Defence Housing Australia, SA Renewal and Palumbo Builders, P.T.A. have developed Australia's first six-star green star rated residential building in Bowden, South Australia. The Princes Terrace Adelaide merges good design with sustainable building practices, all the while proving its commercial viability and preserving our traditional influence and heritage. The Terrace is due for completion in November 2017.
Defence Housing Australia (D.H.A), SA Renewal have developed The Prince's Terrace Adelaide – Australia's first six-star green star rating for a residential development.The joint venture, facilitated by The Prince's Trust Australia, will help locals live better at a community level and deal with the broader global challenges of urbanisation and climate change, whilst preserving our traditional influence and heritage.
Located in the Bowden urban renewal precinct, the eight-house Terrace and four mews apartments emphasize local, low-carbon materials, including local concrete made with fly ash, local granite and bricks re-used from old Bowden industrial buildings.
The Terrace also features:
→ Precision structural orientation to minimise summer solar gain and maximise natural cross ventilation
→ A facade designed to maximise daylight access and views while managing glare
→ Small and high efficiency air conditioning systems coupled with ceiling fans to equip residents for peak summer temperatures
→ LED lighting and photovoltaic solar panels generating renewable energy to reduce the building's peak power demand
→ High efficiency water fittings, with toilets and laundry fittings supplied with 100 per cent recycled water.
Residents are expected to use 50 percent less energy and potable water when compared to a typical house. Carbon emissions are also expected to be 40 per cent less.
During the 2015 Royal Tour, His Royal Highness The Prince of Wales visited the development site in Bowden, turning the first sod.
The Adelaide demonstration build supports knowledge transfer and will also provide:
→ Training and education on sustainable building practices
→ Materials and workshops to equip professionals, graduates, students and others with the skills they need to design, build and preserve sustainable environments
→ Further focus on sustainability, traditional architecture and urbanism, building skills and aesthetics.


text:
Alternatives to currently used antimalarial drugs: in search of a magic bullet
- 2.5k Downloads
- Citations
Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.
To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners' collaboration. However, no reviews were focused following various preclinical and clinical studies published since the MMV initiation (2000) to till date.
We identify promising approaches in the global portfolio of antimalarial medicines, and highlight challenges and patient specific concerns of these novel molecules. We discuss different clinical studies focusing on the evaluation of novel drugs against malaria in different human trials over the past five years.
The drugs KAE609 and DDD107498 are still being evaluated in Phase I trials and preclinical developmental studies. Both the safety and efficacy of novel compounds such as KAF156 and DSM265 need to be assessed further, especially for use in pregnant women. Synthetic non-artemisinin ozonides such as OZ277 raised concerns in terms of its insufficient efficacy against high parasitic loads. Aminoquinoline-based scaffolds such as ferroquine are promising but should be combined with good partner drugs for enhanced efficacy. AQ-13 induced electrocardiac events, which led to prolonged QTc intervals. Tafenoquine, the only new anti-relapse scaffold for patients with a glucose-6-phosphate dehydrogenase deficiency, has raised significant concerns due to its hemolytic activity. Other compounds, including methylene blue (potential transmission blocker) and fosmidomycin (DXP reductoisomerase inhibitor), are available but cannot be used in children.
At this stage, we are unable to identify a single magic bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.
KeywordsMalaria Drug development Medicine for malaria venture Chemotherapy Tafenoquine Fosmidomycin Novel antimalarial drugs Artemisinin derivatives
Artemisinin-based combination therapy
Glucose-6-phosphate dehydrogenase
Global Malaria Action Plan
Minimum inhibitory concentration
Medicines for malaria venture
- PfATP4
Na+-ATPase 4 ion channel
Sub-Saharan Africa
World Health Organization
Multilingual abstract
Please see Additional file 1 for translations of the abstract into the five offical working languages of the United Nations.
Malaria is an infectious disease caused by the protozoa of the genus Plasmodium, transmitted through the bite of the female Anopheles mosquito. It is a major public health problem in many endemic countries including Sub-Saharan Africa (SSA); in 2015, an estimated 438 000 malaria deaths were reported globally [1]. Human pathogenic Plasmodium species include Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Sporozoites are injected into the skin through a mosquito bite, invading hepatocytes and causing liver infection. The merozoites released from the liver rapidly infect the erythrocytes during the erythrocytic stage. Multiple rounds of the erythrocytic stage produce larger numbers of parasites that invade the blood, consequently causing clinical illness. Erythrocytic parasites develop into sexual gametocytes and are transmitted to humans through a mosquito bite.
The Plasmodium-infected female Anopheles mosquito is the deadliest known disease vector causing as many deaths as deaths from HIV/AIDS and tuberculosis [2]. In 2008, the World Health Organization (WHO) initiated the Global Malaria Action Plan (GMAP) to reduce rates of malaria incidence and mortality by at least ten-fold by 2030. Despite numerous advances over the past decade, new drugs are urgently needed. To reduce the malaria burden in developing countries, the not-for-profit organization Medicines for Malaria Venture (MMV) was established in 1999. Its main goal is to initiate collaborations with industry and academic partners in order to develop novel approaches to combat malaria [3]. This has led to the design and discovery of new medicines for human malaria cases. Between 2000 and 2015, malaria incidence rates decreased globally by 37 % and mortality rates decreased by 60 %. Most malaria cases (89 %) and deaths (91 %) from malaria globally were reported in SSA [4]. The emergence of resistance to traditional therapies including chloroquine, primaquine, quinine, and mefloquine has also revealed novel antimalarial targets. In the past decades, a consortium of researchers from academia and industry was created to develop new remedies focusing on chemotypes [5]. Consequently, the discovery of artemisinin-based combination therapies (ACTs) by Chinese scientists has tremendously benefitted hundreds of thousands of patients. However, resistance to antimalarial drugs continues to pose a major threat to malaria eradication [6]. Furthermore, recent advances in the development of species-specific malaria vaccines have emerged as the most prominent approach to eradicating malaria.
24 malarial vaccines are currently being tested in 99 clinical sites in Africa and 30 in Southeast Asia [7]. The most advanced recombinant protein-based malaria vaccine is Mosquirix™ (RTS, S), a combination of 25 % fusion protein RTS and 75 % wild-type hepatitis B surface antigen (HBsAg). The vaccine is effective against P. falciparum malaria and was developed by GlaxoSmithKline (GSK), the PATH Malaria Vaccine Initiative, and other partners. In a late-stage Phase III trial, Mosquirix™ showed poor efficacy with only 27 % protection against severe malaria in infants [8]. The European Medicines Agency approved the use of Mosquirix™ in young African children in July 2015, although final consent from the WHO is still needed. While these vaccines may provide partial protection, their widespread use in Africa may be affected by high costs, as well as compliance and feasibility challenges.
Challenges for the eradication of malaria
Since 2000, malaria infection rates have been reduced by over 50 %, but complete eradication is still a challenge [9]. To completely wipe out malaria, multifaceted strategies are essential. One approach is single exposure radical cure and prophylaxis (SERCaP), proposed as a global agenda in 2007 for identifying ideal drugs to treat malaria [10]. International guidelines have recommended the use of ACTs as a first-line treatment on a three-day course schedule, as ACTs, particularly artesunate, can rapidly reduce the parasitic load by at least 10 000-fold within 48 h of the parasitic life cycle, resulting in >95 % clearance of initial infection. However, subtherapeutic doses and non-adherence are additional barriers promoting the emergence of resistant malarial strains and contributing to treatment failure. Medicines with longer durations of drug action and higher minimum inhibitory concentrations (MICs) in the plasma for at least one week can suppress the parasitic load and offer post-exposure and post-treatment protection. Chemoprotectants are an emerging class of drugs. Sulfadoxine-pyrimethamine is a chemoprotectant combination drug that was widely used among patients until the emergence of resistance last decade [11, 12]. Novel chemoprotective agents acting against the schizont stage of the malaria parasite are needed to prevent merozoite production from blood cells.
In this study, we reviewed various preclinical and clinical studies published during the period directly following the establishment of the Medicines for Malaria Venture (2000) and 2015.
