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Blue Letter Bible offers several daily devotional readings in order to help you refocus on Christ and the Gospel of His peace and righteousness.
Recognizing the value of consistent reflection upon the Word of God in order to refocus one's mind and heart upon Christ and His Gospel of peace, we provide several reading plans designed to cover the entire Bible in a year.
is'-a-kar (yissa(se)khar; Septuagint, Swete Issachar; Tischendorf, Issachar, so also in the New Testament, Tregelles, and Westcott and Hort, The New Testament in Greek):
(1) The 9th son of Jacob, the 5th borne to him by Leah (Ge 30:17 f).
1. The Name:
His birth is in this passage connected with the strange story of Reuben and his mandrakes, and the name given him is apparently conceived as derived from ish sakhar, "a hired workman." There is a play upon the name in this sense in Ge 49:15, "He bowed his shoulder to bear, and became a servant under taskwork." Wellhausen (Textder Buch. Sam., 95) thinks that the second element of the name may denote a deity; and Sokar, an Egyptian god, has been suggested. The name in that case would mean "worshipper of Sokar." Practically nothing is preserved of the personal history of this patriarch beyond his share in the common actions of the sons of Jacob. Four sons were born to him before Jacob's family removed to Egypt (Ge 46:13). In that land he died and was buried.
2. The Tribe:
At Sinai the tribe numbered 54,000 men of war over 20 years of age (Nu 1:29). At the end of the wanderings the numbers had grown to 64,300 (Nu 26:25). In the days of David, the Chronicler puts the figures at 87,000 (1Ch 7:5). See NUMBERS. The place of Issachar in the desert-march was with the standard of the tribe of Judah (along with Zebulun) on the East side of the tabernacle (Nu 2:5), this group forming the van of the host (Nu 10:14 f). The rabbis say that this standard was of 3 colors, sardine, topaz and carbuncle, on which were inscribed the names of the 3 tribes, bearing the figure of a lion's whelp (Tg, pseudo. Jon. on Nu 2:3). The captain of the tribe was Nethanel ben-Zuar (Nu 1:8, etc.). Later this place was held by Igal ben-Joseph, the tribal representative among the spies (Nu 13:7). The prince chosen from Issachar to assist in the division of the land was Paltiel ben-Azzan (Nu 34:26). The position of Issachar at the strange ceremony near Shechem was on Mt. Gerizim, "to bless the people" (De 27:12).
3. The Tribal Territory:
Sixteen cities of Issachar are mentioned in Jos 19:17 ff, but the only indications of boundaries are Tabor in the North and Jordan in the East. We gather elsewhere that the territory of this tribe marched on the North with Zebulun and Naphtali (19:11,33); on the West with Manasseh and possibly Asher (17:10); and on the South with Manasseh (17:11). It does not seem to have had any point of contact with the sea. The portion of Issachar, therefore, included the plain of Esdraelon, Tabor, the hill of Moreh, and the slopes East to the Jordan. The fortresses along the South edge of the plain were held by Manasseh. Tola, a man of Issachar, held Shamir, a stronghold in Mt. Ephraim (Jud 10:1). To Manasseh was given Beth-shean with her "towns" (Jos 17:11). No reliable line can be drawn for the South border. The district thus indicated was small; but it embraced some of the most fruitful land in Palestine. By the very riches of the soil Issachar was tempted. "He saw a resting-place that it was good, and the land that it was pleasant; and he bowed his shoulder to bear, and became a servant under taskwork" (Ge 49:15). "The mountain" in De 33:19 may possibly be Tabor, on which, most likely, there was an ancient sanctuary and place of pilgrimage. This would certainly be associated with a market, in which Issachar and Zebulun, the adjoining tribes, would be able to enrich themselves by trade with the pilgrims from afar. Issachar took part in the battle with Sisera (Jud 5:15). To Israel Issachar gave one judge, Tola (Jud 10:1), and two kings, Baasha and his son (1Ki 15:27, etc.).
4. Men of Issachar:
Of the 200 "heads" of the men of Issachar who came to David at Hebron it is said that they were "men that had understanding of the times, to know what Israel ought to do" (1Ch 12:32). According to the Targum, this meant that they knew how to ascertain the periods of the sun and moon, the intercalation of months, the dates of solemn feasts, and could interpret the signs of the times. A company from Issachar came to the celebration of the Passover when it was restored by Hezekiah (2Ch 30:18). Issachar has a portion assigned to him in Ezekiel's ideal division of the land (Eze 48:25); and he appears also in the list in Re (7:7).
(2) A Korahite doorkeeper, the 7th son of Obededom (1Ch 26:5).
Written by W. Ewing
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EXECUTIVE SEARCH STATUS: Current
POSITION: Human Resources Director
NATURE OF BUSINESS: Automotive-Related Industry
JOB LOCATION: Cape
REPORTS TO: Managing
Director, South Africa
SUMMARY OF EXECUTIVE OPPORTUNITY: Assume responsibility and accountability
for the Human Resources function with particular emphasis on providing
operational human resources support, implementing strategic human resources
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the local business teams.
Degree in Human Resources
• At least 15 years of progressive
leadership experience in Operational Human Resources within the Industrial
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Resources function in a company or division that employs at least 500 people
and has multiple manufacturing plants
• Specialized training in
employment law, compensation, organizational planning, organization
development, employee relations,
training, and preventive labour relations
• Experience
in the administration of benefits and compensation programs and other Human
Resources programs
• Experience
in operational Human Resources within the Industrial Manufacturing sector is
• Should ideally have an active
affiliation with appropriate Human Resources networks and organizations and
ongoing community involvement
• Experience in influencing senior
managers, building strong commercial relationships and driving a Human
Resources strategy
Send your details in confidence to: firstname.lastname@example.com
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subset: commoncrawl


text:
Teaching advanced english language
This book will teach you the first steps of English. It gives you about 500 important words in santences, with the meaning shown through pictures.Or vocabulary words, a person's vocabulary is the set of words in a language which they are familiar (known). Vocabulary often increases with age, and the basic tools and useful in communication and knowledge acquisition.
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A Book of English Idioms English in Tables An Introduction to the Pronunciation of English Build Up Your English The Complete Plain Words Fowler's Modern English Usage The Linguistic Sciences and Language Teaching The Structure of Technical English A Guide to Correct English Guide to Patterns and Usage in English Oxford Advanced Learner's Dictionary of Current English And English Reader's Dictionary Everyman's English Pronouncing Dictionary English Sentence Structure Better English Pronunciation A Grammar of English Words The Use of English English Grammar ...
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Writing Academic English, Fourth Edition, is a comprehensive rhetoric and sentence structure textbook/workbook for high-intermediate to advanced English language learners who are in college or are college bound. The book teaches writing in a straightforward manner, using a step-by-step approach. Clear, relevant models illustrate each step, and varied practices reinforce each lesson. The first part of the book provides a quick review of paragraph writing and summarizing, followed by a chapter that introduces the essay.
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New Headway Advanced Test Book: Advanced Teacher's Book New English Course Amanda Maris Liz and John Soars Mike Sayer
Liz and John Soars are highly experienced teachers and teacher-trainers, well-known for their contributions to EFL teaching and methodology.
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With every release of Visual Basic, Microsoft has added new functionality to enhance the applications that can be created. Visual Basic 6 took the first real step toward a client/server development tool that could create robust Windows applications. This newest release of Visual Basic, titled Visual Basic .NET, makes the jump from a mostly Windows-based application system to a truly dynamic development environment that allows you to design both Windows and Web-centric applications.
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English Today provides accessible cutting-edge reports on all aspects of the language, including style, usage, dictionaries, literary language, Plain English, the Internet and language teaching, in terms of British, American and the world's many other English's. Its global readership includes linguists, journalists, broadcasters, writers, publishers, teachers, advanced students of the language and others with a professional or personal interest in communication. Its debates are vigorous and it is noted for its reader involvement.
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English Today provides accessible cutting-edge reports on all aspects of the language, including style, usage, dictionaries, literary language, Plain English, the Internet and language teaching, in terms of British, American and the world's many other English's. Its global readership includes linguists, journalists, broadcasters, writers, publishers, teachers, advanced students of the language and others with a professional or personal interest in communication. Its debates are vigorous and it is noted for its reader involvement.
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Thirty two fourth level students in the Department of Foreign Languages at King Faisal University have participated in the study. They are 22-24 years old. All the subjects of the study were Saudi female college students enrolled in an advanced course, Language Testing, and most of them have successfully passed all the courses of the English program and are left with only one course, Teaching Practice.
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The Complete Guide to the TOEFL® Test, iBT Edition is the most complete, accurate, and up-to-date preparation book available. It is based on years of experi-ence teaching preparation classes in the United States and abroad. It is simply written and clearly organized and is suitable for any intermediate to advanced English language student.
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It is based on years of experi¬ence teaching preparation classes in the United States and abroad. It is simply written and clearly organized and is suitable for any intermediate to advanced English language student.
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The elements of a teacher identity in language teaching are derived from a review of literature on identity and described in terms of the foundational and advanced competences required for language teaching, as illustrated by excerpts from teacher narratives. The recommendations were produced in the discussion for teacher education and professional development with a focus on identity.
