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/ Africa
Slow progress in investigation into RFI journalists' murders in Mali
Issued on: 03/03/2018 - 18:19 Modified: 04/03/2018 - 10:49
RFI | Claude Verlon (left) and Ghislaine Dupont were murdered in northern Mali in November 2013.
Text by: FRANCE 24 Follow
A French judge visited Mali in February to investigate the 2013 deaths of RFI journalists Ghislaine Dupont and Claude Verlon but was unable to visit Kidal, the site of the murders, a group dedicated to their memory was told at a meeting on Saturday.
Dupont, a reporter, and Verlon, a reporting technician, worked for RFI (Radio France Internationale), FRANCE 24's sister station. They were in Kidal in northern Mali covering the country's legislative elections when they were kidnapped and murdered on November 2, 2013.
Jean-Marc Herbaut, the French judge investigating the killings, traveled to the capital Bamako on February 5 to work with his Malian counterparts, the Friends of Ghislaine Dupont and Claude Verlon group was told at a meeting in Paris on Saturday. For security reasons, he was unable to go to Kidal.
"The judge has been able to talk to local officials," said FRANCE 24 reporter Nicholas Rushworth, who was at the meeting. "He's been able to talk to people who were witnesses there."
"He's learned that one of the suspects in the case has died in recent months," Rushworth continued. "Also, he was able to obtain new phone data and phone recordings that could be useful for the investigation. So, for the Friends here, [there is] some sense of movement after many years of frustration."
None of the alleged perpetrators have been arrested and no concrete progress had been made in the inquiry.
"We're asking the same questions and still getting no response," Christophe Boisbouvier, an RFI journalist and a member of the Friends of Ghislaine Dupont and Claude Verlon, had said before the meeting.
Classified documents
Most of the documents related to the case are classified or were heavily redacted. In the absence of official information, several hypotheses have been put forward to try and explain the killings. For example, a report on the TV news network France 2 in January 2017 suggested they were an act of revenge for an unpaid ransom related to the release of French hostages kidnapped by an al Qaeda affiliate in neighbouring Niger who were freed in October 2017. French judge Herbaut has dismissed this theory.
Another hypothesis that has been put forward was that the kidnapping went wrong and that the militants murdered the two journalists without planning to, after a vehicle broke down or a surprise helicopter patrol emerged.
Another obstacle for the investigation is that it remains impossible for the French and Malian investigators to look at the scene of the crime in Kidal. Malian authorities are only now returning to the city, which was until recently controlled by armed groups.
Ghislaine Dupont
Claude Verlon
Two Senegalese journalists win the 2017 Ghislaine Dupont and Claude Verlon prize
FRANCE - MALI
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Entourage of 7 is luxury eyewear based in Los Angeles and influenced by the city in which it originates. In the City of Angles - an ever-changing multicultural melting pot, we find joy in pushing forward, constantly reminding ourselves to always be courageously creative. We aim to design beautiful spectacles for our rockers and rollers, lovers and sinners at Venice Beach – the birthplace of Entourage of 7.
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Some of its tools, machines, models and documents dating from 1843 are still used by the company for the design and manufacture of prototypes of spectacles. All the assembly and insetting techniques are carried out by hand. The company constantly carries out technical research on the materials and tools. Vuillet Vega has been awarded several prizes for its aesthetically pleasing and user-friendly products. All the new models are registered with the INPI, the National Industrial Property Institute. The company's designer holds the title of Meilleur Ouvrier de France (Best Craft Worker) in spectacles. The company sells its products exclusively to shops specialising in the sale of spectacles (e.g. Krys, Afflelou, Visual, etc.) and to some celebrities. Its products are exported to the Middle East, Asia, Africa and North America. Vuillet Vega is the only eyewear to have been awarded the "Living Heritage Company" the Minister of SMEs. This prestigious label promotes quality, expertise exceptional and original territory.
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Coppe-SID eyewear from Italy
Products are completely HANDMADE IN ITALY. They have a real Lapis Lazuli thin stone inserted in the temple. They come with a serial number warranty card to guarantee the authenticity. Models are identified by a name of International Cities and their Airport codes to confirm the Cosmopolitan soul of this collection. Only available at selected leading optical boutiques throughout Asia and Europe and recently presented in New York for the North American markets
Vincent Kaes Eyewear from Italy
Installed in the Vallée de Morez, capital of the spectacle industry since 1796, Vuillet Vega has specialised in the manufacture of upmarket spectacle frames for the past five generations. Its spectacle frames are made from precious or semi-precious inset materials: mother-of- pearl, tortoiseshell, shagreen, etc.
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Volte Face Eyewear from Paris
Handmade glasses that are made in France. Established in 1997, it is now part of the J.F.Rey brand of High Quality Frames. Designer Fabienne Coudray-Meisel who is also an Optician, knows how to create frames that are comfortable and superior quality.
This concept is only available from approved Face & Cie opticians
Face & Cie interchangeable frames by ZENKA
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Like nature, which adopts a new look each season, we all evolve and reinvent ourselves as our desires and lives change. This is why Zenka has designed interchangeable eyewear that can be transformed to suit our mood and lifestyle. Change of decor The principle is simple and ingenious : an original and colourful clip- on part is added to the top or front of a simple frame, transforming it in just one click into trendy, eye-catching and unique glasses. These decorative elements are as easy to remove as they are to attach. For each new season, a new look To allow glasses wearers to nd the perfect match for their mood of the moment, Zenka offers a wide range of frames and a multitude of clips with new designs each season. Whether glamorous, contemporary, daring, trendy or ultra-stylish, our clips reflect the latest fashion trends. High-quality products Frames are made from TNG and inox, high-tech, robust and ultra- light materials.100% French manufacturing adds a guarantee of quality.
Imagine having a single eyeglass frame durable enough to last for years, yet versatile enough to look great with every outfit in your wardrobe. Using simple design principles for their frame fronts combined with a wide range of temple patterns from wild to subtle, Dilem has created eyeglasses that are truly multifunctional and modern. The temples are easily interchange-able and made using plastic and polymer materials that are strong as well as lightweight. Dilem's extensive catalogue of different temple styles and colours has our customers from Vancou mond, Burnaby, and all over the Lower Mainland creating more and more customized eyeglass looks. These French-made frames are fun, funky, and perfect for any lifestyle.
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ZIGGY Eyewear from Italy
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LAMARCA Eyewear from Italy
Exciting, poetic, appealing, stylish, original – 5 words that sum up the LAMARCA EYEWEAR collection. Our quest is to create a unique product, to break free of narrow market diktats and follow our dream of creating a superb collection in which every model is the fruit of meticulous attention to detail, from concept through design and choice of colours to manufacture, the artisan tradition reflected in such exclusive processes as engraving, thermoforming and bonding.
Eté Lunettes from Italy
Eté lunettes is a fourth generation owned and operated eyewear manufacturer originating in France. The passion for hand-crafted eyewear started in 1924 using materials such as horn and tortoise shell. Over the years each generation has preserved the passion and traditions passed down to them and believe each frame should be an individual work of art. Their modern day frames use unique materials such as plexi and have intricate hand-carved details within the frame.
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Jaguar Eyewear from Germany
The Eyewear The JAGUAR Eyewear collection mirrors the unique elegance and drive of the JAGUAR sports car. Design interpretations from car to eyewear such as carbon fibre details, wood grain and interior materials characterize the collection. Lens shapes that closely adhere to the design language of the car as well as color transfers further add to the JAGUAR magic of these frames, making them truly desirable products for men. The car JAGUAR is known for the development and fabrication of sovereign and ambitious luxury vehicles since 1922. The sensuous premium-automobiles and sports cars ensure extraordinary performance, exceptional luxury and an intense driving experience like only a JAGUAR can do.
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KALEOS Eyewear from Barcelona, Spain
This new brand of sunglasses and eyeglasses originates from Barcelona, Spain. The original styles and unique designs perfectly fit our collections providing the quality, craftsmanship and artistic appeal we expect from European made eyewear. At Impressive Eyewear, we are proud to bring you European brands that you may not easily find in other local stores. Stop by to see and try on these and many other unique brands.
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Bold, Different, Unique,
Stylish and Funky
The Impressive Eyewear Frame collections include many independent European brand names such as JF Rey, Dilem, Zenka, Silhouette, Bellinger, Yves Cogan, Oga, Jimmy Choo, Roger, Blackfin and Dutz to name a few. Our newest additions is the French Face & Cie frame collection that features frames with changeable front faceplates. Pierre eyewear Featuring unique handmade one of a kind frames and Sasura with interchangeable charms are also featured. The luxurious collection by Gold & Wood from Luxembourg, Cazal from Germany and Entourage of Seven from Los Angeles will impress the most discriminating eyeglass wearer. Below, are just a few samples from some of the collections. Please visit our store to see and try-on many more frames from our inventory.
DILEM Frames from France
Imagine having a single eyeglass frame durable enough to last for years, yet versatile enough to look great with every outfit in your wardrobe. Using simple design principles for their frame fronts combined with a wide range of temple patterns from wild to subtle, Dilem has created eyeglasses that are truly multifunctional and modern. The temples are easily interchange-able and made using plastic and polymer materials that are strong as well as lightweight. Dilem's extensive catalogue of different temple styles and colours has our customers from Vancouver, Richmond, Burnaby, and all over the Lower Mainland creating more and more customized eyeglass looks. These French-made frames are fun, funky, and perfect for any lifestyle.
Sasura Frames with inter- changeble charms from Italy
Sasura is the first eyewear brand to introduce the art of pairing jewelry with eyewear. Sasura offers endless possibilities for your eyewear.
Sasura frames are a revolutionary concept that combines eyewear with fine jewelry. With our patented interchangeable jewelry technology, Sasura frames are fully customizable with our fine jewelry beads: Sasura Jewels. Both our optical frames and sunwear, are Made in Italy with the finest acetates and metals using innovation and traditional craftsmanship. All of our Sasura Jewels are made of 925 Sterling Silver and many designs contain crystal and cubic zirconia. With expertise across both eyewear and jewelry, our design team is inspired to create frames and jewelry that PAIR PERFECTLY together.
Entourage of 7 is luxury eyewear based in Los Angeles and influenced by the city in which it originates. In the City of Angles - an ever- changing multicultural melting pot, we find joy in pushing forward, constantly reminding ourselves to always be courageously creative. We aim to design beautiful spectacles for our rockers and rollers, lovers and sinners at Venice Beach – the birthplace of Entourage of 7.
Handmade glasses that are made in France. Established in 1997, it is now part of the J.F.Rey brand of High Quality Frames. Designer Fabienne Coudray-Meisel who is also an Optician, knows how to create frames that are comfortable and of superior quality.
Dutz has designed a collection of modern, elegant frames that uses colour to create unique styles. Each frame uses classic shapes with a hint of edginess, resulting in designs that are wearable, yet funky and different from any other brand on the market.
Installed in the Vallée de Morez, capital of the spec- tacle industry since 1796, Vuillet Vega has specialised in the manufacture of upmarket spectacle frames for the past five generations. Its spectacle frames are made from precious or semi-precious inset materials: mother-of-pearl, tortoiseshell, shagreen, etc. Some of its tools, machines, models and documents dating from 1843 are still used by the company for the design and manufacture of prototypes of spectacles. All the assembly and insetting techniques are carried out by hand. The company constantly carries out technical research on the materials and tools. Vuillet Vega has been awarded several prizes for its aesthetically pleasing and user-friendly products. All the new models are registered with the INPI, the National Industrial Property Institute. The company's designer holds the title of Meilleur Ouvrier de France (Best Craft Worker) in spectacles. The company sells its products exclusively to shops specialising in the sale of spectacles (e.g. Krys, Afflelou, Visual, etc.) and to some celebrities. Its products are exported to the Middle East, Asia, Africa and North America.
An innovative and fun new concept of frames with interchangeable fronts. Like nature, which adopts a new look each season, we all evolve and reinvent ourselves as our desires and lives change. This is why Zenka has designed interchangeable eyewear that can be transformed to suit our mood and lifestyle. Change of decor The principle is simple and ingenious : an original and colourful clip-on part is added to the top or front of a simple frame, transforming it in just one click into trendy, eye-catching and unique glasses. These decorative elements are as easy to remove as they are to attach. For each new season, a new look To allow glasses wearers to nd the perfect match for their mood of the moment, Zenka offers a wide range of frames and a multitude of clips with new designs each season. Whether glamorous, contemporary, daring, trendy or ultra-stylish, our clips reflect the latest fashion trends. High-quality products Frames are made from TNG and inox, high-tech, robust and ultra-light materials.100% French manufacturing adds a guarantee of quality.
with interchangeable temples
Eté Lunettes from France
The Eyewear The JAGUAR Eyewear collection mirrors the unique elegance and drive of the JAGUAR sports car. Design interpretations from car to eyewear such as carbon fibre details, wood grain and interior materials characterize the collection. Lens shapes that closely adhere to the design language of the car as well as color transfers further add to the JAGUAR magic of these frames, making them truly desirable products for men. The car JAGUAR is known for the development and fabrication of sovereign and ambitious luxury vehicles since 1922. The sensuous premium- automobiles and sports cars ensure extraordinary performance, exceptional luxury and an intense driving experience like only a JAGUAR can do
9965 152nd Street, Surrey BC Tel: 604-583-6155 Business Hours: CLOSED MONDAYS Tue to Fri: 9:30am to 6:00pm Saturday: 9:30 to 5:00 Sundays and Holidays: Closed
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Sierra Leone National Premier League – najwyższa klasa rozgrywkowa klubów piłki nożnej w Sierra Leone. Rozgrywki ligi toczą się od 1967 roku.