Overview of some of the ongoing clinical trial performed in Malaria
Target name
Clinical Trial
Study population
Phenotypic assay
Na + −ATPase 4
Phase II
Not specified
Adult (>18 years and older)
800 mg single dose for falciparum patients
Phosphatidylinositol-4 kinase
Phase I
Not specified
Healthy volunteers
20 mg single dose as suspension for falciparum patients
Cyclic amine resistance locus inhibitor
Phase II
Not specified
Adult (>18 years)
800 mg/day for 3 days and 800 mg single dose for uncomplicated falciparum and vivax
Dihydroorotate dehydrogense
Phase II
Not specified
Adults (>18 years)
400 mg single dose for uncomplicated falciparum and vivax
Synthetic Molecules
OZ277 + Piperaquine
Pf-encoded sarcoplasmic endoplasmic reticulum calcium ATPase
Phase II-III
Dihydroartemisinin + piperaquine
Adult (>18 years)
Not specified
OZ439 + Piperaquine
endoperoxide ozonide
Phase II-III
Not specified
6 months to 70 years
OZ439 -800 mg single dose +1440 mg piperaquine for uncomplicated falciparum patients
Artemisone (BAY-44-9585) + Mefloquine
Artemisin derivative
>16 years and older
Artemisone 4 mg/kg/day for 3 days, mefloquine 15 mg/kg/day for uncomplicated falciparum malaria
Aminoquinoline scaffolds
Ferrocene − 4-aminoquinoline
Phase II Terminated
Placebo and Artesunate
>14 years and older
Ferroquine different doses with artesunate 4 mg/kg/day, once daily for 3 days vs placebo for uncomplicated falciparum malaria
Phase II
18 years and older
Two (350 mg) capsules on day 1 and 2. One (350 mg) capsule on day 3 for for uncomplicated falciparum malaria
Phase III
Placebo, chloroquine, primaquine
16 years and older
Tafenoquine 150 mg vs chloroquine different doses vs placebo for plasmodium vivax malaria
Streptomycin lavenduale
DOXP pathway
Phase IIa
1 year to 60 years
Fosmidomycin 450 mg twice daily + piperaquine 320 mg once daily for 3 days for uncomplicated falciparum malaria.
Other agents
Methylene blue + Primaquine
Phenothiazin dye
Phase I
Healthy volunteers
18 to 60 years
Primaquine 45 mg + methylene blue 600 mg single dose compared in patients with Normal G6PD vs G6PD deficiency
To summarize the existing evidence related to the portfolio of novel antimalarial drugs, we conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [14]. We searched publicly available sources such as PubMed, Web of Science, clinicaltrials.gov, and drug company websites. Original and unoriginal peer-reviewed articles published between 2000 (after the establishment of MMV) and 2015 were retrieved. We included preclinical studies and all clinical trial phases. If trial results were unavailable, we referenced the study either by its clinicaltrial.gov identifier or using the company press release newsletters.
Two of the authors of this paper (ASB and AAE) checked all potentially relevant studies and reached a consensus on all items. One of the authors (ASB) screened the titles and abstracts. Two authors (ASB and AAE) selected the studies for inclusion after reviewing full-text articles. The following keywords were entered into the search field to search for titles, abstracts, and index terms: novel* AND antimalarial* AND preclinical* AND clinical trials* AND plasmodium falciparum* AND plasmodium vivax* AND malaria* AND medicine for malaria venture*. Data were updated in January 2016.
Extracted data were based on information reported in or calculated from the included studies. Authors were not contacted for additional information regarding the drug or trial information. The following information was retrieved from clinicaltrials.gov therapeutic agent, class of drug, site of action, clinical phase, control group, study population, and therapeutic doses. We only examined information on antimalarial drug efficacy and safety.
Pharmacological approaches
Phenotypic molecules for malaria
Advances in automation and phenotypic assay screening techniques have aided the discovery of innovative compounds effective against both asexual and sexual stages of P. falciparum. Spiroindolone KAE609 (cipargamin), a potential Na+-ATPase 4 ion channel (PfATP4) inhibitor, was discovered by scientists from the Swiss Tropical and Public Health Institute and developed by the Novartis Institute of Tropical Diseases in Singapore. KAE609 originated from the high-throughput phenotypic screening of nearly 12 000 natural compounds evaluated for their activity against erythrocytic stages of P. falciparum [15]. Encouraging results were reported in a Phase I human trial with elevated MICs in the plasma for several days, and total efficacy doses of 300 mg (single) and 150 mg (multiple) for three days [16, 17]. Interestingly, KAE609 is seven times more potent than artesunate and 40 times more potent than 4-aminoquinolines [18]. Results from a recent Phase II clinical trial conducted among Thai patients indicated a clearance half-life of 0.90 h for P. falciparum and 0.95 h for P. vivax. Furthermore, the mean terminal half-life for the elimination of KAE609 was 20.8 h, supporting a once-daily oral dosing regimen [18]. The promising profile of KAE609 will be evaluated further in upcoming early phase trials. In vitro, KAE609 showed active against artemisinin-resistant K 13 mutant parasite and prevents recrudescence of dihydeoartemisinin (DHA)- arrested ring at minimal concentration (50 nM) [19]. Thus can as a broad range antimalarial and in treatment of multidrug-resistant P.facliparum malaria.
Advances in natural-product-based screening techniques have improved our understanding of medicinal chemistry via chemoinformatics. A high-throughput screening of more than 4 700 compounds resulted in a promising scaffold, which led to the discovery of DDD107498, a novel phenotypic molecule that specifically acts against liver-stage P. falciparum malaria. This molecule was developed at the University of Dundee, UK by a research consortium [20]. The DDD107498 compound is a 2,6-disubstituted quinoline-4-carboxamide scaffold effective against the liver (schizont formation) stage. In vitro assays against different P. falciparum laboratory strains, such as artemisinin-resistant strains, chloroquine-, amodiaquine- and mefloquine-resistant strains, revealed a low micromolar range against the parasite. In addition, the compound impaired the growth of other strains including P. berghei and P. yoelii during their schizont formation stage. DDD107498 may be effective against multidrug resistant Plasmodium strains (Dd2 and 7G8). Remarkably, the ex vivo efficacy of DDD107498 has been shown to be higher than artesunate against P. falciparum (median EC50 = 0.81 nM [range 0.29–3.29 nM]) and P. vivax (median EC50 = 0.51 nM [range 0.25–1.39 nM]) [20]. DDD107498 has shown excellent oral bioavailability and a longer plasma half-life, which is preferable for single-dose treatment in vitro. These results suggest that DDD107498 can achieve complete parasitic clearance in the blood stage by rapid killing for more than 48 h. DDD107498 is currently in the developmental stage and needs to be tested for approval in human clinical trials.
KAF156 (also known as imidazolopiperazine), a promising chemoprevention molecule, is a cyclic amine resistance locus inhibitor (PfCARL) developed by the Novartis research consortium [21]. In vitro KAF156 is active against uncomplicated P. falciparum and P. vivax strains in the liver, asexual erythrocytic, and transmission stages. One recently published paper reported a KAF156 Phase II proof-of-concept trial [22] conducted among Vietnamese and Thai monoinfection patients, who were treated with 400 mg/day for three days and a single 800 mg dose. No efficacy data are yet available on KAF156 and no predictions can be made about its potential as a future antimalarial drug. Adverse events reported with higher doses of KAF156 include sinus bradycardia, thrombocytopenia, and hypokalemia. Further studies are needed to evaluate the molecule's side effects.
DSM265, a dihydroorotate dehydrogenase (DHODH) inhibitor acting against the liver (schizont formation) stage, is proving to be promising as a one-dose (400 mg) malaria cure in a Phase I trial in healthy volunteers, with an encouraging safety profile. DSM265 is currently in the clinical developmental stage (Phase II) in Peru (NCT02123290). Its activity against uncomplicated P. falciparum and P. vivax parasites is being assessed in adult patients using a single dose treatment (400 mg) [23]. However, no clinical data are yet available to confirm DSM265 as a potential antimalarial armory. Although DSM265 showed robust results in Phase I trials, further studies are needed to predict its safety for use in pregnant women.
In most countries in SSA, malaria in pregnancy contributes to significant maternal and perinatal mortality. It is not recommended to use ACTs during the first trimester due to side effects observed in preclinical models [24]. Currently, sulfadoxine-pyrimethamine is used in pregnant women as an intermittent preventive treatment to reduce infections and improve pregnancy outcomes. Several optional antibacterials and antifolate combinations have emerged including azithromycin-chloroquine, mefloquine, and dihydroartemisinin-piperaquine. Antibacterial combinations potentially reduce the risk of sexually transmitted diseases to mothers and newborns [25]. Studies registered in clinicaltrials.gov on co-trimoxazole prophylaxis for prevention of malaria in pregnancy (NCT01053325) and co-infection with malaria and HIV in women (NCT00970879) were completed in 2013, but results have not yet been published. Moreover, mefloquine has shown significant benefits but may cause nausea and neuropsychiatric side effects [26]. To fulfill the GMAP portfolio, determining the safety of novel chemoprotective molecules in pregnancy should be considered a priority in clinical investigations.