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Pyle earned a bachelor's degree in English in 1977 and a master's degree in Linguistics in 1979. He has been involved in the field of English as a Second Language since he began work on his master's degree in 1977. The original TOEFL test preparation book that he co-authored was created while Mike was teaching at the University of Florida's English Language Institute and Santa Fe Community College in Gainesville, Florida in 1982. He also wrote Cliffs Advanced Practice for the TOEFL in 1992. Although Mike no longer actively teaches for any institution, he periodically...
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This book examines the most recent advances in theory and research on communicative grammar instruction and the various instructional options for implementing it effectively in second language (L2) classrooms. A consideration of L2 teaching over the past few decades reveals a fundamental shift in the teaching of grammar from one in which grammar instruction was central, to one in which grammar instruction was absent, and to the recent reconsideration of the significance of the role of grammar instruction....
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This guide was written for readers interested in learning the C++ programming language from scratch, and for both novice and advanced C++ programmers wishing to enhance their knowledge of C++. The text is organized to guide the reader from elementary language concepts to professional software development, with in depth coverage of all the C++ language elements en route.
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This book is intended to survey the most important algorithms in use on computers today and to teach fundamental techniques to the growing number of people who are interested in becoming serious computer users. It is appropriate for use as a textbook for a second, third or fourth course in computer science: after students have acquired some programming skills and familiarity with computer systems, but before they have specialized courses in advanced areas of computer science or computer applications.
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Understanding and Using English Grammar is a developmental skills text for intermediate to advanced students of English as a second or foreign language. While focusing on grammar, it promotes the development of all language skills in a variety of ways. It functions principally as a classroom teaching text but also serves as a comprehensive reference text for students.
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This book is primarily aimed at teaching indie and hobby game developers how to create character animation with Direct3D. Also, the seasoned professional game developer may find some interesting things in this book. You will need a solid understanding of the C++ programming language as well as general object-oriented programming skills.
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Writing an extended text at an advanced level involves not just the language system. It poses significant challenges to our cognitive systems for memory and thinking as well. Indeed, writers can put to use virtually everything they have learned and stored away in long-term memory. But they can only do so if their knowledge is accessible, either by rapidly retrieving it from long-term memory or by actively maintaining it in short-term working memory. Thinking is so closely linked to writing, at least in mature adults, that the two are practically twins.
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Clojure in Action is a hands-on tutorial for the working programmer who has written code in a language like Java or Ruby, but has no prior experience with Lisp. It teaches Clojure from the basics to advanced topics using practical, real-world application examples. Blow through the theory and dive into practical matters like unit-testing and environment set-up, all the way through building a scalable web-application using domain-specific languages, Hadoop, HBase, and RabbitMQ.
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Young Minds Inspired, in cooperation with the Academy of Motion Picture Arts and Sciences, is proud to present this newest addition to our series of study guides that focus on different branches of the Academy. In this guide, students will learn about animation.The kit has been designed for students in high school English, language arts, visual arts and communications courses.The activities capitalize on students' natural interest in current films and the excitement generated by the Academy Awards®.They are designed to teach valuable lessons in critical thinking.
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text:
The Financial Stability Board (FSB) published a new thematic review yesterday of their progress in Shadow Banking regulation. The first "Principle" of the document is to define and update the regulatory perimeter. Realistically, can this be accomplished in the foreseeable future?
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text:
Previous Challenge Entry (Level 4 – Masters)
Topic: Employment (01/26/12)
TITLE: Whose Captives They Were | Previous Challenge Entry
By Amy Michelle Wiley
For a moment the silence stretched between them, thickening, hardening. Then Aliya spoke. "Where is my supper?"
Touthe snapped upright. How dare she speak like that? Who was she to… Touthe swallowed. "I'll fetch it." She'd rather die than add the "my lady" that was expected at the end of every utterance.
It trailed between them, unspoken, as she left the room. In the kitchen she stared at the fire pit. How could she be expected to bend over the hot flames, know when the meat was cooked to the right temperature, choose the right spices, any of it? She lifted a piece of wood. The rough sides bit into her hand.
Anger welled in her toward the men of her village. How could they be so weak? So stupid as to let the Israelites conquer them? To force a lady such as herself to perform work such as this?
She flung the kindling to the floor. It crashed against the wall, sending a basket of food flying.
Aliya appeared in the doorway. "What is the meaning of this?"
"I will not do it. I will not cook or clean or serve my own slave." She spat the words. Spat, like she wished she could spit right into this woman's face.
"Former slave." The Hebrew woman's face twitched, almost as though she dared smirk. "And you will. I am the mistress now." She turned to leave, then hesitated. "There are worse possible fates, you know." Her voice seemed almost gentle. Almost sympathetic.
She left the room.
Touthe sunk to the floor. Her body trembled, with rage and with fear. To her great consternation, tears insisted on overflowing, dripping down her cheeks to make muddy puddles on the floor. The floor wouldn't be muddy if she were still in charge.
How would she do this? How could she do this?
Something brushed her arm. She jerked.
Aliya bent nearby, picking up the spilled basket. She turned to Touthe. "Come, I will show you how to cook. You will learn so you may do it yourself."
What? Touthe dashed away her tears. "Why would you do that?" She expected the answer to be something about wanting unburned food, not accepting badly-done work.
"My God is one to be feared and obeyed. He will not tolerate those who do not follow Him." Aliya held out a hand, offering to help Touthe to her feet. "Yet He is also a God of mercy and love, eager to embrace those who turn to Him. He is a God of forgiveness, willing to put past transgressions behind Him, giving a second chance. I wish to be like Him."
Touthe stared at that hand, rough and work-stained. One she herself had slapped innumerable times.
"Will you learn from me?" Aliya pressed.
Touthe took a breath and grasped her hand. As she stood to her feet, she looked into the Hebrew's eyes and nodded.
"Yes, my lady."
...the house of Israel shall possess them in the land of the LORD for servants and handmaids: and they shall take them captives, whose captives they were; and they shall rule over their oppressors. ~ Isaiah 14:2 KJV
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text:
Burt's Bees Glossy Lipstick gives you medium coverage, glossy lip colour you'll love, with natural, moisturising ingredients that love your lips in return. These long-wearing lipsticks make lips super lustrous and keep them hydrated.
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- Nude Mist is a soft, neutral hue with a pink undertone
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text:
Thank you for your interest in becoming a Comfort Zone volunteer.
STEP 1 – The first step is to create a My Comfort Zone account and fill out the volunteer application, which includes permission for Comfort Zone to conduct a criminal background and personal reference check. Click on green button below.
If you are applying to be a Big Buddy, please provide as much detail as possible regarding your interests and hobbies, as this information will be used to "match" you with a camper.
The information shared in your application will remain confidential within Comfort Zone Camp.
STEP 2 – Sign up for and complete a six hour volunteer training which covers Comfort Zone's volunteer expectations, what to expect at camp and common questions and concerns related to childhood grief.
Once you have selected a training date, you are registered to attend. You will receive a reminder e-mail approximately 1-2 weeks prior to the training session you selected.
STEP 3 – To become a volunteer at camp, sign up for a camp session(s) through your My Comfort Zone account and see steps 4-7 below. Once you sign up, the session(s) will appear under My Upcoming Camps. Please note: we cannot guarantee you will be matched as a Big Buddy or assigned a volunteer role for a camp session that you selected.
If interested in being a volunteer outside of camp, please e-mail Comfort Zone at firstname.lastname@example.com.
STEP 4 – Approximately 4 weeks prior to your selected camp session, Comfort Zone will e-mail you in order to confirm your availability. This is for planning purposes and to ensure you are still interested and available. This does not guarantee you will be assigned a role for camp; however, we ask that you continue to hold the weekend for us until we have notified you of an assignment, or not.
STEP 5 – Approximately 1 week prior to camp, Comfort Zone will notify you if you have or have not been assigned a role at camp by e-mail and through your My Comfort Zone account. At this time, you will also receive additional information you'll need for camp.
STEP 6 – If you have been matched as a Big Buddy, Comfort Zone will make your camper's information available to you through your My Comfort Zone account.
STEP 7 – For the camp weekend, arrive at the camp site at 2:30 p.m. on Friday. Camp ends at approximately 4 p.m. on Sunday.
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text:
Smoke Fire Theme GO SMS Pro
by: Workshop Theme • 9.5K
All Android applications categories
All Android games categories
by: Workshop Theme • 9.5K
Theme smoke fire works only with GO SMS Pro application if you don't have it, download for free from Google Play.
This a new skin for GO SMS Pro Theme = is designed especially for people who like the colors blue, green, and red
There is also orange or yellow glimmer and also purple haze. If you love lots of colors like pink or violet it is an application for you! And it's for free! Background is black and dark to view of smoke This Theme has wallpapers for main background and nice colorful and white icons
Our vision is based also on the fire and flames the warmth rising from the burning process. While some see this as a fume or steam from water vapor created by flame light
Style helps You to customization and personalization your GO SMS Pro with great style - all for FREE!