Drużyny w sezonie 2011/2012
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Zwycięzcy

Podsumowanie

Przypisy

Bibliografia

Sierra Leone
1

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Home News Youths Vow to Protect Themselves and Others
Youths Vow to Protect Themselves and Others
Phakama("Rise,Stand Up"), a theatre troupe in South Africa, educates audiences about HIV and AIDS. Actors shown here perform a scene emphasizing the importance of caregiving to those with virus.
ADDIS ABABA, Ethiopia — Young leaders from 38 African countries have pledged to act as role models for their fellow youths by "protecting ourselves, our partners and families from HIV, sexually transmitted infections, unwanted pregnancies, harmful practices and gender-based violence which negatively affect the sexual and reproductive health and rights of young people."
The young leaders were participating in a three-day training course before the International Conference on AIDS and STIs in Africa (ICASA) this month in Addis Ababa. At the training session, sponsored by UNFPA, United Nations Population Fund and AfriYAN (Africa Youth Network for Population and Adolescent Development), the participants vowed to spur opportunities in their families, at school, in community centres and at reproductive health-care centres to ensure comprehensive sexual and reproductive health information and services. This includes HIV counselling and testing, prevention of mother-to-child transmission and access to condoms.
In addition, they said that they would hold governments accountable to their commitments to young people to provide access to comprehensive sexuality education and youth-friendly services and to ensure reproductive health commodity security.
Changing AIDS advocacy in Africa
The youth leaders called on governments to eliminate "all forms of barriers that dictate and often contravene the rights of the youth to sexual and reproductive health, including socio-cultural issues, legal and policy barriers, the cost of reproductive health commodities, inefficient logistical systems for the distribution of reproductive health commodities, inaccessible geographical locations, lack of information and poor communication between youths, their parents and guardians."
The training also covered various aspects of reproductive health commodity security, including how to achieve results through youth-led advocacy.
In his address, Dr. Akinyele Dairo, UNFPA Africa Region Office Senior Programme and Technical Adviser, highlighted the changes that are taking place in the AIDS movement through youth activism on the continent. He encouraged the assembly to take a broader view of youth-related issues, such as development, investment and employment and, where possible, advance and influence the agenda. Some North African countries, such as Tunisia, are beginning to show interest in continental dialogues and identifying with issues elsewhere in Africa. Therefore, AfriYAN should be prepared to extend such a dialogue. — Adebayo Fayoyin
Population : 115 mil
In Afghanistan, years of inequality and violence give way to a fragile hope
State of World Population 1998
More young people than ever are entering their childbearing and working years. At the same time, the number and proportion of people over age 65 are increasing at an unprecedented rate.
International Conference on Human Rights
On the 20-year anniversary of the adoption of the Universal Declaration of Human Rights, an International Conference on Human Rights was convened to assess progress in its implementation. Representatives of 84 Member States, along with delegates...
see event >


A local nonprofit has expanded its office by 500 square feet.
Grand Rapids-based Emmanuel Hospice expanded its offices at 2161 Leonard St. NW to accommodate eight team members who have been hired in the last six months.
The expansion includes a new conference room with a television and enhanced technology, three new offices — one of which is reserved for grief support sessions — and a new break room for staff and volunteers.
Founded in 2013, Emmanuel Hospice is a nonprofit faith-based provider of hospice care born of a collaboration between St. Ann's Home, Clark Retirement Community, Porter Hills and Sunset Manor.
Emmanuel Hospice currently cares for up to 70 families a day in four West Michigan counties. In 2016, the organization provided care for more than 300 patients and approximately 925 caregivers.
The nonprofit also provides grief counseling services and support and education on end-of-life issues.


Carpe Diem Arts is dedicated to serving diverse audiences with quality arts experiences, representing a broad range of cultural traditions and artistic disciplines. Activities include after-school programs, summer arts and language immersion camps, community dances, concert series, monthly family sings, cultural enrichment programs and residencies in schools, ukulele classes, and performance opportunities for all ages -- in both the greater Washington DC area and Maryland's Eastern Shore. We partner with other area non-profits to expand our reach and deepen our impact, bringing the arts to life in ways that matter and make a difference in building stronger living-learning communities. Please contact us for more information.


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Economy, Business And Markets
Bulls Reign Over Tehran Stock Exchange
Tehran Stock Exchange's benchmark index gained 1130.40 points or 1.27% to end Saturday trading at an all-time high of 90,469.5
Continuously improving global commodity prices, a devaluing currency and better-than-expected company performance have driven TSE to post a return on investment of more than 17% so far this fiscal year (started March 21)
Bulls are reigning over Tehran Stock Exchange these days, after its benchmark index recorded the highest daily growth in 13 months on Saturday and zoomed past its all-time high reached four years ago.
TEDPIX gained further on Sunday, ending trade 0.21% higher to stand at 90,655.5.
Analyzing the index's fluctuation pattern ever since its inception indicates that there is still room for growth and the upward momentum could only be potentially limited by adverse political developments.
Continuously improving global commodity prices, a devaluing currency and better-than-expected company performance have driven TSE to post a return on investment of more than 17% so far this fiscal year (started March 21).
Systematic risks are also abundant. On October 13, US President Donald Trump announced that he would not make the certification required under the Iran Nuclear Agreement Review Act, passing the ball to the congress to decide on the matter in 60 days. The fate of the JCPOA is still up in the air.
There is also the uncertainty over the direction of the Chinese economy and its perseverance in steel and aluminum capacity-cutting over new environmental policies, both of which have the potential to negatively affect global commodity prices.
Yet Iranian stock traders seem to believe that positive market dynamics outweigh the systematic risks, at least for now.
TEDPIX Fluctuations
The analysis of TEDPIX's performance since 1997 indicates that the index has gone through several critical periods.
The period between the fiscal years 2002-4 witnessed TEPDIX growing about 250% from less than 4,000 to 13,882 in mid-July. In fact, the market was not able to cross this high for the next six years.
Notable economic growth and consistently declining deposit interest rates were the main reason behind the growth, the Persian daily Donya-e-Eqtesad reported.
The next boom came in late 2007 and was rather short-lived. TEDPIX grew from less than 10,000 to 12,917 up until early 2008, recording a 30% jump. Global prices' accelerating growth was the market's primary driver, but that also quickly lost momentum as the global financial crisis dragged economies into recession.
Things picked up again for TEDPIX in early 2009, as it followed a sharp rising trajectory from less than 8,000 to 26,675 by late March 2011. Save for a few hiccups, the index was constantly on the rise.
Rampant inflation and low interest rates were the main boosters of firms' nominal profits and consequently the market index. Brakes were pulled by early 2012, however, as housing, forex and gold markets became more attractive.
Then came the forex crisis in mid-2012 and companies' shares started to rocket up to new heights. TEDPIX surged from less than 24,000 to a new high of 89,500 by January 2014, marking a 270% growth. Optimism over Hassan Rouhani's election as the president of Iran and the nuclear talks fueled the uptrend.
Yet the market growth could not be sustained and TEDPIX started going downhill up until December 2015 to drop to 61,500.
The next few months to March 2016, however, witnessed a 30% jump to 81,536 over the implementation of JCPOA. Auto shares were especially instrumental to the market growth, as investors expected the industry to thrive post-sanctions.
The market had no noteworthy movements for the rest of the year other than sporadic corrections, as the post-JCPOA optimism was curbed over the lack of matching economic growth.
Come July 2017, the rising trajectory of TEDPIX resumed, which has continued to date, rising from 78,632 to 90,470.
Room for Further Growth
TEDPIX's fluctuations over the past 20 years show that its current growth can continue even further. There are three points that can support this: First, the market's 17% growth so far this year is considerably lower compared to TEDPIX's historical trend in similar periods. Second, the new historical high reached has psychological potential to lure in new money from other markets. And third, data show that the index is bound to have a much sharper rise as it is still in the first stages of growth, considering the slow upticks and low average trade value.
Moreover, a devaluing currency, rising attractiveness of stocks compared to other markets and the positive outlook of global prices, and the market seems bound for new highs.
TEDPIX, IFX Hover at All-Time High
Investors Gear Up for TSE Profitable Days
TEDPIX Near 4-Year High
Tehran Stock Exchange Gauge Ends H1 10.77% Higher
Where Are TSE Stocks Headed?
Stocks Post Small Gains