Other compounds under development
Novel antimalarial candidates in preclinical stage
Mechanism of action
PfDHFR (Diaminooyridine)
Dihydrofolate reductase inhibitor
Dihydroorotate dehydrogenase
Cyclic amine resistance locus protein
Cytochrome bc1
Hemoglobin digestion
Immucillin G
Purine nucleoside phosphorylation
Histone deacetylase
Falcipain cysteine protease 2-3
Na + −ATPase 4
Trichostatin A
Histone deacetylation
Aspertic protease plasmepsins 1,2,4
Proinflammatory cytokines antagonist
Mitochondrial electron transport chain inhibitor
DHOD inhibition
Hemoglobin digestion
Synthetic medicinal arsenals
OZ277 and OZ439
Quinine, first used in Europe in the 17th century, chloroquine [34], and 4-aminoquinoline scaffolds are some of the semi-synthetic drugs that have shown good antimalarial activity over the years. Fixed-dose combinations of artemisinin derivatives are currently considered to be the gold-standard malaria treatment. Synthetic artemisinin-like endoperoxides and their derivatives (artesunate, artemether, and dihydroartemisinin) have been proven to be more effective than chloroquine. OZ277 (arterolane), a novel non-artemisinin ozonide compound, has been developed by Ranbaxy Laboratories in collaboration with MMV in 2004. The clinical activity of OZ277 in a Phase II dose-finding trial for uncomplicated P. falciparum malaria was shown to be not as effective as artemisinin. This was indicated by the reduced parasitic clearance on day 28 after seven days (60–70 %) compared to artesunate dose–response (95 %) [34]. Thus, increasing the dose does not necessarily decrease parasitic recrudescence. Following a Phase III trial in 2013, a fixed-dose combination of OZ277 (arterolane) (150 mg) and long-acting piperaquine (750 mg) (Synriam™) was tested for treating P. falciparum malaria in India and received mark approval from the Drug Controller General of India. It was subsequently put on the market in seven African countries [35]. Due to a suboptimal half-life and reduced stability in low-level parasitemia (1 % at 45 % haematocrit), OZ277 failed to show efficacy against high parasitic loads [36]. The results of these trials confirmed the safety of the compounds but not the efficacy, even when doses were increased in the presence of a high level of infected erythrocytes. Drug partners may be needed to increase efficacy. These weaknesses have led MMV to develop a potential next generation synthetic endoperoxide ozonide, OZ439 (artefenomel), which has a longer half-life (30 h) and a MIC of more than one week, after a single dose. OZ439 is the first highly active ozonide against Plasmodium [36].
Different doses of artefenomel (200–1 200 mg) were tested in a Phase IIA exploratory, open-label trial and revealed promising safety and efficacy profiles among Southeast Asian adults with uncomplicated P. falciparum and P. vivax malaria. Due to the reduced elimination half-life of 46–62 h, a single dose of OZ439 alone or in combination with piperaquine can eliminate 98.0 % of P. falciparum and 99.6 % of P. vivax within 36 h. Artefenomel has demonstrated a higher parasitic clearance within the first 24 h in P. vivax patients as compared to P. falciparum patients (30–36 h). However, gametocyte clearance was 100 % in patients who were administered 1 200 mg of artefenomel within 48 h [36]. OZ439 is now being evaluated with piperaquine in Phase IIB combination trials.
One of the major concerns about the use of OZ compounds is that they have a similar endoperoxide structure to artemisinin, indicating possible treatment failures. Previous data suggest that artemisinin derivatives are associated with the risk of spontaneous abortions in early pregnancies [37], but recent clinical evidence confirmed the safety of ACTs against P. falciparum and P. vivax in the first trimester, with no risk of spontaneous abortions or major congenital malformations [38]. Similarly, preclinical studies have shown that OZ compounds are also safe for embryos and fetuses [39]. No clinical data are yet available to prove the safety of using these compounds in pregnancy and more tests are therefore needed for their evaluation.
Other compounds
Two interesting endoperoxides from artesunate derivatives including artemisone (BAY 44–9585) and tetraxoane (TDD E209), are examples of other synthetic candidates currently under development. Artemisone is a semi-synthetic second-generation artemisinin derivative developed in collaboration between Bayer HealthCare Pharmaceuticals in Germany and the Hong Kong University of Science and Technology. Results of preclinical studies are highly promising as compared to other novel artemisinins. Artemisone is more effective than artesunate against P. falciparum and multidrug resistant strains [40, 41]. Dose-escalating Phase I trials on healthy volunteers have shown that artemisone is a rapidly effective treatment as it achieves peak plasma concentrations within 30 min following oral administration [41]. A Phase II interventional study testing artemisone for treating uncomplicated P. falciparum malaria planned for Western Cambodia (NCT00936767) has been withdrawn for unknown reasons. Some studies reported neurological and auditory side effects such as ataxia and slurred speech [42, 43] due to ACTs. However, no strong evidence exists to confirm neurological side effects. Furthermore, the activity of artemisone has shown a GM IC50s correlation with pfmdr1 Y184F mutations, which potentially reduces sensitivity to artemisinin-resistant strains and contributes to emerging ACT resistance [44]. Recent genome-wide association studies revealed that artemisone does not interact with Y1915 and has no effect on P.falciparum phosphatidylinositol-3 kinase (PfPI3K) [45].
Aminoquinoline scaffolds
Ferroquine is an ameliorated blood-schizonticidal 4-aminoquinoline developed by Sanofi-Aventis. Along with OZ439, it is a more effective parasite-killing compound against Plasmodium strains when compared to artesunate. Several preclinical studies have shown its benefits, particularly for treating patients infected with chloroquine-, amodiaquine-, and mefloquine-resistant malaria strains [46, 47, 48]. The greatest advantage of using ferroquine is its 30-h half-life, which is highly superior to that of other artemisinin derivatives. Two ferroquine Phase II trials were recently registered in the clinicaltrials.gov database (NCT02497612 and NCT00988507) focusing on P. falciparum and P. vivax malaria at the multicenter level. One study has been completed (NCT00988507) but no results are yet available. Most recently, a ferroquine-artesunate dose-ranging Phase II trial on P. falciparum-infected adults and children in eight African hospitals was conducted [49]. The research findings were astonishing: 97 % polymerase chain reaction (PCR)-confirmed cure rates (95 % CI: 90–100) after treatment with 2 mg/kg ferroquine combined with 4 mg/kg artesunate. However, the cure rate was reduced (79 %; 95%CI: 68–88) when ferroquine monotherapy 4 mg/kg/day for 3-days regimen was used. Furthermore, exacerbated malaria symptoms were observed in 14 % of the individuals in the treatment cohort.
Another 4-aminoquinoline derivative called AQ-13 (Ro47-0543), a similarly structured chloroquine with a modified propyl side chain from the aminoquine panel, was developed in collaboration between Tulane University and Louisiana State University both located in LA, USA. Preclinical studies have indicated increased efficacy of AQ-13 when compared to other derivatives [50]. Phase I first-in-human safety and efficacy studies have shown results similar to those observed with chloroquine. Adverse events include electrocardiac changes, especially prolonged QTc intervals, which are commonly encountered with many quinolones [51]. AQ-13 did not present any advantages over other aminoquinolines, and further observation of this compound has currently been halted.
The majority of clinical trials focus on malaria caused by P. falciparum, while fewer studies evaluate treatments against P. vivax and P. ovale malaria. A deficiency of glucose-6-phosphate dehydrogenase (G6PD) is a hereditary enzyme defect condition that causes episodic hemolysis. Patients with a G6PD deficiency are common in malaria-endemic countries and are at high risk of hemolysis due to treatment with antimalarial drugs (primaquine, chloroquine, quinine, and sulfamethoxazole). These patients are generally not included in trials due genotypic variations. For these individuals, tafenoquine (WR 238605) is a good alternative drug. It is an 8-aminoquinoline derivative and has a similar mode of action to primaquine against hypnozoites, gametocytes, and liver stages [52]. Tafenoquine is more potent during blood stages due its longer half-life (14 days) as compared to primaquine. Nevertheless, slower parasitic clearance was observed with tafenoquine monotherapy. Therefore, combing tafenoquine with other partner drugs may ideally benefit G6PD-deficient patients. So far, chloroquine combined with primaquine has been used for the radical cure of P. vivax malaria. Tafenoquine with chloroquine was tested in studies against P. vivax malaria. In a Phase IIB dose-ranging trial, different doses of tafenoquine alone (50, 100, 300, or 600 mg) or in combination with 15 mg primaquine for 14 days were tested, with a fixed dose of chloroquine for three days. A single dose of tafenoquine (300 mg) co-administered with chloroquine was shown to prevent relapse in 89.2 % (95 % CI: 77–95) of people as compared to chloroquine alone (51.7 %; 95 % CI: 36–69) during the first six months of follow-up [53]. Recent results of a Phase IIB dose-ranging trial (DETECTIVE study) conducted on monoinfected P. vivax patients for radical cure showed that single-dose tafenoquine (300 mg) combined to chloroquine is more efficacious in preventing relapses as compared to chloroquine alone, with a similar safety profile. Based on these observations, GSK and MMV announced two new Phase III studies: 1) a DETECTIVE study (TAF112582) to evaluate the efficacy, safety, and tolerability of tafenoquine co-administered with chloroquine as a radical cure for P. vivax malaria (blood-stage antimalarial treatment); and 2) a GATHER study (TAF 116546) to assess the incidence of hemolysis and the efficacy and safety of tafenoquine over primaquine [54].