To apply the motive and enjoy the beautiful wallpaper (also for GO Chat):
1. Download this motif from Google Play for free
2. Download GO SMS Pro for free
3. Install and launch GO SMS app
4. Press right to see options and press "theme"
5. Click "Local" tab
6. Tap the GO SMS Pro Theme Smoke Fire
This design will change your phone
To personalize appearance settings about conversation list
1. Go to messages Menu
2. Press message Advanced options
3. Click Appearance Settings.
4. Press Conversation List Customization
And now You can adjust for each other, you can customize:
- Background in messages.
- Displayed contact pictures.
- Contact font.
- Contacts font color.
- Time and message fonts.
- Or reset this setting as to default.
To change appearance settings about conversation style
1. Press Menu
2. Go to Advanced
3. Click Appearance Settings.
4. Press Conversation customization
And now You can adjust for each other, you can change:
Conversation style ( bubble setting or list style)
- Background
- Incoming font
- Outgoing font
- Hyperlink color in text
If you want to use avatar icon for any contact simply change it and the new image fuchsia for each contacts are visible on conversation list and messages SMS list.
Disclaimer: this application uses interstitial ads and banners.
Check other our GOSMSPro Themes, GO Locker Themes, and GO Launcher EX, free themes.
Themes are published all the time, so remember to check our developer account regularly.
The style was created by WorkshopTheme.
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text:
HIV Field's Current Contours Show in Boston
HIV prevention was the top story at CROI 2016, but issues of adherence and uptake still loom large in the battle to stop HIV's spread.
By Michael Dumiak
Last summer more than 2,500 women across the sub-Saharan nations of Malawi, South Africa, Uganda, and Zimbabwe completed their participation in a three-year clinical trial of a monthly vaginal ring containing an experimental antiretroviral (ARV) known as dapivirine (DPV). It was the larger of two simultaneous efficacy studies of vaginal rings as pre-exposure prophylaxis, or PrEP—the use of ARVs in healthy individuals to ward off HIV infection.
Researchers gathered for this year's Conference on Retroviruses and Opportunistic Infections (CROI), held Feb. 21-26 in Boston, heard firsthand the results of these two efficacy studies. Overall, the rings were 27 percent to 31 percent effective in reducing the incidence of HIV infection in women ages 18 to 45. The broader implications of this and other HIV prevention strategies set the tone at this year's CROI. Behavioral issues still loom large and researchers discussed how to reach younger, more vulnerable people with HIV prophylaxis, including daily oral PrEP, which so far shows much higher efficacy than the ring.
Meanwhile some of the newer ARVs in development may offer another option for both treating and preventing HIV infection.
Aspiring to protection
The DPV ring was tested simultaneously in two placebo-controlled efficacy trials: A Study to Prevent Infection with a Ring for Extended Use, or ASPIRE trial (MTN-020), and what's called The Ring Study. ASPIRE, led by the National Institutes of Health (NIH)-funded Microbicide Trials Network, is the larger trial with 2,629 volunteers enrolled at 15 study sites: nine in South Africa, three in Zimbabwe, two in Malawi, and one in Uganda. This trial took place from August 2012 to June of 2015. The Ring Study was led by the International Partnership for Microbicides (IPM) and involved 1,959 women volunteers in South Africa and Uganda. The budget for each trial was approximately US$72 million.
DPV-containing vaginal ring development dates back to 2002 with the founding of IPM, which launched in order to develop antiretroviral-based microbicides for prophylaxis in mother-to-child transmission and to prevent sexual transmission between adults as well.
The ring is itself, which has been used for contraception, is essentially a silicone 'o,' which contains 25 milligrams of DPV, a non-nucleoside reverse transcriptase inhibitor never licensed for treatment. The ring is designed to slowly release drug over one month of use. IPM holds a global dapivirine license from Janssen R&D Ireland, one of the Janssen Pharmaceutical companies of Johnson & Johnson, which originally developed the drug as the independent biotechnology company Tibotec.
Volunteers in both trials were counseled to use the ring continuously and return each month for collection of the spent device, to obtain a fresh one, to be tested for pregnancy, HIV, and other sexually transmitted diseases, and to receive HIV prevention and risk-reduction counseling. Follow-up was for a minimum of one year.
Results from ASPIRE and The Ring Study differed only slightly in their overall protection rates, with ASPIRE showing an overall 27 percent reduction in HIV infection and The Ring Study showing a reduction of 31 percent. But the trials showed vastly differing rates of protection when looked at more closely and analyzed by age. In ASPIRE, women aged 18 to 21 showed no overall reduction in HIV risk, whereas in The Ring Study it was only 15 percent. Among older women, there was a 56 percent reduction in risk for women ages 22 to 26, and a 51 percent reduction among women ages 27 to 45. The Ring Study showed 37 percent efficacy in women older than 21.
The main reason the protective effect varied so greatly was adherence. Adherence was significantly lower among women in the 18 to 21 age group. "We really wanted those numbers to be higher. We were disappointed, too, originally," says Annlene Nel, IPM's Paarl, South Africa-based chief medical officer. Even so, the researchers behind the studies say the results are compelling enough to pursue licensure of the DPV ring.
To receive regulatory approval, the group needed two pivotal trials showing statistically significant efficacy. "We've got that," says Nel. "It is modest efficacy. We know that, very much so. But look at the burden of disease in the communities where we are conducting this trial. It is significant. If you can prevent a third of women from contracting HIV, over 10 years you prevent thousands of women from becoming HIV positive. Long term you can really change the incidence. It would be a huge difference coming down from 8 percent to 4 percent."
The ring has many supporters in the HIV community, many of whom expressed their support in Boston. But some there also questioned the ring's very clearly reduced effectiveness in younger women and the overarching problem with adherence. Development of the ring itself comes directly from the effort to improve adherence—insert the ring and forget about it. But adherence is still an issue.
Nel and other researchers suspect non-adherence had to do with volunteers being leery about the safety and efficacy of the product. "There may also be rumors in the community. A negative influence really spreads. And when there's a change of partner, there's a fear component where they will not disclose and then they might just remove the ring."
Sheena McCormack, a clinical epidemiologist at the Medical Research Council Clinical Trials Unit at the University College of London, says the rings are a new beast altogether, and there are issues around vaginal practices that may influence their use. "Women do like to wash after sex. It's possible they take the ring out to do that. It might be something that doesn't fit with their culture, doing that with the ring in," she says.
Finding the best drug
One critique of the overall ring results is that the protective effect was lowest in the young, sexually active women who are at great risk of HIV infection. Another is that the existing alternative, oral PrEP with the drug Truvada (a combination of the ARVs tenofovir and emtricitabine), is between 92 and 99 percent effective in preventing HIV infection when used consistently. Some wonder what accounts for this gap in efficacy.
"I have some questions around the drug. Would we have seen a different result if it had been a tenofovir ring or another drug that once released stays in the genital tract a little bit longer?" McCormack asks. She is co-principal investigator of the Microbicides Development Program and was chief investigator for the PROUD trial, which studied the use of oral PrEP in men who have sex with men.
Dapivirine and tenofovir are very different drugs, McCormack says. Oral PrEP acts systemically, so it takes longer to get into genital tissues; a vaginal ring releases a smaller amount of drug locally so there are high levels in the genital tissues but lower drug levels elsewhere. It's altogether hard to differentiate which is more effective, given all the behavioral factors affecting use.
"It is clear that oral tenofovir, when used daily, has a higher level of efficacy," says Robin Shattock, an immunologist and mucosal infection expert at the Imperial College of London. "That's really when you are taking it every day." Still, Shattock, who is researching combination prevention approaches, including ARV-based gels or rings as well as the use of broadly neutralizing monoclonal antibodies, is optimistic about the dapivirine ring's chances. "When the ring was being designed, they could have put more drug into the ring. I think more drug probably would have given higher efficacy in women that used it," he says. "That can be improved."
A combination of drugs may also provide better protection. Shattock says combining the ring with a contraceptive, as IPM plans to do, would be a no-brainer. "Women may then be using it for the convenience of contraception, and to have a contraceptive ring that also provides some level of protection against HIV may be more appealing than thinking, 'I'm at risk and need to have something that will stop me from getting HIV.'" For any of the PrEP regimens, adherence is the key to efficacy. "For these things to work, people need to use them," Shattock says.
Bruce Walker, an immunologist and director of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology (MIT), and Harvard, says tools need to be independent of behavior. "We need things that are going to work in women at the most vulnerable periods of their lives. The fact the ring didn't really work in women before age 25 is a disappointing finding. I'm less optimistic about that being part of a solution for HIV infection," he says. "The more you can take behavior out of the equation, the more successful these interventions are going to be."
Three of the 15 clinics in the ASPIRE trial were located in Zimbabwe, serving 678 of the study volunteers. Nyaradzo Mgodi of the University of Zimbabwe served as clinical researcher directing the study. "In Zimbabwe we have a saying, home is a woman. We want to take care of women because this is how you make steps in promoting public health. I'm happy about the results," Mgodi says.