Many complex processes are involved in the metastatic spread of cancer cells from the primary tumor to lymph nodes and distant organs. The sentinel lymph node (SLN) is the first node to receive lymphatic drainage from the primary lesion and is of great importance in initiating an effective anti-tumor immune response; it also constitutes a first line of defense against metastatic spread . For many malignancies, the presence of tumor cells in tumor-draining lymph nodes (TDLN), and in the SLN in particular, is a key prognostic factor and, in some cases, predicates the course of treatment . In some tumors, e.g., cervical cancer (CxCa) or oral cancer, a complete lymphadenectomy provides overall survival benefit [3, 4, 5, 6]. However, for other indications, such as melanoma  and breast cancer (BrC), this is not the case .
The main focus of current immunotherapeutic strategies is on targeting the microenvironment of primary tumors and/or metastatic lesions, most notably by checkpoint inhibitors. As therapeutic targets, TDLN, and SLN in particular, are relatively undervalued, and clinically under-utilized. They are, nonetheless, essential players in anti-tumor immunity. In this focused review, we will discuss the importance of, and clinical opportunities for, therapeutic targeting of TDLN, based on findings from pre-clinical and clinical studies carried out by our group.
In the TDLN, tumor-specific T-cell responses are initiated. Here, effective priming of cytotoxic CD8+ T cells takes place upon tumor-specific (neo)antigen recognition, presented by APC, including DC and macrophages . Although DC represent only a small population of all the immune cell subsets in the LN, they are crucial in initiating an effective immune response. In cancer, however, TDLN are under the influence of tumor-derived factors, such as extracellular vesicles , IL-6 , TGF-β , prostaglandin-E2 (PGE2) , and VEGF [12, 13]. As a result, DC are suppressed and acquire an immature and M2 macrophage-like phenotype, and will, therefore, not properly cross-present in TDLN . During tumor progression and prior to metastasis, TDLN undergo many additional profound alterations leading to invasion by cells derived from the primary tumor [1, 2, 15]. Such alterations include increased lymphangiogenesis, blood vessel remodeling, and increased chemokine and cytokine secretion, which can ultimately lead to changes in immune cell composition, resulting in a 'tumor-supportive' microenvironment, i.e., the pre-metastatic niche . Moreover, with the ability of tumor cells to evade immune surveillance by the upregulation of immunosuppressive ligands and downregulation of MHC class I-molecules, this can eventually lead to the metastatic growth of tumor cells that have reached the TDLN .
Thus, immune modulation of TDLN could generate effective tumor-specific T-cell responses and in this way prevent metastatic spread. Considering that only a minor fraction of systemically administered drugs reaches the TDLN , locally applied therapies may be more effective in counteracting immune suppression in TDLN. Based on immune profiling and ex vivo proof-of-concept studies, we have conducted and are currently conducting a number of clinical trials aimed at immune potentiation of the TDLN through local delivery of immune modulatory drugs.
Over the past 2 decades, our group has pioneered the flow cytometry-based immune profiling of TDLN in humans. In these studies, we employ a scraping method (i.e., we scrape the cutting surface of a bisected TDLN) to obtain viable leukocytes from the TDLN, which was shown not to interfere with diagnostic procedures . Compared to dissociation of the entire node, we found similar viabilities and phenotypic characteristics of T-cell and DC subsets in scrapes . In addition, using multiparameter (fluorescent) IHC, we are currently working on improving our understanding of the TDLN architecture and cellular networks by studying (co-)localization of diverse immune cell subsets in their microenvironment [19, 20, 21].
In early pioneering studies on the immune status of melanoma SLN, Cochran and colleagues convincingly demonstrated that DC in SLN were more immune suppressed than DC in further downstream located TDLN [22, 23]. This observation suggested DC to be a prime target of melanoma-induced immune suppression, consistent with their pivotal role in initiating T-cell-mediated anti-tumor immunity. Our group was the first to characterize and functionally test conventional DC (cDC) subsets, distinguishing migratory from LN-resident (LNDC) subsets, in human skin-draining LN using multiparameter flow cytometry  closely followed by Segura and colleagues . We identified two migratory CD1a+ cDC subsets, i.e., dermal DC (DDC) and Langerhans cells (LC), and two LNDC CD1a− cDC subsets, distinguished by absence or presence of CD14 expression (see Table 1). The relative importance and varying roles of these cDC subsets in the priming of immune responses in healthy human LN remains largely elusive, but some clues are emerging. The migratory subsets take up antigens in the skin and will subsequently migrate to the skin-draining LN, where they can present those antigens to T cells. The two LNDC subsets are found in skin-draining LN but not among DC migrated from skin explants and are recruited from the peripheral blood to the LN . They are key players in cross presentation as evidenced by the high surface levels of cross-priming associated markers CLEC9A and BDCA3/CD141 (as well as expression of BATF3 mRNA; van de Ven et al., unpublished data) and by correlation of their frequencies to cross-presentation ability of melanoma SLN single-cell suspensions, which we observed after TLR9-mediated conditioning . Importantly, although the migratory subsets appeared more phenotypically mature under steady-state conditions, ex vivo isolated LNDC (both CD14− and CD14+) subsets proved more powerful in vitro primers of allogeneic effector T cells, which might tie in with higher release levels of T-cell-activating cytokines . Functional differentiation between the CD14− and CD14+ subsets remains obscure, but both may be involved in the priming of systemic anti-tumor effector T-cell responses, as we found the activation state of either to be associated with distant recurrence-free survival in early stage melanoma . Another DC subset in skin-draining LN are plasmacytoid DC (pDC) . These cells are poor antigen presenters, but are powerful producers of type I interferons upon TLR activation . As such, pDC play an important role in the activation of cDC and other immune cells.
In melanoma, we observed a significant negative correlation between the activation state (based on CD83 expression) of DDC and LC in the SLN and primary tumor burden (Breslow thickness) . Interestingly, primary tumor burden was not shown to have a significant effect on either the frequency or activation state of LNDC subsets. However, the presence of SLN tumor metastases did have a significant impact on both the frequency and activation state of conventional LNDC, the latter showing a reverse correlation with the size of the metastasis (Table 1). This suggests that the primary melanoma can create a pre-metastatic niche in the TDLN by suppressing the activation states of migratory cDC subsets, which was shown to be associated with a shorter local recurrence-free survival. Subsequently, TDLN metastasis suppress LNDC which, interestingly, was shown to be associated with a worse distant recurrence-free survival . The latter indicates an essential role for conventional LNDC in the induction of effective systemic anti-tumor immunity.
The 10-year melanoma-specific survival of stage I and II melanoma patients, defined as any primary tumor without regional or distant metastases, ranges from 98 to 75% depending on risk factors, such as Breslow tumor depth and tumor ulceration. After tumor spread to the regional LN, the 10-year melanoma-specific survival can drop to as low as 24% in patients with stage IIID melanoma . The unmet medical need for many of these patients stems from the fact that there is no widely used adjuvant treatment available to reduce the chances of disease recurrence, although systemic treatment (neo-adjuvant, i.e., preceding complete lymph node dissection) with immune checkpoint inhibitors in patients who are at very high risk of recurrence (high-risk stage III) and treatment with dual BRAF and MEK inhibitors in patients with BRAF V600E or V600K mutated stage III melanoma, has shown to improve recurrence-free survival [30, 31, 32, 33], and has recently been approved by the FDA. For all other early stage patients, there is a "wait and see" approach after surgical removal of the primary lesion and SLN.
Interestingly, we were able to show in multiple randomized and placebo-controlled clinical trials that there is a good rationale to treat these early stage melanoma patients with local immunotherapy aiming to prevent loco-regional and, eventually, distant spread, while minimizing immune-related side effects in this essentially healthy population. Our earliest results were published in 2004 and reported on a 2-armed (1:1) randomized placebo-controlled phase II trial in which 12 patients received four daily intradermal injections directly adjacent to the scar from the primary melanoma excision from day − 3 to day 0, just before the sentinel node biopsy (SNB) and re-excision of the (former) primary tumor site. Patients received either 3 μg/kg body weight recombinant human GM-CSF dissolved in 1 mL saline or 1 mL plain saline alone. GM-CSF administration resulted in higher frequencies and enhanced maturation and activation state of CD1a+ migratory cDC in the SLN . In two more recent trials, we showed that low-dose intradermal injections with the TLR9 agonist CpG-B, either alone or combined with GM-CSF, at 1 week prior to the SNB, resulted in enhanced activation of conventional CD14− and CD14+ LNDC as well as of pDC in the SLN [26, 35]. Interestingly, this local immunotherapy instigated local (i.e., in the SLN) as well as systemic tumor-specific CD8+ T-cell reactivity . A recent meta-analysis showed that patients in the treatment arm of these two studies had fewer tumor-positive SLN after SNB and a longer recurrence-free survival . These studies thus deliver an important proof-of-concept, showing that local immune modulation, specifically of TDLN, may lead to systemic protection against later tumor recurrences (see Fig. 1). We are currently planning a confirmatory randomized and placebo-controlled phase II clinical trial with a next-generation CpG oligodeoxynucleotide in 214 patients with stage II melanoma (Netherlands Trial Registry no. NTR7355).