Biomolecular approaches
Methylene blue
A century ago, the German scientist Paul Ehrlich discovered the antiplasmodial activity of methylene blue [55]. The chemotherapeutic use of synthetic methylene blue in treating methemoglobinemia and cancer-induced neurotoxicity was tested in 1995 [56]. Additional experiments were conducted using methylene blue and its analogs against P. falciparum isolates [57]. Methylene blue combined with chloroquine has been shown to prevent hemolysis in G6PD-deficient adult patients. Other studies assessed the use of different doses of methylene blue with chloroquine for three days and showed 90 % recovery rates in patients with uncomplicated P. falciparum malaria. Although results were promising, adverse effects were reported including vomiting, as well as the discoloration of urine, mucous surfaces, and teeth [58]. Drug resistance to chloroquine has also emerged globally [59]. In 2006, methylene blue was evaluated in combination with artesunate but showed poor cure rates despite rapid parasitic clearance [60]. In 2011, treatment with artesunate-amodiaquine-methylene blue was studied in children aged between six and 50 months with uncomplicated P. falciparum malaria. This combination showed poor efficacy (71 %) when compared to the control group (artesunate-amodiaquine; 85 %) [61]. However, after comparing a fixed dose 15 mg/kg of methylene blue co-administered with artesunate or amodiaquine versus artesunate-amodiaquine for three days, decreased gametocytes (from 100 to 36 %) were reported within seven days of treatment. Interestingly, the pronounced effect on gametocyte clearance indicates that methylene blue is a new promising drug component to reduce P. falciparum transmission. A Phase I trial testing the combination of methylene blue with primaquine is currently registered in the clinicaltrials.gov database (NCT01668433), but results are not yet available.
Isoprenoids are derived from the mevalonate pathway in humans, an essential metabolic pathway for parasite synthesis. Jomaa Pharma GmbH developed a synthetic antibiotic agent called fosmidomycin derived from Streptomyces lavendulae bacterial isolates. This compound inhibits the non-mevalonate pathway (also known as the DOXP pathway), essential for the synthesis of parasite isoprenoids [62]. Fosmidomycin has a half-life of only two hours and acts rapidly upon oral administration. Additional trials to evaluate the efficacy of different doses of fosmidomycin monotherapy undertaken for more than four days are required. One study indicated complete parasitic clearance on day seven following administration of fosmidomycin (1 200 mg four times a day) in adult patients with uncomplicated P. falciparum malaria. On day 28, recrudescence was observed in seven out of nine patients, indicating monotherapy failure [63]. Fosmidomycin co-administered with clindamycin has been proven to be effective in adults and older children with acute uncomplicated P. falciparum malaria. Poor efficacy was observed due to poor immunity in children aged between one an>d two years [64]. Two additional short half-life combinations (fosmidomycin with artesunate) were evaluated in 50 children aged between six and 12 years. Five different fosmidomycin-artesunate regimens achieved complete cure rates within three days of administration, and no resistant alleles were detected after seven and 28 days [65]. However, no evidence of prolonged protection by this combination was provided. A Phase IIA open-label efficacy trial focusing on fosmidomycin (450 mg capsule; twice daily) and piperaquine (320 mg; once daily) for treating patients with uncomplicated P. falciparum malaria, aged between one and 60 years and with a body weight between 5 and 90 kg, is currently registered in the clinicaltrials.gov database (NCT02198807). Overall, studies indicated that fosmidomycin is only effective for short-term treatment. Studies on finding a potential partner drug to prove the efficiency of fosmidomycin urgently need to be conducted.
In this review, we summarized the different approaches tested over the years to control the malaria pandemic, and possibly reduce global malaria incidence and mortality by 90 % before 2030. Novel chemotherapeutic approaches have emerged over the past five years, with promising results. Nevertheless, the efficacy and safety of these drugs need to be studied further. These novel antimalarial approaches are multifaceted, thus there is an urgent need for effective single-dose molecules to act during the liver and blood stages of malaria. Effective compounds should be developed before global emergence of resistance to artemisinin derivatives and 4-aminoquinoline. There is currently no low-dose primaquine regimen for pediatric use. Novel blood-stage compounds such as DDD107498 and tafenoquine should focus on blocking parasite transmission in children and adolescents, and pregnant women. Molecules such as ferroquine should be combined with a potential partner drug to enhance efficacy. Additional challenges in preventing the relapse of malaria episodes include hemolysis in patients with a G6PD deficiency, treatment for drug-resistant strains, pediatric dosing, serious drug-drug interactions, transmission blocking, radical cure, and relapse prevention. Potentially targeting mitochondrial electron-transport chain of P.falciparum and protein inhibition in blood- and liver-stage parasites could be ideal for future drug development.
We thank Dr. Damiana Chiavolini for editing the paper.
Authors' contributions
ASB, AAE and AS conceived and designed the study, and drafted the paper. AAE analysed the literature and reviewed the manuscript. All authors read and approved the final paper.
Competing interests
The authors declare that they have no competing interests.
Supplementary material
- 1.World Health Organization. 10 facts on malaria. Available at: http://www.who.int/features/factfiles/malaria/en.html. Accessed 9 Feb. 2016.
- 2.Nosten F, Brasseur P. Combination therapy for malaria. Drugs. 2002;62(9):1315–29.CrossRefPubMedGoogle Scholar
- 3.Medicines for Malaria venture. Available information: http://www.mmv.org/about-us/our-history.html. Accessed 9 Feb. 2016.
- 4.World Health Organization: Malaria fact sheet. Available at http://www.who.int/mediacentre/factsheets/fs094/en.html. Accessed 28 Jan. 2016
- 5.Biamonte MA, Wanner J, Le Roch KG. Recent advances in malaria drug discovery. Bioorg Med Chem Lett. 2013;23:2829–43.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Taming T, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Clinical trials.gov. Available at https://clinicaltrials.gov/ct2/results?term=Phase+3+malaria+vaccine&Search=Search.html. Accessed 10 June 2015
- 8.RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 2014;11:e1001685.Google Scholar
- 9.Alonso PL, Brown G, Arevalo-Herrera M, Binka F, Chitnis C, Collins F, et al. A research agenda to underpin malaria eradication. PLoS Med. 2011;8:e1000406.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Ashley EA, Dhorda RM, Fairhurst C, Amaratunga P, Lim S, Suon S, et al. Spreading of artemisinin resistance in Plasmodium falciparum malaria. N Eng J Med. 2014;371(5):411–23.CrossRefGoogle Scholar
- 11.Vinayak S, Alam MT, Mixaon-Hayden T, McCollum AM, Sem R, Shah NK, et al. Origin and evolution of sulfadoxine resistant Plasmodium falciparum. PLoS Pathog. 2010;6(3):e1000830.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.McCollum AM, Mueller K, Villegas L, Udhyakumar V, Escalante AA. Common origin and fixation of Plasmodium falciparum and dhps mutations associated with sulphadoxine-pyramethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother. 2007;51(6):2085–91.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Clinical trials.gov. Available at https://clinicaltrials.gov/ct2/results?term=novel+antimalarial+drug&Search=Search.html Accessed 22 June 2015.
- 14.Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B, Russell B, et al. Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010;329(5996):1175–80.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Leong FJ, Li R, Jain JP, Lefevre G, Magnusson B, Diagana TT, et al. A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel antimalarial spiroindolone KAE609 (cipargamin), to assess the safety, tolerability and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother. 2014;58:6209–14.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Stein DS, Jain JP, Kangas M, Lefevre G, Machineni S, Griffin P, et al. Open-label, parallel-group study in healthy volunteers to determine in the safety.in healthy volunteers to determine the drug-drug interactions potential between KAE609 (Cipargamin) and piperaquine. Antimicrob Agents Chemother. 2015;59(6):3493–500.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Nicholus JW, Sasithon P, Phyo AP, Reuangweerayut R, Nosten F, Podjanee J, et al. Spiroindolone KAE609 for falciparum and vivax malaria. N Eng J Med. 2014;371:403–10.CrossRefGoogle Scholar
- 19.Chavchich M, Van Breda K, Rowcliffe K, Diagana TT, Edstein MD. The spiroindolone KAE609 does not induce dormant ring stage in Plasmodium falciparum parasites. Antimicrob Agents Chemother. 2016;60(9):5167–74.CrossRefPubMedGoogle Scholar
- 20.Baragana B, Hallyburton I, Lee MC, Norcross NR, Raffaella G, Otto TD, et al. A novel multiple-stage antimalarial agent than inhibits protein synthesis. Nature. 2015;522:315–20.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Vaidya AB, Morrisey JM, Zhang Z, Das S, Daly TM, Otto TD, et al. Pyrazoleamide compounds are potent antimalarials that target Na + homeostasis in intraerythrocytic Plasmodium falciparum. Nature Commun. 2014;5:5521.CrossRefGoogle Scholar
- 22.Novartis Pharmaceuticals. Efficacy, safety, tolerability and pharmacokinetics of KAF156 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection. In:ClinicalTrials.gov. Bethesda (MD). [Cited 2015 Nov 19] Available from: http://clinicaltrial.gov/show/NCT01753323.