She thinks that in Zimbabwe a ring has a better shot of being used, even given the adherence questions. "Most young women in Zimbabwe are unemployed. Some of them have secondary education. They are homemakers, they take care of their family and extended family," Mgodi says. "Any day they may be asked to go to rural areas to look after a sick relative, or attend a funeral, or go to a church conference." Mgodi recalls the VOICE trial that tested oral PrEP in sub-Saharan Africa. "The volunteers used to say they would forget sometimes to take their tablets. They want something which is less user-dependent, so I think this will be good."
IPM is pushing ahead with an open-label, follow-on study of Ring Study volunteers, and is also in discussions for a similar open-label study for ASPIRE participants. Open-label studies may positively influence adherence, according to the University of Washington's Jared Baeten, who led the ASPIRE study. Baeten says what is important now is to understand who are the populations that would use a pill, and who are the populations who would not use a pill but might use a ring. Meanwhile, the group is compiling data for a submission dossier which, if things go as planned, should be delivered to the European Medical Association and regional southern African regulators either by the end of this year or in the first quarter of 2017. The funders—the Bill & Melinda Gates Foundation, UK's Department for International Development, and other European nations—appear to support this plan.
Response to the ring results stands in marked contrast to the disappointment over the RV144 vaccine trials which showed that a combination of two vaccine candidates reduced HIV infection rates among volunteers by 31 percent. Shattock says the overall gloomy reaction to the RV144 trial and the apparent enthusiasm for the DPV ring, despite similar overall efficacy rates, is due to the science.
"It's an important first step and there are some obvious steps to take to improve it," Shattock says of the ring. There are many other possible drugs that can be explored, and most importantly, researchers understand how they work. Human behavior is more complicated, but the science is not such a hard issue as it is with vaccines. "The contrast with the Thai trial is that to this day I don't think anyone really understands what the mechanistic correlates are," Shattock says. "You have lots of immune correlates that reduce risk of infection, but we don't know the mechanism. So to know where to go next takes guesswork."
|A coda for Ebola
For the better part of 18 months, the world's largest Ebola outbreak to date raged through the western African nations of Liberia, Sierra Leone, and Guinea. It devastated villages and families, set the world on edge, and prompted a desperate global health response, heroic in the moment and in some cases criticized afterward for being sluggish. During all this, three vaccine candidates emerged into public view and went through quickly organized clinical trials. Safety and efficacy data emerged last fall (see When Ebola Returns, Will the World be Ready?, IAVI Report, Issue 4, 2015) and the trials continue to yield valuable information, as presented in February at the Conference on Retroviruses and Opportunistic Infections (CROI).
Researchers shared Phase II clinical trials results for the two leading vaccine candidates tested during the 2014-2016 outbreak. The first, a vesicular stomatitis virus-vectored replication-competent vaccine (rVSV-ZEBOV) from Merck and the Public Health Agency of Canada, was tested in Guinea and Sierra Leone. The other was a chimpanzee adenovirus-vectored DNA vaccine (ChAd3-EBO-Z) from GlaxoSmithKline and the National Institutes of Health, which was tested in Liberia. Also discussed at CROI was the Ebola treatment ZMapp, a triple monoclonal antibody cocktail tested in all three nations. The Merck and GSK candidates came under the collaborative umbrella representing dozens of international and local agencies in what's called PREVAIL: PREVAIL I is the effort covering the two vaccine candidates, PREVAIL II covered the ZMapp treatment effort, and PREVAIL III is an ongoing effort to gauge Ebola's longer-term impact on survivors of the virus.
Fatorma Bolay, director of the Liberian Institute for Biomedical Research, pointed out that both vaccine candidates are well tolerated and immunogenic, as has been reported previously. But further analysis of the data is now bringing other aspects into focus: for instance, the trial shows that six percent of volunteers entered the study with detectable levels of Ebola antibodies, suggesting they had been infected with the virus before but had no known history of the disease. The candidates also seemed to induce antibodies at different rates. The ChAd3 candidate produced immune responses in week one in 13 percent of volunteers, the VSV in nine percent, and the placebo in six percent. But by the end of one month, 87 percent of ChAd3-vaccinated individuals developed an antibody response, while 94 percent of VSV-vaccinated individuals did, and only seven percent of placebo recipients had Ebola antibodies. Meanwhile three studies of thousands of Ebola survivors are ongoing. Early data from these efforts provide evidence for a possible syndrome that develops in Ebola survivors, signs that Ebola can cause unrecognized and asymptomatic infection, and growing confirmation of the potential of Ebola to be transmitted through sexual transmission. "There are still many gaps in our knowledge of Ebola," says Gene Richardson, a Stanford field researcher. Bolay and Mosoka Fallah, of the Liberian health ministry, also reported that in the PREVAIL vaccine volunteer group totaling 1,500, 5.2 percent were HIV infected, which is unexpectedly high, according to the National Institute of Allergy and Infectious Diseases. The reported HIV incidence rate in the country overall is 1.9 percent, according to Bolay. This raises questions about whether the incidence is just much higher among younger people or if the estimated incidence doesn't reflect the actual size of the HIV epidemic in these west African countries. —M.D.
Getting word out on PrEP
Given the imprimatur of top health officials and its well-established efficacy, one would think oral PrEP would be a settled issue. But getting at-risk individuals to actually use it is very much a work in progress.
Gilead first launched Truvada for the treatment of HIV-infected adults in the US in August 2004. Based on results from the iPrEx and Partners PrEP clinical trials testing the drug for HIV prevention, the US Food and Drug Administration approved Truvada in 2012 as the first oral PrEP drug. That same year the World Health Organization recommended daily oral PrEP use for serodiscordant couples and also noted the scientific consensus emerging that PrEP reduces the risk of sexual acquisition and transmission of HIV regardless of population or setting. The institution later recommended oral PrEP for all high-risk individuals.
Since then, however, uptake is slower than expected. By the summer of 2014, Johns Hopkins University HIV epidemiologist Chris Beyrer was telling the Guardian that Truvada, to that point, was a "boutique intervention." This was partly due to cost in the US, where it carried a price tag of between $8,000 and $14,000 a year, although Gilead was offering subsidies for those without private insurance. Daily adherence was also being seen as an impediment. These factors were at play especially in minority and poor communities.
The US Centers for Disease Control and Prevention (CDC) estimates 185,000 new HIV infections in the US could be prevented by expanding testing, treatment, and, notably, oral PrEP.
In Chicago and London, efforts are underway to address the lag in PrEP uptake. Chicago's PrEP effort, as outlined by Jim Pickett of the AIDS Foundation Chicago, involves a social and promotional campaign launched in February. Pickett and Chicago health officials were able to enlist volunteer help from a global advertising agency to create a professionally-designed, data-driven marketing, social media, and publicity campaign for PrEP in Chicago.
Pickett says that in 2015 the number of new HIV infections reported in Chicago dipped under 1,000 for the first time since the epidemic began, with 973 new cases occurring in 2014. That's about half of the peak number reported in 2001. But there are disparities: half of new cases are among black people, and of the women who do contract the virus, most of them are black. Three of four new infections are among gay or bisexual men in Chicago; half of this number are black men and another 25 percent are latino.
A CDC study shows 77 percent awareness of oral PrEP in Chicago, but further surveying shows of those aware, only 14 percent had obtained subscriptions. Of those surveyed who were aware of PrEP but did not have a prescription, half reported having unprotected anal intercourse. "We're missing the boat," Pickett says. For his crew in Chicago, time will tell how effective PrEP marketing can be. A second wave of the campaign launches this summer.
Elsewhere, researchers, clinicians, and advocates are also beginning to think about how to incorporate oral PrEP in order to reduce incidence of HIV among the subgroups of individuals at highest risk of infection. In the last decade HIV infections have risen across Europe by 33 percent among men who have sex with men, while falling 61 percent among heterosexuals from countries with generalized HIV epidemics and declining by 36 percent among those injecting drugs. In Europe there's a new urgency for early diagnosis of HIV and other sexually transmitted infections. Since McCormack and her colleagues reported in 2015 on the PROUD study showing up to 85 percent effectiveness for Truvada, some 6,000 new HIV infections have been diagnosed in the UK. "Over half of them have been seen previously in the clinic and could have been offered PrEP," McCormack said during her CROI presentation. "PrEP has to be part of the vision for the future."
McCormack says a small clinic on Dean Street in the Soho neighborhood of London called Dean Street Express, which offers faster, more self-directed testing for HIV and other sexually transmitted infections, may be a natural place to promote PrEP. Dean Street Express neither looks nor feels like a clinic. An aid sets up a client with swabs. The client goes into the screening room, where a digital presentation on the mirror explains how to do the testing. The samples go into a container, which goes into a pneumatic tube. Test results are delivered in six hours by text message.
The UK National Health Service (NHS) is in the process of considering Truvada for listing, which would make PrEP free for UK residents. It is becoming a heated debate, though.
Cutting half life in half
Another realm of prevention research discussed at CROI centers on the hundreds of broadly neutralizing antibodies (bNAbs) researchers have isolated from HIV-infected individuals in recent years. These antibodies, which can effectively neutralize a broad swath of HIV isolates, are the types that vaccine researchers ideally wish to induce through immunization.