Comparable DC-targeting therapeutic approaches may be implemented in patients with BrC, since both melanoma and BrC drain to LN in the skin catchment area with comparable migratory and LN-resident DC subset distribution profiles. In BrC, neoadjuvant chemotherapy (NAC) is one of the treatment options. A pathologic complete response (pCR) upon NAC is an independent predictor for favorable clinical outcome in all molecular subtypes . Interestingly, T-cell infiltration in BrC holds predictive value for response to chemotherapy . Since certain cytostatic drugs can induce immunogenic cell death (ICD), leading to the release of tumor-associated antigens , there is a clear rationale to combine NAC with DC-potentiating strategies to optimize tumor-specific T-cell priming in the TDLN. An early study from 1999 already showed a favorable effect on patient survival of combined GM-CSF with NAC in patients with locally advanced BrC . Patients were treated with doxorubicin, cyclophosphamide (both agents known to induce ICD) and GM-CSF at three-weekly intervals. After a maximum of six cycles, patients underwent surgery and postoperative radiotherapy. We observed higher frequencies of mature DCs in the TDLN of these patients, suggesting that GM-CSF is able to improve patient outcome via DC recruitment and maturation, and a subsequent anti-tumor response . Interestingly, we have observed a similar relationship between hampered activation of LNDC and tumor involvement of SLN in patients with BrC as we previously reported in melanoma (van Pul et al. manuscript submitted). Therefore, in analogy to our clinical findings in melanoma, CpG-based local immune potentiation in combination with NAC may improve response rates in patients with BrC. This certainly deserves further (pre-)clinical exploration.
In contrast to melanoma and BrC, CxCa is caused by a persistent infection with high-risk strains of the human papillomavirus (HPV), mainly HPV16 and HPV18. HPV-specific T cells  as well as T cells that target non-viral tumor-associated (neo-)antigens  have been detected in CxCa TDLN. As HPV-derived antigens are highly immunogenic, it is assumed that an immunosuppressive environment facilitates immune escape and thereby causes lymphatic spread.
CxCa is a locally invading disease and initially metastasizes to pelvic TDLN. The presence of LN metastases in patients with CxCa is a crucial prognostic factor . Importantly, survival benefit was observed for CxCa patients who underwent complete lymphadenectomy upon low-volume disease detection in the SLN, or even upon the removal of solely tumor-negative LN [3, 5], indicating the presence of an unfavorable immune microenvironment in CxCa-draining pelvic LN. To understand the cellular basis for this phenomenon and to find new immunotherapeutic targets that would allow immune stimulatory conversion of the TDLN microenvironment, we performed several studies in which we found various immune escape mechanisms exploited by CxCa.
Interestingly, flow cytometric characterization of diverse immune cell subsets in TDLN of CxCa patients, showed that in contrast to melanoma and BrC, Langerhans cells were hardly present in CxCa LN. Although higher levels of CD1a+ DCs were present in tumor-positive LN (LN+) as compared to tumor-negative LN (LN−) , these cells might have been derived from recruited and tumor-converted monocytes rather than conventional migratory CD1a+ DC. Remarkably, we did not find evidence of decreased LNDC activation. These results point to the requirement for a different immunotherapeutic approach aimed at TDLN conditioning in CxCa, than the one tested and proposed for melanoma and BrC, respectively.
In addition to higher levels of CD1a+ DCs, elevated levels of activated CD8+ T cells in LN+ suggested immune activation . However, this activation was apparently overruled by a highly immunosuppressed microenvironment in LN+ compared to LN−, with high expression levels of the checkpoint molecules PD-1 and CTLA-4 on T cells and the presence of MDSC. Moreover, high rates of Tregs were observed in LN+, which correlated with the rates of M2-like CD14+PD-L1+ APC. A cytokine release profile consistent with an immune suppressive microenvironment was observed as well, with high IL-10, IL-6, TNFα, and low IFNγ expression. In a comparative study of all dissected cervical TDLN from five patients with CxCa, we found that immune suppression (identified as low CD8+ T cell/FoxP3+ Treg ratios) preceded actual metastasis, creating metastatic niches in the tumor-draining lymphatic catchment area . We hypothesize that primary tumors are able to recruit (possibly via the secretion of CCL2)  and polarize CD14+ monocytes into suppressive PD-L1+ M2-like macrophages [(co)-expressing CD14 and/or CD163] . These M2-macrophage-like cells, induced by tumor-derived factors, are incapable of stimulating proper CD8+ T-cell responses, favor Treg expansion, and facilitate tumor progression by the production of pro-angiogenic and pro-tumor-invasive factors [14, 49].
In aggregate, our findings support the clinical exploration of immunotherapies in CxCa aimed at converting the prevailing immunosuppressive conditions in the primary tumor and TDLN into an immune-activated tumor-targeting environment.
Recently, an immune checkpoint inhibitor of PD-1, pembrolizumab, was approved by the FDA for patients with recurrent or advanced CxCa based on an overall response rate of 14.3% and a complete response rate of (only) 2.6% . Based on these results, and the fact that CxCa is mainly a locally invasive disease, we believe that intratumorally administered immunotherapies in earlier stages of CxCa may accomplish tumor control, as TDLN and the PD-L1+ macrophages residing therein are most efficiently targeted in this manner. We hypothesize that interference in the functionality of M2-like macrophages in the TDLN may hamper Treg expansion and break the vicious cycle of metastatic niche formation and tumor spread through the lymphatic catchment area, and subsequently to more distant sites (see Fig. 2). Currently, a phase-I clinical trial is ongoing, testing the safety and feasibility of a single low dose of intratumorally injected durvalumab (anti-PD-L1) in CxCa patients 2 weeks before radical hysterectomy with pelvic LN dissection (Netherlands Trial Registry no. NTR6119). With this strategy, we aim to achieve modulation of the microenvironment in the primary tumor and the TDLN and so break immune suppression. This will hopefully result in the generation of both local and systemic tumor-specific T-cell reactivity , like we previously observed when investigating locally administered CpG-B in melanoma patients, with an even shorter time window of 1 week between drug administration and surgery.
Immune profiling of TDLN in patients with various types of solid tumors enabled us to ascertain the suppressive effects of the tumor on loco-regional cellular immunity and provided a clear rationale for the local application of immune modulating therapies targeting TDLN (see Table 2). It is essential to perform immune profiling for each tumor type and subsequently select the appropriate immune modulating agent, as various possible mechanisms of immune suppression were found per tumor type. Importantly, we found evidence of systemic anti-tumor immune activation which seemed capable of preventing (distant) recurrences, as shown by a profoundly increased 10-year recurrence-free survival rate in melanoma patients treated locally with CpG-B prior to the standard-of-care SLN procedure. With the use of less invasive locally applied therapies, surgical complications resulting from LN dissection (e.g., lymphedema) may be avoided. Moreover, this localized therapeutic approach may stop cancer spread in its tracks at an early stage and trigger a protective systemic anti-tumor T-cell response without the unwanted, and sometimes severe, side effects associated with systemic treatment with immune checkpoint blockade [52, 53]. This may have a major impact on patient survival and quality of life. Moreover, by administering a single low dose, the high costs associated with systemic immunotherapeutic treatments in more advanced stages of cancer could be conceivably reduced .
In conclusion, we believe that TDLN are of major importance in initiating a robust anti-tumor response upon immune modulating therapies and should be targeted by local delivery of immune modulatory agents. Evidence for this was provided by i.t. delivery of CTLA-4 blocking antibodies in a mouse model, showing equivalent tumor control to systemic administration with reduced side effects . Interestingly, Chamoto and colleagues observed absent anti-tumor efficacy of PD-1 blockade in a mouse model with TDLN ablation, and so demonstrated TDLN to be indispensable, even for an immune modulatory agent assumed to be primarily active in the tumor microenvironment . Fransen et al. recently confirmed these results and, importantly, showed equal in vivo anti-tumor efficacy of low dose locally injected anti-PD-1 and of systemically administered high-dose anti-PD-1 .
The rational design of future clinical trials targeting TDLN should encompass combinatorial use of immunotherapeutic agents, such as oncolytic viruses and/or immune checkpoint blocking antibodies. Moreover, it will likely not be limited to the cancer types discussed in this focused review, but may also be applied to other solid tumors proven amenable to immunotherapy, such as, e.g., lung cancer and head-and-neck cancer.
Graphical illustrations were drawn using the images from Servier Medical Art by Servier with slight modifications (http://www.smart.servier.com).
TDG drafted the original outline of the review. JR, BDK, and AMH wrote the paper. TDG and ESJ added content and edited the paper. Final approval was given by all authors.
Data discussed in this review were derived from studies funded by the Dutch Cancer Society (KWF Kankerbestrijding VU 2013-6015 and VU 2015-7864).