- 23.Phillips MA, Lotharius J, Marsh K, White J, Dayan A, White KL, et al. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci Translat Med. 2015;7(269):296ra111.CrossRefGoogle Scholar
- 24.Beckman DA, Youreneff M, Butt MT. Neurotoxicity assessment of artemether in juvenile rats. Birth Defects Res B Dev Reprod Toxicol. 2013;98(2):183–99.CrossRefPubMedGoogle Scholar
- 25.Luntamo M, Rantala AM, Meshnick SR, Cheung YB, Kulmala T, Maleta K, et al. The effect of monthly sulfadoxine-pyrimethamine, alone or with azithromycin, on PCR-diagnosed malaria at delivery: a randomized controlled trial. PLoS One. 2012;7(7):e41123.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Tansley R, Lotharius J, Priestley A, Bull F, Duparc S, Mohrle J. A randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, and pharmacokinetics of single enantiomer (+)-mefloquine compared with racemic mefloquine in healthy persons. Am J Trop Med Hyg. 2010;83:1195–201.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Jimenez-Diaz MB, Ebert D, Salinas Y, Pradhan A, Lehane AM, Myrand-Lapierre ME, et al. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc Natl Acad Sci U S A. 2014;111:E5455–62.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.McNamara CW, Lee MC, Lim CS, Lim SH, Roland K, Nagle A, et al. "Targeting Plasmodium PI(4) K to eliminate malaria. Nature. 2013;504(7479):248–53.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Younis Y, Douelle F, Feng TS, Gonzales Cabrera D, Le Manach C, Nichinda AT, et al. 3,5-Diaryl-2-aminopyridines as a novel class of orally active antimalarials demonstrating single dose cure in mice and clinical candidate potential. J Med Chem. 2012;55(7):3479–87.CrossRefPubMedGoogle Scholar
- 30.Ariey F, Watkowski C, Amaratunga J, Beghain AC, Langois N, Khim S, et al. A molecular-marker of artesmisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–5.CrossRefPubMedGoogle Scholar
- 31.Henriques G, van Schalkwyk DA, Burrow R, Warhurst DC, Thompson E, Baker DA, et al. The Mu subunit of Plasmodium falciparum clathrin-associated adaptor protein 2 modulates in vitro parasite response to artesmisinin and quinine. Antimicrob Agents Chemother. 2015;59(5):2540–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Li J, Chen J, Xie D, Monte-Nguba SM, Eyi JU, Matesa RA, et al. High prevalence of pfmdr1 N86Y and Y184F mutations in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea. Pathog Glob Health. 2014;108:339–43.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.St Laurent B, Miller B, Burton TA, Amaratunga C, Men S, Sovannaroth S, et al. Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquitoes vectors of Southeast Asia and Africa. Nat Commun. 2015;6:8614.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Valecha N, Krudsood S, Tangpukdee N, Mohanty S, Sharma SK, Tyagi PK, et al. Arterolane maleate plus piperaquine phosphate for treatment of uncomplicated Plasmodium falciparum malaria: a comparative, multicenter, randomized clinical trial. Clin Infect Dis. 2012;55(5):663–71. Patil CY, Katara SS, Baig MS, Doifode SM. Fixed dose combination of arterolane and piperaquine: A newer prospect in antimalarial therapy. Ann Med Health Sci Res 2014;4(4):466–471.CrossRefPubMedGoogle Scholar
- 35.Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, et al. Indentification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004;430(7002):900–4.CrossRefPubMedGoogle Scholar
- 36.Phyo AP, Jittamala P, Nosten FH, Pukrittayakamee S, Imwong M, White NJ, et al. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: a open-lable phase 2 trial. Lancet Infect Dis. 2016;16:61–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Ritter S, Laffan SB, Clark RL. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo. Birth Defects Res B Dev Reprod Toxicol. 2006;77:413–29.CrossRefPubMedGoogle Scholar
- 38.Moore KA, Simpson JA, Paw MK, Pimanpanarak MP, Wiladphaingern J, Rijken MJ, et al. Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study. Lancet Infect Dis. 2016. doi: 10.1016/S1473-3099(15)00547-2.PubMedCentralGoogle Scholar
- 39.Wells TNC, van Huijsduijnen RH, Van Voorhis WC. Malaria medicines: a glass half full? Nat Rev Drug Discov. 2015;14(6):424–42.CrossRefPubMedGoogle Scholar
- 40.Vivas L, Rattray L, Stewart LB, Robinson BL, Fugmann B, Haynes RK, et al. Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo. J Antimicrob Chemother. 2007;59(4):658–65.CrossRefPubMedGoogle Scholar
- 41.Nagelschmitz J, Voith B, Wensing G, Roemer A, Fugmann B, Haynes RK, et al. First assessment in humans of the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of the new artemisinin derivative artemisone. Antimicrob Agents Chemother. 2008;52(9):3085–91.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Medhi B, Patyar S, Rao RS, Bayrav DSP, Praksh A. Pharmacokinetic and toxicological profile of artemisinin compounds: an update. Pharmacol. 2009;84(6):323–32.CrossRefGoogle Scholar
- 43.Carrasquilla G, Baron C, Monsell EM, Cousin M, Walter V, Lefevre G, et al. Randomized, prospective, three-arm study to confirm the auditory safety and efficacy of artemether-lumefantrine in Colombian patients with uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg. 2012;86(1):75–83.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Lanteri CA, Chaorattanakawee S, Lon C, Saunders DL, Rutvisuttinunt W, Yingyuen K, et al. Ex Vivo activity of endoperoxide antimalarials, including artemisone and arteolane, against multidrug-resistant Plasmodium falciparum isolates from Cambodia. Antimicrob Agents Chemother. 2014;58(10):5831–40.CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Mbengye A, Bhattacharjee S, Pandhakar T, Liu H, Estiu G, Stahelin RV, et al. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature. 2015;520(7549):628–30.CrossRefGoogle Scholar
- 46.Mombo-Ngoma G, Sapan C, Dal-Bianco MP, Missinou MA, Matsiegui PB, Ospina Salazar CL, et al. Phase I randomized dose-ascending placebo-controlled trials of ferroquine—a candidate anti-malarial drug-in adults with asymptomatic Plasmodium falciparum infection. Malar J. 2011;10:53.CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Marfurt K, Chalfein F, Prayoga P, Wabiser F, Kenangalem E, Piera KA, et al. Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P.vivax. Antimicrob Agents Chemother. 2011;55(9):4461–4.CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Marfurt K, Chalfein F, Prayoga P, Wabiser F, Wirjanata G, Sebayang B, et al. Comparative ex vivo activity of novel endoperoxides in multidrug-resistant Plasmodium falciparum and P.vivax. Antimicrob Agents Chemother. 2012;56(10):5258–63.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomized, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis. 2015;15(12):1409–19.CrossRefPubMedGoogle Scholar
- 50.Ramanathan-Girish S, Catz P, Creek MR, Wu B, Thomas D, et al. Pharmacokinetics of the antimalarial drug, AQ-13, in rats and cynomolgous macaques. Int J Toxicol. 2004;23:179–89.CrossRefPubMedGoogle Scholar
- 51.Mzayek F, Deng H, Mather JF, Wasilevich EC, Liu H, Hadi CM, et al. Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers. PLoS Clin Trials. 2007;2(1):e6.CrossRefPubMedPubMedCentralGoogle Scholar
- 52.Marcsisin SR, Sousa JC, Reichard GA, Caridha D, Zeng Q, Careaganarja J, et al. Tafenoquine and NPC-1161B requires CYP2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compound. Malaria J. 2014;13(2):10–1186.Google Scholar
- 53.Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014;383(9922):1049–58.CrossRefPubMedGoogle Scholar
- 54.GSK and MMV announce start of Phase III programme of tafenoquine for Plasmodium vivax malaria. Available at: http://us.gsk.com/en-us/media/press-release/2014/gsk-and-mmv-announce-start-of-phase-iii-programme-of-tafenoquine-for-plasmodium-vivax-malaria.html. Accessed: 11 Jul 2015.