In the meantime, researchers including John Mascola, director of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, want to determine whether directly injecting these antibodies into people may be able to block HIV infection, an approach referred to as passive administration. To optimize the antibodies for this purpose, researchers are attempting to improve the potency and half-life of these antibodies so that less antibody is necessary and it stays around for a longer time. "The consideration for using the antibodies for prevention has been that we may be able to test them on an interval of about every two months," Mascola said.
Two antibodies targeting the CD4 binding site (VRC01 and 3BNC117) are already in Phase I passive administration studies. Michel Nussenzweig and colleagues at Rockefeller University have started Phase I studies with the antibody 10-1074; Mascola expects studies with PGT121 to begin within the next year. These two antibodies target different vulnerability sites on the virus. Other antibodies, including PGDM1400, CAP256-VRC26, and 10e8, will probably take a year to 18 months to get into the clinic. Within the next couple years, Mascola says, antibodies targeting four major sites on the virus are likely to be in passive-administration studies.
He reported that in Phase I trials VRC01 lingered at titers of up to 10 micrograms per ml in serum for about two months. The question now is whether that concentration of antibody is sufficient to prevent HIV infection. A Phase IIb study, the Antibody-Mediated Prevention (AMP) Study, opened enrollment this month under the umbrella of both the HIV Prevention and Vaccine Trial Networks. "Can a passively infused antibody prevent HIV in humans?" Mascola asked. "That's what needs to be studied and answered." AMP will be a placebo-controlled study of VRC01 administered every two months in 2,700 men who have sex with men and transgendered people in North and South America, and 1,500 women in sub-Saharan Africa. The aim is to associate the level of antibody in a volunteer's plasma with the level of protection and therefore define the optimum dosage.
"If that level turns out to be fairly reasonable, a therapeutic range that we might expect, it translates into the possibility of giving an antibody subcutaneously," Mascola says. Muscle itself could, potentially, be lured into secreting antibody for weeks or months at a time, providing medium-to-long-term protection. "Knowledge of protection in a human setting would tell us something about neutralizing antibody levels and what a vaccine might need to elicit in order to protect."
Mascola says there are many reasons to pursue passive administration: there's a reasonable chance it will work, that because the antibodies are human antibodies they are likely to be well-tolerated, that a single shot could potentially deliver long-term protection, and that clinical efficacy would propel this approach into mainstream use. The ultimate goal, he says, is a sub-cutaneous injectable antibody that could be given every three to four months and safely and effectively protect high-risk individuals from HIV infection. "That's where the field is trying to go," Mascola says.
To do so, any eventual product needs to meet specific targets: it will need to cover 98 to 99 percent of all HIV strains, which may require a combination of bNAbs, cost about as much as ARV-based PrEP, and be given subcutaneously every three to four months. These elements, Mascola says, are already achievable in the lab. The bNAb N6 neutralizes more broadly than VRC01, only missing three percent of viruses as opposed to VRC01's 13 percent, and is much more potent. Other antibodies can be engineered in order to boost their potency, and combining antibodies, at least in the lab, shows it is possible to gain 100 percent coverage and account for the diversity of HIV.
There is also reason to be optimistic about efforts to improve the half-life of the antibodies. Mascola uses an example from AstraZeneca subsidiary Medimmune, which is investigating a monoclonal antibody called motavizumab (the company had pursued it for respiratory syncytial virus infection unsuccessfully, but continues to work with it). A 2012 trial of mutated motavizumab, motavizumab-YTE, extended the half-life of the antibody for up to six months at 10 micrograms per ml of serum. "That's a remarkable feature one would hope to take advantage of for prevention studies," he says.
The VRC scientists introduced mutations into VRC01 to improve its half-life and are now testing the modified antibody in a Phase I trial. "We will know soon if we can take the half-life from about two months of therapeutic range out to four, five, or six months."
|Complex and persistent
Each HIV particle may be alike, but Melbourne immunologist Sharon Lewin's coming to conclude that every HIV infection persists in its own way.
"We're hearing a lot more about the complexity of how and where HIV persists," Lewin says, sitting for a minute in one of the huge halls of the John Hynes Convention Center at the recently held Conference on Retroviruses and Opportunistic Infections (CROI). "The initial dogma was that there was a long-lived resting pool of cells where HIV persisted indefinitely. We're seeing now that there's no one way that HIV persists. It probably persists differently in different immune cells in tissue and blood."
This is the central question for those pursuing an HIV cure: in order to rid a person of HIV, researchers need to understand exactly how the virus gets into specific cells, why it stays there, and how to flush it out. They'll need to flush it out because all indications are that if antiretroviral treatment stops, it's only a matter of time before this latent reservoir of HIV-infected cells causes viral rebound. "There's not one flavor of latency. We're trying to dig it out: in naïve T-cells, T-follicular helper cells, in proliferating T-cells. They all look very different," Lewin says.
Her lab at the University of Melbourne is able to mimic, in vivo, what she says is one of the latest wrinkles in persistence. Emory's Nitasha Kumar, a researcher formerly in Lewin's group, presented results at CROI demonstrating that latency can be established in non-proliferating and proliferating cells. Lewin says the implication is that virus persists not just in non-dividing cells, but also in cells that can proliferate. The virally infected proliferating T-cells divide, and make new infected T-cells. "The virus is intact, yet it doesn't destroy the cell, which challenges a long held dogma in the field," Lewin says. Many researchers believed if a virus was intact, then proliferation would activate the virus and therefore kill the cell. As it turns out, Lewin says, it appears that latency can be established in proliferating cells in vitro and that these cells are long lived. So if researchers are only looking for latency in long-lived resting cells, they may be missing another reservoir of the virus. —M.D.
Long-lasting inhibition
Extending the half-life of ARVs also looks more promising. Jay Grobler, director of infectious disease biology at pharmaceutical company Merck, presented data at CROI on a long-acting, experimental nucleoside reverse transcriptase inhibitor known as MK-8591, which the company licensed from Japanese company Yamasa. Grobler said the drug has the potential for once-weekly oral administration as well as much longer-acting parenteral administration that could persist for up to a year. The drug is being explored for both HIV treatment and prophylaxis.
Grobler reported results from Phase I pharmacokinetic studies of MK-8591, which he says showed the drug had an even greater intracellular persistence and antiviral activity than was observed in in vitro studies and in rhesus macaques. Following a single oral 50 milligram-per-kilogram dose, Merck researchers saw a very rapid uptake of the molecule, with high concentrations reached in blood within an hour. Concentrations stayed over 10 micrograms per ml for more than a week; the absorbed drug has a half-life in monkeys of more than 50 hours.
In the Phase I dosing study, volunteers received varying doses of MK-8591 (10, 30, and 100 milligrams) once a week for three weeks. "At that 10-milligram dose we've already exceeded the target drug concentration with the SIV monkey model," he says. "One week after dosing, the trough concentrations exceeds that target twofold." Doses of up to 400 mg were well tolerated.
Merck considers the molecule ideal for low-dose parenteral formulations, either by injection or patch, which release effective drug levels for up to 180 days. There is potential for the long-acting ARV to even provide coverage for up to a year's time. Either way, this type of treatment would greatly reduce the burden of therapy. As prophylaxis, it could potentially eliminate the reliance on behavior, which has proven problematic even with the monthly rings.
David Margolis, director of drug development at ViiV, the HIV joint venture between GlaxoSmithKline and Pfizer, has been overseeing another long-acting HIV therapeutic—in this case, combining the ARVs cabotegravir, an integrase inhibitor, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor. Both were developed as once-daily pills. But in the LATTE program (Lancet Inf. Dis. 10, 1145-55, 2015), for which Margolis in Boston presented the second round of study results, researchers are testing the combination as an injectable, long-acting HIV treatment.
LATTE 2, a 32-week study aimed at establishing safety and efficacy of the combination and to set a dosing schedule for future trials, involved 286 volunteers randomized to receive gluteal shots of the ARVs either every four weeks or every eight weeks. A third group took oral cabotegravir and rilpivirine daily.
The trial volunteers had suppressed viral loads of less than 50 copies per ml prior to the injection of the ARVs. Maintenance of virologic success was steady over 32 weeks, Margolis said: by the end of the study, 95 percent of those receiving injections every eight weeks, 94 percent of those getting shots every four weeks, and 91 percent of those on oral dosing met virological success, which was an undetectable viral load under 50 copies per ml of blood. Volunteer satisfaction was higher for the injection than the oral dosing: 90 versus 71 percent reported satisfaction. The next step, Margolis says, is a 48-week dose-selection for upcoming Phase III trials.
The long-acting cabotegravir/rilpivirine combination outlined by Margolis could be a "game changer" for treatment and prevention once implemented, according to Steve Deeks, a clinician at the University of California at San Francisco who specializes in HIV inflammation. "The CROI data confirm what most of us expected to see with these regimens. This is an important, but not a particularly new story," he says. MK-8591, however, could be in Deeks' view an even more exciting approach to treatment and prevention. "It is potent and can be formulated for very long-acting delivery methods, due to the limited amount of drug needed to block HIV," the San Francisco clinician says. "In contrast to the cabotegravir-related data at CROI, this data was a complete surprise and quite novel. I find it amazing that 10 mg of a drug could have such a potent and sustained effect."