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Werth most successful Olympic rider as Germany wins dressage
Gold medal winners Germany's Isabell Werth, left, Dorothee Schneider, second left, Sonke Rothenberger, second right, and Kristina Broring-Sprehe, right, after winning the team dressage equestrian competition at the 2016 Summer Olympics in Rio de Janeiro,
RIO DE JANEIRO (AP) Isabell Werth became the most successful rider at the Olympics as she helped the German dressage team to gold on Friday, reclaiming the title in an event that her country has historically dominated.
Germany has won eight of the past nine gold medals in the discipline, with its run interrupted by Britain in the 2012 London Games.
It was Werth's fifth gold medal in the event, tying compatriot and former Olympic champion Reiner Klimke. She now has nine Olympic medals in all.
Werth could also add an individual title to her haul on Monday, although she faces stiff competition in reigning champion Charlotte Dujardin. Her victory also moves her even with compatriot and former Olympic champion Reiner Klimke.
''It's great to have another gold medal of course, that's why we came here, to win. But to work with horses and to win with three different horses, that makes me really happy and proud, that's what I work for day by day.''
Werth, Kristina Broring-Sprehe, Dorothee Schneider and Sonke Rothenberger posted a score of 81.936 percent, while the British team finished with 78.595.
The United States was third with 76.667, with former hairdresser Laura Graves recording a personal best of 80.644 on Verdades in her first Olympic Games.
''The elusive 80 percent, finally we've captured it, it exists,'' Graves said. ''I knew it was going well. You just always hope your reflections match up with the judges. I was happy to see my teammates so happy and then to have a personal best and a score I've been reaching for was just icing on the cake.''
It ends a long wait for German-born Steffen Peters, who helped the U.S to bronze in 1996 but was a reserve when it repeated that feat in 2004.
''If you wanted to see a 52-year-old man act like a 10-year-old boy you should have seen me in the stands when Laura was coming down the center line,'' Peters said. ''I was crying my eyes out, it was just one of those absolutely amazing experiences.''
The results are calculated using the average of the three best riders' scores from each nation from Friday's Grand Prix Special as well as the previous day's Grand Prix.
''We were hoping and a little bit expecting we can go for the gold medal because I can't remember a German team that went to the Olympic Games where four horses could go over 80 percent,'' Werth said.
''So I was hoping that if there was maybe one horse that had problems that the other three are so strong that they could deal with the situation but all four horses were really good over three days and this was much more than we expected.''
Three of the top four finishers were German, with Britain's Dujardin posting the second highest score after an uncharacteristic error from her horse Valegro.
The individual Olympic champion still managed a score of 82.983, with Werth achieving 83.711.
The individual medals are awarded Monday after the Grand Prix Freestyle, where the top 18 riders from the first two grand prix pick their own routine to perform with music.
Carl Hester, who also trains the other riders on the British team, has a special plan to ensure Dujardin successfully defends her title.
''I'm taking her to Christ the Redeemer tomorrow to pray for Monday,'' he said.
More Olympics