- 55.Ehrlich P, Guttmann P. Ueber die Wirkung des Methylenblaubei Malaria. BerlKlinWochenschr. 1891;28:953–6.Google Scholar
- 56.Atamna H, Krugliak M, Shalmiev G, Deharo E, Pescarmona G, Ginsburg H. Mode of antimalarial effect of methylene blue and some of its analogues on Plasmodium falciparum in culture and their inhibition of P. vinckeipetteri and P. yoeliinigeriensis in vivo. Biochem Pharmacol. 1996;51(5):693–700.CrossRefPubMedGoogle Scholar
- 57.Bountogo M, Zoungrana A, Coulibaly B, Klose C, Mansmann U, Mockenhaupt FP, et al. Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso. Trop Med Int Health. 2010;15(6):713–7.CrossRefPubMedGoogle Scholar
- 58.Rengelshausen J, Burhenne J, Frohlich M, Tayrouz Y, Singh SK, Riedel KD, et al. Pharmacokinetic interaction of chloroquine and methylene blue combination against malaria. Eur J Clin Pharmacol. 2004;60(10):709–15.CrossRefPubMedGoogle Scholar
- 59.Takala-Harrison S, Laufer MK. Antimalarial drug resistance in Africa: key lessons for the future. Ann N Y Acad Sci. 2015;1342:62–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 60.Zoungrana A, Coulibaly B, Sie A, Walter-Sack I, Mockenhaupt FP, Kouyate B, et al. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS One. 2008;3(2):e1630.CrossRefPubMedPubMedCentralGoogle Scholar
- 61.Coulibaly B, Pritsch M, Bountogo M, Meissner PE, Nebie E, Klose C, et al. Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomised controlled trial in Burkina Faso. J Infect Dis. 2015;211(5):689–97.CrossRefPubMedGoogle Scholar
- 62.Oyakhirome S, Issifou S, Pongratz P, BorondiF RM, Kun JF, et al. Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci Res. 2011;1:1–8.Google Scholar
- 63.Lee B, Ruangweerayut R, Wiesner J, Missinou MA, Schindler A, Baranek T, et al. Fosmidomycin, a novel chemotherapeutic agent for malaria. Antimicrob Agents Chemother. 2003;47(2):735–8.CrossRefGoogle Scholar
- 64.Ruangweerayut R, Looareesuwan S, Hutchinson D, Chauemung A, Banmairuroi V, Na-Bangchang K. Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin clindamycin in patients with acute uncomplicated falciparum malaria. Malar J. 2008;7:225.CrossRefPubMedPubMedCentralGoogle Scholar
- 65.Borrmann S, Adegnika AA, Moussavou F, Oyakhirome S, Esser G, Matseiegui P, et al. Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2005;49(9):3749–54.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.Abbas S, Jain V, Bhartam PV. Origin of the specificity of inhibitor P218 towards wild-type and mutant PfDHFR: a molecular dynamics analysis. J Biomol Struct Dyn. 2014;17:1–16.Google Scholar
- 67.Corteron JM, Marco M, Esquivias J, Deng X, White KL, White J, et al. Structure-guided lead optimization of triazolopyrimidine-ring substituents identified potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitor with clinical candidate potential. J Med Chem. 2011;54(15):5540–61.CrossRefGoogle Scholar
- 68.Kumar S, Kumari R, Pandey R. New insight-guided approaches to detect, cure, prevent and eliminate malaria. Protoplasma. 2015;252(2):717–53.CrossRefPubMedGoogle Scholar
- 69.Kuhen KL, Chatterjee AK, Rottmann M, Gagaring K, Borboa R, Buenviaje J, et al. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment and prevention of disease transmission. Antimicrob Agents Chemother. 2014;58(9):5060–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.Miley GP, Pou S, Winter R, Nilsen A, Li Y, Kelly JX, et al. ELQ-300 prodrug for enhanced development and single dose cure of malaria. Antimicrob Agents Chemother. 2015. doi: 10.1128/ACC.01183-15.PubMedPubMedCentralGoogle Scholar
- 71.Antoine T, Fisher N, Amewu R, O'Neill PM, Ward SA, Biagini GA. Rapid kill of malaria parasites by artemisin and semi-synthetic endoperoxides involves ROS-dependent polorization of the membrane potential. J Antimicrob Chemother. 2014;69(4):1005–16.CrossRefPubMedGoogle Scholar
- 72.Cassera MB, Hazleton KZ, Merino EF, Obaldia 3rd N, Ho MC, Murkin AS, et al. Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in primate animal model. PLoS One.2011;6(11):e26916.CrossRefPubMedPubMedCentralGoogle Scholar
- 73.Dutta AK, Avery BA, Wyandt CM. Development and validation of a stability-indicating reversed-phase high performance method for NPC1161C, a novel 8-aminoquinoline anti-malarial drug. J Chromatogr A. 2006;1110(1–2):35–45.CrossRefPubMedGoogle Scholar
- 74.Sumanadasa SD, Goodman CD, Lucke AJ, Skinner-Adams T, Sahama I, Haque A, et al. Antimalarial activity of the anticancer histone deacetylase inhibitor SB939. Antimicrob Agents Chemother. 2012;56(7):3849–56.CrossRefPubMedPubMedCentralGoogle Scholar
- 75.Somanadhan B, Kotturi SR, Yan Leong C, Glover RP, Huang Y, Flotow H, et al. Isolation and synthesis of falcitidin, a novel myxobacterial-derived acylretrapeptide with activity against the malaria target falcipain-2. J Antibiot (Tokyo). 2013;66(5):259–64.CrossRefGoogle Scholar
- 76.Bueno JM, Herreros E, Angulo-Barturer I, Ferrer S, Fiandor JM, Gamo FJ, et al. Exploration of 4(1H)-pyridones as a novel family of potent antimalarial inhibitors of the plasmodial cytochromebc1. Future Med Chem. 2012;4(18):2311–23.CrossRefPubMedGoogle Scholar
- 77.Trenholme K, Marek L, Duffy S, Pradel G, Fisher G, Hansen FK, et al. Lysine acetylation in sexual stage malarial parasites is a target for antimalarial small molecules. Antimicrob Agents Chemother. 2014;58(7):3666–78.CrossRefPubMedPubMedCentralGoogle Scholar
- 78.Jaudzems K, Tars K, Maurops G, Ivdra N, Otikovs M, Leitans J, et al. Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit. ACS Med Chem Lett. 2014;5(4):373–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 79.Working together to fight malaria with new medicines: Development of an active Toll-like receptor (TLR) 9 antagonist, Access to medicines: Eisai. Available at http://www.eisai.com/company/atm/activities/04.html Accessed on 12 Feb 2016
- 80.Barker Jr RH, Urgaonkar S, Mazitschek R, Celatka C, Skerlj R, Cortese JF, et al. Aminoindoles, a novel scaffold with potent activity against Plasmodium falciparum. Antimicrob Agents Chemother. 2011;55:2612–22.CrossRefPubMedPubMedCentralGoogle Scholar
- 81.Booker ML, Bastos CM, Kramer ML, Barker Jr RH, Skerlj R, Sidhu AB, et al. Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model. J Biol Chem. 2010;285:33054–64.CrossRefPubMedPubMedCentralGoogle Scholar
- 82.O'Neill PM, Amewu RK, Nixon GL, Bousejra ElGarah F, Mungthin M, Chadwick J, et al. Identification of a 1,2,4,5-tetraoxane antimalarial drug-development candidate (RKA 182) with superior properties to the semisynthetic artemisinins. Angew Chem Int Ed Engl. 2010;49:5693–97.Google Scholar
Copyright information
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


text:
KAMI tracked down the list from When In Manila and Wikipedia sites.We are listing down the top 8 Pinay beauty queens who represented the country the best way they can and reached the top 10 round of the competition.
Here is a video of Pia Wurtzbach in the Final 5 Question and Answer.
So, without further ado, here are the top 9 Pinay beauty queens who made it until the top 10 round of Miss Universe.
8. Charlene Gonzales - Miss Universe 1994 Top 6
Charlene Mae Gonzales Bonnin reached at the top 6 in the Miss Universe competition in 1994.
Here's a video of the infamous high tide or low tide answer of Charlene.
Today, Charlene is already married and a mother of two good looking twins. She married Aga Muhlach.
Charlene Today
Charlene Mae Gonzales Bonnin-Muhlach is 43 today. Though, she hasn't changed a bit. She still looks undeniably beautiful.
7. Miriam Quiambao - Miss Universe 1999 1st Runner-Up
Miriam Redito Quiambao landed on the second spot next to the first and the crowned Miss Universe 1999.
Here's a video of the Final 3 - Final Question of Miriam Quiambao.
Now, Miriam is married. Her love story was quite colorful before she ended with her husband today.
Miriam Today
Miriam Redito Quiambao-Roberto is 42 today, and is an inspirational speaker, author, entrepreneur, actress, television host, real estate broker, endorser, and a model.
6. Venus Raj - Miss International 2010 4th Runner-Up
Maria Venus Bayonito Raj took home the 4th place in the 2010 Miss Universe.
Here's a video of her extremely popular answer that made several rounds throughout the world.