Michael Dumiak reports on global science, technology, and public health and is based in Berlin.


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In the field of educational technology, some apps might be getting too smart.
More and more apps are delivering on-demand homework help to students, who can easily re-purpose the learning tools to obtain not just assistance, but also answers. Whether or not that's cheating—and how to stop it—is one of the concerns surrounding a new app that can solve math equations with the snap of a camera. While the software has inspired teachers to create real-world homework problems that can't be automatically solved, that strategy doesn't hold up to other apps that tap into real-life brains for solutions.
Here's a look at 7 apps that can do your homework for you, and what they have to say about cheating:
Price: Free
Availability: iOS, Android app coming in early 2015
The new, seemingly magic app allows users to take pictures of typed equations, and then outputs a step-by-step solution. As of Wednesday, the app is the number one free app on the App Store. But the biggest issue, one teacher argues, isn't if students will use the app to cheat, because many will. Rather, it's about how teachers will adapt. A PhotoMath spokeswoman said educators have welcomed the app with positive reviews, but the software remains "quite controversial."
"We didn't develop PhotoMath as a cheating tool. We really wanted kids to learn," said Tijana Zganec, a sales and marketing associate at tech company MicroBlink, which created PhotoMath. "If you want to cheat, you will find a way to cheat. But if you want to learn, you can use PhotoMath for that."
Whether you're a high schooler with eight periods of classes or a college student tackling dozens of credits, there's one thing you've got for sure: a mess of assignments. iHomework can help you keep track of all your work, slicing and dicing it in a variety of ways. Sorting it by due date, week, month, or by course, the app is more organized than a Trapper Keeper. And in integrating data from Questia, you can link your reading material to your assignments so you don't have to dig through a pile of papers to find the right information.
A scheduling feature can help you keep track of those random bi-weekly Thursday labs, and you can even mark the location of your courses on a map so you don't end up on the wrong side of campus. And finally, with iCloud syncing, you can access all this information on whatever Apple-compatible device you're using at the moment — no need to dig for your iPad.
Taking the search giant's suite of free browser-based apps and sandboxing them so they are safe for school use, Google Apps for Education is an excellent alternative to the mainstream installable productivity software, but this one has a perk that almost school board will love—it's free. Packaging together favorites like Gmail, Hangouts, Google Docs, Google Sheets, and Google Drive with Classroom, a digital hub for organizing assignments and sending feedback, the goal of this collection is to make learning a more collaborative process.
Though Google Apps for Education is cloud-hosted, the programs can be used offline, ideal for when your student needs to escape the internet and work distraction-free. And since it works on any device, it also helps students avoid buying overly expensive hardware. That means more money for extracurricular activities.
Price: Free, but some homework services require payment
Availability: iOS and Android
HwPic is a tutoring service that allows students to take send pictures of their homework to tutors, who will then respond within minutes to your questions with a step-by-step solution. There's even an option to expedite the answers if a student is in a hurry. HwPic Co-Founder Tiklat Issa said that the app was initially rejected by Apple's App Store, which believed it would promote cheating, but he successfully argued that just because someone uses the app in a way that it's not meant to be used doesn't mean the app should be punished.
Issa added that HwPic prohibits cheating in its terms and conditions. Tutors don't solve homework that has words like "Quiz" or "Exam," and they often know if a student is sending a photo during a test if they've paid for expedited answers, and if the photo is dim, blurry and taken under a desk. "We've minimized cheating," said Issa. "We haven't eliminated it. That's kind of unrealistic."
Price: $2.99
Availability: iOS and Android
Wolfram Alpha is similar to PhotoMath, only that it targets older students studying high levels of math and doesn't support photos. The service also outputs step-by-step solutions to topics as advanced as vector calculus and differential equations, making it a popular tool for college students.
"It's cheating not doing computer-based math, because we're cheating students out of real conceptual understanding and an ability to drive much further forward in the math they can do, to cover much more conceptual ground. And in turn, that's cheating our economies," said Conrad Wolfram, Wolfram Research's Director of Strategic Development, in a TEDx Talk. "People talk about the knowledge economy. I think we're moving forward to what we're calling the computational knowledge economy."
Price: Free
Availability: iOS and Android
Chinese Internet search company Baidu launched an app called Homework Helper this year with which students can crowdsource help or answers to homework. Users post a picture or type their homework questions onto online forums, and those who answer the questions can win e-coins that can be used to buy electronics like iPhones and laptops.
The app has logged 5 million downloads, much to the dismay of many some parents who argue that the students spend less time thinking about challenging problems. A Homework Helper staffer admitted to Quartz, "I think this is a kind of cheating."
Price: Free, but some homework services require payment
Availability: iOS
Slader is a crowdsourcing app for high school and college students to post and answer questions in math and science. While students can post original homework for help, many questions in popular textbooks have already been answered on the app, according to Fast Company. An Illinois high school said earlier this year that it suspected students were using the service to cheat on their math homework.
Slader argues that it's "challenging traditional ideas about math and education," and said that the ideas behind its app "aren't a write-off to teachers," according to its blog. Slader told San Francisco media outlet KQED that it shouldn't be dismissed as a cheating tool, but rather considered a way for students to access real-time help.


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Product 14/18
Jonathan Cape, London. First published in 1954 our copy is a reprint of 1955
Good condition but without dust jacket.
9 x 6 inches. Hardback.
We just love this book so much that we have accidentally ended up with 2 copies. One for each eye you might think but no we have decided to sell one of them (books - not eyes)
This is a translation of a Latin Bestiary* of the 12th century.
Delightfully illustrated throughout it contains vivid (although to the modern mind possibly a tad misleading) descriptions of animals both real and mythical
Here is just a whiff of one of them:
so called from its crocus or saffron colour. It breeds in the River Nile; an animal with four feet, amphibious, generally about thirty feet long, armed with horrible teeth and claws.
. Its dung provides an ointment with which old and wrinkled whores anoint their figures and are made beautiful, until the flowing sweat of their efforts washes it away
Is there no end to the useful information you find on Cybergrot.com?
The footnotes tell us (among other things) that crocodile dung was thought good for freckles, that it could be lighted and the smoke puffed into snake holes (we are not quite sure why one would want to do this but there we go). The teeth were an aphrodisiac provided they were removed while the crocodile was alive (we think we will pass on that one).
Just think 270 pages of pure joy like the above
And for a less beastly price ... visit the price negotiator's den.
T.H. White (Terence Hanbury White nicknamed Timothy as a joke - after a famous chain of shops selling house-wares in the UK in the middle of the 20th century) was a scholar who is perhaps most famous for his novels The Sword in the Stone and The Once and Future King.
*Bestiary: a book consisting of images, descriptions, and stories of animals, both real and fantastic, frequently used as a vehicle for teaching Christian morality; these books were extremely popular during the Medieval period, especially in the British Isles


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in-toto is a proud supplier of the beautiful new sink and tap brand Roux Lifestyle, endorsed by inspiring chef Michel Roux Jnr, as well as other leading brand sinks that complete the quality and design of your kitchen.
We supply a wide range of beautifully-designed taps for everyday needs and more luxurious living, including the new kitchen must-have: boiling water taps from Quooker and Roux Lifestyle.


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TERMS & CONDITIONSJust a page example
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Last updated: February 02, 2016
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BEGINNING SUNDAY, MARCH 15 OUR SERVICES WILL ONLY BE ACCESSIBLE VIA LIVESTREAM FOUND AT THE FOLLOWING LINK. A DOWNLOADABLE COPY OF THE BULLETIN CAN BE FOUND ON THE WORSHIP PAGE. https://livestream.com/rutgerschurchnyc/events/8967087
Hello and welcome to the website of Rutgers Presbyterian Church, which is located at 236 West 73rd Street (just west of Broadway) on New York City's diverse and exciting Upper West Side.
All through the year, Rutgers Presbyterian Church celebrates God's radically inclusive, affirming, unconditional love.
If you're looking for a Christian spiritual home in this part of the Big Apple, we invite you to browse our site and then join us for our Sunday morning service of worship at 11:00 am and for the coffee hour that follows. In 1998, we celebrated our Bicentennial Year and completed a full renovation of our sanctuary. To the glory of God, we have rebuilt for another 200 years! Please share an experience of worship with us.
Whether you're single or a family, gay or straight, younger or older, a seeker or a believer, you'll find us to be a warm hospitable community of faith with the programs you're looking for.
Our Church School has classes for both adults and children/youth aged 3–18 and meets Sunday mornings from mid September through May. Adult classes convene at 9:45 am and for ages 3 through 12 meet at 11:15 am, after the opening part of the worship service. Infant and child care up to age 12 is available every Sunday from 10:30 am (earlier by request) and for most special services during Advent and Holy Week.
Other programs for children and youth include the S.K.A.T.E. youth group, and Community Programs (which offer classes for children and adults of all ages, too). A.A. and Al-Anon groups meet here several times each week. Information about these and other programs plus our social justice ministries is given on this website. So please click the button of your choice and continue your journey of exploration with us.