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JCPenney Closing Stores After Bankruptcy
JCPenney has added a pair of stores to its list of permanent store closures. The retailer confirmed to USA TODAY that the Greenwood, Mississippi and Baytown, Texas stores will soon close and are holding liquidation sales. The Mississippi store is scheduled to close Oct. 24 and the Texas location on Dec. 5.
The department store chain was one of the largest retailers to file for Chapter 11 bankruptcy protection during the coronavirus pandemic. Officials said in May 2020 that they planned to close about 29% of its 846 stores or 242 locations in bankruptcy and hoped to use the process to shed debt and remain in business.
Since then 174 stores have permanently closed and last December emerged from bankruptcy after being acquired by mall owners Simon Property Group and Brookfield Asset Management Inc. Eighteen stores shuttered in May.
JCPenney told USA TODAY that the two closings are unrelated to last year's "store optimization" strategy.
While never a good sign for any business, in this case, bankruptcy seems to have helped this national retailer and its former landlord and new owner, Simon.
Whenever a business declares bankruptcy, you can bet there's going to be a legal dispute. They are EVERYWHERE! And when those things negatively impact you and/or your business including bankruptcies, landlord/tenant matters including unlawful detainers, contract issues, nuisance ADA claims and even collections, call in your good guy business litigator, Dean Sperling to resolve YOUR matter with YOUR best interests in mind!
« University Lease Case Headed to Arizona Supreme Court» Following Your Risk-Adverse Lawyer's Advice