You might think that the question is easy for you as you are just watching her answer that unconventional question that even the most intelligent people have a hard time answering it.
Venus Today
Now, she's 28 and will be turning 29 this July 7, 1988. She just completed her Master's Degree in Community Development from the University of the Philippines Diliman.
5. Shamcey Supsup - Miss Universe 2011 3rd Runner-Up
Shamcey Gurrea Supsup took home the 3rd runner-up place in the 2011 Miss Universe pageant.
Here's Shamcey Supsup answering Vanessa Williams question.
The question here was, "Would you change your religious beliefs to marry the person you love? Why or why not?"
Shamcey Today
Shamcey Gurrea Supsup-Lee is a TV Host, model, businesswoman, and an architect. She's married, and she's 31 today.
4.Janine Tugonon - Miss Universe 2012 1st Runner-Up
Janine Marie Raymundo Tugonon bagged the first runner-up in Miss Universe 2012.
Here's a video of Janine's Question and Answer.
Here's the full script of her answer,
"For me Miss Universe is not about being able to speak a particular language, it's about being able to influence and inspire other people. No matter what language you have as long as you have the heart you can inspire other people."
Janine Today
Janine strutting at New York Fashion Show. She's 28 on October 19, 1989. She's focused now as a fashion model in New York.
Here's her last notable project with Victoria Secrets PINK campaign. Janine is on the left.
3. Arielle Arida - Miss Universe 2013 3rd Runner-Up
Ariella "Ara" Hernandez Arida was Miss Universe 2013 3rd runner-up.
Here's a video of Ariella's question and answer.
She'll be 29 this 20th of November.
She's currently hosting Wowowin, an afternoon TV show with Willie Revillame in GMA.
2. MJ Lastimosa - Miss Universe 2014 Top 10
Mary Jean Lastimosa was able to reach the top 10 round. Though she didn't end up bagging the title, she represented the country well.
MJ Today
After the pageant, she was able to grace the MEGA magazine cover. She was born on 23 November 1987, and a graduate of Bachelor of Science in Computer Engineering. Aside from being a computer engineer, she's also an entrepreneur.
1. Pia Wurtzbach - Miss Universe 2015
Her winning moment was immensely controversial due to the host's mishap. However, she remained graceful, humble, and grateful. Thus, everyone loves her since then.
Here's her notable answer to the question that bagged her the title.
Definitely, she's confidently beautiful with a heart. Over time, she has received enormous positive responses from different people all over the world. She has become one of the most followed celebrities on Instagram.
Pia Today
She recently became one of the judges for Asia's Next Top Model Cycle 5 Finale.
Source: Kami.com.ph


text:
Elegant Gallery Of Sears Sofas Sale
Sears Sofas Sale | We displays the photo Formidablel Sofa Sale Pictures Ideas Furniture Sears Cheapls For intended for 17 Petite Pics Of Sears Sofas Sale is from the source www.lebizhotel.com posted on the date April, 21 2018.
What Material is Ideal For You?
Many sofas Must be assembled with either full-grain Leather or top-grain leather. Both are natural leathers of the highest quality, but top-grain leather has been buffed and sanded to remove imperfections, blemishes and uneven coloring while full-grain is abandoned into a more natural condition. Sofas that promise to be assembled with full-aniline dyed leather are dyed just with watertight materials that shield unique outer features without altering or covering them. Depending upon your living room style and the look and texture of your other furniture, you might find that one matches your aesthetic better than the other. Leather scratches much simpler than cloth but is generally easier to clean, which makes it a appropriate selection for families with children but maybe not for households with pets.
Cotton Blends
Cotton-blend cloths are relatively easy to care for and Pre-washed materials provide the couch an inviting, lived-in look. Non-leather upholstery cloths are generally available in a much wider array of colours than leather and offer a lighter look to the space. If you like the textured look and feel of leather but have kids or pets, consider a cotton-yarn mix fabric–the handweaving generates an elegant textured design. Machine-washable couch slipcovers are also available in a variety of sizes, fabrics and fashions for Simple maintenance and customizable sofa styling
Design Advice
One of your first considerations ought to be space. Just how much Space do you have to spare on your living room or living space and how much distance do you want your couch to take? Next, consider construction. Does leather work with your lifestyle better than cloths or vice versa? Think of functionality first, then style. Leather is a classic, but fabric upholstery is more versatile. Think about the the style of the arms –traditional rolled arms are a graceful throwback, while straightlined arms possess a clean modernity to them. If purchasing full size, you are going to need to pick between two- and three-cushion styles. Three cushions invite a greater number of people to sink into the chair, but the center cushion can be an awkward spot to sit based upon the position of additional furniture, such as the coffee table or living room seats. If your area has an overall modern appearance, keep the couch style minimalist. When it's styled with more of a mid-century modern flair, look at styles with chic brass hardware or elegant tufting, both with buttons and with no. And contemplate colors: If that glowing red color will nonetheless appeal to you in 10 years, brilliant, but it might be better to go neutral and allow the rugs and cushions offer the pop of color when you want to alter it.
Whatever your space looks like along with your furniture needs are, You can find a sofa to fit into your own life and your property.
Complete Photos Click Here.
Description for Formidablel Sofa Sale Pictures Ideas Furniture Sears Cheapls For intended for 17 Petite Pics Of Sears Sofas Sale
|Image atribute
|Formidablel Sofa Sale Pictures Ideas Furniture Sears Cheapls For intended for 17 Petite Pics Of Sears Sofas Sale
|Upload by:
|Upload date:
|June 8, 2018
|Image link:
|605 px
|605 px


text:
I decided to take a short walk without the dogs today. The ducks were cooperating quite well.There were lots and lots of Mallards on the Athabasca
Some of them were pretty loud!
In-sights into moving from an Acreage back to Town, plus a few things I find of interest. Two things that horses are scared about: 1. Things that move 2. Things that don't move


text:
Justin Taylor at Between Two Worlds, does us a favor and placeds all the posts from the Baptism debates which have been occuring, at one location. As Michele at Reformed Chicks Blabbing writes, "This is not an issue at our church since we admit both credo (confessional) and paedo (infant) into membership. We believe that there shouldn't be any unbiblical requirements to membership. I would hate to exclude from fellowship those for whom Christ died, I feel sorry for churches who don't have a problem with it." We too at Christ Church are under the same conviction with our church constitution as Michele's.
Around the Web
Noteworthy Links
- Read-n-Grow Picture Bible
- CBMW New Website Look and a Blog
- Christians "Missionary" Datingand article #2
- ESV Brings us Family Worship at Home
- A Pretty Cool Program for those who are Anagramatical Minded: Anagram Generator
- 25 Skills Every Man Should Know (Mr. Hood, where do you come out?)
- Amazing Grace DVD to be Released in November
- Write a perfect email
- How to Learn 21 Languages with Your iPod
- Hymns of Faith; A New Radio Show Which FPC of Jackson is Airing
- My precious WLW loves to hear Mrs. Mohler. Girl-to-Girl Talk with Mrs. Albert Mohler (Mary)
- 10 Tips to Read More and More Better; "leaders are readers and readers are leaders"
- The Washington Post has an interesting article on Rule of Thumbs: Love in the Age of Texting
- The Code of the West (ht: Evangelical Outpost)
- Solo Femininity Offers her insight into CBMW's New Website, Something for Everyone
- 10 Lessons from the Princess Bride according to the Mommy with 8 in a Shoe
- John Wesley's Mom Whoops Aristotle
- Church Government - Does it actually matter?
- title
Wednesday, August 22, 2007
Between Two Worlds: Baptizoblogodebate Roundup (with Breaking News)
at 8:36 AM
Labels: Baptism, Blog, the church
0 comments:
Subscribe to: Post Comments (Atom)


text:
Spent a very wet day out - into the city, down to Ayrshire and back - ending up at Glasgow Cathedral for a an evening concert put on by the Glasgow Cathedral Choral Society.
It rained steadily all day and only let up upon my arrival at the Cathedral. The day started with a train trip from Helensburgh into town. The train was packed with men; upon my return late evening it was the same again! Apparently they were all sailors - Greek, French, Spanish, American - all here for naval exercises in the Clyde.
Still in the pouring rain the city was awash with ... more men! It turns out the Old Firm, i.e. Rangers were playing Celtic, and kick-off was midday. Great waves of fans poured (quite literally!) out of the underground stations all heading for the game at Ibrox Park.
The is the Cathedral reflection in a puddle. The concert was sacred choral works with orchestra and 4 young soloists, the lads, I read in the programme, who were trained in the church cathedral choir schools in England. All were in their 20's and students at the RSAMD (Royal Scottish Academy of Music and Drama) in Glasgow.