I support Rutgers, and it supports me — in so many ways I can't measure and can't count. It's my home.


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OccupySandy - All-Project Meeting - 11/27/12
- Coney Island
- Sheepshead Bay
- Rockaways
- Staten Island
- Red Hook
- Jacobi
- Clinton
|# This script will tcreate a place holder image
|if [ -z "$1" ]
|echo "Please enter the size you wish to make (ex: 120x300) then press [ENTER]"
|read size
|

|<input id="switch" type="checkbox">Switch
|<input id="switch2" type="checkbox">Switch
|<input id="switch3" type="checkbox">Switch
Drew: @hornbein
|#!/usr/bin/env bash
|echo "Database Name: "
|read -e DBNAME
|echo "Database User: "
|read -e DBUSER
|echo "Database Password: "
|read -e DBPASS
|echo -e "
|DB Name: '$DBNAME'
|#!/usr/bin/env bash
|# By Drew Hornbein @ http://dhornbein.com
|# Description: The following script will take image files from
|# the current folder and run the Imagemagick convert function.
|# A log.txt file will be created in the new folder
|# Dependencies:
|# imagemagick - we use the convert program
|<!DOCTYPE html>
|
|
|
|
|<meta charset="utf-8">
|<meta http-equiv="X-UA-Compatible" content="IE=edge,chrome=1">
|
|<title>Phenological Clock</title>
|# By Drew Hornbein @ http://dhornbein.com
|# Modified from:https://github.com/Sirupsen/sirupsen.github.com/blob/master/static/misc/shoot
|# By Sirupsen @ http://sirupsen.dk
|# Description: Very simple script to make you
|# select a region of your screen, which will be captured, saved, and
|# then uploaded. The URL will then be injected into your clipboard.
So you've started a Facebook group and it's got 15k+ people who are rip roaring ready to organize. Quickly you'll notice that Facebook sucks as a platform for organizing. This is because it is a platform designed to mine data about you in an effort to increase your engagement with advertising partners. It is a crappy digital technology for organizing (great for mobilizing though!).
In this document I'll go over what I think might be some good platforms. I did tech organizing in #OCCUPAYWALLSTREET, Occupy Sandy, and have learned some lessons. I'm no authority and these are my most humble suggestions. That said, here's the core take away before I cover solutions.
We need cultural technology for making group decisions, holding safe space, promoting historically marginilaed voices, and keeping digital spaces from turning into spammy unsafe echo chambers run by people who look like me. There is no magic digital tech that will do that. To put it another way, every platform sucks.
|#!/usr/bin/env bash
|# creates a git repo on a remote server to which to deploy to!
|# Check for git first
|type git >/dev/null 2>&1 || { echo >&2 "I require git but it's not installed. Aborting."; exit 1; }
|while [[ $a == 'N' || $a == 'n' ]]
|# Collect repo name


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Film Reviews with a Drag Queen: Double Feature – Hail, Caesar! and PPZ
Film Reviews with a Drag Queen!
In which Stixen Stones teams up with M. Leigh Hood
to give you a peek at the latest and greatest in a theater near you.
Tonight: A Double Feature!
Hail! Caesar and Pride and Prejudice and Zombies
Moderate spoilers ahead!
M.: Hail, Caesar! – How would Stixen summarize the film?
Stixen would say that it was a visually gorgeous film with lots of pretty costumes and gorgeous guys and gals who all look straight out of the 1940's. As for the story, it had its moments. But the spectacle was well-worth the pandering plotline.
M.: How did you feel walking into the theater versus walking out?
I came in expecting a film about a squad of vintage film stars having to band together to find George Clooney. So I was ecstatic. And I left feeling a bit disappointed. Sure, it was clever and fun. Some of the characters were hilarious and endearing, but on a whole it felt like the film didn't know what it wanted to be. A gritty drama? A screwball comedy? A commentary on religion? It was all those things and more and as a result, it was sort of all over the place.
M.: Best costumes?
The costumes were my favorite. Since costumes are my job, I was really impressed. Not only were they dazzling, but they were, for the most part, historical. They really did a good job of taking this story to the next level. They were the perfect cross between believable and stylized. Tilda Swinton and Scarlet Johansson's costumes were my favorite.
M.: Of all the genres caricatured by the film, which did you enjoy or empathize with?
That's a good question. I think that was a struggle I had: truly connecting with the film on an emotional level. But my favorite part had to have been Alden's character, Hobie Doyle. He stole the show for me. He was charming and genuine and I wanted to see more of his story. But then again, Channing Tatum's homoerotic dance number wasn't bad either.
M.: As you said, the story was a bit haphazard because it WASN'T really a single, unified plot. Of all the plots and subplots racing around, including Hobie Doyle, which do you think would've made the best stand-alone film?
Oh wow. That's a fabulous question! I think that was the issue. Not one of them had enough substance to create an entire film around them. But probably Hobie, since he did have that budding romance scene with that lovely actress. Their chemistry was adorable and I would've liked to see more of that story. But I could also see something with Scarlet's character. While I didn't enjoy the pregnancy plotline, I liked the character. I enjoyed the juxtaposition between this on-screen beauty and her off-screen crass sassiness. I wanted to see more from her and less from Eddie and his family drama.
M.: The film definitely spent a lot of time on the less-interesting characters. Could that be intentional? After all, one of the major plot points was that we never see "The Christ's" face. Either way, that angle seems to have backfired.
Yeah! I agree. It felt like such a shame. I liked Eddie and George's character (whose name escapes me), but I didn't find them interesting enough to base an entire movie around them. Nor did I care about them, if we're being really honest. The writers didn't really give us moments to fall in love with them, you know?
M.: Definitely. Despite the vibe of the trailer and the colorful cast, the story was out to prove a point rather than let the characters drive. Then again, the social commentary was hilariously spot-on, seeing as how the next film we viewed opened with a trailer for a "Christ" film where the POV character is a Roman and we never really get to see Christ.
Yeah! That was quite the moment, wasn't it? But then again, I guess we're due for another movie about Christ since the Passion of the Christ was, what, ten years ago or so?
I never saw it – I just liked the fact that Satan was played by an androgynous woman.
But I digress.
M.: Yes, because nothing is scarier than an androgynous woman. And here is a good bridge into the second film.
M.: Once again: summary, please?
Ah yes! Pride and Prejudice and Zombies was much more up my alley. Fearsome women in pretty dresses kicking zombie ass? Be still my heart! It was very much a Stixen film. I laughed, I gasped, I even forgot myself and said "Yaaaaaas" louder than I should have during a scene where the girls were suiting up.
M.: Yes, you did! But, believe me, it only improved the experience. One more familiar question: impressions going in and impressions going out?
Oh good! I'm glad I could become part of the experience! Going in: I was really excited. Like I said, I love women kicking ass and taking names. But I also was curious to see how well the two genres (classical and horror) would meld. I was also prepping myself for lots of jump scares. Going out: I was enthralled. It was clever, funny with just enough gore. And handsome men to boot (Bingley? Me-OW!). The story flowed well and the characters remained the same ones that I loved from the original. I'm definitely planning to see it again.
M.: Obviously there were some historical alterations – in clothing and culture. For instance, several times I noticed the girls' riding dresses had long splits on the outer layer for ease of access to blades. Did you have any favorite alterations?
Good question! I'd have to agree. I liked the alterations they made to the corsets and riding boots and such to make them more battle-ready. Though, I must say, I don't think the lacy thigh highs were historically accurate.
M.: Not at all, I'm afraid. What altered character did you like best?
While there were a lot of fun character alterations, I did really enjoy the bad-assery they bought to Lady Catherine de Bourgh. In the original she was uptight and proper to the T. But making her a hardened zombie-killing veteran with an eyepatch? On paper, it doesn't make sense. But I enjoyed seeing her in action.
Did you have any favorites?
M.: She was probably my favorite as well. Although I did enjoy the logic behind Darcy's reticence. It was more than pride; it was paranoia.
Yes! I agree with that. It added a lot of colors to his character that weren't there in the original. The same could be said for Wickham, as well.
M.: Was it my imagination or did the training make the Bennet sisters seem closer-knit? In all other versions it seems to be Jane and Elizabeth vs. The Idiots.
I think that's an interesting point. In the original, there was certainly more of a divide. But this film didn't focus much on the relationships between the Bennet sisters as much. Except for, of course, the closeness between Jane and Elizabeth – and Lydia being annoying as hell (what else is new?). But I can agree. There did seem to be a bit more closeness to them. I especially liked the scene where all the girls were fighting each other in the underground battle room. Mary adjusting her glasses and putting down her book before throwing a punch had me laughing.
M.: Obviously the gender roles have been altered from their original historical context. Still, expectations of women, particularly lower class women, seemed to follow a pattern of rules. What are your thoughts on the shifts they chose to make?