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Interview with Chris Rogers from COLOURlovers
People No Comments
Chris Rogers—also known as the lover named ruecian—is the man behind the site blog of COLOURlovers. I already reported about them, when they covered the topic of red-blindness just a bit more than one month ago.
Out of this first contact evolved the idea of an interview-exchange between the color blindness lovers from Colblindor and COLOURlovers.
As Chris is an expert on the topic of colors, in exchange he asked me some more details about color blindness, including positive and negative aspects of it. I hope you enjoy the following answers from Chris and make sure that you also visit the counterpart of this interview-exchange.
Colblindor: What is your favorite color and why?
Chris: I surround myself with blue because it's such a daydreaming, imaginative nature. As someone who experiences synaesthesia, a sort of crossing of senses, blue is also the colour that has the best texture to me. With colours, I experience textures along with the visual aspect, and with music, I experience colours and textures. I like a lot of yellow, brown, and blue songs, so, I'll say that those are my favourite colours.
Colblindor: COLOURlovers is a big resource concerning different aspects of colors. What are the main purposes of your website?
Chris: What I've come to find about COLOURlovers is that it's sort of a playground for creativity, as the site has attracted colour-passionate and colour-oriented professions from fields of design and art. We also have people whom have said they would have never dreamed of playing with colour before stumbling about COLOURlovers, and have since become 'colour addicts.' I'd say we're here to give an open, supportive space to the minds that want to come out and play, and I try to do that with my blog posts by posting something of interest, whether it be science or something inspirational.
Colblindor: Do you think color blindness might be some sort of handicap to join your community of lovers?
Chris: Oh, I don't think so. Some of the palettes that users (colour-deficient or not) create might look a bit off, and the palettes that are based off of emotions might not convey the same message, but it all ends up meaning something to someone, as I feel colour and colour symbolism is loosely based in interpretation. Just as everyone feels differently about Picasso, everyone can find their own enjoyment in seeing a red palette, even if they don't know it's red.
Colblindor: You're writing all about colors. When did it first come to your mind, that there is also a community of colorblind people and do you offer also some information, help or support for them?
Chris: I made a colour maybe what I guess to be about a year ago called 'of Colourblindness,' which was grey. And I remember having a note passed to me asking about colourblindness, and it was really my first venture in trying to explain it to someone. I had always understood the concept, but never had to put it into words. The idea had been in my mind since about that time, and surfaced soon after the blog began as the article that you found, which I wrote on Protanopia.
Colblindor: Do your users ever bring up the topic of color vision deficiency or is it almost not existing among lovers?
Chris: It has been asked before. There was a post on the forum about it, someone mentioned that they suffered from colour-deficiency, and needed some help pulling colours accurately from a painting. I do know that there are at least a few colour-deficient users on the site. It's not a typical topic, though. I think hearing 'COLOURlovers' can be a subject of much fear for someone who can't see colours like others can, but it's really not about who does colour better, it's about a love of colour, and I don't think colour-deficient or colour-blind people are exempt from that.
Colblindor: Can you tell us something about the 'headline' of COLOURlovers "Fight for love in the colour revolution"?
Chris: As far as fighting for love, there is a rating system in place that ranks colours and palettes by how many votes they received and how many users have added them to their favourites lists. I think it's also about how many comments are left, but I'm not sure about that one. I believe that COLOURlovers is changing minds about colour by bringing it to a field where anyone with hand-eye coordination can play, rather than having it restricted to artists with paint, or tailors with cloth. When I first stumbled upon the site in 2005, I was really cautious about my colour choices, and I created a lot of colours that were already in my life. The community is so very supportive. I've yet to see something negative said about something. In fact, I've even seen, "I love how ugly this is," and it gets voted high. In getting used to COLOURlovers, I've essentially discovered a whole new world and my thought process as a synaesthete has been allowed externalisation. That's what I think is meant by the 'colour revolution.'
If you enjoyed Chris answers, be sure to also check out his questions, published at the site blog of COLOURlovers. And if you enjoyed my questions, you might like to subscribe to the RSS feed of Colblindor, which ensures that you get frequently the latest updates and insights on color blindness.
How to Color Charts Respecting Color Blindness
Sunsets, Rainbows, Stop Signs for Colorblind Guys