text: De-stashing Phase 1: Makeup and Skin Care Packing Party August 16, 2013 Related 0 Author Rae Hi, I'm Rae and I am a scatterbrain. I am in my 30s and I write in this blog from the Philippines. I spend a tiny portion of my time de-stressing with makeup and skin care. Email: firstname.lastname@example.com | Instagram: @scatterbraintures Website What do you think? Cancel reply


text:
Fresh Out The Workshop: the MB&F Legacy Machine
Ladies and gentlemen, this is the final edition of the most successful watch in MB&F's "Legacy Machine" Collection, the LM1, closing a 6-year story. Dubbed as the MB&F LM SE – Legacy Machine Split Escapement, this fresh timepiece is going to be available in 4 different versions, each of them equally stunning and packing an impressive movement.
Complex in nature and unique from every point of view, these new MB&F creations are quite different from the timeless and classical Legacy Machine 1. The first Legacy Machine, the LM1, brought to life some design cues that would later define the entire LM collection: a 3D look with a large floating balance wheel, held by a steampunk-inspired skeletonized arch, plus a round case, with classical lugs, featuring a highly domed sapphire crystal on top.
But let's get back to these beauties. All four new editions share the same 18k white gold case, albeit with a slightly different finishing. The case isn't entirely brushed, although the casebands were horizontally brushed and the sides of the lugs show a vertical brushed surface.
The dial looks beautiful, yet it does not stray away that far from the LM1 inspiration, nor does the 'heart' within. The four versions of the MB&F Legacy Machine Split Escapement will come with the dial finished in blue, ruthenium, yellow gold or pink gold, while the impressive hand-wound movement, developed for MB&F by Stephen McDonnell, will get the same look.
These precious watches will also come with 72 hours of backup power, while a black or brown, hand-stitched, alligator strap, with a white-gold folding buckle, will hold these beauties close to you at all times. Please note that only 18 such pieces will be found 'in the wild', priced at exactly CHF 79,000 – do you want one?


text:
VeriFone Names New CEO
SAN JOSE, CA – Earlier this week, the board of VeriFone Systems (NYSE:PAY) announced the appointment of Paul Gallant as the new CEO of the company, effective October 1. Gallant's appointment follows the ouster of Douglas Bergeron who had led the company since Gores Technology Group acquired the payment processing business from Hewlett-Packard (NYSE:HPQ).
Gallant, most recently served as the CEO of Citigroup's (NYSE:C) Enterprise Payments business, where he helped to develop innovative digital payments services for Citi's institutional and government clients. The innovations enabled the Citi division to expand into growth markets by positioning the company to me their customer's needs for secure mobile payments and commerce. Prior to running the Enterprise Payments division, Gallant was CEO of Citigroup's North American and International Consumer Credit Cards business.
According to Dr. Leslie Denend, VeriFone's Interim Non-Executive Chairman, the appointment of Gallant 'followed an extensive search process, that considered a broad list of highly qualified candidates, Paul was deemed unanimously by the Board to have the best combination of professional experience and leadership skills to continue to capitalize on the solid progress we have made in recent months. His experience in guiding businesses through industry change and his track record in multi-channel payment innovation will position the company strategically for continued growth and long-term value creation.'
With the appointment, analysts remained split on the outlook for VeriFone; Barclays Capital reaffirmed their hold rating on shares the company. While analysts at RBC Capital, Raymond James, and the Jefferies Group all raised their price targets for the company; overall VeriFone has a consensus rating of hold and an average target price of $ 22.67. Shares of VeriFone ended the week slightly off their one-month high at $ 23.13; year-to-date VeriFone's share are down nearly 20 percent.
Meanwhile, former CEO Douglas Bergeron, and VeriFone's largest shareholder, announced on Thursday that he has formed a new $ 500 million fund with private equity firm GCTR to buy financial-industry assets and companies. The new partnership between Bergeron and Chicago-based GCTR will be based in Palo Alto and called Opus Global Holdings LLC. Bergeron is kicking in $ 50 million and the private equity firm is investing the rest of the funds.


text:
MOSCOW, December 1. /TASS/. Russian paratroopers will participate in seven maneuvers of different levels next year, including the Interaction-2016 divisional command post exercise, spokesman for the Airborne Forces Yevgeny Meshkov told reporters on Tuesday.
"In the new training year, the Airborne Forces plan to conduct a series of exercises of various scale, including two brigade tactical, three regimental tactical and two divisional command post exercises in the field with airborne insert. One divisional command post exercise in 2016 will involve two formations stationed at a considerable distance from each other," he said.
The Interaction-2016 maneuvers, which will involve units of the Ivanovo and Ulyanovsk Airborne Force formations, are scheduled for September 2016, said Meshkov.
He said that during the previous training year the Airborne Forces conducted about 2,000 firing drills of different levels and about 400 maneuvers of different scale. Among other things, the forces conducted air drops of troops and military equipment on unfamiliar terrain in adverse climatic conditions of the Far East and in extreme conditions of the Far North.


text:
I was a teenager in the 1990s, an experience that I cannot describe to you – you have to have lived it to truly understand it – but that's a subject for another day. Where I was going with this thought is that as a teenager, you're looking for guidance, for a way to frame and structure your world that makes sense to you. Thank God that I was a country kid and that my generation had a poet, a sage, a wise soul named Garth Brooks to give us that much-needed guidance. As one of those terribly awkward, nerdy, bookish teenagers, I needed to figure out how to keep an open heart and a strong soul in the face of shallow high school concerns. Enter Mr. Brooks and his three chords and the truth. Words of wisdom indeed….
♦ The Change – "As long long as one heart still holds on / Then hope is never really gone" and "But it's not the world that I am changing / I do this so, this world will know that it will not change me."
♦ Unanswered Prayers – "Just because he doesn't answer doesn't mean he don't care / Some of God's greatest gifts are unanswered prayers."
♦ We Shall Be Free – "When the last thing we notice is the color of skin /And the first thing we look for is the beauty within" and "When we're free to love anyone we choose / When this world's big enough for all different views / When we all can worship from our own kind of pew / Then we shall be free."
♦ If Tomorrow Never Comes – "Tell that someone that you love / Just what you're thinking of/ If tomorrow never comes."
♦ Do What You Gotta Do – "There ain't nobody in this world / That's gonna do it for you / Do what you gotta do."
♦ To Make You Feel My Love – "The storms are raging on the rollin' sea / Down on the highway of regret / The winds of change are blowing wild and free / But you ain't seen nothing like me yet."
♦ The River – oh hell, just the entire song…listen here…
And now that I am an adult and have actually lived and experienced some of the difficult situations that Mr. Brooks was crooning about, his words still guide me and reassure me that I'm not the only one who has suffered a heartbreak and a rebuilding….
♦ Every Now and Then – "I love my life and I've never trade / Between what you and me had and the life I've made"
♦ I Don't Have to Wonder Anymore – "And I still don't know / Why things happened like they did / But I parked that old pickup / On that lonesome river bridge / I took your ring from my pocket / And I held it one last time / Watched that diamond sparkle /I drew back and I let her fly / And in less time than it takes to tear to fall / Oh that old ring went under / Lord, and now it's gone for sure / And I don't have to wonder anymore."
♦ She's Gonna Make It – "And you know it's not like she's forgot about him / She's just dealing with the pain."
♦ Beaches of Cheyenne – "He promised her he'd turn out / Well it turned out that he lied /And their dreams that they'd been livin' / In the California sand / Died right there beside him in Cheyenne."
♦ Cowboy Song – "He's just chasin' what he really loves / And what's burnin' in his soul / Wishin' to God that he'd been born a hundred years ago."
♦ In Another's Eyes – "Oh in another's eyes / Staring back at me / I see a sinking soul, trying desperately/ To turn the tide, before it dies."
♦ Ask Me How I Know – "You make all the rules, you're set in your ways / You gotta have your freedom, you gotta have your space."
♦ Learning to Live Again – "I'm gonna smile my best smile and I'm gonna laugh like it's going out of style."
♦ How You Ever Gonna Know – "You know failure isn't failure / If a lesson from it's learned / I guess love would not be love / Without a risk of being burned."
♦ The Dance – "Our lives are better left to chance / I could have missed the pain / But I'd have had to miss the dance."
So no matter your age or what stage of life you're in, if you're feeling lost or in need of some guidance, find the Garth Brooks station on Amazon or (for a truly 90s hair entertaining experience), search him on YouTube and watch the old videos. Let some good old country music wisdom guide you…
[on a random side note, the exception to his brilliant writing rule is "Cowboy Cadillac" – it's a catchy tune but damn those lyrics are dumb, is he writing about his woman or his truck?]
[a second random side note, I admit that I have had to overcome some disillusion and disappointment about Mr. Brooks as a human being and a husband as his first marriage ended and his relationship with Trisha Yearwood has unfolded. It's always hard to watch your icons reveal their flawed humanity – and in light of my own personal feelings about infidelity – it was a difficult pill to swallow.]