I liked them! Obviously, as a feminist, I was excited to see this version of altered history. But I think they were able to shift them well. They were intelligent shifts. Like the shame involved in their "lower-class" Chinese training for instance, was a brilliant way to show that the women were still up against a misogynist society. I thought it was interesting that, even though they were fearsome and clearly talented at kicking ass, society was stilling oppressing them – like expecting them to put down their weapons once they got married, for instance.
M.: Which is delightfully pointless since there would, presumably, be children to protect at some point.
Exactly! And as we saw with Bingley, most of the upper-class men, save Mr. Darcy, were helpless at best. Clearly, the women were much more skilled at it then the men. One could even say that the oppression they experienced made them better, more determined fighters.
M.: A very good point. I have to say how much I liked the stage of the zombie apocalypse. It was a fact of life. No one panicked when they saw zombies – unless the zombie was particularly close. And, as we discussed, it had been around long enough to establish a new social order. It allowed zombies to influence, but not overrun the story. No pun intended.
Agreed! I really enjoy films like that. When you stir supernatural elements into anything, there has to be a sense of reality to it to make it believable. It's a delicate balance, but without it, we, as the audience, are often unable to suspend our disbelief. I think this film did a great job of making this plague just like many we've seen in the past. Yes, there's panic, but you also have to adapt to a new way of life. And I think the elements that they added to make us believe the story made sense.
Official Heel Rating – Hail, Caeser!:
I'd say this was a fun film. It was gorgeous visually and the characters were vivid and amusing but the story lost itself to too many plotlines. But the background characters really make this film worth seeing at least once if you're a fan of the old hollywood flair.
I give it 3 high heels, but that's mainly because Hobie's adorableness stole the show.
Official Heel Rating – PPZ:
This film was a blast and a half. It has something for everyone. It's got humor and heart and I really can't say enough good things about it. It was fun to watch and the acting was pretty exceptional all across the board. I'd give it 4 and a half high heels.


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Thursday, November 29, 2012
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Wednesday, November 28, 2012
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Tuesday, November 27, 2012
Launa 'Ana...
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Today was a beautiful day. We celebrated the opening of the Makahiki Season at Halawa Correctional Facility. A newly emerged Pulelehua, or butterfly, joined the celebration of Peace, Love, Forgiveness, Healing, and Redemption and was a powerful Hōʻailona. Ke Akua, na akua, Lono, and our beloved ancestors were all present to bear witness to the gathering. The Pulelehua served as a powerful reminder, that everyone is entitled to positive change, renewal, forgiveness, and re-emergence in a new true beautiful form. Let your Spirit soar into the Heavens...
Posted by Ka`iana at 12:45 PM 1 comments
Sunday, November 25, 2012
This is a Raven from Alaska, the home of our native brothers and sisters as well as the home of Native Hawaiians who left these islands at various times in the past 220 years. This Raven is robust and of varied genetic composition. Our native crow, the ʻalalā has not fared so well. Of at least five species of Native Hawaiian crow which once existed, only the ʻalalā tenuously survives to this day.
Between 1993 and 1998, 27 captive ʻalalā were released into the wild. 21 died. 6 were recaptured and returned to the captive flock. In 2005, the Maui and Keauhou Bird Conservation Centers held the World's population at the time, 55 individuals. In 2008, three years later, there were 56 individuals in the World.
A variety of issues plague the restoration and survival of the ʻalalā including predation, loss of habitat, a dwindling genetic pool and loss of instinctive behaviors. If we come to the precipice of losing the ʻalalā, like so many other of our Native Hawaiian birds, I would support wholeheartedly cross-breeding the ʻalalā with a crow or raven to build resilience and survivability as well as numbers.
I would much rather have a hapa-ʻalalā then no ʻalalā for my great grandchildren to see and hear. A genetic infusion of other ethnic DNA into the blood of my pure Native Hawaiian kupuna is one of the reasons why I am still here. Survival of catastrophic disease and epidemics. The pure Native Hawaiian 'uhane, or spirit, can inhabit any kino, or body. Otherwise, quoth the Raven, "Nevermore..."
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Saturday, November 24, 2012
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Chocolate Waterfall Brownies...
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Friday, November 23, 2012
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'Ike Hawai'i...
To see, know, feel, greet, recognize, perceive, experience, be aware, understand...all things Hawaiian...
Posted by Ka`iana at 1:56 PM 0 comments
Fields of Gold...
Posted by Ka`iana at 1:52 PM 0 comments
I stopped in my tracks as we stared at each other for a brief few seconds. Sharing both time and space in an ephemeral moment once in a billion years. She had every right to attack and sting me...the way humankind has treated her and her extended family. But she didn't. I was very grateful. I don't intentionally kill bugs anymore. Large or small. Live and let live was the lesson she taught me that day. I am eternally grateful and humbled for my little fuzzy hardworking Kumu...my sweet Teacher...
Posted by Ka`iana at 1:39 PM 0 comments
Black Crowned Night Heron. 'Auku'u also means to wretch or vomit. I have seen 'Auku'u 'auku'u before when they ate too many tilapia at a time...
Posted by Ka`iana at 1:27 PM 0 comments
Hawaiian hawk (Buteo solitarius), an endemic and endangered hawk with dark and light color phases, confined to forests on the island of Hawaiʻi, where it is regarded by some as an ʻaumakua. The ʻio signified royalty because of its lofty flight, and hence occurs in such names as ʻIo-lani, royal hawk...
Posted by Ka`iana at 1:24 PM 0 comments
Thursday, November 22, 2012
Tonight, I walked into the boys' bedroom and found Koa sitting on the floor in the dark clutching his little Mr. Piggy stuffed animal and hiding between the couch and closet. I asked him if he was okay. He said yes. I knew he wasn't. So I asked him to come sit on my lap on the couch and let me hold him because I wanted to. He slowly crawled over and up into my lap. He is growing up so fast that I treasure moments where I can hold him again.
I held him and we looked at Mr. Piggy. The seam where his neck attaches to his chest and shoulders is a little ripped open and some of the stuffing is visible. I told him that we will have to perform surgery on Mr. Piggy and sew his head back onto his body better. We both laughed. I showed Mr. Piggy my stomach scar up close from my recent pancreas surgery and told him not to be afraid to get a scar like me. Then I held Koa tighter and began rocking back and forth slightly as I hummed "You Are My Sunshine..." to him.
I remember my Mother singing that song to me when I was little. I felt her presence in the darkened bedroom and I treasured holding my beloved son. As I began humming the song all over again after finishing it the first time, I was amazed that I actually was humming it in key because I never sing that song. It was like it was somewhere deep in my memory from childhood without me realizing it.
I soon felt cold drops on my shoulder and chest. Koa quickly sat up and wiped it off looking a little embarrassed. I could see that tears were streaming down his face. I asked him why he was sad and it took awhile with some little gentle prodding to get him to answer. He said, "I don't want you to ever leave me..." I started to tear up too.
Knowing that I almost lost my life recently and imagining the fear my sons had. My biggest fear as a child was losing my Mother. I kissed his head and squeezed him tighter. I said, "Don't worry...I will never leave you...we will be together forever. No matter what happens in this Life, and after it, we will always be together. Forever. Isn't God beautiful to allow our Souls to be together forever..."
Koa said yes and smiled wiping away his tears. We sat there in the dark, as I held him, feeling his warmth, breathing in his hair, kissing the top of his head. Giving humble Thanks for the amazing miracle of Life, Love, and Forever...
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Hula in Ka'u...
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'Ike Kimepani...
Posted by Ka`iana at 10:28 PM 0 comments
Live your life to the fullest consuming whatever your heart desires with wanton abandon and in the end, you will have no Egrets...
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Days of Summer...
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Wednesday, November 21, 2012
Wishing everyone in the World a most beautiful Thanksgiving. Thankful for so many blessings in this most incredibly profoundly beautiful life. Praying for everlasting Peace, less suffering, more laughter, tears of joy rather than tears of sorrow and for every one to truly love and forgive one another...and for not one single person amongst us to feel lonely and abandoned, but to feel truly loved...
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Tuesday, November 20, 2012
Posted by Ka`iana at 11:46 PM 0 comments
Trying to repatriate the iwi of Henry Opukahaia in 1972, twenty-one years before he was finally able to come home to Hawai'i. My cousin Diane would end up working at the burial excavations at Honokahua at Kapalua, Maui, in the late 1980's which gave rise to the Burial Sites Program where I started in 1994, the year after Henry came home. Life is full of amazing destiny...
Addendum: I remember hearing about Deborah Lee having a dream which initiated the 'ohana effort...amazing... I didn't get to visit his grave in Napo'opo'o until August of 2010...it was like a Mecca for me... I remember breaking down and sobbing at his new grave...so grateful that, unbeknownst to me, he was a guiding spirit throughout my whole life...saved me from certain ruin... I remember talking to him in Cornwall when I was five years old and picturing him as he looked in his Memoirs book, lying under the concrete slab...God is Great... : )
Posted by Ka`iana at 6:36 PM 0 comments
Ku'i Kalo...
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Monday, November 19, 2012
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Sunday, November 18, 2012
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Saturday, November 17, 2012
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Chinatown Markets...
Posted by Ka`iana at 7:54 PM 0 comments