ESPN's intrepid reporter with Bearcats QB Zach Collaros on the eve of homecoming: "Last year, Coach Jones said, this team was physically mismatched. But now everybody really gets the system."
This is going to be a really good football weekend. Rece Davis and I were talking the other (rainy) day, and we're hoping for a Cincinnati-N.C. State shootout to kick things off. You're talking about two teams that have kind of fallen in the same category, where they've got a lot to prove but a lot of points to score.
Considering all the hype over Russell Wilson with him leaving for Wisconsin and everything, Mike Glennon has been a nice breath of fresh air for this N.C. State team. It's kind of put a little hype on his shoulders and taken him from what I wouldn't necessarily call a nobody, but, as coach Tom O'Brien pointed out when I spoke to him yesterday, Glennon's only really had three starts in college football — and he is now definitely proving he can hang. The last time Glennon had started, before this season, was when he was in high school, and then he goes and throws for over 300 yards and three touchdowns against Wake Forest. He even almost broke Philip Rivers's completion-percentage record against South Alabama last week! And now he's playing on national primetime tonight.
With the quarterbacks playing on ESPN on Thursday nights, we always try to see how they handle themselves. Whether it's a hostile atmosphere and being on the road, or just that national stage of millions of people watching at home — it can really affect a QB, especially one that hasn't seen much game time. I'm always looking to see if they're a little too wide- eyed; it's usually evident in the first couple series, when you'll see them overthrowing receivers, but they all seem to settle in eventually.
But all the talk with the N.C. State coaches was about the defense and all of its injuries: Terrell Manning had surgery the other day, their captain J.R. Sweezy is still out with a broken foot — seven of their top 15 players on defense are out, and obviously it's showed.
Meanwhile, Cincinnati coach Butch Jones has really been emphasizing protecting the football. They led the league in turnovers last year. And that was on offense, not defense — not exactly a good thing. They spent the offseason, preseason, and most of camp focusing on eliminating turnovers and protecting the football. The Bearcats have only had one this season, so it seems to be working.
The realignment of the ACC, on the other hand, the coaches haven't really been emphasizing. It's the first thing we talked about, but Coach Jones said, "We're going to be fine." And pretty much all the coaches we talk to about the conference shuffling say they're not focused on it or really even thinking about it. Most of the coaches insist on this kind of wait-and-see approach — that it's out of their hands. But I imagine they're still thinking about it somewhere in the back of their minds.
Alabama-Arkansas is a big-time SEC game, for sure. First off, Bobby Petrino was throwing pretty much everything he could get his hands on the sidelines the other day, and he let QB Tyler Wilson have it more than once. But Arkansas almost beat Alabama last year, and both teams will show up ready to play. That being said, 'Bama is ranked No. 3 for a reason — that defense is really something — but I think Arkansas will come in and at least give them good game.
little extra time after our Thursday game last week, where the thing that impressed me most was their secondary. But Jarrett Lee? He looked really, really good. Now I know that going into Morgantown is tough — and that Geno Smith looked really good, too, and that anything's possible — but LSU has seen that spread offense with Mississippi State and with Oregon. They're ready.
For me, OK State and A&M — No. 7 and No. 8, and two explosive offenses — that's the other big one. We all know Brandon Weedon is awesome, but Ryan Tannehill has been very impressive as well, and these two teams have got a lot to live up to after the game they had last year. So they're calling this one a shootout, too. Like I said, it's going to be a really good weekend. By next week, maybe we'll have some Heisman candidates.
N.C. State plays at Cincinnati on Thursday night at 8 p.m. Eastern on ESPN, and Jenn Brown returns right here every Thursday on Esquire.com. In the meantime, follow her on Twitter.


With my media background, I'm always interested in finding ways to dig in someone's mind, unearth their thoughts, and put those thoughts together in a way that does justice to who they truly are.
You might be able to measure someone's knowledge in your fields of expertiese but you have no ability to measure someone's raw intelligence.
1) Their ability to identify and predict patterns.
2) Their ability to self-reflect.
3) Their ability to apply their existing knowledge to novel problems and situations.
Where do you think your field is headed in the next 5 years? How do you think your friends would describe you to a stranger? If you received a grant to work on any project you could, what would you work on?
In other words, measuring intelligence is not measuring the size of their mental library of facts. Measuring intelligence is roughly gauging their ability to speculate, theorize, and strategize.
This entry was posted in Uncategorized. Tagged communication.


text:
António Cabral (filho de Pedro Álvares Cabral) — filho de Pedro Álvares Cabral
António Cabral (escritor) — escritor português

Desambiguações de antropônimos


text:
require 'test_helper'

class AreasControllerTest < ActionController::TestCase
  # Replace this with your real tests.
  test "the truth" do
    assert true
  end
end

redpajama_set_name: RedPajamaGithub


Goodwin's goals added quality, but the real value in this match came from the atmosphere and intensity generated by both sides. External factors like attendance are often ignored in tactical analysis, but the contribution of the packed, fervent Hindmarsh crowd shouldn't be ignored – it made the game feel very energetic and urgent, right from the start.
There were two tactical reasons for the chaotic nature of the game. Firstly, both teams focused on playing quick, early balls in behind the opposition defence. This was particularly obvious in the first half. Adelaide have started this season with new signing Ben Halloran upfront. Not a natural 9, Halloran's quality is his speed. He makes runs into the channels, constantly looking to get in behind. In the first half, particularly, Adelaide looked to play killer passes for Halloran to receive behind Sydney's back four. Halloran has not always been on the same wavelength as his teammates, who have made killer passes in an opposite direction to, or after, Halloran's runs, and there are question marks about his long-term suitability to that position – but he did give Adelaide an obvious attacking outlet in this final.
Steve Corica's side, meanwhile, were similarly keen to release their strikers in behind. Adam Le Fondre plays high, up against the opposition centre-backs, and tries to slip into space in behind. Early on, Alex Wilkinson attempted a few long diagonals over the top towards Le Fondre. Additionally, Alex Brosque played higher than usual in this game, so Sydney basically attacked with a front two. In doing so, they were able to pin back Adelaide's back four, and open space for Rhyan Grant and Michael Zullo to get forward in wide areas. With Paolo Retre also making runs in behind from his right-wing position, there was lots of pace, forward runs and slightly overhit passes to make the game feel pleasingly open.
The other tactical reason for this was the pressing from either side. Both teams had a similar starting shape when defending high up the pitch – a 4-4-2. The first task of the front two for both teams was to block passes into the opposition's no.6s. When the ball was circulated from one side to the other, however, the nearest player in the first line of defence (the front two) would step forward and apply pressure to the centre-back in possession. If, when they stepped forward to press, they were able to block off nearby forward passing lanes, this was a cue for the rest of the team to step forward and close the spaces in between the lines.
There were slight modifications in either team's structure, but the overall intent of their pressing was similar.
The two tactical features discussed sometimes went hand-in-hand – the defending team would press high, and because they both wanted to play early balls in behind, the attacking team would be happy to play a longer pass forward. This, in fact, partly explains Sydney's equaliser: Sydney press high, force Adelaide into a long ball which is immediately returned forward, and Brosque runs from his high starting position to catch Jordan Elsey out and nip the ball away from Paul Izzo to win the penalty.
Where the game became particularly frenetic, though, was forward passes into midfield. In this zone, both teams had physical, mobile players who closed down their direct opponents ruthlessly. Both of Sydney's no.6s, Josh Brillante and Brandon O'Neill, also ended up in wider areas, conceding fouls for aggressive pressure on Adelaide's players. Unsurprisingly, every midfielder bar Brillante was booked.
These two tactical features contributed to the scrappy but enjoyable flow of the final. There was a large number of fouls as a result, and a lot of the game was also characterised by set pieces. Marco Kurz's side showed interesting variation in their corner and free-kick delivery, causing Sydney problems at times, whilst Sydney posed their own threat – coming close to a second equaliser with a header off the post in extra time.
Overall, the match was actually quite even, and a 'draw' would have been a fair result. Goodwin's outstanding finishes were obviously the difference, and added the gloss to the game, but it was the no-holds-barred, high-tempo style of game that made this final memorable.